Showing papers in "European Journal of Cardio-Thoracic Surgery in 2004"

The Aristotle score: a complexity-adjusted method to evaluate surgical results.

Abstract: Objectives: Quality control is difficult to achieve in Congenital Heart Surgery (CHS) because of the diversity of the procedures. It is particularly needed, considering the potential adverse outcomes associated with complex cases. The aim of this project was to develop a new method based on the complexity of the procedures. Methods: The Aristotle project, involving a panel of expert surgeons, started in 1999 and included 50 pediatric surgeons from 23 countries, representing the EACTS, STS, ECHSA and CHSS. The complexity was based on the procedures as defined by the STS/EACTS International Nomenclature and was undertaken in two steps: the first step was establishing the Basic Score, which adjusts only the complexity of the procedures. It is based on three factors: the potential for mortality, the potential for morbidity and the anticipated technical difficulty. A questionnaire was completed by the 50 centers. The second step was the development of the Comprehensive Aristotle Score, which further adjusts the complexity according to the specific patient characteristics. It includes two categories of complexity factors, the procedure dependent and independent factors. After considering the relationship between complexity and performance, the Aristotle Committee is proposing that: Performance ¼ Complexity £ Outcome. Results: The Aristotle score, allows precise scoring of the complexity for 145 CHS procedures. One interesting notion coming out of this study is that complexity is a constant value for a given patient regardless of the center where he is operated. The Aristotle complexity score was further applied to 26 centers reporting to the EACTS congenital database. A new display of centers is presented based on the comparison of hospital survival to complexity and to our proposed definition of performance. Conclusion: A complexity-adjusted method named the Aristotle Score, based on the complexity of the surgical procedures has been developed by an international group of experts. The Aristotle score, electronically available, was introduced in the EACTS and STS databases. A validation process evaluating its predictive value is being developed. q 2004 Published by Elsevier B.V.

Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial.

Abstract: Objectives: The non-small cell lung cancer (NSCLC) meta-analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery, radical radiotherapy or 'best supportive care'. However, it included many small trials and trials with differing eligibility criteria and chemotherapy regimens. The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta-analysis. Methods: In the surgery setting, a total of 381 patients were randomised to chemotherapy (C, 192 patients) or no chemotherapy (NoC, 189 patients). C was three 3-weekly cycles of cisplatin/vindesine, mitomycin/ifosfamide/cisplatin, mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin. Results: Chemotherapy was given before surgery in 3% of patients whilst 97% received adjuvant chemotherapy. Baseline characteristics were: median age 61 years, 69% male, 48% squamous cell, 93% WHO PS 0-1, 27% stage I, 38% stage II, and 34% stage III. Complete resection was achieved in approximately 95% of patients. In the C group, 13% received no chemotherapy, 21% one or two cycles, and 64% all three cycles of their prescribed chemotherapy (60% of the latter with no delays or modification). 30% had grade 3/4 toxicity, mainly haematological, nausea/vomiting and neutropenic fever, and six patients were reported as having a treatment-related death. 198 (52%) of patients have died, but there is currently no evidence of a benefit in overall survival to the C group: HR 1.02 (95% CI 0.77-1.35), P = 0.90). Conclusions: This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC. However, the hazard ratio and 95% confidence intervals are consistent with the previously reported meta-analysis and two large recently reported trials, which suggest a small survival benefit with cisplatin-based.

First experiences with the da Vinci operating robot in thoracic surgery.

Abstract: Objectives: The da Vincie surgical robotic system was purchased at our institution in June 2001. The aim of this trial was to evaluate the applicability of the da Vincie operation robot for general thoracic procedures. Methods: The da Vincie surgical system consists of a console connected to a surgical arm cart, a manipulator unit with two instrument arms and a central arm to guide the endoscope. The surgical instruments are introduced via special ports and attached to the arms of the robot. The surgeon, sitting at the console, triggers highly sensitive motion sensors that transfer the surgeon’s movements to the tip of the instruments. The so-called ‘EndoWriste technology’ offers seven degrees of movement, thus exceeding the capacity of a surgeon’s hand in open surgery. We evaluated the role of the robot for several thoracic procedures such as thymectomies, fundoplications, esophageal dissections, resection of mediastinal masses and a pulmonary lobectomy. Results: A total of 10 thymectomies, 16 fundoplications, 4 esophageal dissections, 5 extirpations of benign mediastinal masses and 1 right lower lobectomy was performed with the robot. One resection of a paravertebral neurogenic tumor had to be converted due to surgical problems. A lesion to a left recurrent laryngeal nerve caused transient hoarseness after the extirpation of an ectopic parathyroid in the aortopulmonary window in one patient. The postoperative courses were uneventful and patients were discharged between postoperative days 3 and 8 (with the exception of patients who underwent dissection for esophageal cancer and the patient with conversion to an open access). Conclusions: Advanced general thoracic procedures can be performed safely with the da Vincie robot allowing precise dissection in remote and difficult-to-reach areas. This benefit becomes evident most elegantly in thymectomies, which at our institution have become a routine procedure with the robot. The rigid anatomy of the chest seems to be an ideal condition for robotic surgery. A major limitation for robotic surgery is the lack of more appropriate instruments. This disadvantage becomes most evident in pulmonary lobectomies. q 2004 Elsevier B.V. All rights reserved.

Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure.

Abstract: Objective: The application and timing of hemofiltration (continuous veno-venous hemofiltration, CVVH) in patients with acute renal failure (ARF) post cardiac surgery has been called into question because of uncertain short-term outcome. The aim of the present study was to identify how the timing of introduction of hemofiltration affects the morbidity and mortality in patients with ARF after cardiac surgery. Methods: 1264 consecutive patients who underwent adult cardiac surgical procedures performed between January 2002 and January 2003 were audited. Out of these, case notes of 64 patients who required renal supportive intervention were reviewed. Statistical significance was accepted at a level of P!0.05. Results: Of the 64 (5%) patients, who developed ARF and required CVVH, there were 48 males and 16 females. Mean age was 70G6.8 years. The hospital mortality was 43% (12 patients) in Group-I and 22% (8) in Group-II (P!0.05), giving an overall 1.5% mortality associated with ARF. The mean time between the operation and the initiation of CVVH was 2.55G2.2 days in Group-I and 0.78G0.2 days in Group-II (P!0.001). The mean duration of CVVH was 4.57G11.4 days in Group-I and 4.61G2.0 days in Group-II (PZNS). Older age (PZ0.013), elevated preoperative creatinine (PZ0.002), postoperative pulmonary oedema (PZ0.01), sepsis (PZ0.001), multiple organ failure (PZ0.031), hypotension (PZ0.031) and preoperative renal failure (P!0.05) were the independent factors influencing the poor postoperative outcome and cardiac instability. Conclusion: Early and aggressive use of CVVH is associated with better than expected survival in severe ARF after cardiac operations. q 2004 Elsevier B.V. All rights reserved.

EuroSCORE: a systematic review of international performance.

Abstract: The validity of the cardiac surgical scoring system, EuroSCORE, has been assessed by several individual cardiac centres within and outside Europe. We chose to assess the overall international performance by systematic review of peer-reviewed literature. There were six studies meeting our criteria for assessment. Internationally, the evidence is highly suggestive that additive EuroSCORE performance generally over-estimates mortality at lower EuroSCOREs (EuroSCORE 13). The effect of this could have serious misrepresentations for surgeons and hospitals operating on differing case-mixes. We suggest that further studies need to be performed on the logistic EuroSCORE calculation to ascertain whether predictive ability is improved. Overall, however, EuroSCORE is the most rigorously evaluated scoring system in cardiac surgery.

Effects of the patent false lumen on the long-term outcome of type B acute aortic dissection.

Abstract: Objective: To determine the most effective treatment, we performed a detailed comparative study of the clinical course of patients with type B aortic dissection with a patent or thrombosed false lumen who did not undergo surgery in the acute period. We examined the effect of patency of the false lumen on outcome. Methods: Computed tomography scans of 138 patients with type B acute aortic dissection were reviewed. Of 138 patients, 110 were medically treated and survived the acute period. We focused on the outcome of these 110 patients, 62 with medically treated thrombosed false lumen (thrombosed group) and 48 with medically treated patent false lumen (patent group). We investigated factors influencing outcome among the 110 patients. The follow-up period was up to 10 years after the onset of aortic dissection. The three study endpoints were death from any cause, dissection-related death (aortic rupture, perioperative death, or death due to organ ischemia), and a dissection-related event (aortic rupture or surgery). In the patent group, we investigated factors influencing long-term outcome. Results: Patency of the false lumen was an independent risk factor for dissection-related death (P ¼ 0:038; hazard ratio ¼ 5.6, confidence interval ¼ 1.1‐ 28) and for a dissection-related event (P ¼ 0:000; hazard ratio ¼ 7.6, confidence interval ¼ 2.7‐ 22) but not for death from any cause (P ¼ 0:769; hazard ratio ¼ 1.2, confidence interval ¼ 0.45‐ 2.91). In the patent group, location of the most dilated aortic segment at the distal arch was an independent risk factor for dissection-related death (P ¼ 0:026; hazard ratio ¼ 13.6, confidence interval ¼ 1.4‐ 135) and for a dissection-related event (P ¼ 0:048; hazard ratio ¼ 2.6, confidence interval ¼ 1.0‐ 6.9). Conclusions: Patency of the false lumen is a strong independent prognostic factor for type B aortic dissection. Location of the most dilated aortic segment at the distal arch is a significant risk factor in the patients with a patent false lumen. q 2004 Elsevier B.V. All rights reserved.

Myocardial ischemia, stunning, inflammation, and apoptosis during cardiac surgery: a review of evidence

Abstract: Cardiac surgery (CS), in particular cardiopulmonary bypass and cardioplegia, have been reported to trigger myocardial inflammation and apoptosis. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms. Both experimental and clinical studies have ascertained the role of several hormonal mediators, mitochondria, cardioplegia and extracorporeal circulation temperature, apoptosis and even genetic modulators of damage. However, the correlations between these factors in vivo and post-surgery outcome and prognosis have not yet been systematically investigated. In animal models of myocardial cardioplegia and/or ischemia-reperfusion, experimental drugs such as antioxidants have been documented to provide amelioration of post-intervention cardiac performance and reduction of apoptosis suggesting the possibility of new therapeutic strategies. However, these findings have been only partially confirmed in humans. Moreover, markers for the differential detection of early and late phases of apoptosis are subjects of intense investigations. This review will provide an overview of the major studies about the link between ischemia, myocardial inflammation and apoptosis during and after CS, with particular regard to the markers and methods for apoptosis detection.

Primary sternal plating in high-risk patients prevents mediastinitis.

Abstract: Objective Sternal wound infection leading to post-operative mediastinitis is a devastating complication of cardiac surgery carrying nearly a 15% mortality rate despite current treatment methods. Instability of bone fragments pre-disposes a patient to have non-union, mal-union and can subsequently lead to deep sternal wound infections progressing to mediastinitis. Rigid plate fixation has been utilized for acquired and surgically created fractures of virtually every bone in the body to prevent instability. However, the current standard for sternotomy closure remains the method of wire-circlage. Application of rigid plate fixation for sternal osteotomies affords greater stability of the sternum. We report on our preliminary experience with this technique in high-risk patients. Methods From July of 2000 to December 2001, rigid plate fixation was applied to 45 patients designated as having high risk for sternal dehiscence and subsequent mediastinitis. High risk was defined as patients having 3 or more established historical risk factors, including: COPD, Re-Operative Surgery, Renal Failure, Diabetes, Chronic Steroid Use, Morbid Obesity, Concurrent Infection and Acquired or Iatrogenic Immunosuppression. Intra-operative risk factors included off-midline sternotomy, osteoporosis, long cardio-pulmonary bypass runs (>2 h), transverse fractures of the sternum. Rigid plate fixation was performed using a combination of plates secured by bi-cortical screws, after the cardiac surgical procedure was complete and hemostasis was secured. Results Rigid plate fixation was performed on 26 males and 19 females. The average age of patients was 63 (43-88) years. The average follow-up was 15 weeks (range 8-41 weeks). While there were 4 peri-operative deaths unrelated to sternal closure: one from aspiration pneumonia (post-operative day 9), one from a pulmonary embolus (post-operative day 29), one from overwhelming sepsis from pre-existing endocarditis (post-operative day 15), and one for primary respiratory failure (post-operative day 12). All others healed successfully. One patient who had a sterile dehiscence subsequently underwent successful re-operative rigid fixation. Comparing the cohort of patients who received rigid plate fixation to a matched population of high-risk patients during a similar time period who received wire closure, revealed a significant difference in the incidence of post-operative mediastinitis. The wire closed group (n = 207) had 18 deaths unrelated to sternal closure and had 28 patients who developed mediastinitis (14.8%). The rigid plate fixation group had no mediastinitis (Fisher's exact test, P = 0.006). The total incidence of post-operative mediastinitis during the designated study period was 4.2%. Conclusion Patients who benefited from sternal closure with rigid plate fixation showed a significant decrease in the incidence of post-operative mediastinitis when compared to similar population of patients whose sterna were closed with wire.

Do valved stents compromise coronary flow

Abstract: Objective: The aim of the present study is to evaluate a new self-expanding valved stent design for minimal invasive aortic valve implantation and its interference with coronary flow. Methods: An equine pericardial valve mounted onto a self-expanding nitinol stent (3F Therapeuticse, CA, USA), outer diameter 23 mm, was evaluated (A) in vitro in a dynamic pulsatile mock loop and (B) in vivo in six calves (75 ^ 2.5 kg). In four animals valve stents were implanted on-pump and in two animals off-pump after induction of ventricular fibrillation. Target site for deployment was the orthotopic aorta, over the native valves. In vivo assessment was performed with intracardiac (AcuNave) and intravascular ultrasound including leaflet motion, planimetric valve orifice and residual-coronary\sinus-stent-index (RCSSI, distance stent to aortic wall/coronary diameter) calculations, coronary blood flow characteristics, transvalvular gradient, regurgitation and paravalvular leaking, in combination with continuous cardiac output measures. Macroscopic analysis was performed at necropsy. Results: Two-dimensional intracardiac ultrasound showed good leaflet motion, with full valvular opening and closing in five of six valves. Planimetric valve orifice was 1.75 ^ 0.4 cm 2 . There were no signs of coronary flow impairment with an RCSSI of 1.8 ^ 1.2. The implanted valved stents showed a low transvalvular gradient of 5.3 ^ 3.9 mmHg (mean, peak-to-peak) on invasive measurements and 4.7 ^ 2.5 mmHg in two-dimensional intracardiac sonography. One of six valves showed mild to moderate regurgitation and one of six valves a minor to moderate paravalvular leak due to size mismatch. Conclusions: This new self-expanding valved stent design allows for on- and off-pump aortic valve implantation in the orthotopic aorta, over the native valves without interference of the coronary blood flow and excellent acute valve function in properly sized devices. q 2004 Elsevier B.V. All rights reserved.

Current assessment and management of spontaneous pneumomediastinum: experience in 24 adult patients.

Abstract: Objectives: Spontaneous pneumomediastinum (SPM) is an uncommon, benign, self-limited disorder that usually occurs in young adults without any apparent precipitating factor or disease. The purpose of this study was to review our experience in dealing with this entity and detail a reasonable course of assessment and management. Methods: A retrospective case series was conducted to identify adult patients with SPM who were diagnosed and treated in a single institution between 1993 and 2000. Results: Twenty-four patients were identified who included 18 men and 6 women with a mean age of 17.5 years. Acute onset chest pain was the predominant symptom at presentation. Only half of the patients developed clinically evident subcutaneous emphysema. The most frequent precipitating factor was a history of illegal drug abuse seen in 25% of patients. Other factors included asthmatic bronchospasm, physical activity and violent coughing or vomiting. Chest radiography and computerized tomography (CT) were diagnostic in all cases with CT scan revealing six cases with associated pulmonary abnormalities. Esophagogram and flexible bronchoscopy were selectively used. Twelve patients (50%) were admitted to the hospital. Their mean hospital stay was 2 days. All patients were conservatively treated. In a follow-up of 3 ‐ 10 years no complications or recurrences were observed. Conclusions: SPM follows alveolar rupture in the pulmonary interstitium. It shows a rising incidence in young drug users. It has a wide range of clinical features necessitating a high index of suspicion. Chest X-ray and CT scan should be always performed. Hospitalization and aggressive approach should be limited. SPM responds well to conservative treatment and follows a benign natural course. q 2004 Elsevier B.V. All rights reserved.

Video-assisted thoracoscopic surgery for pulmonary nodules: rationale for preoperative computed tomography-guided hookwire localization

Abstract: Objectives: Video-assisted thoracic surgery (VATS) provides a minimally invasive means to resect pulmonary nodules (PN). Deep localization of PN may jeopardize VATS lung resection. The aim of this study was to establish the utility of preoperative computed tomography (CT)-guided hookwire localization of PN. Methods: Between January 1993 and September 2001, we performed 151 VATS resections for PN. Preoperative CT-guided hookwire localization was not performed in 98 patients (group I); it was done just before surgery in 53 patients (group II) when, at CT scan, the distance of PN from the lung surface was .15 and/or when the size was , 10 mm. Results: Pneumothorax occurred in four patients (7.5%). Hookwire dislodged in four patients, but the hematoma left on the visceral pleura made thoracoscopic localization possible in three of these. Seventeen patients (17%) in group I and 4 (7.5%) in group II required conversion to thoracotomy ðP # 0:05Þ: The most common reason for conversion was impossibility to localize PN in group I (nine cases) and deep localization requiring local enucleation in group II (two cases). In 31 group II patients (58%) hookwire positioning led to successful VATS resection that would otherwise have been impossible because PN were neither visible nor palpable. Conclusions: Preoperative CT-guided hookwire localization for pulmonary nodules is an effective technique which allows VATS resection of PN ,10 mm located .15 mm from the pleural surface. Even when PN are subpleural but ,10 mm, hookwire localization makes VATS resection faster. Apical and diaphragmatic localization of PN are limitations to the procedure. q 2003 Elsevier B.V. All rights reserved.

Spontaneous mediastinal emphysema.

Abstract: Objective: Spontaneous mediastinal emphysema is uncommon. Its cause has not been determined precisely, but the entity is usually associated with suddenly raised alveolar pressure. Methods: Between 1980 and 2001, 114 patients with mediastinal emphysema of various causes were hospitalized in the Wolfson Medical Center. In 22 of these patients (19.3%) the emphysema occurred without an obvious preceding event and was classified as spontaneous. The commonest symptoms and signs were chest pain, dyspnea and subcutaneous emphysema. All patients were kept under observation. Contrast esophagogram was performed in two patients who vomited. Pleural drains were inserted in six patients who had concomitant pneumothorax. Results: All patients recovered and were followed for at least one year. There were no complications and no recurrences. Conclusions: Spontaneous mediastinal emphysema is usually a benign condition, which can be treated expectantly. The patients should be observed for 24 h. Recurrences are rare. q 2004 Elsevier B.V. All rights reserved.

Comparison of biomechanical and structural properties between human aortic and pulmonary valve

Abstract: Objective: Pulmonary valve autografts have been reported as clinically effective for replacement of diseased aortic valve (Ross procedure). Published data about pulmonary valve mechanical and structural suitability as a long-term substitute for aortic valve are limited. The aim of this study was to compare aortic and pulmonary valve properties. Methods: Experimental studies of biomechanical properties and structure of aortic and pulmonary valves were carried out on pathologically unchanged human heart valves, collected from 11 cadaveric hearts. Biomechanical properties of 84 specimens (all valve elements: cusps, fibrous ring, commissures, sinotubular junction, sinuses) were investigated using uniaxial tensile tests. Ultrastructure was studied using transmission and scanning electron microscopy. Results: Ultimate stress in circumferential direction for pulmonary valve cusps is higher than for aortic valve (2.78 ± 1.05 and 1.74 ± 0.29 MPa, respectively). Ultimate stress in radial direction for pulmonary and aortic cusps is practically the same (0.29 ± 0.06 and 0.32 ± 0.04 MPa, respectively). In ultrastructural study, different layout and density in each construction element are determined. The aortic and pulmonary valves have common ultrastructural properties. Conclusions: Mechanical differences between aortic and pulmonary valve are minimal. Ultrastructural studies show that the aortic and pulmonary valves have similar structural elements and architecture. This investigation suggests that the pulmonary valve can be considered mechanically and structurally suitable for use as an aortic valve replacement.

Evaluation of brain injury after coronary artery bypass grafting. A prospective study using neuropsychological assessment and diffusion-weighted magnetic resonance imaging.

Abstract: Objective: Neurocognitive dysfunction is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Studies using magnetic resonance imaging (MRI) have demonstrated that new focal brain lesions can occur after coronary artery bypass grafting (CABG), even in patients without apparent neurological deficits. Diffusion-weighted MRI is superior to conventional MRI and allows for sensitive and early detection of ischemic brain lesions. We prospectively investigated cerebral injury early and 3 months after CABG using diffusion-weighted MRI and related the findings to clinical data and neurocognitive functions. Methods: Twenty-nine patients [67.6 ^ 8.6 (52 ‐ 85) years, 5 females] undergoing elective CABG with CPB were examined before surgery, at discharge and 3 months after surgery. A battery of standardized neuropsychological tests and questionnaires on depression and mood were administered. Conventional and diffusionweighted MRI of the brain was performed and new lesions were analyzed. Clinical characteristics, neuropsychological test performance and radiographic data were collected and compared. Results: There was no major neurological complication after CABG. Thirteen patients (45%) exhibited 32 new ischemic lesions on postoperative diffusion-weighted MRI. The lesions were small, rounded and equally dispersed in both hemispheres. Eight patients had at least two lesions. At discharge, significant deterioration of neuropsychological performance was observed in 6 of the 13 tests compared to baseline assessment. By 3 months postoperatively, 5 of the 6 tests returned to preoperative levels. Verbal learning ability, however, remained impaired. The presence of new focal brain lesions was not associated with impaired neuropsychological performance. There was also no correlation between clinical variables, intraoperative parameters and postoperative complications and MRI findings. Conclusions: Although neurocognitive decline after CABG is mostly transient, memory impairment can persist for months. New ischemic brain lesions on postoperative diffusion-weighted MRI do not appear to account for the persistent neurocognitive decline. q 2004 Elsevier B.V. All rights reserved.

Late incidence and determinants of reoperation in patients with prosthetic heart valves

Abstract: Objectives: Reoperation is a relatively common event in patients with prosthetic heart valves, but its actual occurrence can vary widely from one patient to another. With a focus on bioprosthetic valves, this study examines risk factors for reoperation in a large patient cohort. Methods: Patients ðN ¼ 3233Þ who underwent a total of 3633 operations for aortic (AVR) or mitral valve replacement (MVR) between 1970 and 2002 were prospectively followed (total 21179 patient-years; mean 6.6 ^ 5.0 years; maximum 32.4 years). The incidence of prosthetic valve reoperation and the impact of patient- and valve-related variables were determined with actual and actuarial methods. Results: Fifteenyear actual freedom from all-cause reoperation was 94.1% for aortic mechanical valves, 61.4% for aortic bioprosthetic valves, 94.8% for mitral mechanical valves, and 63.3% for mitral bioprosthetic valves. In both aortic and mitral positions, current bioprosthesis models had significantly better durability than discontinued bioprostheses (15-year reoperation odds-ratio 0.11 ^ 0.04; P , 0:001 for aortic, and 0.42 ^ 0.14; P ¼ 0:009 for mitral). Current bioprostheses were significantly more durable in the aortic position than in the mitral position (14.3 ^ 6.8% more freedom from 15-year reoperation; P ¼ 0:018). Older age was protective, but smoking was an independent risk factor for reoperation after bioprosthetic AVR and MVR (hazard ratio for smoking 2.58 and 1.78, respectively). In patients with aortic bioprostheses, persistent left ventricular hypertrophy at follow-up and smaller prosthesis size predicted an increased incidence of reoperation, while this was not observed in patients with mitral bioprostheses. Conclusions: These analyses indicate that current bioprostheses have significantly better durability than discontinued bioprostheses, reveal a detrimental impact for smoking after AVR and MVR, and indicate an increased reoperation risk in patients with a small aortic bioprosthesis or with persistent left ventricular hypertrophy after AVR.

Long-term survival and prognostic factors in thymic epithelial tumours.

Abstract: Objective: The aim of this study is to analyze long-term survival and the prognostic significance of some factors after surgical resection of thymic epithelial tumours. Methods: We performed a retrospective analysis of clinical and histopatological data on 132 patients operated on for thymic tumours, from 1970 and 2001. Histologic diagnosis based on the new WHO classification system was made by a single patologist. A univariate and multivariate analysis of prognostic factors predicting survival was carried out. Results: There were: 108 complete resections (81.8%), 12 partial resections (9.1%) and 12 biopsies (9.1%). Overall 5, 10 and 15-year survival rate was 72, 61 and 52.5%, respectively. The Masaoka staging system showed 44 stage I, 18 stage II, 52 stage III and 18 stage IV. Histologic results were: 14 subtype A, 31 AB, 20 B1, 28 B2, 29 B3 and 10 C; the respective proportions of invasive tumour (stage II‐ IV) was 28.6, 58.1, 50, 75, 86.2 and 100%. There were 16 tumour recurrences (14.8%) of 108 radically resected thymomas, 10 were treated with radical re-resection. In univariate analysis, four prognostic factors were statistically significant: radical resection, Masaoka clinical staging, WHO histologic subtype and resectable tumour recurrence. In multivariate analysis, the independent factors predicting long-term survival were WHO histology and Masaoka stage. Conclusions: The WHO histologic classification seems to be the most significant prognostic factor reflecting the invasiveness of the thymic tumour. Completeness of resection and Masaoka stage I and II assure a better survival. Unresectable recurrence of thymic tumour predicted a worse prognosis. q 2004 Elsevier B.V. All rights reserved.

Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study.

Abstract: Objectives: Adjuvant immunotherapy is an innovative therapeutic option that might potentially improve outcome of early-stage non-small cell lung cancer. Melanoma associated antigen (MAGE)-A3 is a promising target for immunotherapy because it is exclusively presented on the cell surface of cancer cells and might be associated with an aggressive cancer phenotype. The present study was performed to determine the rate of MAGE-A3 expression in early-stage non-small cell lung cancer (NSCLC). Patients and methods: Primary tumor samples from 204 patients with operable clinical Stages I or II NSCLC were collected between March and November 2001. Pathological Stage was determined by the local pathologist in each of the 16 participating institutions. Tissue samples were stored immediately after surgery in a RNA-stabilizing solution and were frozen at -20°C. MAGE-A3 expression was analyzed by detection of MAGE-A3 transcripts using reverse-transcriptase polymerase chain reaction. Results: MAGE-A3 expression was observed in 80 out of the 204 (39.2%) examined Stages I-II primary tumors. Stratification into UICC-Stages showed that 31 out of 105 (29.5%) Stage I non-small cell lung cancers and 49 out of 99 (49.5%) Stage II non-small cell lung cancers expressed MAGE-A3. In comparison to Stage I, the rate of MAGE-A3 positive tumors was significantly increased in Stage II (P = 0.004; Chi-square test). Conclusion: The MAGE-A3 expression rate showed that a promising proportion of operable patients with early-stage non-small cell lung cancers are possible candidates for trials investigating adjuvant therapy with MAGE-A3 immunization. Currently, a phase two trial of adjuvant MAGE-A3 vaccination is in progress.

Systolic ventricular filling.

Abstract: Summary The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart From the earliest Erasistratus’ observations, principal mechanisms responsible for the ventricular filling have still remained obscured Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities The true origin and the precise time frame for generating such force are still controversial Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intracavitary blood volume (hemoskeleton), explain the physical principles involved in this action This contraction occurs during the last part of classical systole and the first part of diastole Therefore, the most important part of ventricular diastole (ie the rapid filling phase), in which it receives 70% of the stroke volume, belongs to the active muscular contraction of the ascendent segment We hope that these facts will give rise to new understanding of the principal mechanisms involved in normal and abnormal diastolic heart function

First experiences with a novel magnetically suspended axial flow left ventricular assist device.

Abstract: Axial flow pumps have gained increased acceptance since their first clinical use in 1998. The present report summarizes the clinical experience with patients treated for severe cardiogenic shock for the first time with a newly developed axial flow pump with magnetically levitated bearings. Material and methods: The axial flow pump Incor was implanted in 24 patients between June 2002 and June 2003. All except one patient were men. In 16 patients dilative cardiomyopathy, in seven ischemic and in one restrictive cardiomypathy had been diagnosed. All patients presented with catecholamine-dependent end-stage heart failure, seven of them were on an artificial ventilator and three were dependent on intraaortic balloon pump support. All patients suffered from organ dysfunction resulting from low cardiac output. Results: There were no perioperative deaths. The 30-day mortality rate was 8% ðn ¼ 2Þ; 79% ðn ¼ 19Þ of patients reached a condition to be discharged home. The cumulative time on the device is 6.9 years; the longest individual time up to July 1, 2003 is 12.6 months. There were no structural defects or failures of the system. In one case the controller had to be exchanged because of intermittent malfunction. Cardiac output ranged between 4 and 6 l in all instances and there were no cases of infection of the drive-line or the system. Hemolysis was present initially but was not detectable in the later course. There were three instances of transient ischemic attacks. Two patients developed late cardiac tamponade with re-opening of the chest after 9 and 14 days. In one patient persistent gastrointestinal bleeding required re-hospitalization and transfusion therapy. Two patients were weaned from the device after 6 and 7 months of support, respectively. Conclusion: The preliminary clinical experience with Incor is promising. The flow is sufficient for recovery from multiorgan failure and the pump allows long-term hemolysis-free support. The concept of magnetically levitated bearings has proven to be durable and reliable. In the case that the heart may recover through unloading, weaning from the pump is possible. q 2004 Elsevier B.V. All rights reserved.

Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm.

Abstract: Objectives: Brief episodes of myocardial ischemia-reperfusion employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of postconditioning on persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart model. Methods: Isolated Langendorff-perfused rat hearts ðn ¼ 46Þ were subjected to 30 min of regional ischemia and reperfusion. The hearts with persistent VF ðn ¼ 11Þ present after 15 min of reperfusion were then randomly assigned into one of the two groups: (1) control hearts ðn ¼ 6Þ; in which perfusion was continued without intervention; (2) postconditioned hearts ðn ¼ 5Þ subjected to 2 min of global ischemia followed by reperfusion. Left ventricular pressures, heart rate, coronary flow, and electrogram were monitored throughout the experiment. Results: Conversion of VF into regular rhythm was observed in all hearts subjected to postconditioning. Regular beating was maintained by all postconditioned hearts during the subsequent reperfusion. None of the hearts in the control group had normal rhythm at the end of the experiment. At the end of reperfusion, the left ventricular developed pressure was lower in beating postconditioned hearts compared to the hearts that did not develop persistent VF. Conclusions: Ischemic postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be an interesting, novel adjunct strategy to protect the heart. q 2004 Elsevier B.V. All rights reserved.

Near-infrared spectroscopy for monitoring cerebral ischemia during selective cerebral perfusion.

Abstract: Objective: To minimize the neurological complications following cardiovascular surgery, it is essential to prevent an occurrence of cerebrovascular embolism and to detect and solve cerebral malperfusion without delay in the operating theater. Although we have introduced near-infrared spectroscopy (NIRS) monitoring for the purpose of detecting cerebral malperfusion, no criterion has been available. We searched for this criterion by examining the relationship of sustained drop in the regional oxygen saturation (rSO2) of the frontal lobes to the occurrence of neurological events. Methods: The 59 consecutive patients undergoing aortic surgery with selective cerebral perfusion (SCP) were examined. The rSO2 was monitored throughout the surgery and the durations of drops in rSO2 to below 55% and those below 60% were determined for each patient. The durations of rSO2 drop and other surgery-related parameters were compared between the patients in whom neurological events occurred and those without such events. Results: A total of 16 cases (27.1%) presented with neurological events. Newly developed cerebral infarction was documented in 6 of these 16 cases. Operation time and the durations for which rSO2 dropped were significantly longer for the 16 patients with neurological events than for the 43 patients without events (Op time: 546.8 versus 448.1 min, PZ 0.0064; rSO2 below 60%: 141.2 versus 49.8 min, PZ0.0032; rSO2 below 55%: 66.6 versus 10.6 min, PZ0.0011), while there was no significant difference in age, bypass time, aortic clamping time, SCP time, and circulatory arrest time between the two groups. In the 3 patients with infarcts suggestive to hypoperfusion, sustained decrease in rSO2 was observed, while it was not significant in the remaining 3 patients with infarcts suggestive to embolism. Among the 53 patients without infarction, transient neurological events occurred more frequently in patients with sustained drop in rSO2 below 55% for over 5 min (44.4% versus 5.7%, PZ0.0014). Conclusions: A sustained drop in rSO2 during aortic surgery is closely related to the occurrence of neurological events following surgery. We recommend that recovery of drop in rSO2 below 55% should be addressed without delay. However, use of NIRS is limited for detecting embolic events or hypoperfusion in the basilar region. q 2004 Elsevier B.V. All rights reserved.

Renal dysfunction after myocardial revascularization

Abstract: Objectives: In this study, we evaluate the incidence of and analyse the pre and intraoperative risk factors for the development of postoperative renal dysfunction (PRD), and the impact of such an event on perioperative mortality and on hospital length of stay. In addition, we sought to investigate the influence of a mildly increased serum creatinine (1.3– 2.0 mg/dl) on perioperative mortality and morbidity. Methods: The study included 2445 consecutive patients who had no pre-existing renal disease (creatinine # 2.0 mg/dl, without dialysis) and who underwent isolated coronary surgery under cardiopulmonary bypass between July 1996 and December 2001. The main outcome measure was PRD, defined as a postoperative serum creatinine level $2.1 mg/dl with a preoperative-to-postoperative increase $0.9 mg/dl. Univariate and multivariate analyses were performed where appropriate. Results: Global 30-day mortality was 0.7%. The incidence of PRD was 5.6% (136 patients). Mortality for patients who experienced PRD was 8.8 vs. 0.1% for patients who did not ðP , 0:001Þ: PRD increased the length of hospital stay by 3.4 days (7.6 vs. 11.0 days; P , 0:001), and patients who needed haemodialysis (11%) had a perioperative mortality of 33.3% and a mean hospital length of stay of 16 days. Multivariable logistic regression identified the following variables as independent predictors of PRD: age (P ¼ 0:017; odds ratio (OR) 1.3 per 10 years), angina class III/IV (P ¼ 0:003; OR 1.7); cardiopulmonary bypass time (P ¼ 0:007; OR 1.01 per minute); preoperative serum creatinine levels: group 1 (1.3 –1.6 mg/dl (P , 0:001; OR 5.5)) and group 2 (1.7– 2.0 mg/dl (P , 0:001; OR 14.2)). Finally, a mild elevation of the preoperative creatinine level (1.3– 2.0 mg/dl) increased significantly the probability of perioperative mortality, low cardiac output, haemodialysis and prolonged hospital stay. Conclusions: Although the likelihood of PRD in patients without pre-existing renal dysfunction is relatively low, it dramatically increases mortality, morbidity and length of stay after CABG. Mildly elevated (.1.2 mg/dl) preoperative serum creatinine level significantly increases the perioperative mortality and morbidity. q 2004 Published by Elsevier B.V.

Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation-a preliminary study.

Abstract: Objectives: Elevated pulmonary vascular resistance (PVR) unresponsive to pharmacological intervention is a major limitation in heart transplantation (HTX). The post-operative course of these patients is associated with an increased risk of life-threatening right heart failure. We evaluated the efficiency of an implantable left ventricular assist device (LVAD) to decrease PVR by unloading the left ventricle and to lower the risk of later orthotopic HTX. Methods: Six patients with end-stage heart failure (NYHA class IV) and 'fixed' pulmonary hypertension (PVR 5.7 ± 0.7, range 4.4-6.5 Wood units) were analyzed. Despite maximal pharmacological intervention at initial evaluation (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a Novacor, and one patient a Jarvik 2000. Results: All patients survived the LVAD implantation, four patients could be discharged from hospital. Cardiac index and pulmonary artery pressure values returned to normal during the early post-operative phase. After a mean support time of 191 ± 86 days PVR had fallen to 2.0 ± 1.2 (range 0.8-3.6) Wood units. All patients could be bridged to transplantation, one patient died 3 months after transplant, five patients are still alive after a mean follow-up of 16.2 ± 10.5 months. Conclusions: Mechanical support using an implantable LVAD is a very efficient approach with an acceptable risk to treat severe pulmonary hypertension in end-stage heart failure patients before HTX. Adequate reduction of PVR can be expected within 3-6 months. Subsequent HTX is associated with a good outcome.

Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.

Abstract: Objective: Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC). Methods: A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system. Results: Overall incidence of air leakage 48 ^ 6h after surgery was 34% for TC and 37% for standard treatment ðP ¼ 0:76Þ: The reduction of intra-operative air leak intensity in the subgroup with grades 1 ‐2 was significantly higher for the TC group ðP ¼ 0:015Þ: Postoperative air leakage intensity in the subgroup with air leakage grades 1 ‐ 2 was lower for TC than standard treatment ðP ¼ 0:047Þ: The mean duration of postoperative air leakage in the subgroup with grades 1 ‐ 2 was shorter for the TC group than for standard treatment, i.e. 1.9 ^ 1.4 vs. 2.7 ^ 2.2 days ðP ¼ 0:015Þ: Conclusions: TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage. q 2003 Elsevier B.V. All rights reserved.

Human umbilical cord cells for cardiovascular tissue engineering: a comparative study.

Abstract: Objective: Tissue engineering of viable, autologous cardiovascular replacements with the potential to grow, repair and remodel represents an attractive approach to overcome the shortcomings of available replacements for the repair of congenital cardiac defects. Currently, vascular myofibroblast cells represent an established cell source for cardiovascular tissue engineering. Cell isolation requires the invasive harvesting of venous or arterial vessel segments prior to scaffold seeding, a technique which may not be preferable, especially in pediatric patients. This study evaluates cells isolated from human umbilical cord artery, umbilical cord vein and whole cord as alternative autologous cell sources for cardiovascular tissue engineering. Methods: Cells were isolated from human umbilical cord artery (UCA), umbilical cord vein (UCV), whole umbilical cord (UCC) and saphenous vein segments (VC), and were expanded in culture. All three expanded cell groups were seeded on bioabsorbable copolymer strips and grown in vitro for 28 days. Isolated cells were characterized by flow cytometry, histology, immunohistochemistry, proliferation assays and compared to VC. Morphological analysis of the seeded polymer strips included histology, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and uniaxial stress testing. Results: UCA, UCV and UCC demonstrated excellent cell growth properties comparable to VC. Following isolation, all three cell groups showed myofibroblast-like morphology and characteristics by staining positive for a-smooth muscle actin (ASMA) and vimentin. Histology and immunohistochemistry of seeded polymers showed good tissue and extracellular matrix formation containing collagen I, III and elastin. TEM showed viable myofibroblasts and the deposition of collagen fibrils and progessive growing tissue formation, with a confluent surface, was observed in SEM. No difference was found among the mechanical properties of UCA, UCV, UCC and VC tissue engineered constructs. Conclusions: Tissue engineering of cardiovascular constructs by using UCA, UCV and UCC is feasible in an in vitro environment. Cell growth, morphology, characteristics and tissue formation were comparable between UCA, UCV, UCC and VC. UCC represent an attractive, readily available autologous cell source for cardiovascular tissue engineering offering the additional benefits of utilizing juvenile cells and avoiding the invasive harvesting of intact vascular structures. q 2004 Elsevier B.V. All rights reserved.

Primary esophageal repair for Boerhaave's syndrome whatever the free interval between perforation and treatment.

Abstract: Objectives: Boerhaave’s syndrome is the most sinister cause of esophageal perforation responsible with mortality rate ranging from 20 to 30%. Combination of mediastinal contamination with microorganisms, gastric acid and digestives enzymes, long free interval between injury and initiation of treatment causes severe mediastinitis which is fatal in most untreated cases. The aim of this paper is to emphasize primary esophageal repair and resuscitation whatever the free interval from rupture and repair. Methods: A retrospective review of patients treated for Boerhaave’s syndrome in our department from January 1980 to February 2003 was performed. The principle of treatment was surgical treatment and avoidance of esophageal exclusion or esophagectomy whichever was possible. Results: There were 25 patients (17 males and 8 females). All patients were operated on by primary esophageal repair, except for three who underwent immediate exclusion of the esophagus and one patient who deceased on arrival before being operated. Patients were classified according to free interval between perforation and treatment: group 1 (n ¼ 9; 36%) within the 24 h (range from 12 to 24 h) and group 2 (n ¼ 16; 64%) more than 24 h (range from 2 to 17 days). Altogether 6 patients deceased (24%). In hospital mortality rate for groups 1 and 2 was, respectively, 44% (four patients) and 13% (two patients), not significantly different. Mean hospital stay was 63 days. Two patients developed anastomotic leakage needing esophagectomy and retrosternal coloplasty in one or more steps. One patient developed pleural abscess treated by percutaneous drainage. Three patients presented temporary symptomatic esophageal stenosis, of whom one underwent dilation. Conclusions: Long free interval before treatment does not preclude primary esophageal repair in Boerhaave’s syndrome. Esophageal exclusion may be more often than not avoided in most cases. q 2003 Elsevier B.V. All rights reserved.

Factors affecting patency of internal thoracic artery graft: clinical and angiographic study in 1434 symptomatic patients operated between 1982 and 2002

Abstract: Objective: The purpose is to define factors influencing long-term patency of the internal thoracic artery (ITA) to optimize the operative strategy. Methods: 1482 left internal thoracic artery (LITA) and 636 right internal thoracic artery (RITA) symptom-directed angiograms were studied in 1434 patients. Data were prospectively collected from patients who had primary coronary artery bypass surgery during the period 1982-2002. The mean age of patients was 59 years; 85% were male. The mean period from operation to re-angiogram was 80 months. LITA was grafted to left anterior descending coronary artery (LAD) in 82% of cases, RITA to right coronary artery (RCA) in 40% and circumflex artery in 35% of cases. Graft failure was defined as ≥80% stenosis. Results: 96.3% of LITA and 88.1% of RITA grafts were patent. No patient variables were significantly associated with graft patency (age, gender, diabetes, hypertension, LVEF, NYHA, AMI). Target coronary artery was associated with patency of both LITA and RITA grafts with maximum patency when grafted to LAD (P = 0.02). RITA had the worst patency to RCA, patency for the left system was identical to LITA. Proximal anastomosis to aorta (free RITA) had significantly better patency when compared with in situ RITA to RCA system (P = 0.005) while similar patency when grafted to left system. ITA diameter and target artery diameter were not associated with graft patency. Recent operations had better RITA patency (P = 0.03). The interval from operation to angiogram was not associated with ITA patency (96% patency for LITA and 88% patency for RITA, remained stable when studied at 15 years). Conclusions: Even in a patient cohort that had adverse symptoms, excellent LITA and RITA patency was achieved which almost remained constant through all time intervals studied.

The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced systemic inflammatory response.

Abstract: Objective: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations. Methods: Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight: group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-a were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points. Results: No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively reduced the increase in TNF-a and IL-6 secretion (P!0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10 mg/kg). Conclusions: The results indicate that a single low-dose of methylprednisolone (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp. q 2004 Elsevier B.V. All rights reserved.

Mild hypothermia protects the spinal cord from ischemic injury in a chronic porcine model.

Abstract: Objectives: During thoracoabdominal aortic aneurysm repair, prolonged compromise of spinal cord blood supply can result in irreversible spinal cord injury. This study investigated the impact of mild hypothermia during aortic cross-clamping on postoperative paraplegia in a chronic porcine model. Methods: The thoracic aorta was exposed and cross-clamped in 30 juvenile pigs (20 – 22 kg) for different intervals at normothermia (36.5 8C), and during mild hypothermia (32.0 8C). Three pigs were evaluated at each time and temperature. Myogenic motorevoked potentials (MEPs) were monitored, and postoperative recovery evaluated using a modified Tarlov score. Results: There were no significant hemodynamic or metabolic differences between individual animals, and the groups had equivalent arterial pressures (mean 64.3 ^ 3.6 mmHg). Time to recovery of MEPs correlated with severity of injury; all animals with irreversible MEP loss suffered postoperative paraplegia. At normothermia, animals with 20 min of aortic cross-clamping emerged with normal motor function, but those cross-clamped for 30 min suffered paraplegia. With mild hypothermia, animals tolerated 50 min of aortic cross-clamping without evidence of neurologic injury, but were all paraplegic after 70 min of ischemia. Animals appeared to recover normal motor function after 60 min of aortic cross-clamping at hypothermia initially, but exhibited delayed-onset paraplegia 36 h postoperatively. Conclusions: Our observations indicate that mild hypothermia dramatically increases the tolerance of the spinal cord to ischemia in the pig, and therefore suggests that cooling to 32.0 8C should be encouraged during surgery which may compromise spinal cord blood supply. An ischemic insult of borderline severity may result in delayed paraplegia. q 2003 Elsevier B.V. All rights reserved.

Computational simulation of intracoronary flow based on real coronary geometry.

Abstract: Objective: To assess the feasibility of computationally simulating intracoronary blood flow based on real coronary artery geometry and to graphically depict various mechanical characteristics of this flow. Methods: Explanted fresh pig hearts were fixed using a continuous perfusion of 4% formaldehyde at physiological pressures. Omnipaque dye added to lead rubber solution was titrated to an optimum proportion of 1:25, to cast the coronary arterial tree. The heart was stabilized in a phantom model so as to suspend the base and the apex without causing external deformation. High resolution computerized tomography scans of this model were utilized to reconstruct the three-dimensional coronary artery geometry, which in turn was used to generate several volumetric tetrahedral meshes of sufficient density needed for numerical accuracy. The transient equations of momentum and mass conservation were numerically solved by employing methods of computational fluid dynamics under realistic pulsatile inflow boundary conditions. Results: The simulations have yielded graphic distributions of intracoronary flow stream lines, static pressure drop, wall shear stress, bifurcation mass flow ratios and velocity profiles. The variability of these quantities within the cardiac cycle has been investigated at a temporal resolution of 1/100th of a second and a spatial resolution of about 10 mum. The areas of amplified variations in wall shear stress, mostly evident in the neighborhoods of arterial branching, seem to correlate well with clinically observed increased atherogenesis. The intracoronary flow lines showed stasis and extreme vorticity during the phase of minimum coronary flow in contrast to streamlined undisturbed flow during the phase of maximum flow. Conclusions: Computational tools of this kind along with a state-of-the-art multislice computerized tomography or magnetic resonance-based non-invasive coronary imaging, could enable realistic, repetitive, non-invasive and multidimensional quantifications of the effects of stenosis on distal hemodynamics, and thus help in precise surgical/interventional planning. It could also add insights into coronary and bypass graft atherogenesis.