Showing papers on "Pulmonary artery published in 1994"
TL;DR: It is demonstrated that basal release of endothelium-derived NO is directly involved in the determination of systemic vascular resistance and, therefore, blood pressure in healthy humans and NO regulates basal normoxic pulmonary vascular tone.
Abstract: BACKGROUNDThe endothelium synthesizes and releases a relaxing factor with the physiochemical properties of nitric oxide (NO). However, the role of endothelium-derived NO in the basal regulation of systemic and pulmonary vascular resistance in humans is not known. Our primary objectives were to determine the effects of inhibiting NO synthesis on blood pressure and systemic vascular resistance and to establish the role of endothelium-derived NO in the regulation of normoxic pulmonary vascular tone.METHODS AND RESULTSWe studied the systemic and pulmonary hemodynamic effects of NG-monomethyl-L-arginine (L-NMMA, 0.03 to 1.0 mg.kg-1.min-1 IV), an NO synthase inhibitor, in 11 healthy volunteers, aged 33 +/- 2 years. An arterial cannula and a pulmonary artery catheter were placed in each subject to measure blood pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. Cardiac output was determined by the Fick technique, and systemic and pulmonary vascular resistances were calculated. Serum NO ...
529 citations
TL;DR: Short-term carvedilol administration reduces heart rate and mean pulmonary artery and pulmonary wedge pressures, whereas it improves both long-term rest and exercise left ventricular systolic function, reduces heart failure symptoms and improves submaximal exercise tolerance in patients with idiopathic cardiomyopathy.
326 citations
TL;DR: Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS, which is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction.
Abstract: Background Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of patients with severe ARDS, we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response. Methods Thirteen patients with severe ARDS (hospital mortality 67%) inhaled 0-40 parts per million (ppm) NO. Seven of these patients continued to breathe 2-20 ppm NO for 2-27 days. Results Inhaling 5-40 ppm NO decreased mean pulmonary artery pressure in a dose-related fashion (from 34 +/- 7 to 30 +/- 7 mmHg at 20 ppm NO). Systemic arterial pressure did not change. The ratio of arterial oxygen tension to inspired oxygen fraction increased (from 126 +/- 36 to 149 +/- 38 mmHg) and the venous admixture decreased (from 31.2 +/- 5.5 to 28.2 +/- 5.2%) without a clear dose-response effect. During prolonged NO inhalation, 2-20 ppm NO effectively reduced mean pulmonary artery pressure (38 +/- 7 vs. 31 +/- 6 mmHg) and increased arterial oxygen tension (79 +/- 10 vs. 114 +/- 27 mmHg) without evidence of tachyphylaxis. The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO (r = -0.72). The reduction of venous admixture correlated with the level of venous admixture without NO (r = -0.78). Conclusions Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS. The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction.
281 citations
TL;DR: Cardiac sympathetic activation is present in severe heart failure, bearing a close relation with pulmonary artery pressures, independent of heart failure etiology.
281 citations
TL;DR: Although the pulmonary-autograft procedure is more complex than simple aortic-valve replacement, it has been safely applied in selected patients, including young adults and may be the best available substitute for diseased aortIC valves in children and young adults.
Abstract: Background The optimal substitute for severely diseased aortic valves in children and young adults is unknown. The use of a mechanical prosthesis requires permanent treatment of the patient with anticoagulants and is associated with thromboembolic and hemorrhagic complications. Aortic-valve allografts and porcine bioprostheses, which do not necessitate anticoagulant therapy, may deteriorate and have limited durability. Methods We therefore evaluated the use of the autologous pulmonary valve (i.e., the patient's own pulmonary valve) and the adjacent pulmonary artery as a replacement for the aortic valve and aortic sinuses in 33 patients. Five of the patients were from 8 to 16 years of age, and 28 were from 20 to 47 years of age. The pulmonary valve and the main pulmonary artery were used to replace the diseased aortic valve and the adjacent aorta. The coronary arteries were detached from the aorta and implanted into the pulmonary artery. The pulmonary valve and artery were replaced with a cryopreserved pul...
279 citations
TL;DR: The findings of concomitant increases in gene transcript levels forET-1 and the ETA and ETB receptors in lung, but not in the great vessels or any other organ examined, are consistent with the hypothesis that increased ET-1 synthesis in the lung contributes to pulmonary vascular remodeling and the maintenance of chronic hypoxic pulmonary hypertension.
Abstract: To test the hypothesis that endothelin (ET)-1 synthesis and ET receptor levels are increased selectively in the lung of rats with chronic hypoxic pulmonary hypertension, the current study examined the effects of exposure to chronic hypoxia (10% O2, 1 atm, 4 wk) on pulmonary arterial pressure, ET-1 levels in plasma and lung, and ET-1 and ETA and ETB receptor mRNA levels in lung, heart, pulmonary artery, aorta, kidney, spleen, and liver. Hypoxic exposure was associated with increases in pulmonary arterial pressure, plasma ET-1 levels, ET-1 mRNA in lung and pulmonary artery, and ET-1 stores and ETA and ETB receptor mRNA levels in lung. In thoracic aorta and the four heart chambers, ETA and ETB receptor mRNA levels were increased, but ET-1 mRNA levels were unchanged from air control levels. No change in ET-1 or ET receptor mRNA levels was seen in organs perfused by the systemic vascular bed, except in liver, where ETA receptor mRNA levels were decreased. The findings of concomitant increases in gene transcript levels for ET-1 and the ETA and ETB receptors in lung, but not in the great vessels or any other organ examined, are consistent with the hypothesis that increased ET-1 synthesis in the lung contributes to pulmonary vascular remodeling and the maintenance of chronic hypoxic pulmonary hypertension.
260 citations
TL;DR: In patients with heart failure due to LV dysfunction, inhalation of NO causes a decrease in the PVR associated with an increase in LV filling pressure, and it is predicted that inhaled NO, if used alone at this dose (80 ppm), may have adverse effects in patients with LV failure.
Abstract: BACKGROUNDPulmonary vascular resistance (PVR) is frequently elevated in patients with advanced heart failure. Nitric oxide (NO), which contributes to the activity of endothelium-derived relaxing factor, causes relaxation of pulmonary arteries and veins in vitro. Inhalation of NO gas causes pulmonary vasodilation in patients with primary and secondary forms of pulmonary hypertension.METHODS AND RESULTSTo test the hypothesis that inhalation of NO gas lowers PVR in patients with heart failure, we studied the hemodynamic effects of a 10-minute inhalation of NO (80 ppm) in 19 patients with New York Heart Association class III (n = 5) and class IV (n = 14) heart failure due to left ventricular (LV) dysfunction. Although inhalation of NO had no effect on pulmonary artery pressures, the PVR decreased by 31 +/- 7% (P < .001) due to a 23 +/- 7% increase (P < .001) in pulmonary artery wedge pressure and despite a 4 +/- 2% (P < .05) decrease in cardiac index. The magnitude of the decrease in PVR with inhaled NO was i...
242 citations
Journal Article•
TL;DR: In this paper, the authors analyzed the relationship between the abnormalities of pulmonary muscular arteries and the degree of VA/Q inequality in patients with chronic obstructive pulmonary disease (COPD).
Abstract: Morphologic changes in pulmonary muscular arteries may modify the mechanisms that regulate the pulmonary vascular tone and contribute to maintaining an adequate ventilation-perfusion (VA/Q) matching in patients with chronic obstructive pulmonary disease (COPD). To analyze the relationships between the abnormalities of pulmonary muscular arteries and the degree of VA/Q inequality, and to assess the effect of these abnormalities on the changes in VA/Q relationships induced by oxygen breathing, we studied a group of patients with mild COPD undergoing resective lung surgery
237 citations
TL;DR: It is suggested that oxygen utilization within skeletal muscle decreased with deterioration of sepsis, thereby increasing skeletal muscle Po2.
Abstract: Objective: In order to obtain direct evidence for tissue hyposa in patients with sepsis oxygen, partial pressure was measured within skeletal muscle. Furthermore, serial intermittent and continuous measurements of skeletal muscle Po 2 in patients with sepsis were used to find out whether skeletal muscle oxygenation may change in the course of sepsis and depends on the severity of sepsis. Design. Prospective study. Setting: Intensive care unit of a university hospital. Patients: Intensive care patients (n=98) with sepsis (group 1, n=39; group 4, n=28), limited infection (group 2, n=16), and cardiogenic shock (group 3, n=15). Interventions: Pulmonary artery catheterization; standard antibiotic therapy and volume replacement
225 citations
TL;DR: Complex Poincaré plots are associated with marked sympathetic activation and may provide additional prognostic information and insight into autonomic alterations and sudden cardiac death in patients with heart failure.
205 citations
TL;DR: It is concluded that chronic treatment with human IL-1ra inhibited the development of pulmonary hypertension in the inflammatory (MCT) model, but not in the chronically hypoxic rats, which indicates thatIL-1 participates in the pathogenesis of some forms of pulmonary pulmonary hypertension.
Abstract: Chronic pulmonary hypertension is associated with significant vascular remodeling. We demonstrated recently in the monocrotaline (MCT) and chronic hypoxia rat models of pulmonary hypertension that treatment with platelet-activating factor (PAF) antagonists inhibited the development of chronic pulmonary hypertension. PAF and other lipid mediators interact with interleukin-1. We postulated that chronic treatment with a recombinant human interleukin-1 receptor antagonist (IL-1ra) would inhibit development of chronic pulmonary hypertension in animal models. Rats were either injected with (60 mg/kg) MCT or exposed to a stimulated high altitude of 16,000 feet; half of the animals were treated with twice-daily injections (2 mg/kg) of IL-1ra. At 3 wk after MCT injection or 3 wk of hypoxic exposure, pulmonary artery pressure and right heart ventricle weight/(left ventricle and septum weight), RV/(LV + S), were measured. IL-1ra treatment reduced pulmonary hypertension and right heart hypertrophy in the MCT model, but not in the chronic hypoxia model. Measurement of lung homogenate IL-1 alpha by radioimmunoassay showed elevated levels in the MCT-treated rats throughout the 3-wk observation period. IL-1ra treatment reduced the levels of IL-1 alpha in lung tissue in most of the MCT-treated rats. MCT treatment was also associated with an increase in lung mRNA for IL-1 alpha, IL-1 beta, and IL-1ra. Immunohistology, using an antibody against rat IL-1 alpha, revealed staining of alveolar structures and of vascular and bronchial smooth muscle. In situ hybridization using a human IL-1 alpha cDNA probe demonstrated increased expression of the IL-1 alpha gene in the lung cells after endotoxin or MCT treatment. Northern blot analysis demonstrated low-level expression of IL-1 alpha mRNA in extracts of normal rat lung and increased expression after endotoxin or MCT treatment. We conclude that chronic treatment with human IL-1ra inhibited the development of pulmonary hypertension in the inflammatory (MCT) model, but not in the chronically hypoxic rats. This result indicates that IL-1 participates in the pathogenesis of some forms of pulmonary hypertension.
TL;DR: The absence of pulmonary edema in these patients in the nitroprusside study reinforces the importance of selective nitric oxide effects in pulmonary circulation.
Abstract: The mechanism of increased pulmonary wedge pressure and cardiac output after nitric oxide inhalation is not clear. Nitric oxide is rapidly inactivated by hemoglobin before it can produce systemic effects. 3 Thus, selective nitric oxide pulmonary vasodilator effects led to these preliminary results. The hypothesis is that acute reduction in right ventricular afterload caused an acute increment of right ventricular cardiac output. The acute increment of blood return to the impaired left ventricle not associated with reduction in afterload caused the increase in wedge pressure and consequently pulmonary edema. In addition, acute reduction in right ventricular afterload could lead to redistribution of blood volume to pulmonary circulation. The absence of pulmonary edema in these patients in the nitroprusside study reinforces the importance of selective nitric oxide effects in pulmonary circulation.
TL;DR: Mitral valve reconstruction, when technically feasible, is the procedure of choice for degenerative or ischemic mitral regurgitation because of significantly lower hospital mortality and late valve-related events.
TL;DR: It is suggested that temporary caval umbrellas are indicated in medically treated patients with shock and massive pulmonary embolism and thrombolysis may provide a life-saving option and a randomised trial is warranted.
TL;DR: It is demonstrated that inhaled nitric oxide exerts a selective pulmonary vasodilation without decreasing systemic arterial pressure in children with congenital heart disease and the increased values of mixed venous oxygen saturation and urinary output suggest that this selective lowering of pulmonary vascular resistance improved the overall hemodynamics.
TL;DR: Patients with ischemic heart disease, congestive heart failure, and low ejection fraction are usually referred for orthotopic heart transplantation, and 46 showing myocardial viability underwent bypass grafting and 40 long-term survivors are in New York Heart Association class II.
TL;DR: Nitric oxide caused a sustained improvement in oxygenation and pulmonary artery pressure during extended therapy at doses of 10 ppm and may be useful in the treatment of pulmonary hypertension and the impaired gas exchange that occurs after lung transplantation.
TL;DR: There were no significant differences in plasma adrenomedullin concentrations in various sites of the right-side circulation and there was no step-up of plasma adrenamedullin levels in the coronary sinus.
Abstract: Adrenomedullin is a novel hypotensive peptide, newly discovered in pheochromocytoma. Because immunoreactive adrenomedullin is present in human plasma, adrenomedullin may play a role in regulating blood pressure. A recent report showed that human adrenomedullin mRNA is expressed not only in pheochromocytoma but also in the normal adrenal medulla, kidney, lung, and ventricle. However, whether or not these organs actually release adrenomedullin into the circulation remains unknown. To investigate the sites of production and degradation of adrenomedullin in human subjects, we obtained blood samples from various sites and measured immunoreactive adrenomedullin concentrations. In study 1, blood samples were obtained from the infrarenal inferior vena cava, suprarenal inferior vena cava, superior vena cava, right atrium, right ventricle, pulmonary artery, pulmonary capillary, left ventricle, and aorta during cardiac catheterization in 15 patients with ischemic heart disease (67 +/- 10 years). In study 2, blood samples were taken from the infrarenal inferior vena cava, suprarenal inferior vena cava, right and left renal veins, and left adrenal vein in 5 hypertensive patients (42 +/- 14 years) suspected of having renovascular hypertension. In study 3, peripheral venous blood samples were obtained in 2 patients (males, 45 and 36 years old) with pheochromocytoma at rest and during hypertensive attacks. Plasma adrenomedullin concentrations were measured by a newly developed radioimmunoassay. In study 1, there were no significant differences in plasma adrenomedullin concentrations in various sites of the right-side circulation. There was no step-up of plasma adrenomedullin levels in the coronary sinus. However, the plasma concentration of adrenomedullin in aorta was slightly but significantly lower than in pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Results indicate that survival for patients after first-stage reconstruction for hypoplastic left heart syndrome has significantly improved in recent years, and older age was a strong risk factor, with a hospital survival of 91% for those patients undergoing first- stage palliation within the first month of life.
TL;DR: Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction.
Abstract: The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defined alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.
TL;DR: A clear biphasic response to hypoxia in pulmonary arteries of the rat is found, but, in contrast to some previous reports, phase 1 was only partially dependent on the endothelium, whereas phase 2 was entirely dependent onThe results are consistent with the involvement of at least two mechanisms for hypoxic vasoconstriction, one of which may involve release of an as yet unidentified endothelia-derived constrictor factor.
Abstract: Hypoxic vasoconstriction was investigated in isolated pulmonary and mesenteric arteries of the rat. Experiments were performed on large (approximately 2 mm pulmonary, approximately 0.8 mm mesenteric) and small (100-350 microns) arteries. Hypoxia [oxygen partial pressure (PO2) approximately 33 mmHg] elicited a biphasic response in arteries precontracted with prostaglandin F2 alpha (10 microM). A transient contraction reaching a peak within 2-3 min was observed in both large and small pulmonary and mesenteric arteries (phase 1). In pulmonary arteries, this was followed by a slowly developing contraction over 45 min (phase 2). In mesenteric arteries, there was no phase 2 but instead a profound relaxation. Mechanical disruption of the endothelium had no significant effect on phase 1 in preconstricted large pulmonary arteries but reduced phase 1 in small arteries by 40%. Phase 2 was abolished in both large and small arteries. Inhibition of endothelium-derived relaxing factor synthesis or cyclooxygenase pathways had no effect on either phase. Verapamil substantially reduced phase 1 but abolished phase 2. In conclusion, we have found a clear biphasic response to hypoxia in pulmonary arteries of the rat, but, in contrast to some previous reports, phase 1 was only partially dependent on the endothelium, whereas phase 2 was entirely dependent on the endothelium. Small and large arteries had qualitatively similar responses. These results are consistent with the involvement of at least two mechanisms for hypoxic vasoconstriction, one of which may involve release of an as yet unidentified endothelium-derived constrictor factor.
TL;DR: CT enables demonstration of pulmonary thromboembolism with criteria pertaining to pulmonary arteries and to lung parenchyma and enables assessment of technical operatibility and confirmation of surgical success.
Abstract: PURPOSE: To evaluate the role of computed tomography (CT) in diagnosis of chronic thromboembolic pulmonary hypertension, assessment of surgical operability, and follow-up after surgery. MATERIALS AND METHODS: Seventy-five patients with chronic thromboembolism were examined with CT; 63 underwent thromboendarterectomy, and postoperative CT scans were acquired in 23. CT scans were analyzed for vascular and parenchymal changes, and findings were compared with those on lung scintigrams and with surgical results. RESULTS: CT findings allowed confirmation of the diagnosis of chronic thromboembolism and ensured technical operability (sensitivity, 77%; specificity, 100%; overall accuracy, 80%) by means of direct visualization of thrombi in central pulmonary arteries in 53 patients. CONCLUSION: CT enables demonstration of pulmonary thromboembolism with criteria pertaining to pulmonary arteries and to lung parenchyma and enables assessment of technical operatibility and confirmation of surgical success.
TL;DR: Bilateral lung transplantation may be a more satisfactory option for patients with pulmonary hypertension with simple congenital heart disease, absent coronary arterial disease, and preserved left ventricular function.
TL;DR: A wide variation in the understanding of the use of the pulmonary artery catheter exists among nurses using this device in the care of seriously ill patients, and the results indicate that current teaching practices regarding the pulmonary arteries catheter need to be reevaluated and specific credentialing policies need to been considered.
Abstract: Objectives:To assess the knowledge and understanding of the use of the pulmonary artery catheter and interpretation of data derived from it in a group of nurses attending the American Association of Critical Care Nurses' National Teaching Institute conference.Design:A 37-question multiple choice exa
TL;DR: It is concluded that fat globules can traverse the pulmonary circulation within 3 h of orthopedic surgery and the difference between solid microspheres and fat in transpulmonary passage suggests that the composition, perhaps the deformability, of embolic material influences the lung's filtering capacity.
Abstract: We investigated the source of intravascular fat in systemic organs (brain, heart, and kidney) after massive pulmonary fat embolism during cemented arthroplasty. We used a bilateral cemented arthroplasty (BCA) in anesthetized mongrel dogs that simulates a cemented total-hip replacement procedure. We hypothesized that deformable fat globules could pass through the lung vasculature under high pulmonary artery pressure (Ppa). Using quantitative morphometry, we showed that the size of pulmonary vessel occluded by fat decreased from 12.8 +/- 15.2 microns 1 min after BCA to 4.9 +/- 5.1 microns at 120 min after BCA (p < 0.01). Ultrastructural studies demonstrated no evidence of acute inflammation around fat-occluded pulmonary vessels 3 h after BCA. Intravascular fat was found in all brain, heart, and kidney specimens examined 3 h after BCA (n = 6). No anesthetized animal in the "sham" (no BCA) group (n = 3) had intravascular fat at the same time period. Radiolabeled microspheres (15 microns diameter) did not reac...
TL;DR: Inhaled low-dose nitric oxide was administered after corrective operations 13 times to 10 infants who were at risk of postoperative pulmonary hypertension because of their congenital heart disease and left-to-right shunt, and caused selective pulmonary vasodilatation.
TL;DR: It is demonstrated that prolonged inhalation of low concentrations of NO induces sustained pulmonary vasodilation and reduces pulmonary vascular remodeling in response to chronic hypoxia.
Abstract: Exposure to hypoxia and subsequent development of pulmonary hypertension is associated with an impairment of the nitric oxide (NO) mediated response to endothelium-dependent vasodilators. Inhaled NO may reach resistive pulmonary vessels through an abluminal route. The aim of this study was to investigate if continuous inhalation of NO would attenuate the development of pulmonary hypertension in rats exposed to chronic hypoxia. In conscious rats previously exposed to 10% O2 for 3 wk, short-term inhalation of NO caused a dose-dependent decrease in pulmonary artery pressure (PAP) from 44 +/- 1 to 32 +/- 1 mmHg at 40 ppm with no changes in systemic arterial pressure, cardiac output, or heart rate. In normoxic rats, acute NO inhalation did not cause changes in PAP. In rats simultaneously exposed to 10% O2 and 10 ppm NO during 2 wk, right ventricular hypertrophy was less severe (P < 0.01), and the degree of muscularization of pulmonary vessels at both alveolar duct and alveolar wall levels was lower (P < 0.01) than in rats exposed to hypoxia alone. Tolerance to the pulmonary vasodilator effect of NO did not develop after prolonged inhalation. Brief discontinuation of NO after 2 wk of hypoxia plus NO caused a rapid increase in PAP. These data demonstrate that prolonged inhalation of low concentrations of NO induces sustained pulmonary vasodilation and reduces pulmonary vascular remodeling in response to chronic hypoxia.
Journal Article•
TL;DR: In conclusion, inhaled nitric oxide is a selective pulmonary vasodilator that can be used safely in the hemodynamic evaluation of heart transplant candidates with elevated pulmonary vascular resistance.
Abstract: The reversibility of elevated pulmonary vascular resistance in heart transplant candidates is currently evaluated with intravenous vasodilators. The aim of this study was to evaluate the effects of increased concentrations of inhaled nitric oxide (20, 40, and 80 ppm) on central hemodynamics and right ventricular function in heart transplant candidates with elevated pulmonary vascular resistance (> 2.5 Wood units). Comparison was made with intravenous vasodilators, sodium nitroprusside, and prostacyclin in doses that lowered the mean arterial pressure by about 15%. Inhalation of nitric oxide did not change systemic or pulmonary arterial pressure, cardiac output, right ventricular function, or systemic vascular resistance. Pulmonary capillary wedge pressure increased and transpulmonary pressure gradient and pulmonary vascular resistance decreased (-34% +/- 4% and -36% +/- 4%, respectively; p < 0.01) during 20 ppm nitric oxide, with no further effects at higher doses. Prostacyclin and sodium nitroprusside decreased pulmonary vascular resistance (-50% +/- 6% and -33% +/- 5%; p < 0.01). Prostacyclin reduced to some extent (p = 0.08) transpulmonary pressure gradient, which was not seen during sodium nitroprusside infusion. Systemic vascular resistance decreased during both sodium nitroprusside (-37% +/- 5%) and prostacyclin (-44% +/- 4%) infusion. The pulmonary vascular resistance/systemic vascular resistance ratio, used as an index of pulmonary selectivity, was decreased by nitric oxide (p < 0.01) but not by the intravenous vasodilators. Metabolic data indicate that inhaled nitric oxide is metabolized in the same way as that formed endogenously. In conclusion, inhaled nitric oxide is a selective pulmonary vasodilator that can be used safely in the hemodynamic evaluation of heart transplant candidates with elevated pulmonary vascular resistance.
TL;DR: Findings are consistent with a role for ET-1, acting through ETA receptors, in the pathogenesis of hypoxia-induced pulmonary hypertension.
Abstract: Our previous studies demonstrated that exposure to hypoxia increases pulmonary artery pressure and plasma endothelin-1 (ET-1) levels and selectively enhances ET-1 gene expression in rat lung. The current study examined the effects of hypoxia (48 h, 10% O2, 1 atm) on ET-1 and endothelin A (ETA) and ETB receptor steady-state mRNA levels in lung, heart, pulmonary artery, thoracic aorta, superior vena cava, kidney, spleen, and liver of the rat. In lung, hypoxic exposure was associated with significant increases in ET-1 mRNA (4.1-fold), ET-1 peptide (1.5-fold) and ETA mRNA (2.3-fold) levels; ETB mRNA levels were unchanged. ET-1 mRNA was increased in response to hypoxia in pulmonary artery but not in aorta; both ETA and ETB receptor steady-state mRNA levels were increased in thoracic aorta, left atrium, and right ventricle, and tended to be increased in right atrium of hypoxia-exposed rats, compared with air controls. ETB but not ETA receptor steady-state mRNA levels were increased in pulmonary artery of hypoxia-exposed rats. No change in expression of either ET receptor steady-state mRNA levels was seen in organs perfused by the systemic vascular bed. In no case were ET receptor mRNA levels in hypoxic rats reduced below air control levels, despite elevations in local and/or circulating ET-1. These findings are consistent with a role for ET-1, acting through ETA receptors, in the pathogenesis of hypoxia-induced pulmonary hypertension.
TL;DR: Left ventricular contraction contributes 24% of left ventricular stroke work to the generation of right ventricularstroke work via the septum in the absence of a contracting right ventricle; this increases to 35% in the face of increased pulmonary afterload.