Showing papers by "Cardiovascular Institute of the South published in 1991"

Differential effects of transforming growth factor-beta 1 and phorbol myristate acetate on cardiac fibroblasts. Regulation of fibrillar collagen mRNAs and expression of early transcription factors.

Abstract: Cardiac fibroblasts are responsible for synthesis and deposition of fibrillar collagen types I and III. Transforming growth factor-beta 1 (TGF-beta 1) has been proved to increase collagen biosynthesis in various systems, both in vivo and in vitro. We have investigated the effect of TGF-beta 1 on collagen gene expression in cultured cardiac fibroblasts and have compared this effect with that of a mitogenic agent, phorbol myristate acetate (PMA). The regulation of collagen types I and III gene expression was examined by using cDNA probes to rat alpha 2 (I) and mouse alpha 1 (III) procollagens. Quiescent cultured cardiac fibroblasts from rabbit heart were treated with TGF-beta 1 (10-15 ng/ml) and PMA (200 ng/ml). After 24 hours of treatment with TGF-beta 1, the abundance of mRNA for pro-alpha 2 (I) and pro-alpha 1 (III) collagens was increased by 112% (p less than 0.001) and 97% (p = 0.05), respectively, in treated fibroblasts compared with untreated cells. However, PMA-treated cells showed an opposite response: a 42% (p = 0.01) decrease in mRNA levels for pro-alpha 2 (I) collagen was observed. Immunofluorescent staining of cardiac fibroblasts in culture with anti-type I collagen antibody showed that alterations in mRNA levels led to altered collagen synthesis: cellular collagen was relatively increased in TGF-beta 1-treated cells and significantly diminished in PMA-treated cells. The abundance of mRNA for pro-alpha 1 (III) collagen was not affected by PMA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of norepinephrine on myocardial collagen gene expression and response of cardiac fibroblasts after norepinephrine treatment.

Abstract: Biosynthesis of the collagen matrix of the heart has been shown to be regulated under various physiologic and pathologic conditions. Biogenic amines have known effects on myocardial function. The authors studied the effects of norepinephrine on myocardial collagen gene expression in the rat heart. Norepinephrine was administered intravenously in a sustained-release manner. Within 1 hour after treatment, the abundance of mRNA for pro alpha 2 (I) collagen increased by 212% (P = 0.05), TGF-beta 1 by 91% (P = 0.05), and cytoskeletal actin by 429% (P less than 0.01) in the ventricular myocardium of the treated rats compared with that in control untreated rats. In extended period of treatment, the abundance of mRNA for pro alpha 2 (I) collagen reached a peak (206% increase, P less than 0.01) at day 3, remained elevated through day 6, and returned to the control levels at 2 weeks after treatment. The expression of mRNA for TGF-beta 1 was coregulated with that of pro alpha 2 (I) collagen. The abundance of mRNA for cytoskeletal actin showed a sharp increase (323%, P less than 0.05) at day 1 and remained elevated through day 6 in treated hearts compared with that in control hearts and returned to the control levels at 2 weeks after treatment. Coadministration of alpha-receptor blocker, phentolamine, led to modest reversal, whereas coadministration of beta-receptor blocker, propranolol, led to about 50% reversal of norepinephrine effects on the abundance of mRNAs. At day 3 of treatment, collagen content of ventricular tissue, as determined by hydroxyproline measurement was increased by 13% (P less than 0.05) in treated hearts. Immunofluorescent light microscopy showed increased collagen deposition and focal areas of necrosis in the endocardial regions in hearts of animals treated with norepinephrine for 2 weeks. In vitro studies on cultured cardiac fibroblasts showed that although norepinephrine treatment does not lead to significant changes in the abundance of mRNA for pro alpha 2 (I) collagen, it leads to increased mRNA for cytoskeletal actin and increased (113%, P less than 0.05) 3H-thymidine incorporation into the cell nuclei of treated cells compared with that in untreated cells. The authors conclude that although norepinephrine has no direct in vitro effects on collagen type I biosynthesis, its in vivo effects may lead to a cascade of events such as induction of growth factors that ultimately result in increased expression of collagen type I in the myocardium.

Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart.

Abstract: Hypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF alpha- and beta-receptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF beta-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF alpha-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF beta-receptor mRNA levels. Aortic PDGF beta-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF alpha-receptor steady-state mRNA levels were unchanged in DOCA-salt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF beta- and alpha-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF beta-receptor. They also indicate that tissue-specific expression of the genes of the PDGF ligand/receptor system are differentially regulated in hypertension.

The study of the mass screening of persons without symptoms and of the screening of outpatients with gastrointestinal complaints or icterus for pancreatic cancer in Japan, using CA19-9 and elastase-1 or ultrasonography.

Abstract: To investigate the possibility of detecting carcinomas of the pancreas at an early stage by mass screening of persons without symptoms or by screening the outpatients with gastrointestinal complaints or jaundice, we performed a multicentral study of the mass screening of 10,162 persons at five local areas and of the outpatient screening of 4506 at 17 hospitals for pancreatic cancer in Japan for two years from 1984 to 1985, using serum CA19-9 and elastase-1 determinations or ultrasonography. Mass screening of 10,162 persons over 40 years old found only four (0.04%) cases of pancreatic cancer, including one case that was curatively treated. According to the screening of 4506 outpatients with gastrointestinal complaints or icterus, 85 (1.9%) patients were found to have pancreatic cancer. Of these 85 patients, 28 could undergo curative treatment. In addition to them, 73 (1.6%) patients with other digestive organ cancer were found. Our results suggest that the mass screening of persons without symptoms is not worthwhile in the early detection of pancreatic cancer, but outpatient screening is useful for detecting curative cancers of the pancreas.

The Venoarteriolar Response in Diabetics

Abstract: Resting skin blood flow and the venoarteriolar response (VAR) were studied in 40 patients with diabetic microangiopathy and neuropathy, in 40 diabetics with microangiopathy, and in 30 normal subjects by means of laser-Doppler flowmetry. In patients with microangiopathy and neuropathy, resting flow (RF) was increased and the VAR was impaired to a greater extent than in patients without neuropathy. There was also a significant delay in the VAR in diabetics, particularly in patients with neuropathy. The microangiopathy index (VAR/RF) was on the average 71.3 in normal subjects, significantly lower (p less than 0.05) in diabetics without neuropathy (34.8), and even lower in those with neuropathy (13.6). The VAR was evaluated with different postural changes; The authors observed that in the passage from supine to standing the VAR is more evident. In conclusion these results confirm that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in patients with neuropathy. The increased skin blood flow and the impaired VAR are causes of edema and may contribute to the thickening of capillary basement membranes observed in diabetes.

Calcium antagonists in cardiology: update on sustained-release drug delivery systems.

Abstract: One limitation of standard oral formulations of calcium antagonists has been the need for multiple daily dosing. Sustained-release dosage forms permit simpler regimens and a smoother therapeutic effect. Differences in drug pharmacokinetic and pharmacodynamic properties have led to development of several sustained-release delivery systems. Three major types are available: the osmotic pump, coated pellet, and slow-dissolving material released from a matrix. Each is currently utilized with specific calcium antagonists. The osmotic pump system with nifedipine (Procardia XL, Pfizer) allows once-daily dosing as well as improvements in certain side effects. Verapamil is available in formulations employing dissimilar release systems. The original sustained-action products (Calan SR, Searle; Isoptin SR, Knoll) utilize a matrix system; a subsequent product (Verelan; Lederle, Wyeth-Ayerst, A. H. Robins) utilizes timed-release pellets. Importantly, clinical efficacy appears to be maintained with these several drugs and formulations for their approved indications. Although a specific formulation may alter the absorption, metabolism, excretion, and blood levels of a drug, it does not alter basic drug properties. Thus, the major impact of sustained-release drug delivery system lies in potential compliance improvement and possible reduction of side effects related to serum drug profiles.

Long-term evaluation of indobufen in peripheral vascular disease.

Abstract: Indobufen--an inhibitor of platelets aggregation--has been used in 306 patients with intermittent claudication due to peripheral vascular disease. Patients were treated and followed up for one year. One patient of every 3 treated with indobufen was treated with ASA, and a control group of patients receiving no treatment was also followed up. The authors studied by means of a treadmill exercise test the pain-free walking distance (PFWD), the global walking distance (GWD), and the recovery time after exercise. The treatment period was completed by 290 patients: 204 claudicants, 51 claudicants with diabetes, and 35 with a short PFWD and GWD (greater than 150 m). Indobufen was more effective than ASA in improving the PFWD and GWD in all groups. There were also fewer side effects with indobufen, and cardiac morbidity and mortality was also reduced. In conclusion indobufen showed its activity and safety in chronic treatment of patients with peripheral disease, and we suggest that it may be used for long periods without side effects.

Transcoronary ethanol ablation of experimental ventricular tachycardia after epicardial ice mapping and localizing.

Abstract: Thirty-seven reproducible ventricular tachycardias (VTs) were induced in 19 dogs after the onset of myocardial infarction. The site of origin of VT was localized in 19 (59%) of 32 VTs by ice epicardial mapping. After 0.3-1.2 ml of 95% ethanol was injected into a small coronary artery supplying the arrhythmogenic area, VT was no longer inducible in 10 of 14 dogs. Intramyocardial ethanol (1-3 ml) was injected into the site of origin of VT in 9 dogs including 4 with VTs reinduced after intracoronary ethanol. Six of these VTs were not reinduced. Thus, the total efficacy rate was 84%. In 7 dogs, after injection of 0.4-1.2 ml (mean 0.5 ml) of 95% ethanol into a small normal coronary artery, the extent of the changes in ECG, CK-MB and pathology was found to be related to the size of myocardial damage and to the dose of ethanol. The smaller the dose of ethanol was given and the more distal the branch of coronary artery into which the ethanol was injected, the smaller the myocardial damage was. The data demonstrated that intracoronary or intramyocardial injection of ethanol may ablate the experimental VT induced by programmed heart stimulation in dogs after myocardial infarction, indicating that this approach may be useful and meaningful in some selected instances. However, it is necessary to limit the myocardial damage as far as possible.

Are some antihypertensive therapies more efficacious than others in preventing complications and prolonging life

Abstract: Antihypertensive therapy has been used for almost 35 years to reduce blood pressure and prevent morbidity and mortality related to the hypertensive state. Malignant, severe, and moderate hypertension have all been shown to be worthy of drug treatment, but controversy remains as to the degree of benefit that is achievable by treating milder hypertension. A variety of clinical trials have demonstrated that antihypertensive therapy reduces the incidence of stroke, congestive heart failure, and left ventricular hypertrophy and the progression in severity of hypertension. The benefits with respect to prevention of coronary heart disease (CHD) have been much less impressive. Thiazide diuretics have been the base therapy for the bulk of the hypertensive subjects studied to date who have not demonstrated reduced incidence of CHD. Therapy with beta-blockers has the potential for reducing CHD, but an analysis of four studies finds only two with positive results. On the other hand, since that study found reduced total mortality as well as CHD compared with thiazide diuretic, its findings cannot be ignored. Other questions deserving further investigation include how other antihypertensive therapies compare with respect to the risk reduction found with thiazide diuretics and beta-blockers, the optimal posttreatment blood pressure, whether persons with mild hypertension benefit from therapy, whether women should be treated differently, and whether atherosclerosis may be affected by specific antihypertensive therapies.

A case of a pseudomalfunction of a DDD pacemaker.

Abstract: DDD pacemaker pseudomalfunction occurred in a 65-year-old man. This was due to premature ventricular contraction (PVC) response option and cross-talk detection window, which are designed to protect against pacemaker related tachycardia or cross-talk. Pseudomalfunction disappeared by eliminating PVC response option.

[The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall. on atherogenesis in rabbits].

Abstract: The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall (PLP) on serum lipids. Plasma lipid peroxides (LPO), TXB2, and 6-keto-PGF1 alpha in cholesterol-fed rabbits have been investigated. Oral administration of nifedipine (15 mg/kg.d), diltiazem (30 mg/kg.d), and PLP (5 g/kg.d) caused 60.8%, 45.2%, and 74.2% reduction in the area of atherosclerosis in the aorta respectively. The levels of plasma LPO and TXB2 and the contents of cholesterol, phospholipid, and calcium in the intimal-media of the aorta in the treated groups were significantly lower than those in the cholesterol group, but the level of plasma 6-keto-PGF1 alpha in the treated groups was significantly higher. The appearance of cholesterol-induced TXB2 elevation and 6-keto-PGF1 alpha decrease in the treated groups was delayed. There are positive correlation between plasma TXB2 and the followings: serum lipids, plasma LPO, and the content of calcium in the intimal-media of the aorta, and the percentage of area of lesion in the aorta, while plasma 6-keto-PGF1 alpha showed significantly negative correlation with the above data. TXB2/6-keto-PGF1 alpha was found to be positively correlated with the percentage of lesion area of the aorta. It was shown that Ca2+ metabolism plays an important role in thromboxane, prostaglandin, and LPO metabolism. In conclusion, the inhibition of LPO production and regulation of TXA2-PGI2 balance may be one of the main mechanisms of the antiatherogenic effects of calcium antagonists and PLP.

Clinical pharmacology education in a division of cardiology.

Abstract: A working model of how clinical pharmacology education can be interwoven into the matrix of an academic cardiology program that includes didactic teaching, clinical research, and patient care has been presented. Essential to the success of such a program is the commitment and dedication of both its full-time and voluntary faculty. Moreover, a comprehensive plan of organization and allocation of efforts is vital to the success of such a complex undertaking. As we look to the future, the discipline of clinical pharmacology will be increasingly relevant to the practicing cardiologist.

Strut fracture and embolization of a Björk-Shiley valve from the tricuspid valve position.

Abstract: Between 1976 and 1986, approximately 83,000 patients had heart valve replacement with the Bjork-Shiley 60 ° CC prosthesis. A recognized complication of this prosthesis is strut fracture with embolization of the occluder disk. 1 This linearized frequency of this complication has been related to prosthetic size and date of manufacture. Whereas this complication is recognized for prostheses used in the mitral and aortic positions it has not yet been described in a prosthesis in the tricuspid position. The case described highlights such an occurrence.

A clinical trial of the secondary prevention of reinfarction with low dose aspirin

Abstract: Patients with acute myocardial infarction (AMI) admitted between 1986 and 1989 were divided into aspirin (ASA) group (216 cases) and control group (211 cases). In ASA group, 50 mg ASA was given daily to each case from the early stage of AMI and continuously after discharge (follow-up in OPD). In control group, no antiplatelet agents were administered during the follow-up period. The other therapies were comparable in both groups. The patients in both groups were scheduled for examination in the OPD every one to two months after discharge. Both groups were followed up until July, 1990. The follow-up periods in ASA group and control group were 19.4 +/- 12.6 vs 20.7 +/- 13.0 months respectively. There were 312 men in this study (175 in ASA group and 137 in control group). In men, incidence of reinfarction was reduced by 65% (P less than 0.001) and platelet aggregation was inhibited obviously in ASA group as compared to control group. However, there were no statistically significant differences of reinfarction and platelet aggregation between ASA group and control group in women. Thus, it is evident that low dose ASA is effective in preventing reinfarction and inhibiting platelet aggregation in men.

[Intravenous recombinant tissue-type plasminogen activator in acute myocardial infarction].

Abstract: The efficacy and safety of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA, made by Boehringer Ingelheim Corp.) was investigated in 10 patients with acute myocardial infarction (AMI). The rt-PA was given as a bolus dose of 10 mg followed by an infusion of 50 mg, 20 mg and 20 mg in successive hours. Heparin and aspirin were given to all the patients. The time interval from the onset of chest pain to thrombolysis was from 2.3 to 6.1 h with mean of 3.9 h. Coronary angiography, performed before administration of rt-PA and every 30 minutes thereafter, demonstrated total coronary occlusion (grade O) in 9 patients and grade 1 in 1 at baseline study. The infarct-related coronary artery were LAD in 5, RCA in 3 and LCX in 2. At 90 minutes after infusion of rt-PA reperfusion of the infarct-related artery was observed in 7 patients, the success rate was 70%. In one case the infarct-related LCX was not opened at 90 minutes, but it was reperfused at 170 minutes, after intracoronary administration of 10 mg of rt-PA. The total dose in this case was 130 mg. During 30 days of hospitalization death occurred in only one case with cardiogenic shock, in whom the infarct-related RCA was not reperfused by rt-PA but was successfully recanalized by PTCA. The patient died from rupture of the left ventricle on the 4th day. No patient had clinical evidence of reinfarction. Follow-up angiography in 2 patients showed that the arteries reperfused initially were patent.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of recombinant human erythropoietin in cardiac surgery with autologous blood transfusion

Abstract: The efficacy and method of administration of recombinant human erythropoietin (EPO) in adult cardiac surgical patients when given preoperatively was evaluated. We used EPO intravenously (iv) with 40 mg ferric oxide for a total of consecutive 47 patients. The patients were divided into group A (n = 14; EPO 200 IU/kg iv 3 times a week from 3 weeks prior to surgery to 2 weeks after surgery, donation of 800 ml) and group B (n = 33; EPO 200 IU/kg iv everyday from 8 days prior to surgery to 2 weeks after surgery, donation of 400 ml). Control groups were group AO (n = 11; donation of 835 +/- 33 ml from 14.8 days prior to surgery) and group BO (n = 7; donation of 406 +/- 34 ml at 7.3 days prior to surgery). All the EPO-treated patients received no homologous blood transfusion while 2 of patients in group BO received some homologous blood transfusion. A hemoglobin change between pre-donation and surgery was +0.14 +/- 1.3 (g/dl) in group A, +0.04 +/- 1.0 (g/dl) in group B, -1.7 +/- 1.3 (g/dl) in group AO and -1.0 +/- 0.6 (g/dl) in group BO. In a comparison of post-surgical hemoglobin levels between group A and group B, we demonstrated that the level in group B, +2.1 +/- 1.8 (g/dl) was significantly higher than that in group A, +11.1 +/- 1.6 (g/dl) 2 weeks after surgery. There was no evidence to show an aggravation of anemia in the pre-surgical period in EPO-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thallium-201 lung uptake in patients with chronic phase of myocardial infarction].

Abstract: To study pathophysiological significance of Tl-201 lung uptake in coronary artery disease Tl-201 lung uptake was studied in 159 patients with chronic phase of myocardial infarction. Tl-201 lung uptake images were collected after rest Tl-201 myocardial imaging. Tl-201 lung uptake was estimated by comparing maximal lung counts with maximal myocardial counts (thallium lung heart ratio: LHR). Good correlation between LHR and mean pulmonary artery wedge pressure (mPw) and between LHR and left ventricular ejection fraction (EF) were obtained, (mPw = 2.7 +/- 10.5 LHR r = 0.52 n = 102, p less than 0.001, EF = 84.9-52.2 LHR r = -0.61 n = 159, p less than 0.001). It was noted that Tl-201 did not accumulate uniformly through the lung field and usually maximal Tl-201 lung uptake was noted at the basal zone of the right lung. Tl-201 lung uptake in the upper zone of the right lung increased in proportion to the hemodynamic deterioration. Interesting differences were noted between Tl-201 lung uptake in patients with chronic phase of myocardial infarction and that in patients with acute phase of myocardial infarction. The prognosis and clinical status of patients with markedly increased Tl-201 lung uptake (LHR greater than 0.8) in chronic phase were more excellent than the patients with similar Tl-201 lung uptake in acute phase. Hemodynamic parameters in patients with markedly increased Tl-201 lung uptake (LHR greater than or equal to 0.8) in chronic phase were significantly better than in those in acute phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of microinjection of clonidine into nucleus tractus solitarii on atrial natriuretic factor in rats

Abstract: In order to study whether atrial natriuretic factor (ANF) is involved in the depressor effect of clonidine, microinjection of the latter into nucleus tractus solitarii (NTS) was carried out in anesthetized stroke-prone spontaneously hypertensive rats (SHRsp) and normotensive Wistar-Kyoto (WKY) rats. Each strain was randomly divided into three groups by injecting: (1) clonidine (1.0 microgram/0.2 microliter); (2) yohimbine (3.3 micrograms/0.2 microliter) followed by (1); (3) artificial cerebral spinal fluid (ACSF, 0.2 microliter) as control. A decrease of blood pressure and heart rate and a suppression of ANF release elicited by clonidine were significantly greater in SHRsp than in WKY rats. After blockade of alpha 2-receptor with yohimbine, the hypotensive effect of clonidine was blocked completely in WKY rats, but only partially in SHRsp, while the suppression effect on ANF release was eliminated in both strains. In addition, the decrease of plasma catecholamine produced by clonidine could also be blocked after yohimbine. The results suggest that ANF probably does not contribute to the depressor effect of centrally administered clonidine, while in SHRsp the decrease of plasma ANF might be a blood pressure-dependent compensatory response.

Evaluation of clinical criteria of coronary artery recanalization in acute myocardial infarction

Abstract: Clinical features of recanalization of infarct-related coronary artery during thrombolytic therapy or emergency PTCA and their correlation with immediate coronary angiography were analysed in 23 patients with acute myocardial infarction (AMI) to evaluate the predictive value of clinical criteria of reperfusion. The coronary angiography was performed before treatment and every 15 to 30 minutes during intravenous (rt-PA) or intracoronary (UK or SK) thrombolysis. Reperfusion was achieved in 16 cases by thrombolysis and in 4 cases by PTCA. The results revealed that in patients with reperfusion chest pain was relieved rapidly at least 70% in a period of 30 minutes, the ST segments fell by 50% or more from their elevated levels during a period of 30 minutes. Transient "paradoxical" increase of ST segment elevation followed by rapid falling was observed in 4 patients. This phenomenon was considered as a reliable marker of reperfusion. The changes in cardiac rhythm and conduction were noticed in 90% of the patients with reperfusion, among them accelerated idioventricular rhythm and disappearance of new-onset AVB and intraventricular conduction defects were useful bedside evidences of reperfusion, and transient significant sinus bradycardia or AVB with or without transient hypotension were useful markers of reperfusion in inferior myocardial infarction. When these clinical criteria were separately used as predictor of infarct-related coronary artery recanalization, the specificity was about 70% to 80%. Using the presence of all 3 criteria, the specificity and predictive value increased to 100% and the sensitivity was 70.6%. The time interval between onset of symptoms and peak CK and CK-MB were significantly shorter in patients with reperfusion than in those without persistent reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)