The acute effects of intravenous nisoldipine on left ventricular function within 24 h after acute myocardial infarction.

Nisoldipine is a calcium antagonist with potent coronary vasodilating effects in patients with chronic stable angina pectoris. We studied the acute effects of nisoldipine in six patients within 24 h (mean 14 +/- 4 h) after the onset of myocardial infarction. Nisoldipine was administered as a 4.5 micrograms kg-1 intravenous bolus over 3 min followed by intravenous infusion of 0.2 microgram kg-1 min-1 during 60 min. Radionuclide angiography, cardiac output and intra-arterial blood pressure measurements were performed before and during nisoldipine. Left ventricular ejection fraction increased from 48.3 +/- 10.3% to 55.3 +/- 11.8% (P = 0.034) during nisoldipine infusion. Regional wall motion score changed during nisoldipine infusion from 3.3 +/- 2.5 to 1.8 +/- 2.6 (P = 0.027). Cardiac output increased from 5.5 +/- 1.0 to 7.3 +/- 1.3 l min-1 (P = 0.0001). Heart rate increased from 78 +/- 12 to 88 +/- 11 beats.min-1 (P = 0.004). Mean arterial blood pressure decreased from 91.7 +/- 20.2 to 78.7 +/- 13.1 mmHg (P = 0.038). The rate-pressure product did not change significantly during nisoldipine infusion. It is concluded that nisoldipine improves global and regional left ventricular function in patients with acute myocardial infarction within the first 24 h. Our findings suggest that this effect is achieved without increasing myocardial oxygen demand.     

Comparison of left and right ventricular blood flow responses during arterial pressure reduction in the autonomically blocked dog: evidence for right ventricular autoregulation

The effect of reducing systemic arterial pressure with an arteriovenous fistula on left and right ventricular myocardial blood flow was studied in 17 anaesthetised, open chest, autonomically blocked dogs. Global and regional myocardial blood flows were measured with radioactive microspheres. As mean arterial pressure was reduced from 133 mmHg to 78 mmHg left ventricular myocardial blood flow and the left ventricular inner to outer flow ratio decreased progressively. By contrast, right ventricular myocardial blood flow remained constant (range 78-81 ml.min-1.100 g-1) whereas right ventricular vascular resistance fell linearly (from 235 to 130 kPa.litre-1.min.100 g-1). The inner to outer right ventricular free wall flow ratio (range 1.04-1.10) and blood flow to the right side of the interventricular septum also did not change significantly. It is concluded that the right ventricular myocardium shows effective autoregulation of total and regional tissue blood flow during changes in coronary perfusion pressure.     

Comparison of the acute hemodynamic effect of nisoldipine (Bay k 5552) and nifedipine in patients with ischemia-induced left ventricular impaired function

Calcium channel blockers of the dihydropyridine type have different sites of action that may cause negative inotropic effects in some patients; therefore, their use as systemic vasodilators in left heart failure may be limited. In 10 patients with coronary heart disease we compared the acute peripheral and central hemodynamic effects of i.v. nisoldipine vs. i.v. nifedipine intraindividually, using a sequential crossover protocol. All patients were subjected to right heart catheterization, arterial pressure monitoring, and simultaneous radionuclide angiography. The infusion of either calcium channel blocker was titrated to a similar steady-state reduction of mean arterial pressure by 15 +/- 3% and 15 +/- 2%, respectively, which reduced systemic vascular resistance by 25 +/- 5% and 17 +/- 2%, respectively. The required equally effective dosage was 0.17 +/- 0.06 micrograms/min/kg for nisoldipine and 0.58 +/- 0.1 micrograms/min/kg for nifedipine. In contrast to nifedipine, the administration of nisoldipine was associated with an increase in cardiac index by 0.45 +/- 0.33 l/min/m2 (p less than 0.05), stroke volume index by 3.91 +/- 3.0 ml/m2 (p less than 0.05), and left ventricular ejection fraction by 4.6 +/- 2.8% (p less than 0.05). Mean pulmonary capillary wedge pressure decreased with nisoldipine from 11.8 +/- 3.4 to 8.0 +/- 3.4 mm Hg (p less than 0.005) and mean pulmonary artery pressure decreased from 20.4 +/- 4.06 to 16.1 +/- 3.2 mm Hg (p less than 0.005), but was unaffected by nifedipine. Left and right ventricular endsystolic and enddiastolic volumes were not significantly altered by either drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous carbochromen: a potent and effective drug for estimation of coronary dilatory capacity

Systemic and coronary haemodynamic effects of carbochromen (0.125 mg kg-1 min-1 for 40 min i.v.) and dipyridamole (0.05 mg kg-1 min-1 for 10 min i.v.) were investigated in 18 patients without detectable heart disease. Both drugs induced a comparable increase in coronary blood flow (carbochromen: from 82 +/- 23 to 337 +/- 68 ml.100 g-1.min-1; dipyridamole: from 78 +/- 9 to 301 +/- 61 ml.100 g-1.min-1). This resulted in a minimal coronary resistance of 0.23 +/- 0.04 mmHg.ml-1.100 g.min for dipyridamole and of 0.24 +/- 0.04 mmHg.ml-1.100 g.min for carbochromen. In response to dipyridamole (n = 12) heart rate increased from 73 to 94 beats min-1 (P less than 0.005) and mean aortic pressure fell from 89 to 78 mmHg (P less than 0.001). After administration of carbochromen (n = 6) no significant systemic effects occurred. Dipyridamole induced a significant increase in myocardial oxygen consumption by 46% (P less than 0.001); after application of carbochromen myocardial oxygen consumption remained unchanged. From these data it can be concluded that for the evaluation of coronary dilatory capacity carbochromen may be more suitable than dipyridamole because (1) maximal coronary vasodilation is induced without changes in myocardial oxygen consumption and (2) no systemic effects occur.     

Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity.

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.     

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adriamycin cardiomyopathy in the rabbit: an animal model of low output cardiac failure with activation of vasoconstrictor mechanisms

Chronic administration of intravenous adriamycin (1 mg . kg-1 twice weekly for 8 weeks) to rabbits resulted in a cardiomyopathy which was similar to that occurring in patients with adriamycin cardiotoxicity. We studied systemic and renal haemodynamics and the activation of vasoconstrictor mechanisms reflected by changes in plasma renin activity (PRA), noradrenaline (NA) and vasopressin (AVP) levels during the development of heart failure in this animal model. By 8 weeks cardiac failure was clearly established. At postmortem all animals had dilated hearts, pleural and pericardial effusions, ascites and hepatic congestion. Heart weights were increased (8.1 +/- 0.7 g in treated animals n = 9 vs 6.0 +/- 0.2 g in controls n = 9 p less than 0.05). Cardiac output (measured by thermodilution) fell at 8 weeks from 799 +/- 61 ml . min-1 to 624 +/- 44 ml . min-1 (n = 6 p less than 0.05) with a parallel fall in mean blood pressure from 85 +/- 2 mmHg to 75 +/- 4 mmHg. Total peripheral resistance rose in four of the six rabbits. Renal blood flow fell from 108 +/- 4 ml . min-1 to 61 +/- 6 ml . min-1 (p less than 0.05) by 8 weeks. Renal vascular resistance increased in all animals. PRA increased from 5.1 +/- 0.5 ng AI . ml-1 . h-1 to 11.6 +/- 2.6 ng AI . ml-1 . h-1 by 4 weeks (p less than 0.05) and remained elevated thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac function, coronary flow and MVO2 in hypertrophy induced by pressure and volume overloading.

Myocardial function, flow and O2 consumption were compared in cardiac hypertrophy induced by pressure-loading (P) and by volume overloading (V). Increases in LV-to-body weight ratios in P and V hypertrophied hearts were comparable. Indices of LV function such as cardiac output, stroke volume, stroke work, minute work, peak LV dP/dt, ratio of peak LV dP/dt-to-isovolumic pressure and -to-LVEDP, and Vmax were significantly reduced from normal only in hypertrophy induced by V. Left ventricular coronary flow was reduced from 167.1 +/- 27.2 in normal dogs to 146.2 +/- 17.1 cm3/min-100 g-1 in P hypertrophy, and was reduced further to 82.5 +/- 8.2 cm3/min-100 g-1 in V hypertrophy. Flows decreased similarly in epicardium and endocardium in both hypertrophied hearts. Cardiac O2 extraction in P and V hearts was greater than in control hearts. Myocardial O2 consumption was maintained at control values in P hypertrophy, and decreased by 54 +/- 3% in V hypertrophy. These findings indicate that LV function is impaired at rest in hypertrophy induced by V and is normal in hypertrophy induced by P.     

Indirect relation between rises in oxygen consumption and left ventricular output at birth in lambs.

To examine the relation between increased newborn oxygen requirements and the postnatal rise in cardiac output, we measured left ventricular (LV) output, organ blood flows, and whole-body oxygen consumption using radioactive microspheres in late-gestation sheep fetuses and in the same animals 1 and 4 hours after cesarean section delivery. LV output rose from 264 +/- 23 ml.min-1.kg body wt-1 in fetuses to 444 +/- 33 ml.min-1.kg body wt-1 in lambs at 1 hour after delivery (p less than 0.005) and was unchanged at 4 hours after delivery. This rise in LV output was associated with a more than fourfold increase in the LV flow contribution to tissues situated distal to the ductus arteriosus (fetus, 51 +/- 9 ml.min-1.kg body wt-1; lamb, 226 +/- 22 ml.min-1.kg body wt-1; p less than 0.005), which were mainly perfused by the right ventricle in utero. However, average blood flow to body tissues was similar in fetuses (37 +/- 4 ml.min-1.100 g tissue-1), 1-hour lambs (39 +/- 4 ml.min-1.100 g tissue-1), and 4-hour lambs (40 +/- 5 ml.min-1.100 g tissue-1). Oxygen consumption increased by 58%, from 7.84 +/- 0.43 ml.min-1.kg body wt-1 in fetuses to 12.38 +/- 2.4 ml.min-1.kg body wt-1 in 1-hour lambs (p less than 0.01), and was unchanged in 4-hour lambs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular dynamics and plasma catecholamines during isometric exercise in patients following cardiac transplantation

Haemodynamics and plasma catecholamine responses to isometric exercise were evaluated invasively in 11 orthotopic heart transplant recipients and seven control subjects. Differences in haemodynamic responses between the two groups were already apparent after one min of handgrip at 30% of maximal voluntary contraction, and very pronounced at the end of the fourth minute. At this point transplanted patients showed smaller increments in heart rate (4.8 +/- 3.2 vs 20.4 +/- 14.1 beats.min-1, P less than 0.001), mean arterial pressure (13.7 +/- 7.2 vs 31.5 +/- 12.2 mmHg, P less than 0.001) and cardiac index (0.51 +/- 0.22 vs 1.02 +/- 0.53 L.min-1.m-2, P less than 0.01), whereas left ventricular end-diastolic pressure increased to a greater extent (8.8 +/- 4.9 vs 2.2 +/- 1.8 mmHg, P less than 0.01). Stroke volume index increased similarly (3.8 +/- 1.8 vs 2.0 +/- 3.5 ml beat-1.m-2, NS) and systemic vascular resistance remained unchanged in both groups. The slopes of the left ventricular function curves (ratio of change in left ventricular work to change in left ventricular end-diastolic pressure) indicated depressed left ventricular function in the transplanted patients. The two groups showed similar increments in mixed venous plasma norepinephrine and epinephrine indicating normal sympathoadrenal activation in the transplanted patients. In conclusion, transplanted hearts respond to handgrip with attenuated increases in heart rate, cardiac output and arterial pressure and by increasing left ventricular filling pressure, suggesting a poor contractile reserve probably due to denervation. Circulating catecholamines, especially epinephrine, probably contribute to the cardiac responses to isometric exercise.     

Effects of nisoldipine on systemic and leg blood flow, oxygen transport and metabolism, and hemodynamics during exercise in effort angina pectoris

The acute effects of 10 mg of oral nisoldipine on hemodynamics, oxygen transport and metabolism, and distribution of cardiac output, at rest and during semiupright bicycle exercise, were evaluated in 10 men with effort angina receiving long-term beta 1 blockade. Cardiac output and leg blood flow were measured using the thermodilution technique. At rest, nisoldipine decreased systemic resistance from 18.9 +/- 1.0 to 15.9 +/- 1.2 dynes.s.cm-5.10(2) (p less than 0.05) and cardiac output increased from 4.8 +/- 0.2 to 5.3 +/- 0.3 liters/min (p less than 0.05) without changing leg blood flow. During maximal exercise with nisoldipine, systemic resistance was reduced (10.6 +/- 0.9 to 8.6 +/- 0.5 dynes.s.cm-5.10(2), p less than 0.05) and cardiac output increased 18% (10.3 +/- 0.7 to 12.2 +/- 0.6 liters/min, p less than 0.05) when compared with control values. Exercise heart rate was higher with nisoldipine (113 +/- 4 vs 106 +/- 4 beats/min, p less than 0.01), but the mean arterial pressure was not significantly changed, giving a higher rate-pressure product. The increase in mean pulmonary artery wedge pressure was attenuated (26 +/- 3 vs 30 +/- 3 mm Hg during control exercise, p less than 0.05), but ST depression was unaltered. Exercise leg flow was reduced by nisoldipine from 4.3 +/- 0.4 to 3.9 +/- 0.3 liters/min (p = 0.07) and the proportion of cardiac output distributed to the legs was reduced from 42 +/- 3 to 33 +/- 3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic aortic insufficiency with major left ventricle failure.ion. Results of aortic valve replacement and study of prognosis

Twenty four patients with chronic aortic incompetence and major left ventricular dysfunction underwent aortic valve replacement. Left ventricular failure was responsible for severe symptoms: NYHA Classes III and IV. It was defined by the following haemodynamic criteria: LV ejection fraction (EF) 40 p. 100 (mean 37 +/- 13 p. 100), LV end diastolic volume 250 ml/m2 (mean 254 +/- 82 ml/m2), LV end diastolic pressure 20 mmHg (mean 26 +/- 10 mmHg), AV difference 6 vol p. 100 (mean 7,07 +/- 1,77). The mean cardiac index was 2,03 +/- 0,59 l/m2. Of the 24 patients, 9 died (Group A). There were 3 perioperative deaths and 6 deaths 5 to 60 months after surgery. One patient died suddenly after improving 3 years after surgery; 3 patients died with moderate persistent cardiac failure and 2 patients died without regression of cardiac failure after surgery. Of the 15 survivors, (mean follow-up 16 months), Group B, 6 were operated within the last three months and rapidly improved. Nine patients were followed up for 8 to 55 months after surgery and had significant symptomatic improvement (NYHA: Class II). No preoperative clinical, electrocardiographic or echocardiographic prognostic criteria were found to distinguish between these two groups of patients. There were no significant differences in cardiac surface area (1,89 +/- 34 compared to 1,95 +/- 23), LVEDP (26 +/- 11 compared to 26 +/- 10 mmHg), LVEDV (257 +/- 21 compared to 252 +/- 60 ml/m2), EF (31 +/- 11 compared to 40 +/- 13) or cardiac index (2,0 +/- 0,58 compared to 2,0 +/- 0,61 l/m2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of dopamine in conscious rats with secondary biliary cirrhosis

Dopamine may be used in cirrhotic patients with renal or circulatory failure, but this drug can also increase the degree of portal hypertension. Hence, the systemic and splanchnic hemodynamic effects of dopamine have been studied in portal hypertensive rats with secondary biliary cirrhosis. The dose-response curves showed that dopamine significantly increased portal pressure at the same dose (80 micrograms min-1 kg-1 body wt.) in normal and biliary cirrhotic rats. Arterial pressure only increased with higher doses of dopamine in rats with biliary cirrhosis (160 micrograms min-1 kg-1 body wt.) while in normal animals it increased (80 micrograms min-1 kg-1 body wt.). Dopamine (160 micrograms min-1 kg-1 body wt.) significantly increased mean arterial pressure in normal and biliary cirrhotic rats. It significantly increased cardiac output in biliary cirrhotic rats from 134 +/- 6 to 153 +/- 7 ml/min but not in normals. Accordingly, systemic vascular resistance increased significantly in normal rats but not in cirrhotics. Portal pressure increased significantly in normal rats from 8.0 +/- 0.3 to 12.1 +/- 0.6 mmHg and in rats with biliary cirrhosis from 15.9 +/- 1.0 to 19.0 +/- 1.3 mmHg. Portal tributary blood flow increased significantly in normal and biliary cirrhotic rats (14.1 +/- 1 to 20.9 +/- 2.3 ml/min and 18.0 +/- 0.9 to 25.5 +/- 1.8 ml/min, respectively). This study shows that an elevated dose of dopamine increases the hyperkinetic syndrome in rats with secondary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Demonstration of dissimilar acute haemodynamic effects of ethanol and acetaldehyde.

To determine whether the acute cardiac depressant effects of ethanol could be attributed to its metabolite (acetaldehyde), either ethanol or acetaldehyde was intravenously infused into pentobarbital anaesthetised, closed-chest dogs. At a venous blood ethanol level of 199 +/- 43 (SE) mg . dl-1, ejection fraction had decreased from 35 +/- 2 to 30 +/-2%, P less than 0.05, max dP/dt/end-diastolic volume from 14.0 +/- 2.1 to 8.6 +/- 1.1 kPa . s-1 . cm-3 (105 +/- 16 to 65 +/- 8 mmHg . s-1 . cm-3), P less than 0.02, whereas end-diastolic volume (P less than 0.005), myocardial oxygen consumption (P less than 0.05) and coronary blood flow (P less than 0.005) had increased. Higher ethanol levels exaggerated these changes when peak arterial acetaldehyde was 20.2 +/- mumol . litre-1. By contrast, infusion of acetaldehyde to a peak blood level comparable with that produced by ethanol increased cardiac output from 2.4 +/- 0.2 to 2.8 +/- 0.2 litre-1 . min-1 P less than 0.01), coronary sinus oxygen saturation from 46 +/- 4 to 55 +/- 3% (P less than 0.25) and reduced systemic resistance from 8.0 +/- 0.7 to 6.3 +/- 0.5 kPa . litre-1 . min-1 (60 +/- 5 to 47 +/- 4 mmHg . litre-1 . min-1) (P less than 0.001). High dosage of acetaldehyde to a level of 129 +/- 23 mumol . litre-1 produced elevation of cardiac output (P less than 0.001), ejection fraction (P less than 0.01), coronary blood flow (P less than 0.02), whereas systemic resistance (P less than 0.001), heart rate (P less than 0.05) and myocardial oxygen consumption (P less than 0.05) decreased. Discontinuation of acetaldehyde infusion significantly reversed these changes. Max dP/dt/left ventricular end-diastolic volume and left ventricular end-diastolic volume were not significantly altered by acetaldehyde. Thus, ethanol depresses cardiac performance and increases myocardial oxygen consumption. By contrast, acetaldehyde at levels produced by ethanol metabolism improves cardiac performance, consequent to afterload reduction, and reduces myocardial oxygen consumption.     

Effect of a bradycardic agent on the isolated blood-perfused canine heart

Bradycardic agents could limit the consequences of myocardial ischemia via two mechanisms: by decreasing myocardial oxygen demand (MVO2) and by increasing diastolic coronary blood flow (CBF). We investigated whether the benzazepinone UL-FS 49 affects only sinus node cells or also smooth muscle and/or myocardial cells. To avoid confounding interactions with the periphery, we performed experiments on 11 isolated, blood-perfused canine hearts. Injection of UL-FS 49 (1 mg/kg i.c.) significantly reduced heart rate (HR) from 104 +/- 7 to 93 +/- 7 min-1 (mean +/- SEM) and increased stroke volume (n = 6: 9.8 +/- 1.1 vs. 13.2 +/- 1.6 ml), so that cardiac output remained unchanged (n = 6: 1.1 +/- 0.1 vs. 1.2 +/- 0.1 l/min). The contractile state, assessed by isovolumic peak systolic pressure, was unaltered by UL-FS 49 (n = 5: 72 +/- 6 vs. 72 +/- 6 mmHg). At a constant coronary arterial pressure (CAP) of 80 mmHg, mean CBF was slightly decreased (102 +/- 11 vs. 97 +/- 10 ml/[min.100 g]) by UL-FS 49, such that mean coronary resistance remained unchanged (0.9 +/- 0.1 vs 1.0 +/- 0.1 mmHg.min.100 g/ml). The slight decreases in arteriovenous oxygen content difference (n = 6: 6.6 +/- 0.7 vs. 6.5 +/- 0.7 ml/100 ml) and in CBF lead to a calculated, significant decrease in MVO2 (n = 6: 6.9 +/- 0.5 vs. 6.0 +/- 0.4 ml.100 g/min). In conclusion, UL-FS 49 at the dose used decreases MVO2 by reducing HR in isolated canine hearts. In the absence of negative inotropic and vasodilating effects, cardiac output is maintained via increased stroke volume, and CAP will likely be preserved in situ. Thus, this specific bradycardic agent could be useful in treating ischemic myocardial disease.     

Acute haemodynamic effects of oral prazosin in severe mitral regurgitation.

Acute haemodynamic effects of single dose oral prazosin were studied in eight patients with mitral regurgitation. Heart rate, mean systemic arterial pressure, pulmonary arterial pressure, left ventricular filling pressure, and forward cardiac output were measured in all patients. At peak effect, prazosin reduced mean systemic arterial pressure (95 +/- 4 to 86 +/- 4 mmHg), pulmonary arterial pressure (45 +/- 6 to 23 +/- 4 mmHg), and left ventricular filling pressure (30 +/- 4 to 21 +/- 3 mmHg). Pulmonary and systemic vascular resistance also fell (316 +/- 49 to 208 +/- 43 dynes s cm-5 and 2132 +/- 148 to 1491 +/- 94 dynes s cm-5, respectively). Forward cardiac index increased from 1.89 +/- 0.12 to 2.43 +/- 0.13 l/min per m2 and stroke volume from 43 +/- 5 to 57 +/- 6 ml/beat after prazosin. The onset of these changes occurred between 15 and 30 minutes, peaked between 45 and 60 minutes, and persisted for six hours. These data indicate that in patients with mitral regurgitation oral prazosin promptly improves cardiac performance (judged by increased forward cardiac output and reduced left ventricular filling pressure) as systemic and pulmonary vascular resistance are reduced.     

Effect of xamoterol on myocardial energetics in man

We analyzed the effect of xamoterol (beta 1-partial agonist) on myocardial energetics in 8 patients with normal left ventricular function. We measured resting systemic and coronary hemodynamics before and after a single intravenous injection of xamoterol (0.1 mg/kg). This agent increased heart rate from 70 +/- 7 to 80 +/- 11 beats/min (p less than 0.05) and cardiac index from 2.9 +/- 0.5 to 3.2 +/- 0.5 L/min.m2 (p less than 0.01), respectively. Left ventricular peak positive dp/dt (1870 +/- 350 vs 2620 +/- 580 mmHg/sec (p less than 0.01) and left ventricular ejection fraction (62 +/- 7 vs 70 +/- 7% (p less than 0.01] also increased, while left ventricular end-diastolic pressure (9 +/- 3 vs 5 +/- 3 mmHg (p less than 0.01] and volume index (70 +/- 14 vs 58 +/- 16 ml/m2 (p less than 0.01] decreased. Coronary blood flow and total myocardial oxygen consumption did not change significantly after intervention. As a result, xamoterol enhanced left ventricular external mechanical work versus myocardial oxygen consumption ratio (mechanical efficiency) from 20 +/- 4 to 24 +/- 5% (p less than 0.01). Myocardial oxygen extraction ratio decreased significantly (p less than 0.01) from 66 +/- 5 to 62 +/- 5% after xamoterol. We conclude that xamoterol augments left ventricular mechanical efficiency accompanied by a decrease in coronary vascular tone in patients with normal cardiac function.     

Elevated coronary vascular resistance in the presence of reduced resting blood flow distal to a severe coronary stenosis

Vascular reserve in underperfused myocardium has recently been described. This seemingly paradoxical observation conflicts with older concepts of the coronary circulation which hold that flow deficits do not develop until reserve is fully exhausted. To examine this phenomenon in greater detail in an animal model mimicking a fixed human coronary artery stenosis, we analysed the records of 25 carefully selected, sedated pigs all instrumented with a rigid intralumenal coronary stenosis (82% lumenal diameter reduction). Each animal satisfied the following criteria: 1) perfused myocardial mass beyond the stenosis was within a narrow weight range (16 to 24 g); and 2) post stenosis (distal) epicardial (Epi) and endocardial (endo) flows were less than or equal to 90% of respective flows in a region perfused by the non-stenosed circumflex (CX) coronary artery. Accordingly, distal flow was reduced compared to circumflex zone flow (p less than 0.01) in the Epi (173 +/- 51 to 113 +/- 32 ml . 100g-1 . min-1), Endo (146 +/- 39 to 116 +/- 27) and transmural (Tm) regions (164 +/- 45 to 124 +/- 31). Despite a flow deficit and constant severity of stenosis, distal zone Tm resistance (0.55 +/- 0.21 mmHg/ml . 100 g-1 . min-1) exceeded the minimum level achievable with intravenous infusion of adenosine (0.25 +/- 0.07) in a separate group of eight animals without a stenosis. Distal transmural resistance also varied over a five fold range (0.27 to 1.33) and in 20/25 animals exceeded the highest level (0.37) seen in non-stenosis animals during adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen consumption and transport in stable patients with chronic obstructive pulmonary disease

We studied the relationship between oxygen consumption and systemic oxygen transport in 30 clinically stable patients with chronic obstructive pulmonary disease (COPD) before and after increasing oxygen transport by passive leg elevation to raise the cardiac output. Results were compared with those observed in 10 patients with silicosis. The effect of leg elevation on oxygen consumption was also studied in 12 normal subjects. Oxygen consumption was measured by a closed circuit system, cardiac output by the direct Fick method, and arterial oxygen content by a cooximeter. Supine oxygen consumption was correlated with oxygen transport in patients with COPD (r = 0.50, p less than 0.01), and with leg elevation transport increased from a mean of 516 +/- 23 (SEM) to 567 +/- 26 ml X min-1 X m-2 and consumption increased from a mean of 136 +/- 3 to 148 +/- 4 ml X min-1 X m-2 (both p less than 0.01). In patients with silicosis, leg elevation raised mean oxygen transport from 620 +/- 40.0 to 745 +/- 54.0 ml X min-1 X m-2 and mean consumption from 161 +/- 6 to 192 +/- 6 ml X min-1 X m-2 (both p less than 0.01). In normal subjects, no change in oxygen consumption was observed with leg elevation (154 +/- 8 to 152 +/- 6 ml X min-1 X m-2).(ABSTRACT TRUNCATED AT 250 WORDS)     

The significance of heart rate for stress hemodynamics following heart transplantation

Since 1985, orthotopic heart transplantation had been carried out in 20 patients. Seventeen patients are still alive. 341 +/- 156 days after cardiac transplantation hemodynamics at rest were normalized. Left ventricular ejection fraction at rest and during exercise was within normal ranges for all patients except one. During symptom-limited bicycle exercise (121 +/- 35 Watt), pulmonary capillary wedge pressure (PCP) and right atrial pressure (RAP) increased to unphysiological high levels (PCP: 8.2 +/- 2.7 mmHg at rest, 19.1 +/- 4.9 mmHg at exercise; RAP: 4.1 +/- 2.3 mmHg at rest, 12.1 +/- 3.9 mmHg at exercise), whereas cardiac index was elevated to a normal level (3.6 l/min.m2 at rest; 6.9 l/min.m2 at exercise). Increase in heart rate, however, was subnormal (from 90 +/- 13/min at rest to 122 +/- 15/min at exercise). To examine the influence of heart rate on hemodynamics, in 8 patients with normal tricuspid valve function, heart rate was gradually increased by atrial stimulation during continuous exercise; PCP maximally could be reduced from 19.1 +/- 4 mmHg to 10.8 +/- 2.7 mmHg (p less than 0.01) at an optimum heart rate of 139 +/- 9/min. Reduction of RAP was by far less pronounced and normalization could not be achieved (from 12.2 +/- 3.7 mmHg to 9.5 +/- 3.4 mmHg, p less than 0.01), suggesting an impaired right ventricular function. By atrial stimulation stroke volume was reduced from 109.8 +/- 17.7 ml to 91.8 +/- 14.2 ml (p less than 0.01). These results indicate that, at exercise, the denervated transplanted heart, to a large extent, increases cardiac output by means of the Frank-Starling mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)