Hemodynamic effects of felodipine at rest and during exercise in exertional angina pectoris

To examine the antianginal effects of felodipine, a new calcium antagonist, 8 patients with coronary artery disease and exertional angina pectoris were studied. Hemodynamic measurements were made at rest, during submaximal exercise and during angina-limited exercise before and 30 minutes after oral administration of 0.1 mg/kg of felodipine. Angina pectoris was always prevented after the drug was given and the exercise intensity was increased until recurrence of angina (5 patients) or exhaustion (3 patients). Hemodynamic data were also recorded at this higher exercise capacity. At rest and during submaximal exercise, felodipine increased heart rate and decreased arterial blood pressure and systemic vascular resistance. The prevention of angina pectoris was accompanied by lower mean pulmonary capillary wedge pressure, systemic vascular resistance and ST-segment depression; the pressure-rate product was unchanged. The 20% greater exercise capacity after felodipine was attended by a 20% increase in maximal cardiac output, a 17% increase in maximal heart rate and a 13% increase in maximal pressure-rate product; the maximal arterial blood pressure and ST-segment abnormalities were unchanged and the systemic vascular resistance was lower. The relation between ST-segment depression and the pressure-rate product during exercise was favorably influenced by felodipine. Thus, felodipine is an active antianginal drug; its major mechanism of action is to lower the systemic vascular resistance. The data also suggest that it improves coronary blood flow during exercise.     

Antianginal effects of corwin, a new beta-adrenoceptor partial agonist

The hemodynamic effects of corwin were evaluated in 9 patients with coronary artery disease and without clinical signs of heart failure at rest, during submaximal exercise and during exercise-induced angina pectoris before and after administration of corwin. Angina pectoris was always prevented after the drug was given and the exercise intensity was increased until recurrence of angina pectoris; hemodynamic data were also recorded at this higher exercise capacity (+16%: p less than 0.001). At rest, corwin increased heart rate (from 80 to 84 beats/min) and pressure-rate product. During submaximal exercise, heart rate decreased from 105 to 96 beats/min, and pressure-rate product and ST-segment depression also decreased after corwin. The prevention of angina pectoris in all patients was accompanied by a lower heart rate (from 132 to 117 beats/min), pressure-rate product and ST-segment depression. At rest and during exercise, the cardiac output was unchanged and the pulmonary capillary wedge pressure was slightly decreased after corwin (from 12.5 to 10 mm Hg; p less than 0.001). At the 16% greater exercise capacity after corwin, angina pectoris recurred at the same values of cardiac output, pulmonary wedge pressure and ST-segment depression; maximal heart rate decreased from 132 to 124 beats/min, and the pressure-rate product was lower. Thus, corwin is an active antianginal drug. Its effects are likely due to a decrease in pressure-rate product and myocardial oxygen requirements during exercise. In contrast to beta-antagonists devoid of partial agonist activity, corwin does not depress left ventricular function either at rest or during exercise.     

Early hemodynamic adaptations to physical training in patients with healed myocardial infarction.

Seven patients with coronary heart disease (CHD) but no angina pectoris had hemodynamic studies at rest and during submaximal and maximal exercise levels 2 mth after an acute uncomplicated myocardial infarction. The hemodynamic study was repeated after 3 mth of regular physical training. Maximal oxygen intake (VO2max) increased by 16.1% after physical training while maximal heart rate unsignificantly decreased (minus 3.3%). Higher VO2max after training resulted from an increase in maximal cardiac output (+7%) and stroke volume (+9.2%) and from a widening of the maximal arterio-venous oxygen (A-VO2) difference (+7.3%). The fall in stroke volume observed from submaximal to maximal exercise level was not affected by training. During submaximal exercise, the lower heart rate after training was attended by both a greater stroke volume and a wider A-VO2 difference; the cardiac output slightly decreased. We conclude that the increase in VO2max observed with early physical training in CHD results on one hand from an increased stroke volume whose specificity is not established, and on the other hand from a wider maximal A-VO2 difference; the latter is entirely due to a greater extraction of oxygen from the blood by the working muscles during maximal exercise.     

Effects of molsidomine on exercise tolerance in patients with coronary heart disease

We performed a double-blind crossover study with molsidomine in 10 patients with coronary heart disease. A single dose of molsidomine and placebo were given sublingually 1 hour before an exercise tolerance test. Molsidomine significantly reduced systolic blood pressure at rest and at all work-loads. There was also a significant reduction in electrocardiographic ST-segment depression at submaximal exercise. At maximal exercise the drug significantly increased symptom-limited oxygen consumption and total mechanical work.Molsidomine could prove useful in the treatment of angina pectoris. It has no adverse effects on pulmonary function.     

Acute effects of oral propranolol on hemodynamic responses to upright exercise.

Noninvasive measurements of maximal oxygen intake and invasive measurement of systemic and pulmonary arterial pressures, arterial and mixed venous oxygen contents and direct Fick cardiac output are reported for 3 healthy men and 14 men with coronary heart disease. Observations were obtained at supine and sitting rest, during graded levels of upright exercise on a treadmill up to symptom-limited maximal effort and in two periods of recovery. The effects of 40 mg of propranolol orally were ascertained by repeating the measurements 1 to 1 1/2 hours later. The most consistent effect of propranolol was reduction of pressure-rate products at all phases; slowing of heart rate was significant only during exercise and recovery, and the greater slowing was accompanied by a significant increase in stroke volume. These changes were similar in patients with and without evidence of left ventricular impairment greater than 15 percent on exercise testing. Maximal oxygen intake decreased in healthy subjects and decreased slightly in patients with coronary heart disease with less than 15 percent left ventricular impairment or percent deviation of pressure-rate product from age-predicted normal values during the control study. Maximal oxygen intake increased in patients with more than 15 percent left ventricular impairment. Arterial-mixed venous oxygen difference increased after propranolol because of a reduction of mixed-venous oxygen content attributed to greater peripheral extraction of oxygen.     

Induction of a reduction in haemoglobin concentration by enalapril in stable, moderate heart failure: a double blind study.

OBJECTIVE--To study the long term effects (12 weeks) of enalapril on central haemodynamic function and on arterial oxygen content and its determinants--haemoglobin concentration and oxygen saturation--in patients with stable moderate heart failure. DESIGN--Double blind placebo controlled randomised study. PATIENTS--17 patients with stable moderate heart failure caused by dilated cardiomyopathy which was treated with diuretics and digoxin. METHODS--Central haemodynamic function, arterial oxygen content, arterial haemoglobin concentration, and arterial oxygen saturation were measured at rest and during submaximal exercise. Plasma volume and total body haemoglobin were determined at rest. RESULTS--With enalapril treatment heart rate, pulmonary capillary wedge pressure, mean arterial pressure, and systemic vascular resistance decreased significantly both at rest and during submaximal exercise. Cardiac output did not change at rest but tended to increase (p = 0.06) during submaximal exercise. Arterial oxygen saturation remained unchanged while haemoglobin concentration and arterial oxygen content were significantly reduced. Total body haemoglobin was significantly reduced but the plasma volume remained unchanged. At rest, the reduction in arterial oxygen content resulted in a significantly reduced mixed venous oxygen content. However, during submaximal exercise the increase in cardiac output fully compensated for the reduction in arterial oxygen content and this effect was indicated by the unaltered mixed venous oxygen content. No changes were found in the placebo group after twelve weeks. CONCLUSIONS--Enalapril unloads the heart and reduces haemoglobin concentration. During submaximal exercise, the improvement in systemic blood flow was counterbalanced by this negative effect on the oxygen carrying capacity and systemic oxygen delivery was unchanged.     

Induction of a reduction in haemoglobin concentration by enalapril in stable, moderate heart failure: a double blind study

OBJECTIVE--To study the long term effects (12 weeks) of enalapril on central haemodynamic function and on arterial oxygen content and its determinants--haemoglobin concentration and oxygen saturation--in patients with stable moderate heart failure. DESIGN--Double blind placebo controlled randomised study. PATIENTS--17 patients with stable moderate heart failure caused by dilated cardiomyopathy which was treated with diuretics and digoxin. METHODS--Central haemodynamic function, arterial oxygen content, arterial haemoglobin concentration, and arterial oxygen saturation were measured at rest and during submaximal exercise. Plasma volume and total body haemoglobin were determined at rest. RESULTS--With enalapril treatment heart rate, pulmonary capillary wedge pressure, mean arterial pressure, and systemic vascular resistance decreased significantly both at rest and during submaximal exercise. Cardiac output did not change at rest but tended to increase (p = 0.06) during submaximal exercise. Arterial oxygen saturation remained unchanged while haemoglobin concentration and arterial oxygen content were significantly reduced. Total body haemoglobin was significantly reduced but the plasma volume remained unchanged. At rest, the reduction in arterial oxygen content resulted in a significantly reduced mixed venous oxygen content. However, during submaximal exercise the increase in cardiac output fully compensated for the reduction in arterial oxygen content and this effect was indicated by the unaltered mixed venous oxygen content. No changes were found in the placebo group after twelve weeks. CONCLUSIONS--Enalapril unloads the heart and reduces haemoglobin concentration. During submaximal exercise, the improvement in systemic blood flow was counterbalanced by this negative effect on the oxygen carrying capacity and systemic oxygen delivery was unchanged.     

Comparative haemodynamic dose response effects of propranolol and labetalol in coronary heart disease.

The immediate haemodynamic dose response effects of beta blockade (propranolol: 2 to 16 mg) were compared with those of combined alpha beta blockade (labetalol: 10 to 80 mg) in a randomised study of 20 patients with stable angina pectoris. After control measurements, the circulatory changes induced by four logarithmically cumulative intravenous boluses of each drug in equivalent beta blocking doses were evaluated at rest, after which comparison of the effects of the maximum cumulative dose of each was undertaken during a four minute period of supine bicycle exercise. Propranolol, at rest, induced significant dose related reductions in heart rate and cardiac output, with reciprocal increases in the systemic vascular resistance and pulmonary artery occluded pressure; systemic arterial pressure was unchanged. Labetalol was followed by significant dose related decreases in systemic blood pressure and vascular resistance associated with a significant increase in cardiac output; heart rate and pulmonary artery occluded pressure were unchanged. The slope of the left ventricular pumping function curve relating output to filling pressure from rest to exercise was significantly depressed by propranolol but unchanged after labetalol. The less deleterious effects on left ventricular haemodynamic performance after alpha beta blockade in contrast to beta blockade alone in ischaemic heart disease may be attributable to the concomitant reduction in left ventricular afterload associated with the alpha blocking activity of labetalol.     

Pathophysiological aspects of predominant preload lowering on pulmonary circulation, gas exchange, and the biventricular function in patients with chronic obstructive lung disease

A group of 21 patients with various degrees of chronic obstructive pulmonary disease underwent radionuclide ventriculography with hemodynamic monitoring to assess the extent to which pulmonary artery pressures and pulmonary vascular resistance can be lowered by the vasodilator molsidomine. Molsidomine (N-carboxy-3-morpholino-sydnonimin-ethylester) is similar to nitroglycerin in its mode of action. After hemodynamic and radionuclide data acquisition, at rest and during submaximal exercise in the steady state, 2 mg molsidomine was injected intravenously. Rest and exercise measurements were repeated 45 min after molsidomine injection. In patients with mild to moderate disease (group 1), pulmonary artery resting pressures decreased by 12% (p less than 0.05) at rest by 22% (p less than 0.01) during exercise after the administration of the drug. Total pulmonary resistance during exercise decreased significantly (p less than 0.01) as a result of marked decrease of pulmonary artery pressure (PAP) compared with a minimal decrease in cardiac index (CI). In patients with severe disease (group 2), only the resting values of PAP decreased while the relationship between pressure and flow was unchanged. During the exercise period, the preload parameters of the right and left ventricles decreased by an average of 30%. With regard to gas exchange, only the arterial PO2 at rest decreased slightly but significantly (p less than 0.05) after molsidomine, while the coefficient of oxygen delivery was not affected by the drug. However, in four patients arterial PO2 was markedly reduced by the drug. Right ventricular ejection fraction increased significantly (p less than 0.01) both at rest and during exercise in group 1 and during exercise in group 2 after administration of molsidomine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of physical training in established arterial hypertension

Six patients with established arterial hypertension have been studied before and after a three months period of regular intense physical training. After training the maximal oxygen uptake was 9.6% higher (P < 0.02) and the heart rate was lower at rest (-8 beats/min; NS) and during submaximal exercise (-12 beats/min; P < 0.001). This bradycardia was attended by a slight decrease in cardiac output and an increase in the arterio-mixed venous oxygen difference; the blood pressure was unchanged and, accordingly, the peripheral resistance were slightly increased after training (+ 17%, P < 0.005 at rest and + 6.5% NS during exercise). We concluded that physical training has no specific hypotensive effect in patients with established arterial hypertension; in these patients the changes induced by training are very similar to those observed in normal subjects or in patients with coronary artery disease.     

Effects of nifedipine on arterial oxygenation at rest and during exercise in patients with stable angina

The effects of nifedipine on arterial oxygenation and hemodynamics were studied at rest and during bicycle exercise in 12 men (mean age 55 years, range 41 to 67) with stable exertional angina. The study was conducted double-blind on 2 days, 1 week apart, using a placebo-controlled crossover design. On each day, measurements at rest were made before and 20 minutes after 20 mg sublingual nifedipine or placebo and were followed by measurements made during exercise. Compared with placebo, nifedipine reduced mean arterial pressure, systemic vascular resistance and pulmonary vascular resistance, and increased heart rate and cardiac output at rest and during exercise. It did not alter mean pulmonary artery or pulmonary artery wedge pressures at rest, but decreased them during exercise. Nifedipine decreased arterial oxygen tension (PaO2) from 96 +/- 10 to 90 +/- 13 mm Hg (p less than 0.05) at rest and from 99 +/- 11 to 92 +/- 12 mm Hg (p less than 0.005) at submaximal exercise (33 +/- 21 W), but did not alter it (100 +/- 12 versus 100 +/- 16 mm Hg, p = NS) at maximal exercise (68 +/- 30 W). The reduction in PaO2 was not due to alveolar hypoventilation, because nifedipine did not alter arterial carbon dioxide tension, or to changes in mixed venous oxygen tension, which nifedipine increased at rest (39 +/- 2 versus 43 +/- 3 mm Hg, p less than 0.001) and during submaximal exercise (31 +/- 4 versus 33 +/- 4 mm Hg, p less than 0.03) and maximal exercise (27 +/- 3 versus 31 +/- 3 mm Hg, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Improvement in supine bicycle exercise performance in refractory congestive heart failure after isosorbide dinitrate: radionuclide and hemodynamic evaluation of acute effects

The acute effects of oral isosorbide dinitrate on exercise performance in congestive heart failure were evaluated in 11 patients. All patients underwent rest and supine bicycle exercise equilibrium radionuclide ventriculography and hemodynamic measurements before and after oral administration of isosorbide dinitrate, 40 mg four times a day for 24 hours. Ninety minutes after the last dose, isosorbide dinitrate increased the duration of exercise (+ 28 percent, probability [p] < 0.01) and the total work performed (+ 32 percent, p < 0.01); with this drug, significantly (p < 0.05) fewer patients terminated exercise because of dyspnea. At rest, the left ventricular ejection fraction increased after administration of isosorbide dinitrate (+ 14 percent of value before administration, p < 0.02); there were decreases in mean pulmonary arterial pressure (? 23 percent, p < 0.02), mean arterial pressure (? 8 percent, p < 0.05), systemic vascular resistance (? 18 percent, p < 0.005) and pulmonary vascular resistance (? 46 percent, p < 0.001). During comparable levels of exercise, isosorbide dinitrate decreased pulmonary capillary wedge pressure (? 19 percent, p < 0.001), mean pulmonary arterial pressure (? 23 percent, p < 0.001), mean arterial pressure (? 7 percent, p < 0.001), heart rate (? 5 percent, p < 0.01), systemic vascular resistance (? 20 percent, p < 0.01) and pulmonary vascular resistance (? 37 percent, p < 0.01), and increased cardiac index (+ 15 percent, p < 0.02), stroke volume index (+ 19 percent, p < 0.01) and stroke work index (+ 16 percent, p < 0.05). Ejection fraction did not change significantly (+ 7 percent, difference not significant [NS]). During maximal exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (? 15 percent, p = 0.05), mean pulmonary arterial pressure (? 15 percent, p < 0.01), systemic vascular resistance (? 23 percent, p < 0.05) and pulmonary vascular resistance (? 30 percent, p < 0.01) and increases in cardiac index (+ 30 percent, p < 0.001), stroke volume index (+ 31 percent, p < 0.001) and stroke work index (+ 40 percent, p < 0.001). Ejection fraction did not change significantly (+ 9 percent, p = NS). Ten minutes after exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (? 34 percent, p < 0.02), mean pulmonary arterial pressure (? 23 percent, p < 0.02), mean arterial pressure (? 10 percent, p < 0.01) and systemic vascular resistance (? 24 percent, p < 0.001) and increases in stroke volume index (+ 18 percent, p < 0.05) and ejection fraction (+ 12 percent, p < 0.05). It is concluded that oral isosorbide dinitrate, by causing reductions in preload and afterload, produces significant beneficial acute effects on left ventricular performance during exercise in patients with refractory chronic congestive heart failure.     

Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure

We studied the central hemodynamic, leg blood flow, and metabolic responses to maximal upright bicycle exercise in 30 patients with chronic heart failure attributable to severe left ventricular dysfunction (ejection fraction, 24 +/- 8%) and in 12 normal subjects. At peak exercise, patients demonstrated reduced oxygen consumption (15.1 +/- 4.8 vs. 32.1 +/- 9.9 ml/kg/min, p less than 0.001), cardiac output (8.7 +/- 3.2 vs. 18.6 +/- 4.4 l/min, p less than 0.001), and mean systemic arterial blood pressure (116 +/- 15 vs. 135 +/- 13 mm Hg, p less than 0.01) compared with normal subjects. Leg blood flow was decreased in patients versus normal subjects at rest and matched submaximal work rates and maximal exercise (2.1 +/- 1.9 vs. 6.4 +/- 1.4 l/min, all p less than 0.01). Mean systemic arterial blood pressure was no different in the two groups at rest or at matched submaximal work rates, whereas leg vascular resistance was higher in patients compared with normal subjects at rest, submaximal, and maximal exercise (all p less than 0.01). Although nonleg blood flow was decreased at rest in patients, it did not decrease significantly during exercise in either group. Peak exercise leg blood flow was related to peak exercise cardiac output in patients (r = 0.66, p less than 0.01) and normal subjects (r = 0.67, p less than 0.01). In patients, leg vascular resistance was not related to mean arterial blood pressure, pulmonary capillary wedge pressure, arterial catecholamines, arterial lactate, or femoral venous pH at rest or during exercise. Compared with normal subjects during submaximal exercise, patients demonstrated increased leg oxygen extraction and lactate production accompanied by decreased leg oxygen consumption. Thus, in patients with chronic heart failure compared with normal subjects, skeletal muscle perfusion is decreased at rest and during submaximal and maximal exercise, and local vascular resistance is increased. Our data indicate that nonleg blood flow and arterial blood pressure were preferentially maintained during exercise at the expense of leg hypoperfusion in our patients. This was associated with decreased leg oxygen utilization and increased leg oxygen extraction when compared to normal subjects, providing further evidence that reduced perfusion of skeletal muscle is important in causing early anaerobic skeletal muscle metabolism during exercise in subjects with this disorder.(ABSTRACT TRUNCATED AT 400 WORDS)     

Exercise training in patients with severe left ventricular dysfunction. Hemodynamic and metabolic effects

We studied the effects of exercise training in patients with chronic heart failure attributed to left ventricular dysfunction (ejection fraction, 24 +/- 10%). Twelve ambulatory patients with stable symptoms underwent 4-6 months of conditioning by exercising 4.1 +/- 0.6 hr/wk at a heart rate corresponding to 75% of peak oxygen consumption. Before and after training, patients underwent maximal bicycle exercise testing with direct measurement of central hemodynamic, leg blood flow, and metabolic responses. Exercise training resulted in a decrease in heart rate at rest and submaximal exercise and a 23% increase in peak oxygen consumption from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min (p less than 0.01). Heart rate, arterial lactate, and respiratory exchange ratio were unchanged at peak exercise after training. Maximal cardiac output tended to increase from 8.9 +/- 2.7 to 9.9 +/- 3.2 1/min and contributed to improved peak oxygen consumption in some patients, although this change did not reach statistical significance (p = 0.13). Rest and exercise measurements of left ventricular ejection fraction, left ventricular end-diastolic volume, and left ventricular end-systolic volume were unchanged. Right atrial, pulmonary arterial, pulmonary capillary wedge, and systemic arterial pressures were not different after training. Training induced several important peripheral adaptations that contributed to improved exercise performance. At peak exercise, systemic arteriovenous oxygen difference increased from 13.1 +/- 1.4 to 14.6 +/- 2.3 ml/dl (p less than 0.05). This increase was associated with an increase in peak-exercise leg blood flow from 2.5 +/- 0.7 to 3.0 +/- 0.8 l/min (p less than 0.01) and an increase in leg arteriovenous oxygen difference from 14.5 +/- 1.3 to 16.1 +/- 1.9 ml/dl (p = 0.07). Arterial and femoral venous lactate levels were markedly reduced during submaximal exercise after training, even though cardiac output and leg blood flow were unchanged at these workloads. Thus, ambulatory patients with chronic heart failure can achieve a significant training effect from long-term exercise. Peripheral adaptations, including an increase in peak blood flow to the exercising leg, played an important role in improving exercise tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term effect of isosorbide dinitrate and nifedipine, singly and in association, in patients with chronic heart failure

The effect of 2-month treatment with isosorbide dinitrate (120 mg day-1), nifedipine (2 x 20 mg day-1) and their combination has been assessed in 16 patients with mild to moderate chronic cardiac failure. Isosorbide dinitrate decreased right atrial (-23%), pulmonary wedge (-20%) and pulmonary arterial (-17%) pressures but did not significantly change either cardiac output or systemic and pulmonary vascular resistance. Nifedipine increased cardiac output (+13%) and decreased systemic and pulmonary vascular resistance (both -17%) with no change of pressures. Combined therapy with both drugs decreased ventricular filling pressures (-8% and -15%), systemic (-20%) and pulmonary (-13%) arterial pressures, increased cardiac output (+26%) and decreased both systemic (-29%) and pulmonary (-29%) vascular resistances. Changes during exercise were almost the same as at rest. The effect of both drugs was more pronounced in patients with more severely pathological haemodynamic measurements before treatment. We conclude that combined treatment with both preload- and afterload-reducing agents can preserve or even potentiate a favourable haemodynamic effect of individual drugs.     

Prediction of peak exercise oxygen uptake by cardiopulmonary measurements at rest in heart transplant candidates

OBJECTIVE: Peak oxygen uptake (VO2) is a powerful prognostic index, but maximal exercise testing in heart transplant candidates has a number of disadvantages. It is unknown whether it is possible to predict peak VO2 from a comprehensive dataset with parameters of heart and lung function at rest. METHODS: One hundred adult patients in sinus rhythm and with either idiopathic or ischaemic heart failure performed a graded cycle ergometer test until volitional fatigue and underwent radionuclide ventriculography, heart catheterization, and lung function measurements at rest. RESULTS: Weight, height, age, gender and aetiology of heart failure explained 48% of the variance of peak VO2. On top of these anthropometric, demographic and clinical patient characteristics, 12% of the variance of peak VO2 was additionally explained by all resting measurements combined, i.e. radionuclide left ventricular ejection fraction, peak ejection rate, peak filling rate, cardiac frequency, mean right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressures, cardiac output, forced vital capacity, forced expiratory volume in one second, and pulmonary diffusing capacity (cumulative R2 = 0.60); among these, pulmonary vascular resistance was the most important predictor (+6%; P < 0.001). Analyses in a subset of 43 male patients pointed out that systemic pressures and vascular resistance were not related to peak VO2. CONCLUSION: On the basis of resting left ventricular function, haemodynamics, and routine pulmonary measurements, it is unlikely to accurately predict exercise tolerance in the majority of heart transplant candidates, i.e. patients with either idiopathic or ischaemic heart failure and able to exercise until exhaustion.     

Nifedipine in chronic stable angina: a double-blind placebo-controlled crossover trial

Thirty patients with chronic stable angina pectoris were randomized in a double-blind prospective placebo-controlled crossover trial to assess the efficacy of nifedipine (30 to 60 mg/day orally) in controlling symptoms and objective signs of myocardial ischemia using a symptom-limited treadmill exercise test. Adverse effects that occurred during both nifedipine and placebo treatment were minor and generally well tolerated. Twenty-three patients were analyzed from the crossover phase of the study. Nifedipine significantly reduced the frequency of angina by 55% and nitroglycerin consumption by 59%, and increased exercise time by 34%. These changes were significantly greater than those in the placebo group. Hemodynamic evaluation during exercise revealed a significant reduction in systolic and diastolic blood pressures in the nifedipine group at the onset of angina and at maximal exercise without significant differences in heart rate responses in the nifedipine and placebo groups. The pressure-rate product during submaximal exercise was significantly smaller in the nifedipine group than in the placebo group, but did not differ significantly in the 2 groups at the onset of angina or on maximal exercise. Furthermore, S-T segment depressions that occurred during exercise at the same pressure-rate products were smaller in the nifedipine period than in the placebo period. Thus, it appears that the antianginal effects of nifedipine are caused by a reduced myocardial oxygen demand for a specific work load and possibly by an increased blood supply to ischemic myocardium.     

Acute and chronic systemic and pulmonary hemodynamic effects of angiotensin converting enzyme inhibition with captopril in hypertensive patients

The effects of the angiotensin converting enzyme inhibitor captopril were studied in 14 patients with essential or renovascular hypertension 75 minutes after ingestion of 25 mg of the drug, and after 2 months of therapy with 150 to 600 mg/day. Captopril acutely decreased mean brachial arterial pressure by 16.3 mm Hg (p < 0.001); the decrease was 7.6 mm Hg (p < 0.01) during long-term therapy at the higher dose level. The changes in mean brachial arterial pressure were significantly related to control plasma levels of angiotensin II. The acute hypotensive effect of captopril was based on a 10 percent decrease (p < 0.01) in systemic vascular resistance with essentially unchanged cardiac output and heart rate. Pulmonary capillary wedge pressure decreased by 2.3 mm Hg (p < 0.001) with unchanged pulmonary vascular resistance. During long-term treatment systemic vascular resistance decreased by 29 percent (p < 0.001). Oxygen consumption increased by 15 percent (p < 0.01) with a concomitant 16 percent Increase in cardiac output (p < 0.01), characterized by an increased stroke volume and unchanged heart rate; one patient experienced angina pectoris that may have been related to these hemodynamic changes. The decrease in pulmonary capillary wedge pressure was maintained, and right atrial pressure decreased (?1.4 mm Hg; p < 0.05).The data indicate that the action of captopril is characterized by arteriolar and possibly venous dilatation. The increase in cardiac output during long-term treatment seems to be associated with a hypermetabolic state and in patients with very severe hypertension, with restoration to normal of mildly decreased left ventricular function.     

The effects on left ventricular performance of verapamil and metoprolol singly and together in exercise-induced angina pectoris

Concurrent therapy with the calcium channel blocker, verapamil, and the beta-blocking group of compounds is usually felt to be clinically contraindicated due to the former's potent dromotropic and negative inotropic actions. The basis of this assumption was examined in a rest and exercise hemodynamic study of the effects of verapamil and the cardioselective beta-blocking drug, metoprolol, in 22 patients with stable angina pectoris and angiographically confirmed coronary artery disease. In a randomized study, 11 patients were assessed following intravenous verapamil (16 mg) alone, 11 following intravenous metoprolol (10 mg) alone, and all 22 were assessed on combination therapy. The plasma levels achieved at the time of each hemodynamic assessment were in the therapeutic range. At rest, verapamil alone significantly lowered systemic arterial pressure and vascular resistance; metoprolol alone lowered heart rate and increased systemic vascular resistance without change in systemic arterial pressure. Combination therapy reduced systemic arterial pressure and heart rate without change in cardiac output and systemic vascular resistance. During upright bicycle exercise, the changes were directionally similar. Depression of cardiac function (i.e., reduced cardiac output at increased pulmonary artery occluded pressure) occurred following metoprolol but not following verapamil; the addition of verapamil did not accentuate the depression of function induced by metoprolol. These results suggested that in patients with stable coronary artery disease, without manifest conduction system abnormality, the cardiac depressant actions of verapamil were countered by its vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of nifedipine during upright exercise in stable angina pectoris and either normal or severely impaired left ventricular function

The immediate effects of sublingual nifedipine (20 mg) were evaluated in 18 men with stable, exercise-related angina pectoris and angiographically confirmed coronary artery obstructions, stratified at the time of left ventricular (LV) angiography according to the degree of LV dysfunction supine at rest (Group 1: n = 9, left ventricular end-diastolic pressure [LVEDP] less than 20 mm Hg; Group 2: n = 9, LVEDP greater than 20 mm Hg). At rest, in the upright posture in both groups, nifedipine reduced the systemic vascular resistance (p less than 0.01). The systemic arterial mean (p less than 0.05) and diastolic (p less than 0.01) pressures were reduced despite an increase in the cardiac output (p less than 0.05). Heart rate was increased only in Group 1 (p less than 0.05). Pulmonary artery occluded pressure was unchanged in both groups. During upright bicycle exercise in all patients, compared to control measurements, systemic arterial pressure (p less than 0.01) and vascular resistance (p less than 0.05) were similarly reduced, while exercise cardiac output response and LV filling pressure did not change after nifedipine. Heart rate was increased in Group 1 (p less than 0.05) and decreased in Group 2 (p less than 0.05). Stroke volume during exercise after nifedipine decreased 1 ml/m2 in Group 1 (p greater than 0.05) and increased 2 ml/m2 in Group 2 (p greater than 0.05) compared to control measurements; the between-group difference in the exercise heart rate and stroke volume responses after nifedipine were significant at the 5% level.(ABSTRACT TRUNCATED AT 250 WORDS)