Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.     

Cardiovascular and neurohumoral postural responses and baroreceptor abnormalities during a course of adjunctive vasodilator therapy with felodipine for congestive heart failure

Studies in patients with congestive heart failure (CHF) have demonstrated an abnormal beta-adrenergic reflex vasodilation during orthostatic tilt. Baroreflex modulation of vascular resistance in patients with CHF was investigated during therapy with a vasoselective calcium antagonist, felodipine. Eight patients on conventional therapy for severe CHF were studied after a 3 week course of additional felodipine or placebo treatment under randomized, double-blind, and crossover conditions. Forearm subcutaneous vascular resistance (FSVR) was estimated with use of the local 133Xe washout. Aortic pulsatile stretch, expressed as the systolic distension in percent of diastolic diameter, was calculated from echocardiographic measurements of aortic root diameters. At 3 weeks, felodipine reduced the arterial pressure, systemic vascular resistance, and FSVR, preserved cardiac filling pressures and heart rate, and increased cardiac output, stroke volume, and aortic pulsatile stretch. Upright tilt (45 degrees) was used to study baroreflex-mediated cardiovascular responses. The unloading of cardiopulmonary baroreceptors during upright tilt was substantial and about equal during both treatment courses, but the pulse pressure was maintained during the placebo and decreased during the felodipine period. During tilt, the patients on placebo failed to increase heart rate and their FSVR, systemic vascular resistance, and arterial mean pressure were decreased, whereas during tilt after felodipine, heart rate and systemic vascular resistance increased to maintain arterial mean pressure and FSVR also tended to increase. Both the stroke volume and aortic pulsatile stretch increased during tilt in patients on placebo but they decreased in those on felodipine. The tilt caused increments in circulating norepinephrine and epinephrine levels during both treatment regimens. Regulation of FSVR during the sympathetic stimulation of orthostatic stress was further elucidated. Proximal neural blockade caused an increase in FSVR during tilt in patients on placebo and a decrease in FSVR during tilt in those on felodipine. Local beta-adrenoceptor blockade caused similar increments in FSVR during tilt in patients on both treatments. Combined proximal and local blockade still increased FSVR during tilt in those on placebo, but caused no change in FSVR during tilt in those on felodipine. This study demonstrates that felodipine normalizes baroreflex control of vascular resistance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nicorandil on left ventricular hemodynamics and volume at rest and during exercise-induced angina pectoris

The hemodynamic effects of nicorandil (20 mg) were compared with placebo in a double-blind study of 20 patients with angiographically proved coronary artery disease at rest before and 7, 15, 30 and 60 minutes after oral dosing. The impact of the drug on left ventricular (LV) hemodynamics and volume during exercise-induced angina was determined by repeating exercise 60 minutes after drug administration, at the same work load that reliably induced angina during control predrug exercise.

At rest, nicorandil reduced all components of systemic arterial pressure without change in cardiac or stroke volume indexes or heart rate. Pulmonary artery occluded pressure was reduced without change in LV ejection fraction or systemic vascular resistance index. Effects were evident at 7 minutes and peaked at 30 minutes with attenuation at 60 minutes. Compared with control supine bicycle exercise, the drug (at 60 minutes) reduced mean systemic arterial pressure and LV filling pressure without change in cardiac stroke volume indexes and heart rate. There was a smaller increase in LV ejection fraction.

These data suggested greatest impact on LV function during exercise when substantial decreases in filling pressure occurred at maintained cardiac pumping indexes.     

Response to upright exercise after myocardial infarction

The left ventricular response to upright bicycle exercise was studied in 39 unselected, non-beta blocked patients (mean(SEM) age 54.2(1.7)yr) (mean(SEM) resting ejection fraction 41.9(2.3)%) 8-10 weeks after myocardial infarction. Nine healthy, age matched, sedentary adult men were studied for comparison (mean(SEM) age 49.8(0.9)yr). The stroke volume and cardiac output were measured by impedance cardiography at rest and after each 3 min workload until symptom limited maximum. The patients were separated into three groups based on stroke volume response to graded exercise. Group 1 (n = 14) had a normal stroke volume response to increasing heart rate. In group 2 (n = 13) stroke volume increased initially then decreased by greater than 15% at a heart rate greater than 100-105 beats.min-1. In group 3 (n = 12) stroke volume failed to increase during exercise. In group 1 cardiac output and mean arterial pressure increased whereas vascular resistance decreased during exercise in a normal fashion. Group 2 had an increased mean arterial pressure and systemic vascular resistance throughout exercise while heart rate increased in a similar fashion to group 1 until work of greater than 70 W was undertaken, at which time heart rate increased in a curvilinear fashion and cardiac output was attenuated. Group 3 had an attenuated cardiac output and a higher heart rate during exercise. In this group of patients systemic vascular resistance failed to decrease normally during exercise.(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)     

Haemodynamic and humoral responses to chronic ketanserin treatment in essential hypertension.

Ketanserin (120 mg/day) or placebo was given orally to 14 patients with mild to moderate essential hypertension according to a double blind crossover protocol, each treatment period lasting six weeks. Resting intra-arterial pressure in the recumbent position was reduced from 150/84 to 141/77 mm Hg; the hypotensive effect persisted throughout an uninterrupted graded exercise test to the point of exhaustion. The haemodynamic effects were similar at rest and during exercise. Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased. Mean pulmonary arterial pressure and capillary wedge pressure were not significantly affected, but pulmonary vascular resistance decreased by 15%. The pressor response to methoxamine was significantly reduced by ketanserin. Both plasma noradrenaline and adrenaline concentrations increased, plasma renin activity and angiotensin II concentration decreased, and plasma aldosterone concentration was unchanged. The data indicate that ketanserin induces arteriolar dilatation, possibly related to an alpha-1-antagonistic action and to a reduced circulating angiotensin II concentration. The haemodynamic response is complex, and an increase in cardiac output limits the hypotensive effect. There is no firm evidence of an effect on venous tone as cardiac filling pressures do not change.     

Effect of preload change on resting and exercise cardiac performance in hypertrophic cardiomyopathy

The purpose of this study was to investigate the hemodynamic responses, at rest and on exercise, of patients with hypertrophic cardiomyopathy to changes in circulating volume. After Swan-Ganz and radial arterial cannulation, 13 patients with hypertrophic cardiomyopathy performed maximal exercise tests after diuretic (frusemide 20 mg intravenously) and after fluid loading (0.9% saline at 10 ml/kg body weight intravenously) on different days. At rest, right atrial and pulmonary capillary wedge pressures increased with volume loading and decreased with a diuretic. There were no significant changes in the resting, supine cardiac or stroke indexes but in the upright position, the cardiac index and stroke index were higher after volume loading (2.5 +/- 0.7 vs 2.2 +/- 0.5 liters/min/m2, p less than 0.05; 33 +/- 11 vs 27 +/- 9 ml/m2, p less than 0.005, respectively). Although the right atrial, pulmonary arterial and pulmonary capillary wedge pressures were higher during exercise after volume loading, there were no significant differences in exercise heart rate, systemic blood pressure, cardiac index, stroke index, systemic vascular resistance index or overall exercise capacity compared to exercise after diuresis. The data show that the cardiac index and stroke index, at supine rest and during upright exercise, were not influenced by the preload changes induced in these patients with hypertrophic cardiomyopathy. The results suggest that these patients are operating on the plateau of left ventricular Frank-Starling function (filling pressure/output) curve.     

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.     

Cardiovascular response to orthostatic tilt in patients with severe congestive heart failure

Baroreflex mediated haemodynamic responses and aortic pulsatile stretch were studied in patients with congestive heart failure due to ischaemia. Seven patients with severe congestive heart failure (baseline angiographic ejection fraction 21(3)% (mean(SEM); left ventricular end diastolic volume and pressure 351(43) ml and 22(3) mmHg respectively) were compared with seven control subjects whose angiographic ejection fraction was 74(3)%. Passive 45 degrees upright tilt was used to unload baroreceptors. Aortic pulsatile stretch (pulsatile distension as percentage of diastolic diameter) was calculated from echocardiographic measurements of aortic diameters. Upright tilt caused a significant decrease in cardiac filling pressures in patients with congestive heart failure, as in control subjects. During tilt control subjects had substantially increased systemic vascular resistance and heart rate and decreased stroke volume, but arterial pressure, cardiac index, and aortic pulsatile stretch were maintained constant. Patients with congestive heart failure developed peripheral vasodilatation, had no increase in heart rate, and failed to maintain arterial mean and systolic pressures in the tilted position. They had, however, maintained a constant pulse pressure and increased cardiac index, stroke volume, and aortic pulsatile stretch. The response to upright tilt in patients with congestive heart failure may be explained by faulty sympathetic reflexes, causing vasodilatation and hypotension rather than vasoconstriction, and a rise in stroke volume due to the decrease in afterload.     

Haemodynamic adaptation at rest and during exercise to long-term antihypertensive treatment with combination of beta-receptor blocking and vasodilator agent.

Systemic and pulmonary haemodynamics were studied at rest in the supine and upright position, and during exercise in the sitting position at 75 and 150 Watt, in 13 hypertensive men aged 50-8 +/- 8-7 years before and after 13 months treatment with oral oxprenolol (120 to 160 mg t.i.d.) supplemented by oral hydrallazine (50 to 75 mg t.i.d.) during the last 6 months. Pressures were recorded by means of catheters inserted percutaneously into the pulmonary and brachial artery; cardiac output was determined according to Fick. Treatment resulted in a significant reduction of systemic systolic, diastolic, and mean pressures at rest in the supine position and during exercise, and of systolic pressures in the upright posture. Pulmonary systolic and mean pressures increased slightly at rest in the supine position and during exercise, and no changes occurred at rest in the upright position. The left ventricular filling pressure was unchanged at rest both in the supine and upright position; it increased slightly during exercise. The haemodynamic changes by which systemic pressure was reduced were those typical of beta-adrenergic blockade: reduction of cardiac output resulting from a decrease of both heart rate and stroke volume, while the total systemic vascular resistance was unchanged at rest in the supine position but increased in the upright posture and during exercise. The A-V O2 difference increased remarkably. This long-term observation again suggests that the acute haemodynamic effects of an antihypertensive regimen can be modified during long-term application. It did not give evidence of a readjustment of the vascular resistance occurring, at least not in the upright position and during exercise, as has been suggested for long-term beta-adrenergic blockade.     

Hemodynamic effects of felodipine in congestive heart failure

Summary The hemodynamic effects of increasing dosages of felodipine, a new calcium antagonist with selective vasodilator properties, were studied in 13 patients with chronic cardiac failure. A Swan-Ganz thermodilution catheter was positioned in the pulmonary artery and hemodynamic parameters were monitored from 9 am to 6 pm for five days. On the first and the fifth day patients received placebo (P) and on the second, third, and fourth day patients received felodipine 5, 10, and 20 mg, respectively. Symptom-limited exercise tests with a bicycle ergometer were performed on both days of P and on the fourth day. A marked reduction of systemic vascular resistance (SVR) and a significant increase of cardiac index without increments of heart rate (HR) were observed after felodipine at rest. A dose response effect could be demonstrated. During exercise a significant increment of cardiac index and decrease of pulmonary wedge pressure was observed after felodipine. Felodipine showed a potent vasodilator action on systemic circulation with significant changes on both stroke volume and filling pressures at rest and during exercise without side effects.Part of the data in this paper was presented at the Cardiovascular Pharmacotherapy International Symposium in Geneva, Switzerland, April 1985     

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.     

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.     

Haemodynamic analysis of the effects of nicardipine and metoprolol alone and in combination in coronary artery disease

The circulatory consequences of concurrent slow-calcium channel(nicardipine) and cardioselective beta blockade (metoprolol)were evaluated in 20 patients with angiographically proven coronaryartery disease. The rest and exercise haemodynamic impact ofintravenous nicardipine (10mg) or metoprolol (10mg) alone wasdetermined by randomly allocating 10 patients to each drug;finally all patients were assessed on combination therapy. Theplasma levels of nicardipine (17 ±3 to 53 ±6 ngml-1) and metoprolol (36 ±5 to 97 ± 16 ng ml-1)achieved at the time of each study were in the established therapeuticrange.At rest nicardipine reduced systemic mean arterial pressureand systemic vascular resistance index; cardiac and stroke volumeindices increased without change in pulmonary artery occludedpressure. Metoprolol alone reduced systemic blood pressure,heart rate and cardiac index, and increased systemic vascularresistance index. Combination therapy reduced systemic arterialblood pressure and heart rate with relatively modest effectson cardiac index, systemic vascular resistance index and pulmonaryartery occluded pressure.During dynamic exercise nicardipinereduced systemic mean and diastolic arterial pressure and strokework index without change in other haemodynamic variables. Metoprololreduced exercise systemic arterial pressures, heart rate andcardiac index, and increased systemic vascular resistance indexand pulmonary artery occluded pressure. Combination therapyproduced changes similar to those at rest; at peak nicardipinepharmacodynamic activity, the cardiac depressant actions ofmetoprolol were largely offset by the induced reduction in leftventricular afterload.Thus these data suggest that nicardipineis safe to use concurrently with cardioselective beta-adrenoceptorblockade; moreover it may prove useful in offsetting some ofthe adverse haemodynamic effects of beta-blocking drugs in patientswith severe coronary artery disease.     

Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects of a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3,100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean +/- SD, -17 +/- 14%), increases in mean right atrial (31 +/- 21%), mean pulmonary artery (14 +/- 14%) and mean pulmonary capillary wedge (17 +/- 14%) pressures and an increase in cardiac index (18 +/- 10%) due to an increased heart rate without any significant change in stroke volume. During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease. It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients.     

Haemodynamic effects of physical training in essential hypertension.

The haemodynamic effects of four weeks of daily intensive training on bicycle ergometer were studied in 10 men with essential hypertension of grade II (WHO). Three weeks before training all medication was replaced by placebo. Five days before onset of training all patients underwent a haemodynamic examination using floating catheter and direct brachial arterial pressure at rest and during effort. The same examination was repeated within five days after the completion of the training. Resting measurements did not demonstrate any effect of the training on systemic pressure or central haemodynamics. At the given load, however, a significant decrease for the pressor response occurred, i.e. lowering of systolic, mean and diastolic arterial pressure. Peripheral vascular resistance was not affected. Cardiac output (Fick) decreased insignificantly both at rest and during effort after training. Heart rate decreased significantly only during exercise. The training lowered significantly both tension time index and left ventricular stroke work index. No adverse clinical or haemodynamic effects of short intensive training were detected in hypertensive patients. There was no evidence of changes in pulmonary artery diastolic pressure considered as an indicator of the left ventricular filling pressure. The heart volume remained unchanged after training.     

Cardiovascular response to exercise after the Mustard operation for simple and complex transposition of the great vessels

After the Mustard operation, patients have reduced exercise tolerance, abnormal right and left ventricular responses to exercise and cardiac rhythm disturbances. The cardiovascular response to exercise was measured noninvasively in 19 patients from 4.5 to 20 years (mean 10.3) after operation. Mean work performed and maximal oxygen uptake for the group were substantially subnormal (42 +/- 23% and 59 +/- 18% [mean +/- 1 standard deviation] of the predicted values, respectively). Resting heart rate, blood pressure, systemic arterial blood oxygen saturation, cardiac index, stroke volume and systemic vascular resistance were not significantly different from control values. At maximal exercise, heart rate, systemic arterial blood oxygen saturation, cardiac index and stroke volume were significantly reduced in comparison with control values. After the Mustard operation, cardiovascular status at rest may be relatively normal, but during maximal exercise, marked abnormalities occur in nearly all indexes of cardiovascular function. Decreased cardiac output response to exercise is a result of decreased stroke volume response and, to a lesser extent, diminished heart rate. It is associated with abnormally increased total systemic vascular resistance.     

Haemodynamic effects of frusemide and its influence on repetitive rapid volume loading in acute myocardial infarction

The haemodynamic effects of intravenous frusemide (1 mg/kg)were studied in 22 male patients with left ventricular failurefollowing acute myocardial infarction. Radiographic pulmonaryoedema was present in all patients and their average left heartfilling pressure was 20 mmHg. Bolus injection of the drug wasfollowed by immediate increases in systemic arterial pressure(P < 0.05) and heart rate (<0.05); these declined to pre-injectionvalues after 60 min. Following frusemide there were progressivereductions in left heart filling pressure (P < 0.01), thermodilutioncardiac output (P < 0.01) and stroke volume (P < 0.05)and a progressive increase in the derived systemic vascularresistance (P < 0.05). There was an average diuresis of 860ml during the 90 min following the frusemide injection. Theinfluence of frusemide on left ventricular performance was studiedby comparing the circulatory effects of passive leg raisingin the control period with those at 30, 60 and 90 min afterthe drug. In the control period this manoeuvre increased leftheart filling pressure, but not heart rate, cardiac output,stroke volume or systemic vascular resistance. Ninety minutesafter frusemide, but not before, passive leg raising resultedin a significant increase in cardiac output (P < 0.01) andstroke volume at a similar increment in filling pressure anda significant reduction in the systemic vascular resistance(P <0.05). These circulatory actions of intravenous frusemideare compatible with initial arteriolar constriction and venodilatationfollowed by depletion of blood volume with subsequent changein left ventricular pumping performance.     

Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure

Enalapril is a recently developed angiotensin-converting enzyme inhibitor that improves cardiac function at rest in patients with congestive heart failure. This study investigated the acute effects of enalapril on the cardiovascular response to exercise, and then evaluated the long-term effects of enalapril on exercise capacity and functional status during a 12 week placebo-controlled trial in patients with heart failure. Ten patients underwent hemodynamic monitoring while at rest and during incremental bicycle exercise before and after 5 to 10 mg of enalapril orally. At rest, enalapril decreased mean blood pressure 13% (p less than 0.01) and systemic vascular resistance 20% (p less than 0.05) and increased stroke volume index 21% (p less than 0.01). During maximal exercise, enalapril decreased systemic vascular resistance and increased both cardiac and stroke volume indexes. Enalapril acutely increased exercise duration (p less than 0.05) and maximal oxygen consumption (p less than 0.001). These 10 patients and an additional 13 patients were then randomized to either placebo or enalapril treatment and followed up for 12 weeks. Of the 11 patients assigned to active treatment, 73% considered themselves improved compared with 25% of the patients assigned to placebo treatment (p less than 0.02). During long-term treatment, exercise capacity increased in patients receiving enalapril (p less than 0.001) but was unchanged in patients receiving placebo (intergroup difference, p less than 0.05). During long-term treatment, no adverse effects of enalapril occurred. Thus, enalapril improves cardiac function at rest and during exercise. Compared with placebo, maintenance therapy with enalapril results in symptomatic improvement and increased exercise capacity.