Total Systemic Vascular Resistance Research Articles

Diastolic vibration improves systolic function in cases of incomplete relaxation.

Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved. Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation. These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.

Pulmonary circulatory dysfunction in rats with biliary cirrhosis. An animal model of the hepatopulmonary syndrome.

We studied hypoxic pulmonary vasoconstriction (HPV) and pulmonary gas exchange in unanesthetized rats with biliary cirrhosis induced by chronic bile duct ligation (BDL) (5 to 6 wk) and compared pulmonary vascular reactivity in perfused lungs isolated from BDL and control rats. Awake, catheter-implanted, cirrhotic rats exhibited increased cardiac output, normal systemic and pulmonary arterial pressures, and decreased total systemic (TSR) and pulmonary (TPR) vascular resistances in comparison with those in sham-operated control rats. HPV was markedly depressed in cirrhotic rats (percent increase in TPR while breathing 8% O2: 42.3 +/- 13.7% in control and 0.9 +/- 3.6% in cirrhotic rats, p less than 0.05), and this was associated with an increased AaPO2 (control rats, 15.7 +/- 1.1 mm Hg; cirrhotic rats, 23.1 +/- 1.9 mm Hg; p less than 0.05). In contrast, the pulmonary pressor response to angiotensin II was intact, and the depression of HPV in cirrhotic rats was ameliorated after angiotensin II infusion. These changes in cirrhotic rats were not due to the accompanying cholestasis since noncirrhotic rats with severe cholestasis had intact HPV and normal AaPO2. Lungs isolated from cirrhotic rats and perfused with blood from normal rats exhibited two patterns of response to hypoxia. In one group, HPV was blunted compared with that in control rats (change in pulmonary arterial perfusion pressure after 3% O2: control rats, 23.2 +/- 2.8 mm Hg; cirrhotic rats, 4.8 +/- 1.4 mm Hg; p less than 0.01). Similar to the result in intact rat, angiotensin-II-induced vasoconstriction was preserved in lungs from cirrhotic rats, and HPV increased significantly after angiotensin II infusion (to 17.3 +/- 4.8 mm Hg). In the second group, baseline pulmonary arterial pressure progressively increased during normoxia, and this increase was attenuated by hypoxic ventilation (hypoxic vasodilation).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dobutamine and salbutamol on haemodynamics and atrial natriuretic factor in patients with severe congestive heart failure

The influence of two cardiac inotropic drugs, dobutamine and salbutamol, on plasma atrial natriuretic factor (ANF) was investigated in 20 patients with congestive heart failure. All were in New York Heart Association class-III or IV. The patients underwent right heart catheterization with determination of central pressures, cardiac output, and pulmonary arterial plasma ANF during incremental infusions with dobutamine or salbutamol. Fourteen patients completed the study. Both drugs induced comparable increases in cardiac index and decreases in total systemic vascular resistance (P less than 0.01) without significant changes in central pressures. Heart rate rose after salbutamol (P less than 0.05), but not after dobutamine. No changes in plasma ANF were observed after either of the drug infusions. ANF secretion rate was calculated from simultaneous measurements of ANF in right atrial and pulmonary arterial plasma before and after salbutamol infusion, and median values rose more than seven-fold (P less than 0.05). The results demonstrate that ANF secretion rate is augmented after beta-adrenergic agents, possibly by a direct beta 2-adrenergic stimulation, in patients with severe congestive heart failure, and that changes in plasma ANF are an insufficient measure of ANF release when patient samples are small.

Interrelation between Esophageal Varices, and Systemic and Hepatic Hemodynamics in Male Patients with Compensated Cirrhosis.

The interrelation between endoscopic findings in esophageal varices, and systemic and hepatic hemodynamic abnormalities was studied in 76 male patients with compensated cirrhosis. Observation of these patients revealed a hyperdynamic systemic circulation, represented by an increased cardiac output and reduced total systemic vascular resistance with an enlarged circulating plasma volume and without an increase in heart rate, in comparison with 23 male patients with chronic hepatitis. In patients with cirrhosis and esophageal varices, the hyperdynamic circulatory state was closely related to the condition of the varices, in which a progress in the form was accompanied by an advance in the degree of hyperdynamism with an increase in circulating plasma volume. Whereas the extent of the varices as indicated by the location was closely related to a rise in the wedged hepatic venous pressure. The shunt volume through the portal-systemic collaterals requires further study to elucidate the mechanism of hyperdynamic circulation.

Value of carvedilol in congestive heart failure secondary to coronary artery disease

Despite considerable interest in the use of β-blocking agents in congestive heart failure (CHF), their clinical application is limited because of their negative inotropic effects. Beta blockers with vasodilating properties may have the advantage of overcoming this, however. Carvedilol, a β-blocking agent with vasodilating properties, was evaluated in 17 patients with chronic CHF secondary to ischemic heart disease with a resting left ventricular ejection fraction ≤45%, who were being maintained on diuretics. Exercise testing, radionuclide ventriculography, and right-sided cardiac catheterization were performed and intraarterial blood pressure measured before and after 8 weeks of carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood pressure were both reduced by chronic therapy. Mean ± standard deviation exercise time improved from 4.3 ± 1.6 to 7.1 ± 2.7 minutes (p < 0.0001), as did resting left ventricular ejection fraction, from 27 ± 9 to 31 ± 11% (p < 0.02). Pulmonary arterial wedge pressure fell from 19 ± 7 mm Hg to 12 ± 5 mm Hg (p < 0.001) and total systemic vascular resistance from 1,752 ± 403 to 1,497 ± 310 dynes/ s/cm −5/m 2 (p < 0.02). Stroke volume index improved also, from 31 ± 6 ml to 40 ± 6 ml (p < 0.0005). These hemodynamic changes were mediated partly by vasodilatation, diminished myocardial oxygen demand and reduction of sympathetic overactivity in the failing heart. These data suggest that carvedilol may have beneficial effects in patients with chronic CHF secondary to coronary artery disease.

Pulmonary and systemic haemodynamic effects of cromakalim in conditions of normoxia and hypoxia in dogs

1. In anaesthetized-closed chest dogs, exposure to hypoxia (60 min) caused a sustained increase in arterial pulmonary pressures (diastolic: DPP, mean: MPP and effective capillary: EPCP by 132, 66 and 104% respectively) and increased total pulmonary vascular resistance (TPVR, 143%) with minimal changes in systemic haemodynamics. 2. Under normoxia, cromakalim infusion (2 micrograms kg-1 min-1 for 30 min) progressively decreased diastolic systemic arterial pressure (DBP, 30%) and total systemic vascular resistance (TSVR, 54%). In contrast, DPP was increased by 45%, due to an increase in cardiac output (CO: 55%), while TPVR was essentially unchanged. 3. Under hypoxic conditions, cromakalim (2 micrograms kg-1 min-1 for 30 min) induced changes in systemic haemodynamics comparable to those seen under normoxia. However, DPP was decreased by 37% at the end of infusion. The compound progressively decreased TPVR in a dose-related manner and PaO2 (55.9 mmHg) was maintained since cardiac output was increased. 4. Thus, under normoxia, cromakalim induced haemodynamic effects on the pulmonary circulation which were directly related to an increase in CO, but were clearly different from those observed under hypoxia. In the hypoxia-induced constricted pulmonary vascular bed, cromakalim effectively reduced the elevated pulmonary vascular resistance at low doses but showed comparable vasodilator effects on the systemic circulation under both conditions. The findings suggest that a vasodilator agent like cromakalim may be useful in patients with respiratory conditions associated with elevated pulmonary vascular resistance.

Effects of Diltiazem on the Functional Recovery of the Myocardium at Organ and Cellular Level During Prolonged Hypothermic Ischemic Cardiac Arrest

The effectiveness of diltiazem on the functional recovery of the heart, calcium (Ca++) uptake and binding, Ca++ ATPase of cardiac sarcoplasmic reticulum (SR), and MB fraction of creatine kinase (MBCK) of coronary sinus blood was investigated after one and a half hours of reperfusion following three hours of ischemic cardiac arrest. The dogs were divided into three groups: group I, sham bypass; group II, cold crystalloid cardioplegia; and group III, cold crystalloid cardioplegia with diltiazem. There was a decrease in aortic pressures left ventricular pressure development (dp/dt), left ventricular work index (LVWI), total systemic vascular resistance (TSVR), and left ventricular systolic pressure (LVSP) in the sham bypass group. There was a decrease in cardiac index (CI), LVWI, and mean right atrial pressure (mRAP) and an increase in TSVR and pulmonary vascular resistance (PVR) in group II as compared with group I. Although there was a tendency for a decrease in the indices of myocardial contractility in group II, they were not significantly different from those in group I. The indices of myocardial contractility, CI, and LVWI in group III were slightly higher than in group II, but they were not significantly different from each other. The values for calcium uptake by SR in groups II and III were similar but significantly lower than those in group I. Calcium binding in group III was significantly lower than that in group I. Calcium ATPase of SR in the three groups were similar. Although MBCK increased in all the groups, the increases were not significantly different among the three groups. The results of this study indicate that cold crystalloid cardioplegia with diltiazem was not better than cold crystalloid alone in preserving the cardiac contractility and cellular function during prolonged ischemic cardiac arrest. However, the cardiac function in terms of cardiac index was better preserved with diltiazem.

Endotoxin (LPS) Increases Mesenteric Vascular Resistance (MVR) and Bacterial Translocation (BT)

Endotoxemia is responsible for many of the pathophysiologic alterations that occur with Gram-negative sepsis. We utilized a chronic ovine model to determine the hemodynamic disturbances in the gastrointestinal tract during endotoxemia. Sheep with indwelling arterial, venous, and pulmonary arterial catheters were used. An ultrasonic flow probe was placed on the cephalic mesenteric artery. The animals were subjected to: 1) Ringer's lactate infusion (sham n = 6); or 2) 1.5 mcg/kg E. coli endotoxin (n = 6) over over a period of one half hour and were monitored for 48 hours. They were then sacrificed and specimens of mesenteric lymph node, liver, spleen, kidney, and lung obtained for bacteriologic cultures and histologic analysis. Sheep receiving endotoxin showed more than 50% reduction in the mesenteric blood flow. Mesenteric vascular resistance increased while non-mesenteric systemic vascular resistance decreased. The increase in the total systemic vascular resistance, noted during endotoxemia, was thus likely due to the increase in the mesenteric vascular resistance. At autopsy there were positive cultures for microorganism in the mesenteric lymph nodes in six out of six sheep with endotoxemia as compared to one out of six of control. Thus the vasoconstriction in the mesenteric areas may have resulted in bacterial translocation from the GI tract.

Role of sulfidopeptide leukotrienes in synthetic smoke inhalation injury in sheep

Acute lung injury with smoke inhalation results in significant morbidity and mortality. Previously we have shown that synthetic smoke composed of carbon and acrolein, a common component of smoke, causes delayed-onset noncardiogenic pulmonary edema. To study the possible role of the vasoactive and edemagenic sulfidopeptide leukotrienes (SPLT) in smoke inhalation injury, we measured pulmonary hemodynamics, lung lymph flow, and SPLT and leukotriene (LT) B4 in lung lymph before and after 10 min of synthetic acrolein smoke exposure. After smoke exposure there was a significant rise in pulmonary vascular resistance caused by a rise in pulmonary arterial pressure, a fall in cardiac output, and no change in pulmonary capillary wedge pressure. This was accompanied by an increase in total systemic vascular resistance (P less than 0.05), lung lymph flow (P less than 0.05), and extravascular lung water-to-lung dry weight ratio (P less than 0.05). Both SPLT and LTB4 clearance rose significantly (P less than 0.05), but there was a 10-fold increase in SPLT over LTB4 clearance. In sheep pretreated with FPL55712, a SPLT antagonist, the early rise in pulmonary vascular resistance was attenuated, and the rise in systemic vascular resistance was blocked. This was associated with an attenuated and delayed fall in cardiac output. FPL55712 had no effect on lung lymph flow or extravascular lung water-to-dry weight ratio. SPLT, and especially LTD4, may have a role in increased pulmonary and systemic vascular resistance after smoke inhalation injury but does not appear to affect vascular permeability.

The Hemodynamic Effects of ACE Inhibitors in the Treatment of Congestive Heart Failure

To determine the safety and efficacy of single oral doses of quinapril in the treatment of congestive heart failure (CHF), an open-label, hemodynamic trial was conducted in 11 patients with severe CHF [New York Heart Association (NYHA) class III or IV] in whom previous or current therapy with diuretics and digitalis had been inadequate. After participating in this single-dose trial (acute phase), all 11 patients were entered into a 16-week, multiple-dose investigation (chronic phase). In the acute phase of the study, single oral doses of quinapril (2.5, 5, and 10 mg/day) achieved beneficial hemodynamic changes within 1 h after the onset of therapy. Maximal improvements in key hemodynamic variables (i.e., pulmonary capillary wedge pressure, mean arterial blood pressure, cardiac output, and total systemic vascular resistance) were observed within 4 h after dosing. The hemodynamic changes after 16 weeks of chronic quinapril therapy (5, 10, 15, and 30 mg/day) were equivalent or superior to those observed after acute therapy, indicating that quinapril produces a sustained hemodynamic benefit after chronic oral dosing. Quinapril was shown to be safe and effective in the treatment of patients with severe CHF.

Effects of food on the central and peripheral haemodynamic response to upright exercise in normal volunteers.

The central and peripheral haemodynamic effects of a modest meal were investigated in healthy volunteers at rest and in response to submaximal exercise. The meal increased heart rate, cardiac output, oxygen consumption, carbon dioxide production, and minute ventilation at rest and during exercise. The effects of food were additive to those induced by the exercise. Food had no effect on limb blood flow and lowered total systemic vascular resistance suggesting that there were no compensatory changes in regional blood flow to help redirect blood to the gut. An increase in cardiac output, and therefore myocardial work, is the predominant cardiovascular response to eating and this may help explain the postprandial deterioration in symptoms of some patients with cardiovascular disorders.

Hemodynamic and electrophysiologic effects of amlodipine, a new calcium channel blocker

The effects of amlodpine (300 μg/kg administered intravenously), a new, long-acting, dhydropyridne class, calcium channel blocking drug, were studied in atrially paced (120 beats/min), autonomicaly blocked dogs. Hemodynmnic and electrophysiologic parameters were measured before and up to 3 hours after amlodpine. Coronary blood flow was significantly increased 10 and 30 minutes after drug administration, whereas cardiac output and mean arterial pressure were unaffected. Coronary vascular resistance was decreased but total systemic vascular resistance did not change. Atrioventricular (AV) nodal conduction was slightly prolonged, as reflected by increases in strial-His bundle and AV conduction times and PR interval, 30 minutes after administration. AN parameters returned toward their control values within 3 hours after drug administration. Comparison of coronary vascular resistance and AV conduction changes with those previously reported for other calcium channel blocking drugs where autonomic blockade existed suggests that at equivalent levels of coronary vasodilation, amlodipine's effects more closely resemble the effects of ditiazem or verapamil than other dihydropyrtdines.

Physiological mechanisms for calcium-induced changes in systemic arterial pressure in stable dialysis patients.

The mechanisms by which variations in blood ionized calcium (Ca2+) influence systemic arterial pressures independent of changes in extracellular fluid volume, pH, and electrolytes are unknown. To study this issue, we dialyzed eight stable hemodialysis patients on three separate occasions during 1 week with dialysates differing only in calcium concentration. Ultrafiltration was adjusted to achieve the patient's estimated dry weight. Postdialysis Ca2+ was measured, as were arterial blood gases, electrolytes, magnesium, blood urea nitrogen, creatinine, and hematocrit. Blood pressures and two-dimensional, targeted M-mode echocardiograms were recorded with the patient in the supine position after 15 minutes of rest. Postdialysis, three different levels of Ca2+ were achieved. Other measured biochemical variables and body weight did not differ among the three study periods. Changes in Ca2+ correlated directly with changes in systolic, diastolic, and mean blood pressures, left ventricular stroke volume, and cardiac output. In contrast, heart rate, left ventricular end-diastolic dimension, and total systemic vascular resistance were not altered significantly by changes in Ca2+. Thus, alterations in Ca2+ within the physiological range affect systemic blood pressure primarily through changes in left ventricular output rather than in peripheral vascular tone in stable dialysis patients.

Hemodynamic Effects of Smoking in Congestive Heart Failure

This study was designed to investigate the hemodynamic effects of smoking in patients with congestive heart failure. Hemodynamic measurements were made in seven patients with heart failure before, during, and after smoking two unfiltered cigarettes (approximately 2.4 mg of nicotine). Smoking significantly (p less than .05) increased heart rate and decreased stroke volume. Cardiac output remained unchanged. Significant increases were noted in systemic systolic and diastolic blood pressures concomitant with significant increases in total systemic vascular resistance and systemic arteriolar resistance. Pulmonary arterial pressure and total pulmonary vascular resistance increased as well. Mean right atrial pressure and pulmonary capillary wedge pressure rose modestly during smoking. Finally, the double product, an index of myocardial oxygen consumption, increased considerably during the smoking and postsmoking periods. Smoking elicits significant hemodynamic effects in patients with congestive heart failure, many unfavorable and potentially detrimental.

Role of cardiopulmonary baroreflexes during dynamic exercise.

To examine the role of cardiopulmonary (CP) mechanoreceptors in the regulation of arterial blood pressure during dynamic exercise in humans, we measured mean arterial pressure (MAP), cardiac output (Q), and forearm blood flow (FBF) during mild cycle ergometer exercise (77 W) in 14 volunteers in the supine position with and without lower-body negative pressure (LBNP). During exercise, MAP averaged 103 +/- 2 mmHg and was not altered by LBNP (-10, -20, or -40 mmHg). Steady-state Q during exercise was reduced from 10.2 +/- 0.5 to 9.2 +/- 0.5 l/min (P less than 0.05) by application of -10 mmHg LBNP, whereas heart rate (97 +/- 3 beats/min) was unchanged. MAP was maintained during -10 mmHg LBNP by an increase in total systemic vascular resistance (TSVR) from 10.3 +/- 0.5 to 11.4 +/- 0.6 U and forearm vascular resistance (FVR) from 17.5 +/- 1.9 to 23.3 +/- 2.6 U. The absence of a reflex tachycardia or reduction in arterial pulse pressure during -10 mmHg LBNP supports the hypothesis that the increase in TSVR and FVR results primarily from the unloading of CP mechanoreceptors. Because CP mechanoreceptor unloading during exercise stimulates reflex circulatory adjustments that act to defend the elevated MAP, we conclude that the elevation in MAP during exercise is regulated and not merely the consequence of differential changes in Q and TSVR. In addition, a major portion of the reduction in FBF in our experimental conditions occurs in the cutaneous circulation. As such, these data support the hypothesis that CP baroreflex control of cutaneous vasomotor tone is preserved during mild dynamic exercise.

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.

Simultaneous Evaluation of Left Ventricular End-systolic Pressure-volume Ratio and Time Constant of Isovolumic Pressure Decline in Dogs Exposed to Equivalent MAC Halothane and Isoflurane

The effects of 1.5, 2.0, and 2.5 MAC halothane (N = 8) and isoflurane (N = 6) upon systolic performance and isovolumic relaxation were evaluated in open chest dogs. Left ventricular internal volume was determined using piezoelectric crystals. Left ventricular end-systolic pressure-volume points were determined for a series of normal sinus beats during transient venae caval occlusions. The slope of the line formed by those points is a load-independent inotropic index (EES). Left ventricular pressure points during isovolumic relaxation were plotted for computing the time constant of isovolumic pressure decline (T). Both drugs dose-dependently decreased mean arterial blood pressure with no change in heart rate, end-diastolic pressure, or end-diastolic volume. Increasing halothane concentration decreased the values of EES, the maximum rate of rise of left ventricular pressure (dP/dtMAX), and systolic ejection fraction (SEF). Total systemic resistance was unchanged by halothane. Increasing isoflurane concentration decreased EES and dP/dtMAX. The EES was significantly larger (P less than 0.05) with 2.5 MAC isoflurane than 2.5 MAC halothane. The SEF was unchanged by increasing isoflurane. Total systemic vascular resistance was decreased by increasing isoflurane. Isovolumic relaxation was prolonged and became more load-dependent with increasing halothane concentration. Isoflurane did not alter T, but the load-dependency of T was increased by 2.5 MAC isoflurane. There were no differences in T or its load-dependency between drug groups. These results indicate that both anesthetics evoke load-independent negative inotropic effects. Systolic ejection fraction is maintained during isoflurane anesthesia by decreased systemic vascular resistance and less pronounced negative inotropic effects than equivalent MAC halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of vasodilators on rates of change of nasopharyngeal temperature and systemic vascular resistance during cardiopulmonary bypass in anaesthetized dogs.

The effects of various vasodilating agents on the rates of change of nasopharyngeal temperature and total systemic vascular resistance of anaesthetized dogs during cardiopulmonary bypass were studied. Intravenous administration of nitroglycerine (14 micrograms/kg per min, infused at 35 degrees C and 36 degrees C), sodium nitroprusside (5 micrograms/kg per min, infused at 36 degrees C) and phenoxybenzamine (1 mg/kg bolus, given at 32 degrees C and 36 degrees C) did not have any effect on the total cooling time or the rate of cooling from 36 degrees C to 18 degrees C. However, in dogs treated with phenoxybenzamine the time taken to rewarm to 36 degrees C was significantly shorter than those observed in the control, nitroglycerine or sodium nitroprusside treated animals. This difference in rewarming time was mainly due to the more even rate of rewarming induced by phenoxybenzamine. Moreover, a significantly greater reduction in systemic vascular resistance was observed in phenoxybenzamine treated animals than in the other treatment groups.

Vasodilators as first-line therapy for congestive heart failure: A comparative hemodynamic study of hydralazine, digoxin, and their combination

Although digitalis and vasodilators both enhance cardiac performance in patients with congestive heart failure, their relative efficacy is unknown. Accordingly, the acute hemodynamic effects of intravenous hydraiazine (0.15 mg/kg), digoxin (1.0 mg), and the hydralazine-digoxin combination were evaluated in 14 normotensive heart failure patients at sitting rest, nine of whom were also studied during submaximal upright bicycle exercise. Hemodynamic responses at rest and exercise were similar. Cardiac output and stroke volume rose with both agents, the increase in cardiac output with hydralazine exceeding that with digoxin at rest. Left and right ventricular filling pressures declined equally. Systemic arterial mean pressure and total systemic vascular resistance fell with hydralazine, while, with digoxin, systemic arterial mean pressure increased and total systemic vascular resistance was unchanged. The hydralazine-digoxin combination produced increases in cardiac output and stroke volume that were greater than with either drug alone, and that equalled the sum of the drugs' individual effects; reductions in ventricular filling pressures were similar to the single-drug interventions. Thus, hydralazine is at least as effective as digoxin in improving cardiac function over the short term. Vasodilators may constitute an acceptable alternative to digitalis as initial therapy for congestive heart faillure, except where a reduction in systemic arterial pressure is potentially deleterious. Use of combined treatment produces greater increases in cardiac output than with either drug alone, but requires risking the toxicities of two agents.

Effects of captopril on cardiorenal hemodynamics in patients with severe chronic congestive heart failure.

The effects of captopril on cardiorenal function were studied in patients with chronic congestive heart failure. A single oral dose of captopril in 16 patients significantly increased cardiac indices and decreased total systemic vascular resistance. These changes were greater in subjects with higher baseline plasma renin activity (PRA). The increase in PRA and decrease in plasma aldosterone were also greater in this group. During 7 days of captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase in renal blood flow was greater in subjects with higher PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow: these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through the inhibition of the renin-angiotensin system and the preferential renal vasodilating effect of captopril seems exclusively to be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.