Analgesic response in offspring of crosses between heroin delta (Swiss Webster) and mu (ICR) responding mice

To indirectly test the hypothesis whether serotonin (5-HT) might have a role in the increase in pulmonary vascular resistance, we evaluated the haemodynamic and gas exchange response of intravenous ketanserin (K), a 5-HT receptor inhibitor, in eight severe but stable patients with chronic obstructive pulmonary disease with secondary pulmonary hypertension (mean pulmonary artery pressure (Ppa) 30.3 +/- 7.3 mmHg). Measurements were done at baseline, after oxygen breathing (2 L.min-1), K bolus (6-15 mg) and finally during oxygen breathing (2 L.min-1) added to K infusion (3-6 mg.h-1). K bolus induced a significant reduction of mean Ppa (p < 0.05), mean systemic arterial pressure (p < 0.01) and total systemic resistance (p < 0.01). Cardiac index (+7%), oxygen delivery (+7%) and pulmonary vascular resistance (magnitude of the reduction: -12%) did not change significantly. When oxygen was added to K infusion, the cardiac index significantly dropped when compared to K bolus (p < 0.05), but oxygen delivery remained stable because of the resulting increase in arterial oxygen concentration; against baseline, the mean Ppa showed the same magnitude of reduction as with oxygen breathing or K bolus alone (p < 0.05). Ventilation and gas exchange were not significantly influenced by K bolus. When we individually analysed the changes of pulmonary vascular resistances by plotting the driving pressure through the pulmonary circulation against the cardiac output, we observed that an active vasodilating effect on the pulmonary circulation occurred with K in only one patient, while in three other patients there was rather a recruitment effect of the pulmonary vessels due to the systemic effects of the drug. In conclusion, this study of a small number of patients with severe chronic obstructive pulmonary disease associated with pulmonary hypertension shows that the parenterally given serotonin antagonist ketanserin predominantly affects the systemic circulation. Our results do not support the hypothesis that in stable chronic obstructive pulmonary disease patients with pulmonary hypertension, serotonin might have a role in the increase of pulmonary vascular tone.     

Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs

We have studied the effects of i.v. bolus doses of magnesium sulphate (MgSO4) 60, 90 and 120 mg kg-1 on haemodynamic state, the coronary circulation and myocardial metabolism in nine dogs anaesthetized with pentobarbitone and fentanyl. MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI) and an increase in the time constant of left ventricular isovolumic relaxation. Stroke volume increased, systemic vascular resistance decreased and cardiac output did not change significantly. MgSO4 produced decreases in coronary perfusion pressure, coronary vascular resistance and myocardial oxygen consumption (MVO2). Coronary sinus blood flow, lactate extraction ratio and the ratio of LVMWI to myocardial MVO2, that is an index of cardiac efficiency, did not change significantly. This study indicated that the depressant effect of MgSO4 on cardiac function was offset by lowering of peripheral vascular resistance, so that cardiac pump function remained effective, and the almost constant coronary sinus blood flow resulted from the decrease in coronary vascular resistance even at higher doses.     

Early hemodynamic effects of olprinone hydrochloride after coronary artery bypass grafting

Our purpose was to evaluate the hemodynamic effects of olprinone hydrochloride early after coronary artery bypass grafting (CABG). Fifteen patients undergoing CABG were administered a constant infusion of 0.1 microgram/kg/min of olprinone and continued for 4 hours. No bolus infusion of olprinone was administered before continuous infusion. Systolic systemic arterial pressure, systolic pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance were significantly decreased. There were no significant changes in heart rate, mean central venous pressure, mean left atrial pressure and left ventricular stroke work index. Cardiac index was significantly increased, but a correlation between cardiac index and mixed venous blood oxygen saturation was not found. Double product was significantly decreased, which described above suggest that olprinone achieved improvement of left cardiac function without more myocardial oxygen consumption. Severe transient hypotension (systolic arterial pressure < 80 mmHg) after infusion of olprinone was observed in three patients. Olprinone administered soon after CABG surgery had beneficial effects in terms of improvement of hemodynamic status without more oxygen consumption and reduction of pulmonary vascular resistance. However transient hypotension was a serious clinical problem in patients after open heart surgery, especially in CABG patients who need suitable systolic arterial pressure to keep enough blood perfusion of arterial bypass grafts.     

Haemodynamic changes in heart failure induced by a new vasodilator tolmesoxide

The haemodynamic effect of Tolmesoxide, a new sulphoxide chemically dissimilar from other vasodilators, was investigated in eight patients with chronic heart failure subsequent to ischaemic heart disease and/or hypertension. Tolmesoxide significantly increased the cardiac output and reduced the indices of systemic vascular resistance, the mean pulmonary arterial pressure and left ventricular filling pressure in most patients studied. These changes were observed both as acute and chronic effects. No significant effect on the mean arterial pressure, heart rate or myocardial oxygen supply/demand was observed. Tolmesoxide appeared to be therapeutically potent by both intravenous and oral routes.     

Use of a new Russian antihypertensive drug dilazin in surgery of the coronary arteries and abdominal aorta

Dilazin in a dose of 0.2 mg/kg/min (n = 20) and 0.4 mg/kg/min (n = 20) was used to normalize arterial blood pressure during and after surgery. Intravenous infusion of the drug decreased the arterial pressure to baseline values within 2-3 min by reducing the elevated systemic vascular resistance. Dilazin did not affect the heart rate, mean pulmonary capillary wedge pressure, or central venous pressure. The drug brought about a marked increase of cardiac output and cardiac index. Prompt effect and easy control, when dilazin is infused in a dose of 0.2 to 0.4 mg/kg/min, recommend it as an alternative antihypertensive agent to be used during various procedures.     

Dopexamine unloads the impaired right ventricle better than iloprost, a prostacyclin analog, after coronary artery surgery

OBJECTIVE: To evaluate the ventricle-unloading properties of dopexamine and iloprost and to compare their effects on right ventricular (RV) function and oxygen transport in patients with low RV ejection fraction (RVEF) after cardiac surgery. DESIGN: A prospective, randomized, double-blind, cross-over, clinical study. SETTING: University hospital. PARTICIPANTS: Twenty patients with proximal total stenosis of the right coronary artery studied immediately after coronary artery surgery. INTERVENTIONS: Treatment drugs were administered in a random order in doses equipotent with respect to cardiac output response. Infusion rates were increased stepwise to induce a 25% increase in cardiac index. A washout period of 60 minutes was allowed between treatments. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics, RV function assessed by the EF (fast-response thermodilution), end-systolic and end-diastolic volumes, and systemic oxygenation were measured before and after the first drug, after the washout period, and after the second drug. Central filling pressures remained constant during treatments. Both drugs decreased pulmonary vascular resistance index, but iloprost was more effective (p < 0.05). Iloprost decreased mean arterial and pulmonary artery pressure, which were unaffected by dopexamine. Dopexamine increased EF significantly more than iloprost (p < 0.001). End-systolic volume index decreased subsequent to dopexamine only (p < 0.001). Iloprost increased intrapulmonary shunt more than dopexamine (p < 0.001). Changes in oxygen delivery, consumption, and extraction were similar. CONCLUSION: The findings suggest that dopexamine is more effective than iloprost for support and unloading of the postoperatively disturbed RV in terms of RVEF and end-systolic volume. The reduction of pulmonary vascular resistance after administration of iloprost without a decrease in end-systolic volume might not be considered a reduction of RV afterload. Iloprost increases the pulmonary shunt fraction, however, more than dopexamine, indicating a more prominent vasodilator effect.     

Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials

1. The effects on the coronary and systemic haemodynamics of intravenous and intracoronary injections of two benzfuran derivatives, amiodarone and its brominated analogue (L8040), were studied in open-chest anaesthetized dogs. The effects of L8040 on cardiac intracellular potentials after 6 weeks of 20 mg/kg intraperitoneal injections in rabbits were also investigated. 2. Both compounds produced dose-related and quantitatively similar decreases in coronary vascular resistance following their intracoronary administration; threshold effects occurred with about 0-25 mg of each drug and maximal effects with 4 mg. Larger intracoronary doses produced measurable systemic effects. 3. Intravenous injections of amiodarone and L8040 (2-5-10 mg/kg) produced dose-related decreases in heart rate and aortic pressure with a fall in total peripheral resistance. The left ventricular output was either unaffected or increased with a consistent augmentation in stroke volume. 4. The bradycardia produced by both drugs was associated with prolongation of the P-R interval of the electrocardiogram with no significant effect on the QRS duration or the Q-T interval. 5. Each drug produced a decrease in the total peripheral vascular resistance with no change in left ventricular end diastolic pressure except after 10 mg/kg doses which led to an increase in this parameter. 6. Cardiac contractile force and peak LV dp/dt were reduced by both drugs in a dose-related manner. 7. Chronic intraperitoneal administration of L8040 in rabbits caused a prolongation of the duration of the atrial and ventricular intracellular potential without an effect on the maximal rate of depolarization. 8. The effect of amiodarone or L8040 on the coronary circulation and arterial pressure may be attributed to their vasodilator properties but their depressant actions on cardiac contractile force and peak LV dp/dt with an increase in left ventricular end diastolic pressure at high doses, also suggest intrinsic negative inotropic propensity for both compounds. 9. It is concluded that the overall effects on coronary and systemic haemodynamics of amiodarone and its brominated analogue are likely to permit a favourable influence on the balance of oxygen supply and demand in myocardial ischaemia; in addition, their actions on sino-atrial and atrio-ventricular conduction as well as those on cardiac repolarization suggest potential antiarrhythmic properties which merit investigation.     

Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukemia

The acute hemodynamic effects of the phosphodiesterase (PDE) III inhibitor saterinone were compared with dobutamine and sodium nitroprusside in 12 patients with idiopathic congestive cardiomyopathy (NYHA III). Hemodynamic measurements were obtained with a Swan-Ganz thermodilution catheter. At the peak of its dose-response curve, saterinone induced an increase in cardiac index (+102%), stroke volume (+97%), and heart rate (+6%), paralleled by a decrease in pulmonary capillary wedge pressure (-46%), right atrial pressure (-51%), pulmonary arterial pressure (systolic -32%, diastolic -45%, mean -38%), systemic blood pressure (systolic -3%, diastolic -13%, mean -9%), systemic vascular resistance (-54%), and pulmonary vascular resistance (-58%). Dobutamine had similar effects on cardiac index (+106%) and stroke volume (+87%) but lacked vasodilatory characteristics. In contrast to dobutamine, both nitroprusside and saterinone demonstrated more pronounced vasodilatory effects. Nitroprusside was less effective on cardiac index (+66%) and stroke volume (+56%) than was saterinone. The double product was markedly increased by dobutamine (+28%), did not change with saterinone treatment (+2%), and decreased with nitroprusside (-10%). This indicates that according to double product, only the application of dobutamine caused a relevant increase in myocardial oxygen consumption. Saterinone was demonstrated to be a safe and potent drug on short-term application; it combines the vasodilating properties of sodium nitroprusside with the positive inotropic effects of dobutamine without major changes in myocardial oxygen consumption.     

Effects of toborinone on systemic circulation in patients under general anesthesia

Patients with suppressed systemic circulation under general anesthesia received a 20-minute continuous infusion of toborinone at a rate of 5, 10, or 15 micrograms.kg-1.min-1, and the efficacy and safety of the drug were evaluated. Toborinone increased cardiac index (CI) and stroke volume index (SVI) dose-dependently, with significant increases at 10 and 15 micrograms.kg-1.min-1. An increase in CI was observed from 10 minutes after the start of infusion, with a return to the baseline value at 20-30 minutes after the completion of infusion. Toborinone did not affect heart rate at any dose tested, but the drug tended to decrease mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial blood pressure tended to decrease after the start of infusion at all doses tested, and was significantly decreased at 20 minutes after the start of infusion at 10 and 15 micrograms.kg-1.min-1. Systemic vascular resistance and pulmonary vascular resistance decreased at all doses tested. T-wave amplitude on electrocardiaogram (ECG) and oxygen partial pressure in arterial blood decreased at 10 and 15 micrograms.kg-1.min-1. Toborinone increases cardiac output and decreases pre-load and after-load with no effects on heart rate, and, therefore, is thought to be a positive inotropic agent useful in the treatment of circulatory insufficiency. Due care should be exercised to monitor blood pressure, ECG, and arterial blood gas parameters of the patients. The effects of toborinone need to be further investigated in patients with complicated cardiac diseases under general anesthesia and in patients with circulatory insufficiency after surgery, including patients following extracorporeal circulation.     

Central haemodynamic and forearm vascular effects of morphine in patients after open heart surgery

Central haemodynamic and forearm vascular changes following administration of morphine i.v. were studied in patients 24--30 h after open heart surgery. Right atrial pressure, heart rate, mean arterial pressure, cardiac output and stroke volume were measured before and after morphine 5 and 10 mg per 70 kg in 14 subjects. In a further group of eight subjects, forearm blood flow was measured after morphine 10 mg per 70 kg. Total systemic and forearm vascular resistance were derived from these measurements. In spite of wide individual variations, significant decreases in mean arterial pressure occurred in most of the patients and appeared to be dose related. Significant decreases in mean cardiac index were noted only after morphine 10 mg per 70 kg. Forearm blood flow increased consistently and significantly and there was a corresponding decrease in vascular resistance. The decrease in mean arterial pressure and the change in forearm vascular resistance indicated that vasodilatation was probably the principle cause of the decrease in arterial pressure, whereas the sustained decrease in cardiac output seemed to indicate an effect on venous capacitance. The predominant action of morphine appears to be peripheral, causing a decrease in vascular resistance and, possibly, an increase in venous capacitance.     

Effects of human atrial natriuretic peptide on hemodynamics and pulmonary gas exchanges in cardiac surgery patients

We investigated the effects of human atrial natriuretic peptide (hANP) on hemodynamics and pulmonary gas exchanges in 22 cardiac surgery patients without pulmonary hypertension. In 10 patients, hANP was infused at a rate of 0.2 microgram.kg-1.min-1 throughout the surgery (hANP group), while in other 12 patients hANP was not infused at all (control group). Before cardiopulmonary bypass (CPB), mean arterial pressure and systemic vascular resistance decreased and cardiac output increased significantly in hANP group as compared with those in control group. After weaning from CPB and at the completion of surgery there was no significant difference in these hemodynamic variables between the two groups. Mean pulmonary arterial pressure, pulmonary vascular resistance, arterial pH, arterial oxygen tension, arterial carbon dioxide tension and shunt ratio did not show any significant difference between the two groups throughout surgery. These findings indicate that hANP infusion causes greater systemic vasodilation with less pulmonary vasodilation, and suggest that this systemic vasodilating effect contributes to the improvement of left ventricular function in patients undergoing open heart surgery.     

Timing variability in children with early-treated congenital hypothyroidism

Hypertonic acetate solution in small volumes greatly improves cardiac output and corrects acid-base disturbances in hemorrhaged animals. We hypothesized that the combination of alpha alpha-crosslinked human hemoglobin (alpha alpha Hb), an oxygen carrier and vasoconstrictor, with hypertonic sodium acetate (HAHb), a vasodilator, may be effective for small volume resuscitation of hemorrhagic shock. Six pigs hemorrhaged to a mean arterial pressure of 40 mmHg for 60 min (bled volume: 23.6 +/- 2.5 ml.kg-1) received a single bolus of 4 ml.kg-1 of HAHb infused over two min. HAHb restored arterial pressure, increased systemic vascular resistance and caused a modest increase in cardiac output and SvO2, while pulmonary arterial pressure and vascular resistance were markedly increased. In two animals, transient severe hypotension and low cardiac output may have been due to acute pulmonary hypertension during injection. Compared to our previous study, in which animals received 4 ml-kg-1 of alpha alpha Hb alone, HAHb produced higher cardiac output and a smaller increase in systemic and pulmonary vascular resistance. However, slower, titrated infusions may be needed when hemoglobin solutions are combined with drugs or solutions that cause vasodilation in order to decrease the likelihood of acute hemodynamic instability.     

The effects of coronary vasodilatation on cardiac performance during endotoxin shock

Results of studies have suggested that endotoxin and lowered coronary arterial perfusion pressures are detrimental to cardiac performance and lead to failure. Prevention of cardiac failure in the isolated canine heart preparation confronted with endotoxin and decreased coronary perfusion pressure was possible by perfusing these hearts with sodium nitroprusside. Prevention of failure was manifested by a lowered left ventricular endiastolic pressure and was associated with increased coronary flow and decreased coronary resistance with increased oxygen delivery and decreased oxygen extraction. Possible explanations for improved performance by dilator perfusion include increased delivery of oxygen and nutrients to myocardial tissue as well as a reduction of ventricular wall tension by dilating the coronary vascular skeleton. Prevention of extravasation of interstitial fluid into myocardial tissue by reducing overperfusion of potentially damaged coronary vessels could serve to maintain myocardial integrity and ventricular compliance. The potential use of such therapy warrants further study, with emphasis on evaluating the hemodynamics of the intact animal.     

The haemodynamic effects of adrenergic receptor blockade or stimulation druing nitrous oxide anaesthesia in dogs

The effects of ventilation with nitrous oxide in oxygen on myocardial blood flow any oxygen metabolism were investigated in 31 mongrel dogs. The results of this study showed that, compared with controls, hyperoxic nitrous oxide mixtures did not cause any great changes in myocardial haemodynamics, despite a decrease in cardiac output and an increase in systemic vascular resistance. Normoxic nitrous oxide mixtures produced an increase of the coronary blood flow due to decreased coronary vascular resistance. To what extent this coronary vasodilatation resulted from a increased myocardial metabolism or from a direct effect of nitrous oxide on the coronary vascular bed cannot be quantified from the present results.     

The hemodynamic effects of the in-vivo administration of insulin-like growth-factor I

BACKGROUND: Recent studies have demonstrated that IGF-I has several biological activities that correlate with the GH axis, by acting as a cell protecting factor and a promoting compound in different tissues and organs. Our latest findings have demonstrated a potential application of IGF-I in the treatment of postischemic renal injury, which frequently appears after a kidney transplant. The beneficial effect of the renal postoperative recovery probably correlates with the regulation of the vascular tone, in which IGF-I plays a role with other cytokines. However, this rises the question whether IGF-I has any effect on the general hemodynamic status. This study was designed to underline the intraoperative hemodynamic effect of exogenous IGF-I in an experimental setting of renal transplantation in swine. METHODS: Twelve female swine underwent a left renal autotransplantation. At the reperfusion the animals were separated in two groups. Group one served as control. Group two received 400 micrograms of IGF-I (added to the flushing solution). The animals were kept under complete hemodynamic monitoring over the operation. RESULTS: Among the different parameters studied (mean arterial pressure, mean pulmonary arterial pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), any statistically significant difference between group one and two were observed. CONCLUSIONS: While the clinical administration of IGF-I requires further studies, the in vivo administration of this peptide is apparently well tolerated, and does not cause any hemodynamic instability to the operation.     

Oxygen delivery and consumption in critically ill pregnant patients: association with ophthalmic artery diastolic velocity

OBJECTIVES: We aimed to investigate the relation between orbital vessel flow velocity and oxygen delivery, oxygen consumption, cardiac index, and systemic vascular resistance index in critically ill pregnant patients. STUDY DESIGN: Eighteen pregnant or early postpartum patients requiring invasive monitoring were prospectively studied with Doppler ultrasonography. The blood flow velocity and resistance index from the central retinal and ophthalmic arteries were plotted against the oxygen delivery index, oxygen consumption index, cardiac index, and systemic vascular resistance index. Linear and polynomial regression analysis and receiver-operator characteristic curves were used to examine the data. RESULTS: The ophthalmic artery resistance index correlated with oxygen consumption, oxygen delivery index, and cardiac index. Only the cardiac index was independently related to the the ophthalmic artery resistance index. The ophthalmic artery diastolic velocity correlated with oxygen consumption index, oxygen delivery index, and cardiac index. The ophthalmic artery diastolic velocity correlated independently with mixed venous oxygen content and arteriovenous oxygen content difference. The central retinal artery Doppler index did not correlate with any of the invasively measured parameters. An ophthalmic artery diastolic velocity of > 7.12 cm/sec identified 75% of patients with an oxygen consumption index of < 140 ml/min per square meter and 91% of patients with an oxygen delivery index of < 600 ml/min per square meter. CONCLUSIONS: These data suggest that the ophthalmic artery flow velocity is correlated with systemic oxygen delivery and consumption. This relationship may have potential research applications in the noninvasive assessment of oxygen delivery index and oxygen consumption index in critically ill pregnant patients.     

Benign tumors of the liver: primum non nocere

PURPOSE: This study evaluates the haemodynamic effects of oxygen inhalation on pulmonary artery pressure and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. METHOD: In 47 patients with chronic thromboembolic pulmonary hypertension haemodynamic parameters were measured before and after oxygen inhalation. RESULTS: In moderately severe and severe pulmonary hypertension oxygen inhalation significantly reduced mean pulmonary artery pressure by about 11.1% and 4.6%, respectively. However, pulmonary vascular resistance was not significantly affected. Oxygen saturation improved and heart rate was reduced. Cardiac index decreased in severe pulmonary hypertension. Systemic vascular resistance increased. CONCLUSION: We conclude that oxygen inhalation reduces pulmonary artery pressure and improves oxygen supply in patients with moderately severe and severe chronic thromboembolic pulmonary hypertension.     

Hemodynamic effects of dobutamine after cardiopulmonary bypass in children

The synthetic inotropic agent, dobutamine, has reportedly increased cardiac output in adults after cardiopulmonary bypass with minimal side effects. Its use in children, after surgical correction of congenital heart disease, was tested by infusing the drug at 1, 4, 7, and 10 micrograms/kg x min in 11 children. While significant increases in cardiac index above control (23, 23, and 16% at 4, 7, and 10 micrograms/kg x min, respectively) were observed, this was achieved at the expense of significant increases in heart rate (15, 24, and 10%). This increase in heart rate (47% in one child) necessitated discontinuing the infusion in 4 subjects. There were also significant increases in systolic and mean blood pressure with no change in stroke volume or peripheral vascular resistance. The authors conclude that in children, dobutamine is an effective inotropic agent acting principally by stimulating beta 1-receptors in the myocardium producing a predominantly chronotropic effect without significant changes in peripheral vascular resistance. Given the intrinsically higher heart rate of children, the levels of tachycardia produced by the drug in some instances reach unacceptable levels and as such, may make dopabutamine unsuitable for use in children after cardiopulmonary bypass.     

Migrant health: a harvest of poverty

The aim of the study was to assess prestarium effects on central and renal hemodynamics, blood lipids in hypertensive subjects. Prestarium was given in a daily dose 4-6 mg to 30 patients with essential hypertension stage II free of cardiac decompensation and renal failure. Echocardiography, tetrapolar chest rheoplethysmography with assessment of hemodynamics, radionuclide tracing of renal blood flow, tests for cholesterol and blood electrolytes were made before treatment, on treatment weeks 2-3 and 12. It was found that prestarium lowers blood pressure and total peripheral vascular resistance. Myocardial conductivity was not affected, whereas renal circulation activated. Low-density lipoproteins cholesterol fell. No significant changes in electrolytes were seen. The drug was well tolerated. In view of good clinical effect and tolerance prestarium is recommended for treatment of essential hypertension stage II in the absence of cardiac decompensation and renal dysfunction.     

Mechanism of the interaction of propranolol and a potent vasodilator antihypertensive agent - minoxidil

A study, using non-invasive techniques, was carried out in ten patients with essential hypertension to examine the mechanism of the hypotensive effect of propranolol when used in combination with a potent vasodilator antihypertensive - minoxidil. The hypotensive effect of minoxidil, a mean (+/- SEM) decrease of 42.4 +/- 4.3 mm Hg, was accompanied by a marked increase in heart rate, cardiac index and plasma renin activity and a significant decrease in total peripheral resistance, limb vascular resistance and pre-ejection period. Addition of propranolol further reduced mean arterial pressure by an average of 12.9 +/- 2.0 mm Hg. Propranolol returned cardiac index to control values and total peripheral resistance index rose but not to control levels. Plasma renin activity was significantly reduced by propranolol. By multiple regression analysis no correlation was found between propranolol-induced decrease in mean arterial pressure and changes in cardiac index, total peripheral resistance index or plasma renin activity. Quantitatively, the reduction in cardiac index observed probably accounted for the hypotensive effect of propranolol. The role of plasma renin activity reduction in the hypotensive effect of propranolol in this situation remains to be clarified. The findings in the present study were consonant with the known actions of vasodilator antihypertensive agents and propranolol and indicate the applicability of non-invasive methodology to the investigation of cardiovascular drugs in man.