Fall In Total Peripheral Resistance Research Articles

Role of arginine vasopressin and angiotensin II in cardiovascular responses to combined acute hypoxemia and hypercapnic acidosis in conscious dogs.

The physiological relationship of increased circulating angiotensin II and vasopressin to circulatory changes during combined hypoxemia and hypercapnic acidosis is unclear. To evaluate the role(s) of angiotensin II and vasopressin, seven unanesthetized female mongrel dogs with controlled sodium intake (80 meq/24 h X 4 d) were studied during 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 mmHg; PaCO2, 55 +/- 2 mmHg; pH = 7.16 +/- 0.04) under the following conditions: (a) intact state with infusion of vehicles alone; (b) beta-adrenergic blockade with infusion of d,l-propranolol (1.0 mg/kg bolus, 0.5 mg/kg per h); of the vasopressin pressor antagonist d-(CH2)5Tyr(methyl)arginine-vasopressin (10 micrograms/kg); and (d) simultaneous vasopressin pressor and angiotensin II inhibition with the additional infusion of 1-sarcosine, 8-alanine angiotensin II (2.0 micrograms/kg per min). The rise in mean arterial pressure during the combined blood-gas derangement with vehicles appeared to be related to increased cardiac output, since total peripheral resistance fell. Beta-adrenergic blockade abolished the fall in total peripheral resistance and diminished the rise in cardiac output during combined hypoxemia and hypercapnic acidosis, but the systemic pressor response was unchanged. In addition, the rise in mean arterial pressure during the combined blood-gas derangement was unaltered with vasopressin pressor antagonism alone. In contrast, the simultaneous administration of the vasopressin pressor and angiotensin II inhibitors during combined hypoxemia and hypercapnic acidosis resulted in the abrogation of the overall systemic pressor response despite increased cardiac output, owing to a more pronounced fall in total peripheral resistance. Circulating catecholamines were increased during the combined blood-gas derangement with vasopressin pressor and angiotensin II blockade, suggesting that the abolition of the systemic pressor response in the last 30 min of combined hypoxemia and hypercapnic acidosis was not related to diminished activity of the sympathetic nervous system. These studies show that vasopressin and angiotensin II are major contributors to the systemic pressor response during combined acute hypoxemia and hypercapnic acidosis.

The effect of Gaboon viper ( [formula omitted]) venom on cardiac stroke work in the anaesthetized rabbit

The effect of Bitis gabonica venom administered intravenously in the rabbit at the dose of 0.125 mg/kg (approximately 10% of LD 50) has been studied. Venom caused marked changes in cardiovascular parameters principally a precipitous but transient fall in total peripheral resistance and arterial blood pressure. Furthermore in the period occurring between 5 and 30 min after the injection of venom, a transient increase in stroke work was observed as a result of the ejection of an increased stroke volume against a blood pressure which had already returned to normal. Such a transient inotropic effect has also been observed in other small mammals and could be attributed to an adrenergic mechanism.

Immediate hemodynamic changes produced by urapidil in normotensive and spontaneously hypertensive rats.

The immediate effects on regional and systemic hemodynamics of urapidil (1 mg/kg IV), a recently synthesized vasodilator with a possible combined central and peripheral action, were studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Maximal decrease in mean arterial pressure was achieved within the first minute after injection (154 +/- 4 vs 113 +/- 6 mm Hg in SHR and 111 +/- 4 vs 82 +/- 4 mm Hg in WKY, p less than 0.01). This effect was accompanied by a transient (10 min) significant increase in heart rate in both strains. There was a significant fall in total peripheral resistance (0.43 +/- 0.02 vs 0.30 +/- 0.02 U/kg in WKY and 0.62 +/- 0.03 vs 0.43 +/- 0.03 U/kg in SHR, p less than 0.01) and rise in cardiac index 15 min after drug injection (371 +/- 9 vs 425 +/- 12 ml/min/kg in WKY and 395 +/- 8 vs 432 +/- 112 ml/min/kg in SHR, p less than 0.01). Organ vascular resistance decreased significantly in all the organs of /KY and most of the organs of SHR rats. However, a significant increase in blood flow was observed only in skeletal muscle. The data indicate that urapidil is a potent hypotensive agent. The pressure fall is mediated through a decreased total peripheral resistance that is distributed through all circulations. The increased cardiac output and heart rate are most likely reflexly induced.

Systemic and arterial hemodynamic effects of nifedipine (20 mg) in mild-to-moderate hypertension.

Systemic and arterial hemodynamic effects of the new 20 mg tablet of nifedipine were studied in seven patients with mild-to-moderate essential hypertension. Hemodynamics of the forearm arterial circulation were investigated using a new pulsed Doppler system, enabling the simultaneous determination of the brachial artery diameter and the arterial blood flow velocity. After nifedipine administration, blood pressure decreased significantly, due to a fall in total peripheral resistance. Simultaneously, brachial blood flow increased significantly, due both to an increase in arterial diameter and blood flow velocity. The study provided evidence that, with nifedipine, there is both 1) a dilation of small arteries, causing a decrease in blood pressure; and 2) a dilation of peripheral large arteries, leading to an increase in peripheral blood flow.

Effects of intracisternal and intravenous alpha-methyldopa and clonidine on haemodynamics and baroreceptor--heart rate reflex properties in conscious rabbits.

We determined the doses of intracisternal (i.c.) and intravenous (i.v.) clonidine and alpha-methyldopa (alpha-MD) that produced near-maximal falls in mean arterial pressure (MAP) in conscious rabbits. We then studied the haemodynamic mechanisms underlying the fall in MAP and changes in the properties of the baroreceptor-heart rate reflex. Intracisternal and intravenous administration of both drugs lowered MAP by approximately 25% of control, and the fall was about half due to the reduction in cardiac output and about half due to a fall in total peripheral resistance. Baroreceptor-heart rate reflex properties were studied by transiently inflating perivascular balloons to alter blood pressure and by deriving sigmoid curves relating MAP to heart period (HP, pulse interval). Both drugs produced very similar vagal facilitation during transient rises in MAP when given by the i.c. and i.v. routes; HP range (between upper and lower plateaus) increased to 145% of control, and gain rose to 190%. The effects of i.c. administration of both drugs on the cardiac sympathetic component of the baroreflex were studied in methscopolamine-treated rabbits. Clonidine produced more pronounced suppression of HP range and gain, while alpha-MD had little effect. These differences between drugs were still present with much larger i.c. doses. Our findings suggest that both drugs influence resting haemodynamics and the vagal component of the baroreflex through similar effects on the central autonomic pathways. But there are some differences in their central actions on cardiac sympathetic motoneurons.

Hemodynamic mechanism of blood pressure response to captopril in human malignant hypertension.

The hemodynamic mechanism of blood pressure response to angiotensin blockade is well established in "benign" but not in human malignant hypertension. We studied the changes in mean arterial pressure (MAP), cardiac index (CI), pulmonary wedge pressure (PWP), and in plasma volume (PV) induced by a single oral dose of captopril (150 mg) in 11 patients with malignant hypertension. Two hours after captopril, MAP fell from 178.5 +/- 5.8 to 151.8 +/- 7.8 mm Hg (p less than 0.001) (means +/- SEM) due to a fall in total peripheral resistance (TPR) (from 54.8 +/- 6.8 to 46.4 +/- 1.6 arbitrary units, p less than 0.001). However, there was a simultaneous increase in CI (from 3.29 +/- 0.13 to 3.70 +/- 0.15 liter/min/m2, p less than 0.001), and a decrease in PWP (from 15.3 +/- 3.5 to 11.0 +/- 2.5 mm Hg, p less than 0.001), while PV remained unchanged (from 4.02 +/- 0.26 to 4.12 +/- 0.12 liters, n.s.). Our data show that, in human malignant hypertension, blood pressure response to captopril is due to a decrease in TPR, but in contrast to benign hypertension, there is also a simultaneous increase in CI. Our results suggest that, in malignant hypertension, potentially high CI levels are artificially normalized by the increased TPR and may be fully disclosed by vasodilation.

Arterial-venous nitroglycerin gradient during intravenous infusion in man.

We assessed the concentration of nitroglycerin (GTN) measured in plasma at different sampling sites in the circulation during a constant i.v. infusion. Twenty patients with chronic congestive cardiac failure underwent hemodynamic monitoring during i.v. GTN infusion. Our end point was a reduction in pulmonary capillary wedge pressure by at least 25% of its control value or a 10-fold increment over the initial infusion rate. Nitroglycerin infusion produced no change in heart rate, a reduction in mean arterial pressure from 90 +/- 21 (+/- SD) to 83 +/- 17 mm Hg (p less than 0.001), a fall in total peripheral resistance from 24.3 +/- 10.8 to 20.8 +/- 7.0 units (p less than 0.02), and a substantial reduction in both pulmonary capillary wedge pressure (from 27 +/- 6 to 20 +/- 6 mm Hg, p less than 0.001) and right atrial pressure (from 12 +/- 4 to 8 +/- 4 mm Hg, p less than 0.001). The concentrations of GTN in the pulmonary artery and systemic artery were similar (29.8 ng/ml +/- 52.8 and 25.1 +/- 48.4 ng/ml, respectively) and considerably higher than the concentration in the peripheral vein (7.3 +/- 15.4 ng/ml). There was a 17.4 +/- 19.1% extraction of GTN across the pulmonary vascular bed and a 60.8 +/- 27.2% extraction across the arterial-venous bed (p less than 0.001). There was no relationship between the arterial-venous extraction and the magnitude of arterial plasma (GTN concentration, the duration of the infusion of GTN or the total dose administered. These data show that a better understanding of GTN pharmacokinetics is provided by simultaneous arterial and venous samples.

Acute hemodynamic effects of labetalol in severe hypertension.

Intravenous injection of labetalol induced an immediate fall (-22.4%) in blood pressure (BP) in 11 patients with severe hypertension. Hypotensive episodes were avoided by repeated injections of 0.2-0.8 mg/kg. The pressure reduction was associated with a mean fall in total peripheral resistance of 13.6%. Cardiac output fell 10.1% owing to a fall in heart rate of 10.8%, while stroke volume remained virtually unchanged. Despite excellent acute control of BP by intravenous injection, oral labetalol alone or in combination with hydrochlorothiazide was not effective in long-term treatment of these patients with severe hypertension. After 1 week, mean arterial pressure was still 10.4% below the pretreatment level, but after 4 months BP was back to pretreatment level in all except one patient whose BP is still well controlled after more than 2 years on labetalol.

A critical examination of dialysis-induced hypotension.

Dialysis-induced hypotension has received considerable attention recently because of its high incidence of occurrence. Several factors have been proposed as etiologic mechanisms. They include hypovolemia, autonomic dysfunction, decreasing serum osmolality, vasodilation (or the inhibition of compensatory vasoconstriction), efficiency of diffusive solute transport, depletion of vasoactive substances and blood gas and acid-base changes. The primary determinants of blood pressure being cardiac output and total peripheral resistance, the magnitude and direction of change of these two parameters determines the blood pressure response. If the rate of ultrafiltration exceeds the rate of vascular refilling, hypovolemia results. Intracellular fluid shifts secondary to preferential solute removal from the extracellular space may compromise vascular refilling and contribute to hypovolemia. If the hypovolemia is not compensated for by increases in heart rate or stroke volume, the cardiac output falls. Autonomic dysfunction, a previous history of myocardial infarction or impaired tissue oxygenation secondary to hypoxia may limit compensatory increases in heart rate and stroke volume. Even if the cardiac output falls, if compensatory vasoconstriction is elicited, blood pressure can be maintained. The experimental evidence suggests that the diffusive aspect of dialysis therapy plays an important role in inhibiting compensatory vasoconstriction. Such inhibition is not observed with hemofiltration, a therapy based on convective rather than diffusive solute removal. While autonomic dysfunction and the diffusive removal of vasoactive substances may play a role in inhibiting the vasoconstrictive response, the use of acetate as a buffer source and the decreasing serum osmolality seem to be of greater importance. Acetate produces vasodilation. It also has a positive inotropic effect. Studies suggest that the vasodilation produced by acetate is compensated for by a proportionate increase in cardiac output except during the early stages of the therapy when the fall in total peripheral resistance may overwhelm the increase in cardiac output. The substitution of bicarbonate for acetate results in a decrease in the incidence of symptomatic hypotension in some patients. This alleviation of symptoms appears to be significant only when the dialystate sodium concentration is relatively low (130–135 m M ). At higher dialysate sodium concentrations (140–145 m M ), the blunting of the fall in serum osmolality seems to be of greater importance than the nature of the buffer source in reducing the incidence of symptomatic hypotension. It is not clear if blunting the fall in serum osmolality has a greater beneficial influence on the cardiac output or on the total peripheral resistance. While the etiology of dialysis-induced hypotension is complex, controversial, and multifactorial, amelioration of symptomatic hypotension with a higher dialysate sodium concentration offers a practical solution. The substitution of bicarbonate for acetate is a technically more complex and expensive alternative.

Haemodynamic changes after surgical reversal of chronic two-kidney, one-clip hypertension in the rat.

1. Within 24 h of surgical reversal of chronic Goldblatt two-kidney, one-clip hypertension in the rat, of greater than 4 months duration, blood pressure had fallen to normal levels. At this time there was no difference between the effects of removal of the clip or the ischaemic kidney but, at 60 days after reversal, the blood pressure of rats which had been nephrectomized was significantly higher than that of normal controls. 2. The fall in blood pressure was associated with a fall in total peripheral resistance to normal by 24 h despite the previous established fact that structural vascular changes take much longer to reverse. There was a corresponding rise in cardiac output, mainly due to an increase in stroke volume. Nephrectomized rats had a significantly higher stroke volume compared with those unclipped 24 h after operation. 3. As blood pressure can become normal in the presence of structural cardiovascular change by a fall in total peripheral resistance it would seem unlikely that resistance vessel hypertrophy is responsible for the maintenance of blood pressure in this model. Another peripherally acting mechanism therefore has to be postulated.

Systemic Haemodynamic Effects of Biofeedback in Borderline Hypertension

1. Six patients with borderline hypertension underwent training in exteroceptive biofeedback (BFB) in order to increase or decrease arterial pressure. 2. Systemic haemodynamics, intravascular volume and peripheral renin activity were determined before, during and after training sessions. 3. BFB training resulted in a significant reduction in mean arterial pressure (from 116 +/- 4.6 to 101 +/- 2.5 mmHg) mediated through a fall in total peripheral resistance; cardiac output, heart rate, intravascular volume and plasma renin activity remained unchanged. 4. In contrast, the increase or decrease of arterial pressure that occurred during BFB training was produced predominantly through changes in cardiac output and heart rate respectively, whereas total peripheral resistance under these circumstances remained unaffected. 5. The haemodynamic effects of BFB seem remarkably similar to the immediate or chronic effects of beta-adrenoreceptor blockade, initially producing a fall in cardiac output followed by a reduced arterial pressure associated with a decreased total peripheral resistance.

Short-term Therapy of Severe Hypertension

Ten severely hypertensive patients were randomized into five treatment groups: vasodilators; vasodilators plus diuretics; sympatholytics; sympatholytics plus diuretics; and sympatholytics, diuretics, and vasodialtors. Cardiac index was measured daily by echocardiography, and total peripheral resistance (TPR) calculated. Plasma renin activity (PRA) and creatinine clearance (CCR) were measured every other day. There was no difference in antihypertensive response. Seven patients, whose initial TPR was high, responded to treatment with a fall in TPR, regardless of regimen. Three patients with a high pretreatment cardiac index responded with a fall in cardiac index. Changes in TPR or cardiac index were not related to changes in CCR. There was no correlation between PRA and either blood pressure or TPR. It is concluded that the pretreatment hemodynamic status of severely hypertensive patients is the major determinant of the hemodynamic response to antihypertensive therapy.

Haemodynamics of Orally-Active Converting Enzyme Inhibitor (SQ 14225) in Hypertensive Patients

1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension. 2. Mean arterial pressure fell (149 +/- 5 to 127 +/- 8 mmHg, P less than 0.02), because of a fall in total peripheral resistance (6.9 +/- 0.53 to 5.7 +/- 0.40 kPa 1(-1)s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 +/- 8 to 111 +/- 12 mmHg, P less than 0.05) through further resistance reduction (6.5 +/- 0.53 to 5.2 +/- 0.40 kPa 1(-1)s m2, P less than 0.05). 3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake. 4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels.

Cardiovascular responses to blockade of angiotensin and alpha-adrenergic receptors

Both angiotensin and alpha-adrenergic blocking agents reduce arterial blood pressure in hypovolemic states. We have compared the effects of an angiotensin antagonist (saralasin) and an alpha-adrenergic blocking agent (phenoxybenzamine) in supramaximal dosage on cardiac output, total peripheral resistance, and venous tone in rabbits rendered hypovolemic by restriction of sodium intake, supplemented by a furosemide-induced diuresis 48 h prior to study. Saralasin (10 microgram/kg per min) reduced arterial blood pressure significantly (-15 +/- 1.2 mmHg) despite an unchanged cardiac output (P less than 0.025) due to a fall in total peripheral resistance. Phenoxybenzamine (5 mg/kg) induced a much larger fall in arterial blood pressure (-28 +/- 3.6 mmHg), despite an identical reduction in total peripheral resistance, because cardiac output also fell (+/- 9 ml/kg per min). The reduction in cardiac output was associated with a significant increase in hindlimb venous distensibility (P less than 0.001) after alpha-adrenergic blockade. Saralasin, conversely, had no influence on venous tone. Adrenergic mechanisms contribute to cardiovascular homeostasis through an influence on both arteriolar and venous tone, whereas the effect of angiotensin is directed entirely to the arteriolar side of the circulation.

Histamine, histamine antagonists and regional blood flow

The effects of mepyramine, a selective histamine H 1-receptor antagonist, and metiamide, a selective histamine H 2-receptor antagonist, have been determined on the cardiovascular response to intravenous infusions of a large dose of histamine, 1 × 10 −7 mol/kg/min. Pretreatment with either mepyramine, 2.5 × 10 −6 mol/kg, or metiamide, 2 × 10 −6 mol/kg/min, had no significant effect on the fall pressure or fall in total peripheral resistance during histamine infusion. Pretreatment with mepyramine, 2.5 × 10 −6 mol/kg, and metiamide, 2 × 10 −6 mol/kg/min, abolished the fall in blood pressure and total peripheral resistance during infusion of histamine. Histamine-induced vasodilatation in the stomach was unaltered by pretreatment with mepyramine but abolished by pretreatment with metiamide. Histamine-induced coronary vasodilatation was reduced slightly by pretreatment with mepyramine and substantially by pretreatment with metiamide. Coronary vasodilatation was abolished by treatment with mepyramine and metiamide.

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.

Renal prostaglandins.

The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.

HYPOTENSIVE AND VASODILATOR ACTIONS OF SK&F 24260, A NEW DIHYDROPYRIDINE DERIVATIVE

1 The blood pressure of conscious normotensive, Goldblatt-hypertensive and genetic-hypertensive rats and normotensive dogs was lowered by SK&F 24260 (1,4-dihydro-2,6-dimethyl-4-(2-trifluormethylphenyl)-3,5-pyridinedicarboxylic acid diethyl ester).2 Tachycardia always accompanied the hypotension. In rats propranolol abolished the tachycardia but in dogs there was only a small reduction in the heart rate response.3 In conscious dogs there was an increase in left ventricular output and a marked fall in total peripheral resistance.4 SK&F 24260 dilated resistance vessels in rat hindquarters. Dilatation was caused by doses of SK&F 24260 some 50 times smaller than those of hydrallazine.5 In preparations of cat skeletal muscle and intestinal vascular beds SK&F 24260 selectively dilated resistance vessels in preference to capacitance vessels and resembled hydrallazine rather than papaverine which has no such selectivity.6 Pre-capillary sphincter vessels were also dilated by SK&F 24260. Changes in fluid equilibrium caused by SK&F 24260 were consistent with selective dilatation of resistance vessels.

Differentiation of physiologically significant coronary artery lesions by coronary blood flow measurements during isoproterenol infusion.

At cardiac catheterization, the effect of isoproterenol on coronary blood flow was compared in six patients with normal coronary arteries and normal left ventricular function, and eight patients with angiographically defined coronary lesions. Coronary blood flow was measured by selective coronary artery injection of xenon-133 and external monitoring of disappearance curves with a dual probe, digital scintillation counter. Resting values did not differ in the two groups. In the normal group isoproterenol increased mean coronary blood flow 93 ml/100 g/min (152%) and cardiac output 2.3 liters/min (42%); coronary resistance/100 g decreased 60 ± 4% ( sem ), while total peripheral resistance decreased 29 ± 4%. In the coronary disease group coronary blood flow increased 20 ml/100 g/min (33%) and cardiac output increased 2.8 liters/min (62%); coronary resistance decreased 26 ± 9% and total peripheral resistance decreased 37 ± 4%. In all normal patients the percent increase in coronary blood flow markedly exceeded the percent increase in cardiac output and the percent fall in coronary resistance markedly exceeded the percent fall in total peripheral resistance. In six of the eight patients with coronary lesions the percent increase in coronary blood flow was less than the percent increase in cardiac output and the fall in coronary resistance was less than the fall in total peripheral resistance. Thus measurement of coronary blood flow, cardiac output, and aortic pressure before and during isoproterenol infusion may permit differentiation of those subjects with physiologically significant coronary obstructions.

Effects of bradykinin and autonomic nervous system inhibition on systemic and regional hemodynamics in the unanesthetized rhesus monkey.

Studies were performed in unanesthetized monkeys to determine if bradykinin infusions reproduce the circulatory events of early endotoxemia. Kinin infusions before and during autononiic ganglionic blockade with trimethaphan were significantly correlated (P <0.05) with decreases in mean arterial pressure. Kinin infusion at 15-18, µg/kg min - produced 26 mm Hg fall in mean blood pressure at 3 min, due to fall in total peripheral resistance of 14 mm Hg/liter min -1 . Heart rate rose 23 beats/min. After 10 minutes of infusion, peripheral resistance had returned to base line, blood pressure remained low due to fall in cardiac output of 0.53 liters/min (P <0.01). Ganglionic blockade prevented recovery of resistance. Plasma bradykinin levels at 3 and 10 minutes were 14 and 15 µg/ml, respectively. Regional and systemic hemodynamic effects of kinin (15-18 µg/kg min were determined in 10 monkeys. After 10 minutes of infusion, bradykinin produced systemic effects. Regional flow measurement (by radioactive microsphere technique) demonstrated a pattern similar to that seen during hemorrhage. Canglionic blockade lowered mean arterial pressure 33 mm Hg by generalized vasodilatation, Kinin infusion then resulted in further vasodilatation and fall in blood pressure of 12 mm Hg, and cardiac output of 0.74 liters/min. Regional flow distribution during combined infusion was similar to that seen during early endotoxemia.