Effects of hydralazine and sodium nitroprusside on plasma catecholamines and heart rate

Hydralazine and sodium nitroprusside induce different effects on systemic hemodynamics, but their effects on sympathetic neuronal activity have not been compared. Five hypertensive subjects receiving only hydrochlorothiazide were studied during two sessions. During one session, four doses of hydralazine, 0.1 to 0.6 mg/kg, were given intravenously at least 3 days apart, and during the other session, sodium nitroprusside was infused in stepwise doses, 0.05 to 4.8 micrograms/kg/min for 10 min per dose. Mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) and epinephrine concentrations were determined before and after dosing. The following correlated linearly for hydralazine and sodium nitroprusside: delta HR/delta MAP, delta NE/delta MAP, and delta HR/delta NE. Comparison of these relationships, however, indicated significant differences between the sympathetic neuronal and hemodynamic responses to hydralazine and sodium nitroprusside. Increase in HR relative to decrease in MAP was greater for hydralazine than for sodium nitroprusside. There were greater increases in plasma NE concentration relative to falls in MAP with sodium nitroprusside than with hydralazine, but increases in HR relative to increases in plasma NE concentration were smaller for sodium nitroprusside than for hydralazine. Such responses may reflect differential effects of hydralazine and sodium nitroprusside on the systemic clearance of NE or of the activity of cardiopulmonary baroreceptors.     

Hemodynamic effects of vasodilators on pulmonary hypertension in decompensated chronic obstructive pulmonary disease

Vasodilators have been reported to improve the hemodynamic status of some patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). We investigated the effects of sodium nitroprusside (50 micrograms/min) and hydralazine (25 mg) on pulmonary hemodynamics in 12 patients during acute exacerbation of COPD. Apart from its known systemic effects, nitroprusside decreased significantly mean pulmonary artery pressure (MPAP) from 36 +/- 10 to 31 +/- 12 mm Hg (p less than .04), decreased slightly pulmonary vascular resistance, and did not change cardiac index. Except for a slight but significant increase in MPAP from 35 +/- 5 to 38 +/- 5 mm Hg (p less than .002), hydralazine produced no significant hemodynamic changes. These results suggest that vasodilator therapy with sodium nitroprusside and hydralazine for pulmonary hypertension secondary to acute COPD is probably not helpful.     

Therapy of arterial hypertension with verapamil hydrochloride in patients after myocardial revascularization

Verapamil hydrochloride, a calcium blocker from a group of phenyl alkylamines, was tested for its effect on central hemodynamics (CH) and blood oxygen-transporting function (BOTF) in 14 patients with arterial hypertension after surgical myocardial revascularization. CH and BOTF were studied by using a Swan-Hanz catheter and directly measuring blood pressure (BP). There was a significant reduction in BPmean, total peripheral vascular resistance index, left ventricular stroke outcome index, and oxygen delivery index. Verapamil in an average dose of 80.4 +/- 18.02 mg at the injection rate of 24.6 +/- 3.9 micrograms/kg/min was shown to make BPmean normal 16.8 +/- 6.35 min later. The agent is comparable with other calcium blockers, such as nifedipine and isradipine in its action on CH and BOTF, as well as in its efficiency and safety.     

Analysis of whole blood viscosity in patients with acute myocardial infarction using a rotation viscosimeter

Rheologic characteristics of arterial and venous blood have been examined by Rotovisco RV-100 (Haake, FRG), a present-day rotation viscosimeter. Sixty-three acute myocardial infarction cases with intravenous infusion of sodium nitroprusside are analyzed. The detected time course of the reduction of arterial and venous blood viscosity during sodium nitroprusside infusion helps specify the pattern of this drug action in patients during the acute period of myocardial infarction.     

Effects of BRL 34915 (cromakalim) on renal hemodynamics and function in anesthetized dogs

The effects of BRL 34915, a newly developed potassium channel opener, on renal hemodynamics and function were investigated in anesthetized dogs. An i.v. injection of BRL 34915 (4, 20 and 100 micrograms/kg) caused a dose-related reduction of mean arterial pressure but there were no significant changes in renal blood flow. The agent at lower doses (4 and 20 micrograms/kg) produced a slight increasing action on urine formation. When BRL 34915 was infused intrarenally at nonhypotensive doses (0.04 and 0.2 micrograms/kg/min), there were no significant increases in renal blood flow and glomerular filtration rate. At 1.0 micrograms/kg/min, a dose which produced a slight reduction in mean arterial pressure, significant decreases in calculated renal vascular resistance were observed, thereby indicating that BRL 34915 has vasodilator action on the renal vasculature. In cases of infusion at higher doses (0.2 and 1.0 micrograms/kg/min), the levels of urine flow, urinary excretion of sodium and fractional excretion of sodium were elevated significantly and these events were accompanied by decreases in urine osmolality. Although the intrarenal administration of BRL 34915 at higher doses produced no alterations in the fractional excretion of lithium (index of sodium excretion at the proximal tubules), the agent did increase the calculated value of the fractional distal excretion of sodium. These effects seen when BRL 34915 was infused intrarenally were suppressed markedly by glibenclamide (6 mg/kg i.v.), a putative inhibitor of the ATP-sensitive potassium channel. Our results suggest that BRL 34915 has renal vasodilating and diuretic effects as a result of opening the potassium channels within the kidney. The agent-induced diuresis may be due partly to an inhibitory effect on sodium reabsorption at the distal portion of the tubules beyond the proximal tubules.     

Labetalol to control blood pressure after cerebrovascular surgery

Fifteen patients who had undergone neurovascular surgery for arteriovenous malformations or cerebrovascular aneurysms and had intracranial pressure (ICP) monitors were studied. The patients had been treated initially with sodium nitroprusside to maintain their arterial BP in a prescribed range, but, because of excessive nitroprusside dose requirements, they were considered either to have refractory BP or to be at risk for thiocyanate toxicity. Intravenous labetalol therapy was started either by frequent bolus pulse therapy every 1 to 2 h or by continuous infusion therapy. The degree of desired arterial BP control and the effects on ICP and cerebral perfusion pressure (CPP) were assessed and compared with the results during nitroprusside therapy. The degree of arterial BP control with labetalol was assessed to be good; 11 patients were weaned off nitroprusside and the remaining four patients had a substantial reduction in their nitroprusside requirements, needing an average of only 1.5 micrograms/kg.min of nitroprusside to control their BP compared with average requirements of 10 micrograms/kg.min of nitroprusside before labetalol therapy. Labetalol therapy improved CPP in six patients and ICP in five patients, with no significant change in cerebral pressure in the remainder. Overall, the CPP in the 15 patients improved from 63 +/- 15 (SD) mm Hg with nitroprusside to 65 +/- 10 mm Hg with labetalol therapy and the ICP decreased from 11.3 +/- 6.1 mm Hg with nitroprusside to 8.6 +/- 3.1 mm Hg with labetalol therapy (p less than .05 by Wilcoxon matched pairs).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform

BACKGROUND: Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin-resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN. DESIGN AND RESULTS: Dose-response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 +/- 1 year, BMI 25 +/- 2 kg m(-2)). Three doses of sublingual GTN (500 microg for 1, 3 or 5 min) and insulin (0.5, 1 or 2 mU kg(-1) min(-1) for 120 min) were administered on three separate occasions. Both agents dose-dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg(-1) min(-1) for 120 min) and sublingual GTN (500 microg for 5 min) in 20 nondiabetic subjects (age 50 +/- 2 year, BMI 21.0-36.3 kg m(-2)). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r=0.92 (95% confidence interval 0.81-0.97), P<0.0001], the time-course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 +/- 3 vs. 121 +/- 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 +/- 3 vs. 107 +/- 3 mmHg, 0 vs. 30 min, P<0.01). Similarly, GTN decreased aortic systolic blood pressure from 119 +/- 4 to maximally 112 +/- 3 mmHg (P<0.001) without significantly decreasing systolic blood pressure in the brachial artery. CONCLUSIONS: The effects of insulin and GTN on large arterial haemodynamics are dose-dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established.     

Antiarrhythmic properties of tetrodotoxin against occlusion-induced arrhythmias in the rat: a novel approach to the study of the antiarrhythmic effects of ventricular sodium channel blockade

Blockade of ventricular sodium conductance (gNa) is believed to play an important role in the beneficial antiarrhythmic effects of class I antiarrhythmic agents. The present study was undertaken to examine the importance of ventricular gNa blockade by assessing the antiarrhythmic profile of tetrodotoxin (TTX), a selective sodium channel blocker. Experiments were performed in pentobarbital-anesthetized and artificially ventilated rats. Two doses of TTX were tested for antiarrhythmic action: a low dose (low TTX, 10 micrograms/kg of bolus + infusion of 10 micrograms/kg/hr) which blocked only neuronal activity, and a high dose (TTXh, 50 micrograms/kg of bolus + infusion of 50 micrograms/kg/hr) which also produced signs of ventricular gNa blockade in normal hearts. To control for the decreases in blood pressure and heart rate caused by TTX, hexamethonium, nitroprusside and propranolol were also used. Only TTXh possessed antiarrhythmic activity in rats subjected to myocardial ischemia (produced by ligation of the left anterior descending coronary artery). Arrhythmia scores (mean, n = 9) were: saline, 3.8; hexamethonium, 3.8; nitroprusside, 3.2; nitroprusside + propranolol, 4.3; low TTX, 3.9; and TTXh, 0.9. Only TTXh reduced dV/dt max. of the action potential (recorded in vivo by means of 3 M KCl filled microelectrodes) as well as action potential height, and concomitantly prolonged the P-R and QRS intervals of normal hearts. In conclusion, our study demonstrated that drugs which produced hypotension, bradycardia and loss of autonomic function were not antiarrhythmic. On the other hand, the marked antiarrhythmic activity of TTXh appeared to depend upon ventricular gNa blockade. Thus, TTX provides a useful tool for examining the antiarrhythmic properties of ventricular gNa blockade.     

New approaches to the study of the mechanism of action of nitrates

The effects of nitrates on a Ca+2 increase and the content of cyclic nucleotides in human platelets were studied. Nitroglycerin (GTN), isosorbide dinitrate (ISDN) and sodium nitroprusside (NP) were found to inhibit dose-dependently the intracellular Ca+2 increase induced by the platelet activating factor (PAF). The inhibiting effect of NP was at lower concentrations than those of GTN and ISDN. GTN calcium blocking action did not change significantly regardless of vasopressin, serotonin or PAF used as inducers of the intracellular Ca+2 increase. GTN suppressed the PAF provoked Mn+2 entering into the cells. NP and GTN induced increase of the cGMP content correlated with their calcium blocking activity. They did not augment the level of cAMP. Methylene blue (MB), a guanylate cyclase and glutathione reductase inhibitor, decreased the calcium blocking effect of GTN and its influence on the cGMP content but failed to suppress the inhibitory effect of NP. Ascorbic acid increased the calcium blocking effect of NP but did not influence the inhibitory effect of GTN. An increase in Ca+2 content induced by PAF in platelets from patients with chronic congestive heart failure was significantly higher in the group with dilatation cardiomyopathy. The effect of 10 mg of ISDN sublingually on forearm venous tone was higher in patients with initially elevated venous tone. There was a direct statistical correlation between the IC50 of GTN calcium blocking effects in platelets and the elevation of a forearm venous tone reaction from a statistic mean reaction to ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin B12 levels in the prolonged use of sodium nitroprusside

Long-term (greater than 48 h) sodium nitroprusside (SNP) infusion significantly reduced cobalamin (vitamin B12) levels in 23 patients treated in a CCU after myocardial infarction. There was no evidence of vitamin B12 deficiency or SNP toxicity. Low vitamin B12 levels should not limit the use of SNP, because prolonged infusion of SNP at maximum doses of 2.5 micrograms/kg X min did not adversely affect hemodynamic stability.     

Cytochrome P-450 mediates bioactivation of organic nitrates.

The cellular mechanism of bioactivation underlying guanylate cyclase activation by organic nitrates was investigated. In cultured rat lung fibroblasts (RFL-6 cells), the inhibitor of cytochrome P-450 proadifen (0.1 mM) decreased cyclic GMP stimulation by glyceryl trinitrate (GTN, 1-100 microM) by up to 81%. Cyclic GMP stimulation by isoidide dinitrate was inhibited to a similar degree under these conditions. However, proadifen did not affect cyclic GMP stimulation by sodium nitroprusside that spontaneously releases nitric oxide. Cyclic GMP stimulation in RFL-6 cells by GTN remained unaltered in the presence of the inhibitor of glutathione S-transferase sulfobromophthalein. In the same cell type, a 24-hr pretreatment with the inducer of cytochrome P-450 3-methylcholanthrene (10 microM) augmented cyclic GMP stimulation by GTN or isoidide dinitrate by up to 102%. Cultured porcine aortic endothelial cells were found to be without a cyclic GMP response to GTN, although sodium nitroprusside produced a marked cyclic GMP elevation in these cells. The endothelial cells remained unresponsive to GTN even in the presence of N-acetylcysteine (5 mM). Moreover, in a cell-free preparation from rat liver, glutathione-dependent biotransformation of GTN was not accompanied by activation of soluble guanylate cyclase. These findings suggest that in intact cells bioactivation of, i.e., nitric oxide formation from organic nitrates is mediated by a cytochrome P-450 enzyme system rather than by glutathione S-transferase or free thiols.     

Role of renal nerves in excretory responses to exogenous and endogenous opioid peptides

The present study was designed to investigate opioid peptide-mediated changes in renal function in conscious Sprague-Dawley rats after administration of the native opioid agonist methionine enkephalin (ME), its synthetic analog D-Ala2-methionine enkephalinamide (DALA) and the opioid antagonist naloxone. Intravenous infusion of DALA (25 micrograms/kg/min) and ME (75 micrograms/kg/min) produced no changes in mean arterial pressure, heart rate, glomerular filtration rate or effective renal plasma flow in rats with intact or bilaterally denervated kidneys. In contrast, i.v. infusion of these opioid agonists produced differing effects on the renal excretion of water and sodium; DALA produced an increase in urinary flow rate and sodium excretion and ME produced a decrease in these parameters. Changes in renal sympathetic nerve activity were not involved in producing these effects as supported by measurements of renal sympathetic nerve activity and the finding that prior bilateral renal denervation did not alter the renal responses to either agonist. The renal excretory responses to both DALA and ME infusion were prevented by pretreatment with the opioid receptor antagonist naloxone, thus suggesting an opioid receptor-mediated effect of both agonists. Intravenous bolus injections of naloxone alone produced a dose-dependent diuresis and natriuresis without producing changes in systemic or renal hemodynamics or renal sympathetic nerve activity. These studies, therefore, provide evidence that the administration of opioid receptor agonists and antagonists produce changes in the renal excretion of water and sodium via an action on renal tubular reabsorptive mechanisms which are independent of changes in systemic or renal hemodynamics or renal sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of nitroglycerin to prevent arterial hypertension during general anesthesia using ketamine

Central hemodynamics was studied in 82 patients during surgery performed under various types of general intravenous ketamine anesthesia. Ketamine was shown to have a stimulating effect on hemodynamics both alone and in combinations with droperidol and diazepam. Single intravenous injection (0.25 mg) or drip infusion (0.3 micrograms/(kg.min) of nitroglycerin effectively prevented arterial hypertension, decreased peripheral vascular resistance and myocardial oxygen demand.     

A comparison of the hemodynamic effects of labetalol and sodium nitroprusside in patients undergoing carotid endarterectomy

The hemodynamic effects of labetalol and sodium nitroprusside were compared in 19 subjects who became hypertensive at the conclusion of elective carotid endarterectomy. Following randomization and standard anesthetic protocol, treatment was administered when blood pressure exceeded 160 mmHg systolic or 90 mmHg diastolic at the conclusion of surgery. Group 1 subjects (n = 9) received 0.25 mg/kg labetalol in divided doses, followed by repeat doses of 0.50 mg/kg until blood pressure was less than 160/90 mmHg or until they had received 300 mg total dose. Group 2 subjects (n = 10) were started on a nitroprusside infusion at 0.5 micrograms/kg/min, titrated to achieve blood pressure less than 160/90 mmHg, or up to a rate of 6.0 micrograms/kg/min. Data were collected at 15-minute intervals for 12 hours. Analysis with repeated measures analysis of covariance (p less than 0.05) found no significant differences between groups in any measured parameter. A significant time effect was found for both groups. The results suggest that labetalol is an effective alternative to nitroprusside for the management of postoperative hypertension in this patient population. For the majority of such patients, labetalol may be the drug of choice for postendarterectomy hemodynamic control.     

Effects of 1-epinephrine on hemodynamics and cardiac function in coronary disease: dose-response studies

To assess the effects of elevated epinephrine levels on cardiovascular performance in patients with coronary artery disease (CAD), epinephrine was infused intravenously into eight patients with normal coronary anatomy and 22 patients with CAD at dose rates of 0.06, 0.12, 0.18, and 0.24 micrograms/kg/min. Hemodynamic responses to epinephrine were not significantly different between the two groups. However, contractility increased significantly more (P less than 0.05) and end-systolic volume decreased significantly more (P less than 0.025) in normal subjects than in those with CAD. Plasma norepinephrine concentrations increased significantly (P less than 0.05) at 0.24 micrograms/kg/min epinephrine, indicating activation of sympathetic nervous system. Epinephrine ischemic thresholds ranged from 652 to 3362 pg/ml. Patients with CAD compared with normal subjects had more frequent ventricular arrhythmias (55% vs. 25%), chest pain (50% vs. 13%), and ischemic ECG changes (73% vs. 13%). These results indicate that although epinephrine induced myocardial ischemia in CAD, hemodynamics and ventricular pump function were maintained.     

Endothelial dysfunction in patients with recent myocardial infarction and hyperhomocysteinaemia: effects of vitamin supplementation

Hyperhomocysteinaemia is a prothrombotic condition that may cause oxidative endothelial injury and impair endogenous fibrinolysis. Vitamin supplementation enhances endothelial function in hyperhomocysteinaemic patients, but responses in patients with co-existing coronary artery disease have been variable. It is also unknown whether hyperhomocysteinaemia is associated with reduced fibrinolytic responses in patients with coronary artery disease. The study aims were to test the hypothesis that patients with recent myocardial infarction and hyperhomocysteinaemia have impaired endothelium-dependent vasomotion and fibrinolysis that is rectified by vitamin supplementation. From a cohort of 120 patients admitted with acute myocardial infarction, 18 patients were recruited from the upper (n=9) and lower (n=9) plasma homocysteine quartiles into a randomized double-blind placebo-controlled crossover trial. Following a 4-week course of placebo or folate/cyanocobalamin/pyridoxine supplements, FBF (forearm blood flow) was measured using venous occlusion plethysmography during intra-arterial substance P (4-16 pmol/min), acetylcholine (5-20 microg/min) and sodium nitroprusside (2-8 microg/min) infusions. All vasodilators caused dose-dependent increases in infused FBF (P<0.05). Patients in the upper homocysteine quartile (16.8+/-2.9 compared with 7.9+/-0.7 micromol/l; P=0.003) had reduced vasodilatation to acetylcholine (P=0.01) and substance P (P<0.05), but not sodium nitroprusside. There were no differences in substance P-induced tissue plasminogen activator release. Vitamin supplementation increased serum folate and vitamin B12 concentrations (P<0.05), but did not significantly lower homocysteine, or affect FBF or fibrinolytic responses. In patients with recent myocardial infarction, hyperhomocysteinaemia is associated with impaired endothelium-dependent vasodilatation, but no alteration in the acute fibrinolytic capacity. This endothelial vasomotor dysfunction is unaltered by vitamin supplementation.     

Comparison of calcium channel inhibitors on vagal heart rate responses elicited by arterial baroreceptor reflexes in anesthetized dogs

Actions of the calcium channel inhibitors, nimodipine, nifedipine, verapamil and diltiazem, and the direct-acting vasodilator, sodium nitroprusside, were compared on baroreceptor reflex-induced bradycardia elicited by pressor responses produced by norepinephrine and on reflex-induced tachycardia elicited by the hypotensive responses to acetylcholine in alpha-chloralose anesthetized dogs. Beta adrenoceptor blockade with propranolol was maintained throughout the experiments to assure that the cardiac reflexes were vagal in origin. The reflex vagal bradycardic ratio (-delta heart rate/+delta blood pressure) elicited by norepinephrine-induced pressor responses was reduced dose-dependently by nimodipine (0.1-1.0 micrograms/kg/min i.v.) and diltiazem (3.0-30 micrograms/kg/min i.v.) at 20 min after starting each dose and by verapamil (100 micrograms/kg i.v. loading dose plus 1.0-30 micrograms/kg/min i.v.) at 10 min after each dose. In contrast, nifedipine (0.1-3.0 micrograms/kg/min i.v. at 20 min) and sodium nitroprusside (3.0-20 micrograms/kg/min i.v. at 20 min) did not inhibit the bradycardic ratio. Resting mean arterial blood pressure was reduced similarly by all of the agents and tonic heart rate was essentially unchanged. Studies on the site of action revealed that nimodipine (0.3 and 1.0 micrograms/kg/min i.v. at 20 min) attenuated the reflex vagal bradycardia evoked by pressure elevations in the isolated carotid sinus, but did not change the reflex responses elicited by electrical stimulation of afferent fibers in the carotid sinus nerve. The reflex tachycardic ratio (+ delta heart rate/-delta blood pressure) evoked by acetylcholine-induced hypotensive responses was reduced in a dose-related fashion by all of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelin-I-mediated vasoconstriction: specific blockade by verapamil.

The capacity of three vasodilators that act by distinct mechanisms to reverse endothelin-I-mediated vasoconstriction was studied in 11 healthy nonsmoking male subjects (mean age +/- SEM, 26 +/- 2 years; mean weight +/- SEM, 74 +/- 2 kg) by use of brachial artery infusion and forearm strain-gauge plethysmography. Isoproterenol (cyclic adenosine monophosphate-mediated vasodilation), sodium nitroprusside (cyclic guanosine monophosphate-mediated vasodilation), and verapamil (L-type calcium channel blocker) were compared for capacity to reverse endothelin-I-mediated increase in forearm vascular resistance (FVR). Endothelin-I infusion increased FVR 1.9-fold in the control state. Isoproterenol infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable isoproterenol infusion rates, endothelin-I increased FVR similar to the control state (for 5 ng/min isoproterenol, endothelin-I increased FVR 1.85-fold; for 12.5 ng/min isoproterenol, endothelin-I increased FVR 2.03-fold). Similarly, sodium nitroprusside infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable sodium nitroprusside infusion rates the endothelin-I increase in FVR was similar to control (for 0.48 micrograms/min sodium nitroprusside, endothelin-I increased FVR 1.89-fold; for 0.96 micrograms/min sodium nitroprusside, endothelin-I increased FVR 2.36-fold). In contrast, verapamil infusion decreased FVR with or without endothelin-I infusion. At a verapamil infusion rate of 19.1 microns/min, endothelin-I increase in FVR was comparable to control (for 19.1 microns/min verapamil, endothelin-I increased FVR 1.36-fold, less than the 1.0-fold increase in the control state; p < 0.05). Isoproterenol and sodium nitroprusside decreased FVR during concurrent endothelin-I infusion but did not reverse the endothelin-I effect. In contrast, verapamil reversed endothelin-I--induced vasoconstriction to control FVR, suggesting a specific antagonism of endothelin-I--mediated increase in FVR.     

Characteristics of the action of strophanthin on central hemodynamics, pulmonary and intrahepatic blood circulation and myocardial contraction

The effects of strophanthin treatment given in courses on the central hemodynamics, pulmonary, intrahepatic circulation and myocardial contractility were studied in 97 patients with decompensated chronic cor pulmonale depending on the hemodynamic type of circulation. In patients with CNPD and circulatory failure having the hypokinetic circulation, the treatment with strophanthin brought about improvement of the pulmonary and hepatic hemodynamics, increase in myocardial contractility, reduction of congestion. This may be accounted for by an elevation of the MOS, removal of the peripheral spasm on the part of the vascular system, elimination of prolonged venous congestion in the lungs and liver, and improvement of arterial blood flow in these organs. It was shown that in patients with hyperkinetic circulation, administration of strophanthin has an untoward effect on the hemodynamics in the lungs, liver and heart, thereby maintaining and increasing myocardial hyperfunction and venous hypervolemia. The data obtained indicate that it is inadvisable to prescribe strophanthin at early stages of the decompensated chronic cor pulmonale in patients with hyperkinetic circulation.     

Comparison of Nitroglycerin-, Nitroprusside-, and Phentolamine-Induced Changes in Coronary Collateral Function in Dogs

The recent use of vasodilators to improve ventricular function in acute myocardial infarction led us to investigate the effects of nitroglycerin, nitroprusside, and phentolamine on coronary collateral flow. Dogs were studied 2-4 wk after an ameroid constrictor was placed around the left anterior descending (LAD) coronary artery. Retrograde flow and peripheral coronary pressure were measured from a cannula inserted in the LAD distal to the ameroid. Systemic arterial pressure was held constant by an aortic cuff. When administered intracoronary (i.c.), nitroglycerin, 0.3-100 mug/min, or nitroprusside, 3-100 mug/min, produced quantitatively similar, dose-dependent increases in retrograde flow. Neither drug, i.c., changed peripheral coronary pressure. Nitroglycerin, 3-300 mug/min, intravenous (i.v.), produced dose-dependent increases in retrograde flow; nitroprusside, i.v., increased retrograde flow only in high doses (100-300 mug/min). Nitroglycerin and nitroprusside, i.v., produced similar increases in peripheral coronary pressure. Phentolamine, 1-300 mug/min, i.v., decreased retrograde flow, and did not change peripheral coronary pressure. Nitroprusside was considerably more potent than nitroglycerin in decreasing systemic arterial pressure and in reducing total coronary resistance. Thus, (a) although i.c. nitroglycerin and nitroprusside produce similar effects on collateral function, i.v. nitroglycerin is more effective than i.v. nitroprusside in augmenting collateral flow; (b) phentolamine has deleterious effects on collateral function; and (c) the relative vasodilator potencies of nitroglycerin and nitroprusside vary in different vascular beds; thus, for a given reduction in systemic arterial pressure, nitroprusside is less effective in increasing retrograde flow.