Nitroprusside infusion in experimental acute myocardial infarction with systemic hypertension: effects on systemic hemodynamics and regional myocardial blood flows

The effects of graded doses of nitroprusside on regional myocardial blood flow were studied in awake, acutely hypertensive dogs with acute myocardial infarction. Acute systemic hypertension was produced by infusing a mixture of norepinephrine and epinephrine for 80 minutes after coronary artery occlusion. The increase in aortic pressure produced by catecholamine infusion was accompanied by increases in heart rate, left ventricular (LV) end-diastolic pressure, first derivative of LV pressure (dP/dt), dP/dt at an LV developed pressure of 50 mm Hg (dP/dt/P) and pressure-rate product, but total peripheral vascular resistance did not change significantly. Two graded doses of nitroprusside were then infused, each for 25 minutes, beginning 30 minutes after the onset of coronary artery occlusion. The smaller dose of nitroprusside returned aortic pressure to control levels and significantly reduced total peripheral vascular resistance and LV end-diastolic pressure, but did not affect cardiac output, heart rate, LV dP/dt, dP/dt/P and pressure-rate product. Regional blood flow increased to both the ischemic and normal myocardium. The larger dose of nitroprusside further reduced aortic pressure and total peripheral vascular resistance and LV end-diastolic pressure and significantly increased heart rate and cardiac output. However, LV dP/dt, dP/dt/P and pressure-rate product remained unchanged. Regional blood flow to normal myocardium increased, but the increase in ischemic endocardial blood flow produced by the smaller dose of nitroprusside was no longer significant when the larger dose was administered. These changes were not produced by administration of normal saline solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preserved cardiac beta-adrenergic sensitivity in early renovascular hypertension

To determine the mechanism of blunted sympathetic reflex responses in early renovascular hypertension, we measured inotropic and chronotropic responses of the heart to beta-adrenergic stimulation in vivo and myocardial beta-adrenergic receptor number and adenylate cyclase activity in 10 dogs during an early stage of one-kidney renal hypertension. Mean aortic pressure was higher in the hypertensive dogs (152 +/- 4 mm Hg) than in eight sham-operated dogs (122 +/- 1 mm Hg; p less than 0.001), but heart rate, cardiac output, and left atrial pressure did not differ between the two groups. Blood pressure reduction with a direct-acting vasodilator, pinacidil, resulted in marked increases in heart rate (+97 +/- 12 beats/min) and rate of change of left ventricular pressure (dP/dt; +1447 +/- 367 mm Hg/sec) in normotensive dogs but only blunted heart rate (+54 +/- 12 beats/min) and minimal left ventricular dP/dt (+376 +/- 264 mm Hg/sec) responses in hypertensive dogs. In contrast, intravenously administered isoproterenol produced similar increases in heart rate and left ventricular dP/dt in the two groups. These two groups also did not differ in either left ventricular beta-adrenergic receptor number and affinity or basal, isoproterenol-stimulated, and fluoride-stimulated adenylate cyclase activity. Thus, despite blunted reflex responses to blood pressure reduction, hypertensive dogs showed neither reduction in chronotropic and inotropic responses to direct beta-adrenergic stimulation nor beta-adrenergic desensitization of the myocardium, as assessed by beta-adrenergic receptor number and adenylate cyclase activity. Blunted reflex responses in this model of early hypertension must be due to factors operating at some locus other than the beta-adrenergic receptor-adenylate cyclase complex.     

The role of endogenous opioids in congestive heart failure: effects of nalmefene on systemic and regional hemodynamics in dogs

We studied the role of endogenous opiates and their interrelationships with the sympathetic nervous system in an experimental preparation of right-sided congestive heart failure (CHF) produced by surgical tricuspid avulsion and progressive pulmonary arterial constriction. Three groups of dogs with CHF and one group of sham-operated dogs were studied. One group of dogs with CHF was given normal saline as pretreatment, while the other two groups were pretreated with either propranolol alone (beta-blockade) or propranolol plus prazosin (alpha- plus beta-blockade). CHF was characterized by weight gain, ascites, elevated right atrial pressure, tachycardia, and reduced cardiac output. Compared with sham-operated animals, animals with CHF exhibited significantly higher baseline levels of plasma beta-endorphin and cortisol. Furthermore, only the animals with CHF responded to the opiate receptor-antagonist nalmefene with significant increases in plasma beta-endorphin, cortisol, and adrenocorticotropic hormone. Administration of nalmefene increased aortic blood pressure, cardiac output, left ventricular dP/dt and dP/dt/P, and blood flow to the myocardium, skeletal muscle, and kidneys in dogs with CHF, but had no appreciable effects in sham-operated dogs. beta-Receptor blockade abolished the increase in cardiac output, left ventricular performance, and blood flow produced by nalmefene, but had no effect on the pressor response to nalmefene. The increase in mean aortic pressure in the beta-blockade group was accompanied by an increase in skeletal muscle vascular resistance. Addition of prazosin in the alpha- plus beta-blockade group abolished the increases in mean aortic pressure and skeletal muscle vascular resistance, suggesting that the changes after propranolol probably resulted from unmasking of alpha-receptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

BACKGROUND. The reductions of myocardial beta-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by beta-receptor blockade. METHODS AND RESULTS. We administered the oral beta-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of beta-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure. CONCLUSIONS. Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.     

Consequences of reperfusion after coronary occlusion. Effects on hemodynamic and regional myocardial metabolic function

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion.These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.     

Effects of altered site of electrical activation on myocardial performance during inotropic stimulation

The effects of altering the site of electrical activation on responses to isoproterenol (ISO) and treadmill exercise were examined in mongrel dogs instrumented for long-term measurement of left ventricular pressure, left ventricular dP/dt, coronary blood flow, cardiac output, left ventricular diameters, and mean arterial pressure and O2 content in the coronary sinus and aorta. During spontaneous rhythm, 0.2 micrograms/kg/min ISO increased heart rate by 90 +/- 7 beats/min, left ventricular dP/dt by 2479 +/- 301 mm Hg/sec, cardiac output by 3.5 +/- 0.9 liters/min, coronary blood flow by 30.4 +/- 3.9 ml/min, and myocardial oxygen consumption (MVO2) by 3.91 +/- 0.84 ml/min. During right atrial pacing at 193 +/- 7 beats/min, the effects of ISO were not different from the effects during spontaneous rhythm, with the exception of a lesser increase in coronary blood flow and lesser reductions in coronary resistance and left ventricular end-diastolic diameter and pressure. During right ventricular pacing at an identical rate, ISO increased left ventricular dP/dt (1140 +/- 158 mm Hg/sec) and cardiac output (2.2 +/- 0.5 liters/min) significantly less (p less than .025) than during either sinus rhythm or right atrial pacing, while MVO2 rose to a higher value. During right ventricular pacing the changes in mean arterial pressure and left ventricular end-diastolic diameters with ISO were not significantly different from those during right atrial pacing. Treadmill exercise induced significantly smaller (p less than .025) increases in left ventricular dP/dt during right ventricular pacing as compared with during either right atrial pacing or sinus rhythm, while MVO2 rose to a higher value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adverse hemodynamic effects of intravenous disopyramide compared with quinidine in conscious dogs.

Disopyramide resembles quinidine electrophysiologically, but its effect on left ventricular function has not been clarified. Twelve awake dogs were instrumented for measurement of cardiac output, left ventricular pressure and its maximal first derivative (dP/dt max), and left atrial and aortic pressures. Disopyramide or quinidine at identical, clinically relevant doses (1 and 5 mg/kg i.v.) was infused over 5 minutes at each level. Peak changes after disopyramide 1 mg/kg included increases in heart rate (34%), mean aortic pressure (24%) and systemic vascular resistance (33%), and decreases in stroke volume (16%) and dP/dt max (19%). With disopyramide at 5 mg/kg these changes were of greater magnitude (e.g., dP/dt -- 36%). Quinidine at both doses caused no changes except a 13% decrease in vascular resistance at 5 mg/kg. Heart rate with disopyramide increased after propranolol (1 mg/kg i.v.), was unchanged after atropine (0.1 mg/kg i.v.), and slowed after propranolol and atropine. Phenoxybenzamine (2 mg/kg i.v.) did not prevent the rise in systemic vascular resistance produced by disopyramide. Thus, disopyramide in clinical dosages exerts opposing direct and indirect effects on cardiac pacemakers and, unlike quinidine, is a potent myocardial depressant and vasoconstrictor in the conscious dog.     

Comparative studies of the systemic hemodynamics and myocardial oxygen consumption of FRC 8653, a new Ca++ channel blocker, and nifedipine in anesthetized dogs.

Effects of FRC 8653, a new dihydropyridine derivative, on regional blood flow, cardiac function and myocardial oxygen consumption were examined and compared with those of nifedipine in anesthetized open-chest dogs. Intravenous administration of FRC 8653 at doses of 1, 3 and 10 micrograms/kg dose-dependently decreased aortic pressure and increased aortic, vertebral and coronary blood flow similar to nifedipine. No significant change was observed in left ventricular end-diastolic pressure, left ventricular positive dP/dt and heart rate following i.v. administration of FRC 8653. Myocardial oxygen consumption was dose-dependently decreased by FRC 8653. When changes in mean aortic pressure and aortic and coronary blood flow were compared at the same dose of 10 micrograms/kg i.v., both FRC 8653 and nifedipine showed almost the same degree of reduction of mean aortic pressure, but the time from drug administration to peak responses and the duration for which half the maximal effects were maintained, were significantly longer with FRC 8653 than nifedipine. Results suggest that FRC 8653 may be useful for the treatment of patients with hypertension and ischaemic heart disease.     

Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis

Experimental renovascular hypertension or supravalvular aortic constriction results in left ventricular hypertrophy and impaired minimum coronary vascular resistance. However, these experimental models expose the coronary arteries to increased intra-arterial pressure, so that hypertensive vascular changes might be responsible for the impaired minimum coronary resistance. This study was performed to test the hypothesis that left ventricular hypertrophy in the absence of increased coronary pressure results in abnormalities of myocardial perfusion. Aortic valve stenosis was produced by plication of the noncoronary aortic cusp of 11 dogs at 6-8 weeks of age. Studies were carried out when the animals reached adulthood; mean left ventricular:body weight ratio was 7.1 +/- 0.4 as compared to 4.4 +/- 0.3 g/kg in 11 normal dogs (P less than 0.01). Under quiet resting conditions, myocardial blood flow measured with microspheres was significantly greater than normal in dogs with aortic stenosis. However, during maximum coronary vasodilation with adenosine, mean left ventricular blood flow in dogs with hypertrophy (3.29 +/- 0.39) was substantially less than in normal dogs (6.19 +/- 0.54 ml/min per g; P less than 0.01), whereas minimum coronary resistance was increased from 14.1 +/- 1.7 in normal dogs to 23.7 +/- 5.4 mmHg. min X g/ml (P less than 0.01). To examine the response of myocardial perfusion to cardiac stress, blood flow was measured during pacing at 200 and 250 beats/min. Compared with normal dogs, animals with hypertrophy had a subnormal increase in myocardial blood flow during tachycardia; this perfusion deficit was most marked in the subendocardium. These data demonstrate that left ventricular hypertrophy alone, without increased coronary artery pressure, is associated with impaired minimum coronary vascular resistance and with abnormalities of myocardial blood flow during pacing stress.     

Effects of an inotropic agent, RO 2-2985 (X-537A), on regional blood flow and myocardial function in chronically instrumented conscious dogs and anesthetized dogs.

RO 2-2985 produced a marked positive inotropic effect in unanesthetized, chronically instrumented dogs, measured as an increase in left ventricular dP/ dt and an increase in maximum velocity of myocardial fiber shortening. Similar changes produced in dogs in hemorrhagic shock lasted for 2-3 hours. RO 2-2985 increased peripheral blood flow and caused marked increases in both coronary and renal blood flows. The drug altered the response of the renal vascular bed to subsequent norepinephrine administration. After administration of a single dose of RO 2-2985, norepinephrine produced sustained increases in renal blood flow, and this altered responsiveness to norepinephrine persisted for periods ranging from 1 to 3 weeks.     

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.     

Reflex control of coronary vascular tone by cardiopulmonary receptors in humans

To examine whether cardiopulmonary receptors participate in the reflex control of coronary vascular resistance, systemic and coronary hemodynamics were assessed before and during -10 mm Hg lower body negative pressure in eight normal subjects and eight hypertensive patients with left ventricular hypertrophy. In both study groups, lower body negative pressure induced a significant decrease in right atrial pressure, left ventricular filling pressure and cardiac output, an increase in systemic vascular resistance and no change in mean arterial pressure and heart rate. In normal subjects, there was also a significant increase in plasma norepinephrine concentration (from 294 +/- 39 to 421 +/- 47 pg/ml, p less than 0.01). This increase was accompanied by a reduction in coronary blood flow, assessed by the continuous thermodilution method (from 101 +/- 5 to 79 +/- 4 ml/min, p less than 0.05). An increase in coronary vascular resistance (from 0.865 +/- 0.1 to 1.107 +/- 0.1 mm Hg/ml per min, p less than 0.05) and in myocardial oxygen consumption was detected in normal subjects during cardiopulmonary baroreceptor unloading. In contrast, in hypertensive patients, -10 mm Hg lower body negative pressure failed to induce any change in plasma norepinephrine, coronary blood flow or vascular resistance. Intravenous propranolol administration caused no significant change in the systemic hemodynamic response to -10 mm Hg lower body negative pressure in either study group, but it did abolish the decrease in coronary flow and the increase in plasma norepinephrine, coronary vascular resistance and myocardial oxygen consumption observed in normal subjects in control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and coronary effects of intravenous verapamil in coronary insufficiency

Verapamil inhibits calcium influx through the slow calcium canals. The coronary an haemodynamic effects of intravenous Verapamil were studied in 8 patients with chronic coronary insufficiency documented by coronary arteriography. The following measurements were made in spontaneous rhythm and during atrial pacing under basal conditions and 10 minutes after intravenous Verapamil (0.10 to 0.17 mg/kg) relayed with a continuous infusion of 5 x 10(-3) mg/Kg/mn: heart rate, cardiac output, left ventricularr pressure (Millar 5 F micromanometer), femoral artery pressure, coronary sinus flow by continuous thermodilution, oxygen and lactate concentrations in arterial and arterio-venous oxygen difference, and index of myocardial oxygen consumption and the coefficient of lactate extraction were then calculated. The coronary and haemodynamic effects of atrial pacing were similar before and after Verapamil at a given rate. Left ventricula end diastolic pressure decreased, cardiac output and total systemic resistance were unchanged, dP/dt max increased but to a lesser degree after Verapamil (P less than 0.05). Coronary arterio-venous oxygen difference decreased after Verapamil. The coronary and haemodynamic effects of Verapamil were similar in spontaneous rhythm and during atrial pacing. In spontaneous rhythm, the heart rate and left ventricular end diastolic pressure increased. In spontaneous and paced rhythm, femoral artery pressure, total systemic resistance and dP/dt max decreased. Cardiac output remained the same. Myocardial oxygen consumption decreased mainly because of a reduced coronary arterio-venous oxygen difference and because of unchanged coronary flow in spontaneous rhythm oxygen consumption seems to have a favourable effect on the myocardial energy equilibrium as shown by the increased coefficient of lactate extraction during atrial pacing after Verapamil. This study shows the negative inotropic and arterial vasodilator effects of Verapamil to be responsible for the reduced myocardial oxygen consumption. It also caused coronary artery vasodilation.     

Left ventricular failure induced by long-term hypertension in rats

To determine whether the duration of hypertension is an essential component in the evolution of myocardial dysfunction, renal artery constriction was performed in male Fischer 344 rats at 4 months of age, and in vivo global cardiac performance of sham-operated and experimental animals was evaluated 8 months later. Systemic arterial blood pressure increased to 173 +/- 5 mm Hg 2 weeks after the arteries were clipped and remained elevated for the following 5 months. Blood pressure decreased over the remaining 3 months to a value not significantly different from control rats that were killed, 132 +/- 4 mm Hg. After 8 months of renovascular hypertension, we observed that the elevated level of systolic arterial pressure was accompanied by a distinct absence of left ventricular hypertrophy when measured at the ventricular weight level. Moreover, left ventricular end-diastolic pressure increased in hypertensive animals from 6.0 to 24.0 mm Hg while peak left ventricular pressure was identical to controls. In addition, peak +dP/dt and -dP/dt were depressed in hypertensive animals. Although stroke volume was unaltered, cardiac output in renal artery clipped animals was depressed by 34% while total peripheral resistance was elevated by 50%. Ventricular chamber remodeling in the hearts of hypertensive animals was evidenced as a 19% increase in the transverse and a 16% increase in the longitudinal axes of the left ventricle with a 27% diminution of wall thickness. Myocardial damage, in the form of myocyte loss and replacement fibrosis, increased in the hearts of hypertensive animals resulting in a ninefold augmentation in the volume fraction of collagen within the ventricular wall. These alterations in the architectural properties of chamber geometry coupled with the abnormalities in contractile performance resulted in a severe reduction in ejection fraction from 82% to 47% and a marked elevation in transmural diastolic and systolic stress in hypertensive animals. The gradient in stress across the ventricular wall, from epicardium to endocardium, revealed a direct correlation with the regional distribution of myocardial damage. In conclusion, the loading state of the myocardium, tissue injury, and myocardial fibrosis all appear to be critical determinants in the genesis of left ventricular failure in long-term pressure overload.     

Disparate effects of substance P on systemic and coronary beds in conscious dogs.

BACKGROUND. Previous studies in anesthetized animals indicated that substance P is a coronary and peripheral vasodilator. However, coronary vasodilation was only transient perhaps because of tachyphylaxis. In the present study, the steady-state effects of intravenous substance P on systemic and coronary beds were investigated in conscious, instrumented dogs. METHODS AND RESULTS. With intact autonomic reflexes, 5 ng/kg/min i.v. substance P resulted in increases (p less than 0.01) in cardiac output by 22 +/- 5%, in decreases (p less than 0.01) in mean arterial pressure by 9 +/- 2%, and in total peripheral resistance by 23 +/- 4% 7-9 minutes after the beginning of substance P infusion. Heart rate increased (p less than 0.01) by 35 +/- 7% and left ventricular dP/dt (p less than 0.05) by 13 +/- 4%. In this situation, coronary blood flow decreased (p less than 0.01) by 19 +/- 4% and coronary vascular resistance increased (p less than 0.05) by 13 +/- 5%. Myocardial oxygen delivery was reduced (p less than 0.05) by 13 +/- 5% and the arteriovenous oxygen difference widened (p less than 0.01). After ganglionic blockade, increases in cardiac output, heart rate, and left ventricular dP/dt with substance P administration were abolished, but total peripheral resistance and mean arterial pressure decreased (p less than 0.01) by 12 +/- 3% respectively. Under these conditions, coronary blood flow decreased (p less than 0.01) by 37 +/- 5% and coronary vascular resistance increased (p less than 0.01) by 47 +/- 8%, which were more (p less than 0.01) than control responses. In this situation, myocardial oxygen delivery was reduced (p less than 0.01) by 37 +/- 4% and the arteriovenous oxygen difference widened (p less than 0.01). Intracoronary infusion of substance P (0.4 ng/kg/min) resulted in significant and sustained decreases in coronary blood flow, which were similar before and after ganglionic blockade. CONCLUSIONS. Thus, in conscious dogs, systemic vasodilation is the prevailing effect of substance P, but paradoxically, this peptide simultaneously elicits coronary vasoconstriction.     

Effects of Neuropeptide Y on Cardiac Performance and Renal Blood Flow in Conscious Normotensive and Renal Hypertensive Rabbits

The effects of neuropeptide Y (NPY, 10 ug/kg bolus iv) on cardiac output, renal blood flow and myocardial contractility were determined in intact renal hypertensive and normotensive rabbits instrumented with ultrasonic flow transducers or left ventricular catheters.

The basal plasma concentration of NPY-like immunoreactivity in arterial blood was greater in the hypertensive rabbits (4.2 ± 0.7 ug/1) than in normotensive animals (2.2 ± 0.4 ug/l, p < 0.05). There were similar moderate increases in arterial blood pressure and total peripheral resistance following NPY, but a small NPY-induced reduction in cardiac output in normotensive rabbits was not seen in hypertensive animals. Resting peak left ventricular dP/dt (an index of myocardial contractility) was higher in hypertensive rabbits (73972 ± 619 vs 5551 ± 2342 mmHg/sec, p < 0.05), but there was no significant difference between the maximum NPY-induced falls in peak dP/dt.

NPY produced significant peak reductions in renal blood flow in both hypertensive (from 2.5 ± 0.2 to 1.22 ± 0.2 kHz, p < 0.05) and in normotensive rabbit groups (from 2.2 ± 0.1 to 0.3 ± 0.1 kHz, p<0.05), but the fall in renal blood flow and the corresponding rise in renovascular resistance were smaller in the hypertensive animals (p < .0 5). The cause of this apparent decrease in renovascular reactivity in the renal hypertensive model was not determined.     

Effects of nifedipine on the hemodynamic response to clamping and declamping of the abdominal aorta in dogs

Clamping and declamping of the infrarenal abdominal aorta may adversely affect cardiovascular function, particularly in the presence of heart disease. This effect may be further altered by drugs used in the treatment of symptomatic coronary artery disease. The effect of nifedipine on the hemodynamic response to aortic clamping and declamping was determined in 12 dogs anesthetized with 50% nitrous oxide and 0.6% end-tidal isoflurane and monitored with aortic, left ventricular (LV), and thermodilution pulmonary artery catheters. Six dogs received a nifedipine bolus of 100 μg/kg followed by an infusion of 4 /gmg/kg/min. Six dogs did not receive any nifedipine and served as controls. Before clamping, nifedipine produced immediate decreases in arterial pressure, systemic vascular resistance (SVR), and LV dP/dt, and a modest increase in cardiac output (CO). During aortic clamping, nifedipine-treated dogs demonstrated marked increases in heart rate (HR), dP/dt, and CO while maintaining a low SVR. There were no significant changes upon declamping. The nifedipine-treated animals maintained a high CO and low SVR. Thus, nifedipine greatly altered the hemodynamic responses to aortic clamping and declamping. Awareness of these alterations is important when caring for patients being treated with nifedipine who are undergoing aortic surgery.     

Effect of 8-bromo-cyclic guanosine monophosphate (cGMP) on coronary artery constriction in isolated rabbit hearts

The vasodilator 8-bromo-guanosine 3':5'-monophosphate (8-bromo-cGMP) effectively counteracts vasopressin-induced coronary artery constriction in a supported perfused working rabbit heart. In this preparation, the coronary arteries remain in contact with the beating heart. The obtuse marginal artery and portions of the left anterior descending coronary artery were deprived of endothelium. Perfusion was carried out with Krebs-Henseleit solution, oxygenated with a disposable infant oxygenator. The internal diameter of large coronary arteries was determined by color arteriography (injection of patent blue dye and gated photography). The effect of vasopressin with and without the addition of 8-bromo-cGMP on cardiac performance (cardiac output, left ventricular systolic pressure, left ventricular end-diastolic pressure, maximal rate of rise in left ventricular pressure [dP/dtmax], mean aortic pressure) and large coronary vessel and total coronary vascular resistance was determined in nine experiments. In addition, changes in coronary sinus partial pressure of carbon dioxide (PCO2) and pH were observed. Vasopressin alone caused a significant decline in coronary flow, myocardial oxygen consumption and coronary sinus pH. Cardiac performance declined, probably because of myocardial ischemia. Large coronary vessel and total coronary vascular resistance rose. The vasodilator 8-bromo-cGMP strongly inhibited the vasoconstrictor action of vasopressin, counteracted the increase in large and total coronary vascular resistance, prevented the fall in myocardial oxygen consumption and eliminated changes in pH or PCO2 of coronary sinus effluent. Because of the elimination of myocardial ischemia by 8-bromo-cGMP, cardiac performance was normalized.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of brief myocardial ischemia on sympathetic coronary vasoconstriction.

The purpose of the present study was to determine whether sympathetic coronary vasoconstrictor responses are altered after brief ischemia and reperfusion. Adult mongrel dogs were anesthetized and instrumented for measurements of heart rate, arterial pressure, left ventricular pressure, left ventricular dP/dt, anterior myocardial wall thickening, and left circumflex coronary artery (LCX) and left anterior descending coronary artery (LAD) blood flow velocities. Changes in coronary vascular resistance were recorded during intravenous bolus doses of norepinephrine and bilateral electrical stimulation of the stellate ganglia. After beta-adrenergic blockade and bilateral vagotomy, electrical stimulation of the stellate ganglia increased coronary vascular resistance in the LAD and LCX beds by 38 +/- 5% and 39 +/- 5%, respectively. After a 15-minute LAD occlusion, repeat electrical stimulation produced increases in coronary resistance of 16 +/- 3% and 45 +/- 8%, respectively (p less than 0.05 for the LAD before versus after the occlusion). The peak increase in coronary vascular resistance to two doses of norepinephrine was unchanged. After a shorter period of myocardial ischemia (7 minutes), similar increase in coronary resistance to stellate stimulation were observed before (27 +/- 4%) and after (26 +/- 6%) myocardial ischemia. The mechanism of this impaired sympathetic coronary vasoconstriction was further tested by examining the responses to bretylium and tyramine. Brief ischemia did not alter the coronary constrictor responses to either bretylium or tyramine, suggesting that mechanisms governing prejunctional release of norepinephrine are intact in the postischemic coronary arterial bed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact dogs with prolonged coronary artery occlusion.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact, unsedated dogs with myocardial infarction resulting from chronic occlusion of the proximal left anterior descending coronary artery was studied. tmannitol given to increase serum osmolality 20 mOsm increased regional myocardial blood flow to that portion of the left ventricle supplied by the occluded left anterior descending coronary artery by 22 +/- 2.8% (1.06 +/- 0.19 to 1.36 +/- 0.23 ml/min with g-1) without changing the inner:outer wall flow ratio. Mannitol also significantly increased regional myocardial blood flow to other areas of the left ventricle and the ventricular septum. Mean aortic pressure, maximal LV dP/dt, LV dP/dt/P, and cardiac output also increased significantly after mannitol. Thus hypertonic mannitol increases regional myocardial blood flow and ventricular performance in the awake, unsedated dog with prolonged occlusion of the proximal left anterior descending coronary artery. The increase in regional myocardial blood flow after mannitol under these circumstances probably is at least in part secondary to the increase in blood pressure and contractility. The increases in regional myocardial blood flow after mannitol in this study are less impressive than those that have been previously reported in the setting of either no myocardial ischaemia or acute myocardial ischaemia; this is probably due to the vasodilatation that chronic myocardial ischaemia itself produces in the canine heart.