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Biomedical subjects

S F Vatner

Publications and source records attributed to S F Vatner.

At least 199 records · Page 11Linked to original sources
PubMed1982

Myocardial function in areas of heterogeneous perfusion after coronary artery occlusion in conscious dogs.

Regional myocardial function and blood flow in endocardial layers were correlated in myocardial segments subtending severely ischemic and adjacent, normally perfused myocardium in conscious dogs 1--3 weeks after recovery from coronary artery occlusion. With coronary artery occlusion induced by a hydraulic occluder, endocardial blood flow (measured with radioactive microspheres) and function (determined with an ultrasonic dimension gauge) in homogeneously nonischemic segments increased slightly but not significantly. In homogeneously ischemic segments, blood flow and function decreased (p less than 0.01) by 96 +/- 1% and 98 +/- 4%, respectively. In segments subtending zones of unequal perfusion, endocardial blood flow increased nonsignificantly in the myocardium surrounding the nonischemic crystal, while decreasing by 93 +/- 2% (p less than 0.01) in myocardium surrounding the ischemic crystal. Surprisingly, these segments behaved like homogeneously ischemic segments, i.e., endocardial shortening decreased by 92 +/- 6% (p less than 0.01). Thus, the failure to detect shortening despite normal perfusion of the myocardium surrounding one of the transducers suggest a potential problem with interpretation of regional function measurements or an inability of the apparently nonischemic myocardium to contract.

Acute Disease↗
PubMed1982

Regulation of large coronary arteries by beta-adrenergic mechanisms in the conscious dog.

We examined, in conscious dogs, the effects of beta-adrenergic stimulation on measurements of left circumflex coronary arterial diameter and blood flow and on calculations of late diastolic coronary resistance (LDCR) and left circumflex coronary internal cross-sectional area (CSA). Isoproterenol (0.1 microgram/kg) initially decreased mean arterial pressure by 25 +/- 2% (mean +/- SEM), and LDCR by 62 +/- 4%, and increased heart rate by 82 +/- 10%, left ventricular (LV) dP/dt by 79 +/- 12%, and mean coronary blood flow by 85 +/- 5%, while CSA rose slightly. The peak effects on CSA (24 +/- 2%) occurred later, along with decreases in mean arterial pressure (7.4 +/- 1.0%) and LDCR (25 +/-5.3%) and increases in coronary blood flow (14 +/- 2%), LV dP/dt (12 +/- 3%), and heart rate (24 +/- 4%). Pirbuterol (1.0 microgram/kg) induced changes that were qualitatively similar to those induced by isoproterenol. Prenalterol (20 micrograms/kg), a cardioselective beta 1-adrenergic receptor agonist, did not affect mean arterial pressure, but increased heart rate by 40 +/- 5%, LV dP/dt by 72 +/- 10%, mean coronary blood flow by 34 +/- 11%, and CSA by 26 +/- 3%, and decreased LDCR by 29 +/- 5+. Isoproterenol and pirbuterol, but not prenalterol, increased coronary sinus O2 content and decreased A-VO2 difference. After beta 1-adrenergic receptor blockade with atenolol (1 mg/kg), prenalterol no longer induced significant effects, whereas isoproterenol and pirbuterol decreased mean arterial pressure similarly to what was observed prior to blockade, but did not increase LV dP/dt, and induced attenuated increases in mean coronary blood flow, CSA, and decreases in LDCR. Thus, in the intact, conscious animal, large coronary arteries are regulated by beta-adrenergic mechanisms. Surprisingly, a major fraction of large coronary arterial dilation appeared to be either directly or indirectly due to beta 1-adrenergic receptor mechanisms, although beta 2-adrenergic effects were also significant.

Animals↗
PubMed1981

Effects of aminophylline in the conscious dog after coronary occlusion.

The effects of aminophylline were examined in 19 conscious dogs subjected to coronary arterial occlusion. Measurements were made of left ventricular pressure and its first derivative (dP/dt), segment length and the velocity of segment length shortening in normal an severely ischemic zones. Regional blood flow was measured in these zones using the radioactive microsphere technique. Coronary occlusion increased heart rate, mean arterial pressure and left ventricular end-diastolic pressure but did not change left ventricular systolic pressure or dP/dt significantly. It also resulted in increased end-diastolic segment length and reduced segment length shortening (114 +/- 6 percent, that is, paradoxical bulging) associated with marked reduction of blood flow to ischemic myocardium. Aminophylline, 1 mg/kg per min for 9 to 15 minutes administered after occlusion, increased heart rate 6 +/- 2 beats/min, mean arterial pressure 5 +/- 1 mm Hg, left ventricular systolic pressure 9 +/- 2 mm Hg and left ventricular dP/dt 670 +/- 50 mm Hg/s while reducing left ventricular end-diastolic pressure by 3.4 +/- 0.3 mm Hg. In severely ischemic zones aminophylline increased transmural blood flow by 21 +/- 8.0 percent (p less than 0.02), reduced end-diastolic segment length by 0.23 +2- 0.05 mm (p less than 0.01) and reduced paradoxical bulging by 0.15 +/- 0.06 mm (p less than 0.02). Thus, in the presence of coronary arterial occlusion, aminophylline increased mean arterial pressure, left ventricular dP/dt and heart rate while reducing left ventricular end-diastolic pressure. In severely ischemic myocardium aminophylline appeared to exert a salutary effect and improved both regional perfusion and function.

Aminophylline↗
PubMed1981

Morphine effects on cardiac output and regional blood flow distribution in conscious dogs.

This study documents the changes in selected regional hemodynamics occurring in response to large doses of intravenous morphine. It was performed in normal conscious dogs. Their cardiovascular systems was unaltered by the presence of other drugs or recent surgery. The animals had been surgically prepared previously by implantation of chronic indwelling electromagnetic and Doppler ultrasonic flow probes on the aorta and the cranial mesenteric, renal and iliac arteries and placement of aortic catheters. Morphine, 1 mg/kg, produced mesenteric vascular dilation (30 per cent maximum decrease in resistance), renal vascular dilation (11 per cent maximum decrease in resistance) and nonsignificant changes in iliac vascular resistance. Morphine, 3 mg/kg, resulted in a similar amount of renal dilation (maximum 12 per cent decrease in resistance) but constricted the mesenteric vasculature (maximum 120 per cent increase in resistance) and the iliac vasculature (68 per cent maximum increase in resistance). These changes were observed despite the lack of sustained major changes in cardiac output, blood pressure, total peripheral resistance, or heart rate. It is therefore concluded that morphine has only minimal effects on systemic hemodynamics, but has significant effects when the alterations it produces in regional hemodynamics are considered. Such alterations may be physiologically significant when perfusion to these individual organs is a concern. The minimal systemic effects of high dose morphine is a phenomenon, for the most part, common to both dogs and humans. Whether similar regional hemodynamics changes as these occur in humans cannot be determined at this time since continuous flow monitoring techniques have, as yet, not been applied to humans.

Animals↗
PubMed1981

Bainbridge reflex in conscious, unrestrained, and tranquilized baboons.

The effects of volume loading were examined in conscious, unrestrained, and tranquilized baboons (20-25 kg) 1-3 mo after instrumentation with miniature left ventricular pressure and diameter gauges. The response to volume loading was accompanied by significant increases (P less than 0.01) in cardiac rate (32 +/- 4 beats/min) in tranquilized baboons. When rapid saline infusion was accomplished in conscious unrestrained baboons by means of activating a remote-controlled interrogator, heart rate also rose significantly (41 +/- 8 beats/min, P less than 0.01). After cholinergic blockade with atropine, ganglionic blockade with hexamethonium, bilateral vagotomy, or combined cholinergic and beta-adrenergic blockades, volume loading failed to increase heart rate. In two smaller (12-14 kg) intact conscious baboons with relatively high spontaneous heart rates, volume loading did not alter heart rate. These experiments suggest that the Bainbridge reflex exists in larger primates with relatively low spontaneous heart rates.

Animals↗
PubMed1981

Effects of coronary artery reperfusion on myocardial infarct size and survival in conscious dogs.

The effects of coronary artery reperfusion at 1 and 3 hours after coronary artery occlusion were examined on myocardial infarct size and survival in conscious dogs. Left circumflex coronary artery occlusion was induced by inflating an hydraulic occluder and confirmed thereafter by measuring the absence of coronary blood flow. Of the 77 dogs that underwent coronary artery occlusion, 18 died within 1 hour. Of the 59 remaining dogs, permanent coronary artery occlusion was carried out in 31 dogs, 12 underwent reperfusion after 1 hour and 16 underwent reperfusion after 3 hours. Survival at 1 week was enhanced significantly (p < 0.01) by reperfusion carried out at either 1 or 3 hours; only 29% of dogs with permanent coronary artery occlusion survived, whereas 83% and 75% of dogs survived 1 week with reperfusion at 1 hour and 3 hours, respectively. Average infarct size at 1 week was smaller in dogs with reperfusion (NS). The inability to reach statistical significance was most likely the result of two factors: (1) There was a marked variation in infarct size in dogs with permanent coronary artery occlusion--infarcts averaged 21.3 +/- 7.5% and ranged from 0.7-72.6% of the left ventricle. (2) Dogs that died 1-7 days after coronary artery occlusion had significantly (p < 0.05) larger infarcts (40 +/- 4% of left ventricle) than those that survived 1 week in any of the three groups. Thus, if all dogs had survived 1 week, a beneficial effect on infarct size could have been demonstrated. Nevertheless, coronary artery reperfusion at either 1 or 3 hours after coronary artery occlusion induces a striking beneficial effect on survival, which is of the utmost clinical significance.

Animals↗
PubMed1981

Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.

The effects of aminophylline, 1 mg/kg/min infused intravenously for 10 minutes, were examined on left ventricular (LV) diameter, pressure, an indexes of myocardial contractility, as well as systemic, coronary and regional hemodynamics in conscious dogs. Aminophylline increased mean arterial pressure 12 +/- 2%, LV systolic pressure 8 +/- 1%, LV dP/dt 20 +/- 2%, velocity of myocardial fiber shortening 13 +/- 2% and heart rate 5 +/- 2%, and reduced LV end-diastolic diameter 2 +/- 0.5%. Vascular resistance rose in the systemic bed 13 +/- 5%, the coronary bed 26 +/- 3%, the mesenteric bed 26 +/- 5% and the iliac bed 36 +/- 4%, but did not rise in the renal bed. Both beta-adrenergic receptor blockade with propranolol and chronic treatment with reserpine attentuated but did not abolish the positive inotropic response induced by aminophylline. Alpha-adrenergic receptor blockade with phentolamine prevented aminophylline-induced vasoconstriction in the systemic, coronary, mesenteric and iliac beds. In contrast to the vasoconstriction with i.v. aminophylline, when the drug was infused directly into the iliac artery, it elicited marked iliac vasodilation. Thus, in the intact conscious dog, i.v. aminophylline, in a dose that had little effect on heart rate, increased LV contractility and reduced preload. The increase in contractility was dependent in part on intact beta-adrenergic nervous activity and endogenous catecholamine stores. The increase in systemic, coronary, iliac and mesenteric resistances involved alpha-adrenergic mechanisms. These actions appear to involve autonomic mechanisms, because the only direct effect of aminophylline on the iliac artery was marked vasodilation.

Adrenergic alpha-Antagonists↗
PubMed1981

Effects of nitroglycerin and nitroprusside on large and small coronary vessels in conscious dogs.

The effects of nitroglycerin (NTG) and nitroprusside (NPR) were examined in conscious dogs on measurements of left circumflex coronary blood flow and coronary diameter and on calculations of late diastolic coronary resistance (LDCR) and left circumflex coronary internal cross-sectional area (CSA). The effects of infusions of NTG, 8 microgram/kg/Min for 7 minutes, and NPR, 2.5 microgram/kg/min for 7 minutes, were compared. These doses of NTG and NPR induced similar effects on mean arterial and left ventricular (LV) systolic and end-diastolic pressure, heart rate and LV dP/dt. However, NTG induced significantly greater (p less than 0.05) increases in CSA than NPR, while NPR induced significantly greater (p less than 0.05) reductions in LDCR than NTG. Just before cessation of infusion, CSA rose by 29.2 +/- 4.7% with NTG and by 22.7 +/- 3.9% with NPR, while LDCR fell by 8.8 +/- 3.3% with NTG and by 21.6 +/- 2.7% with NPR. Moreover, the effects of NTG on CSA were significantly more sustained than those for NPR. Thus, NTG and NPR in conscious dogs, in doses that exert similar general hemodynamic effects, elicit qualitatively similar but quantitatively different effects on small vs large coronary vessels. Whereas NTG induced significantly less dilation of small coronary vessels, it exerted significantly larger and longer lasting effects on large coronary arteries.

Animals↗
PubMed1981

Reduction of maximal coronary vasodilator capacity in conscious dogs with severe right ventricular hypertrophy.

Right coronary reactive hyperemia and the maximal coronary vasodilator response to adenosine were examined in conscious, normal dogs and dogs with right ventricular (RV) hypertrophy. RV hypertrophy was induced by chronic (5-7 months) pulmonary artery stenosis. With RV hypertrophy, RV weight to body weight ratio rose by 70% (P < 0.001), right coronary artery blood flow (Doppler ultrasonic technique) rose from 17 +/- 1 to 51 +/- 5 ml/min, and RV transmural blood flow (radioactive microsphere technique) increased from 0.78 +/- 0.06 to 1.62 +/- 0.10 ml/min per g, while the RV endocardial:epicardial perfusion ratio decreased from 1.36 +/- 0.04 to 1.0 +/- 0.02. Excess blood flow debt repayment following release of a 15-second right main coronary artery occlusion was attenuated markedly (P < 0.001) to 107 +/- 22% from the normal value of 325 +/- 41%. Maximal coronary vasodilator capacity (to iv adenosine) was reduced in the hypertrophied right ventricle, as reflected by a lower (P < 0.05) level of maximal transmural blood flow and a higher (P < 0.02) level of minimum coronary vascular resistance per gram of hypertrophied right ventricle compared to normal. During maximal coronary vasodilation, the endocardial:epicardial perfusion ratio decreased (P < 0.001) below unity in the hypertrophied right ventricle to a level (0.83 +/- 0.06) significantly lower (P < 0.001) than normal (1.16 +/- 0.03). Thus, the development of severe RV hypertrophy is characterized by an attenuated coronary response to acute ischemia and by a reduction in maximal coronary vasodilator capacity. We conclude that the increase in cardiac mass which results from chronic pulmonary artery stenosis is not accompanied by a proportionate increase in cross-sectional area of coronary vessels supplying the hypertrophied ventricle.

Adenosine↗
PubMed1981

Effects of anesthesia on the canine carotid chemoreceptor reflex.

We studied the effects of alpha-chloralose (100 mg/kg, iv), Na pentobarbital (25 mg/kg, iv) and halothane (1 vol% and 2 vol%) on the response to carotid chemoreceptor stimulation (CCRS) in eight chronically instrumented dogs. CCRS was accomplished by means of intracarotid injections of nicotine while ventilation was held constant in the unanesthetized state and following administration of one of three different anesthetics. In the conscious state, CCRS elicited intense bradycardia and peripheral vasoconstriction as reflected by a 173 +/- 14% increase in initial cardiac cycle length and a 216 /+- 22% increase in mean iliac vascular resistance. Each anaesthetic, studied on separate days, attenuated these responses to CCRS strikingly (P less than 0.01). For instance, after alpha-chloralose, CCRS increased iliac resistance by only 55 +/- 14% and cardiac cycle length by only 27 +/- 13%. After Na pentobarbital, CCRS increased iliac resistance by 12 +/- 4% and cardiac cycle length by 8 +/- 5%. After inhalation of halothane (1 vol%), CCRS increased iliac resistance by 28 +/- 7% and cardiac cycle length by 11 +/- 5%, whereas halothane (2 vol%) abolished these responses to CCRS. Thus, general anesthesia interferes severely with carotid chemoreceptor control of the circulation. Whereas halothane and Na pentobarbital altered responses to CCRS the most, we found that even alpha-chloralose, which has been thought to maintain or augment reflex responses, was able to depress the response to CCRS strikingly.

Anesthesia↗
PubMed1981

Regulation of large coronary arteries by increases in myocardial metabolic demands in conscious dogs.

In order to assess the effects of increasing myocardial metabolic demand on the large epicardial coronary arteries, we measured left circumflex coronary artery diameter (ultrasonic transit time technique) and blood flow in conscious dogs with chronically implanted transducers. Myocardial oxygen consumption was increased by pacing-induced tachycardia and aortic constriction, and monitored by multiplying left circumflex coronary arterial blood flow by coronary arterio-venous oxygen content difference. Increase of heart rate by 90 beats/min caused myocardial oxygen consumption to increase by 34 +/- 4.3% (1 SEM); coronary blood flow at constant arterial pressure to increase by 32 +/- 6.8%; and coronary diameter to increase by 0.07 +/- 0.01 mm, P less than 0.01. Aortic constriction, producing a 53 +/- 5.1% increase of left ventricular systolic pressure, caused myocardial oxygen consumption to increase by 49 +/- 7.2%, coronary blood flow to increase by 50 +/- 6.0%, and coronary diameter to increase 0.03 mm, P less than 0.01. The increases in coronary artery diameter were gradual, not immediate, in onset and not altered by beta-adrenergic blockade. Thus, increased myocardial metabolic demand dilates large epicardial coronary arteries, but with a slower response time than the rapid dilation of the smaller resistance vessels.

Adrenergic beta-Antagonists↗
PubMed1981

Cellular mechanisms of impaired adrenergic responsiveness in neonatal dogs.

The myocardial responsiveness of conscious, instrumental dogs to exogenously administered isoproterenol and norepinephrine was investigated in neonatal, 6-wk-old, and adult animals. Comparable base-line values for peak left ventricular derivative of pressure with respect to time were observed in all age categories. However, when compared with adult responses, the sympathomimetic amine-induced increases in neonatal left ventricular dP/dt were significantly blunted at each concentration of adrenergic agonist examined, whereas the 6-wk-old puppies displayed an intermediate inotropic response. To investigate the cellular mechanisms of this blunted neonatal response, we correlated physiologic and biochemical measurements of the myocardial responses to catecholamines in each age category. When compared with adult myocardial membrane preparations, neonatal cardiac membranes were characterized in vitro by an increased density of beta-adrenergic binding sites, comparable affinity for adrenergic agonists and antagonists, and an enhanced coupling of adenylate cyclase activation to receptor occupancy. Simultaneous changes in either the serum catecholamine concentration or the membrane content of other intrinsic proteins failed to account for the observed neonatal increase in beta-adrenergic receptor density. These findings are most consistent with a compensatory mechanism of the cardiac cell membrane, whereby an inherent depression in the adrenergic responsiveness of the immature myocardium appears to induce the increase in receptor density and activation of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1981

Effects of acute increases in left ventricular preload on indices of myocardial function in conscious, unrestrained and intact, tranquilized baboons.

The effects of acute volume loading were examined on indices of left ventricular (LV) function in conscious, unrestrained and intact, tranquilized baboons. Experiments were conducted 1-3 mo after implantation of ultrasonic transducers to measure LV internal diameter and wall thickness, and miniature LV pressure gauges and aortic and left atrial catheters. In 10 intact, tranquilized baboons, rapid volume loading with saline increased LV end-diastolic pressure by 23.7+/-2.6 mm Hg, LV end-diastolic diameter by 7.8+/-1.5%, LV stroke work by 37.5+/-7.8%, while mean arterial pressure and peak LV wall stress did not change significantly. Despite the increase in preload and activation of the Frank-Starling mechanism, LV dP/dt(max) and the maximum velocity of myocardial fiber shortening (LV dD/dt(max)) did not change. Volume loading after beta-adrenergic or combined beta-adrenergic and cholinergic blockades or volume loading with blood instead of saline also failed to augment LV dP/dt(max) and LV dD/dt(max) despite the increase in preload. In order to volume load the baboons in the conscious state, a radiofrequency (RF) interrogator system was devised, which upon receipt of a radio command, activated a battery operated pump to infuse 1,000 ml of saline i.v. to the baboons. In these experiments, preload rose, i.e., LV end-diastolic diameter increased by 13.9+/-2.1% and the Frank-Starling mechanism could be demonstrated, i.e., stroke work rose by 42.8+/-7.4%, but LV dP/dt(max) and LV dD/dt(max) did not change. After preload was depressed by hemorrhage, the rapid infusion of either blood or saline increased LV dP/dt(max) by 92.7+/-18.5% and LV dD/dt(max) by 64.3+/-10.1%. Thus, acute volume loading in the conscious baboons increased LV end-diastolic size and even stroke work substantially. However, preload dependency of LV dP/dt(max) and the maximum velocity of myocardial fiber shortening was only encountered at low levels of LV preload.

Animals↗
PubMed1981

Abnormal coronary vascular response to exercise in dogs with severe right ventricular hypertrophy.

Measurements of right coronary artery blood flow, aortic and right ventricular (RV) pressures and heart rate were radiotelemetered during strenuous, spontaneous exercise in normal dogs and dogs with severe RV hypertrophy induced by chronic (5-6 mo) pulmonary artery stenosis. With fixed pulmonic stenosis, dogs with RV hypertrophy exhibited a decrease (P less than 0.01) in arterial pressure during exercise. Under these conditions, exercise increased right coronary artery blood flow and decreased right coronary vascular resistance less (P less than 0.05) in dogs with RV hypertrophy compared with normal. This attenuated response of right coronary artery blood flow of dogs with RV hypertrophy was not observed when arterial pressures remained at preexercise values during exercise. However, regardless of changes in arterial pressures during exercise, all dogs with RV hypertrophy demonstrated a striking postexercise coronary hyperemia (P less than 0.01), suggesting a perfusion deficit of the hypertrophied right ventricle during exercise. These results imply a fundamental defect in the ability of the coronary circulation of the severely hypertrophied right ventricle to provide sufficient nutrient supply in the face of elevated metabolic demands of exercise.

Animals↗
PubMed1981

Generalized cardiovascular and regional hemodynamic effects of meperidine in conscious dogs.

Changes in both total cardiovascular function and regional hemodynamics associated with large doses of intravenous meperidine were studied in conscious dogs in the absence of other drugs or recent surgery. The animals had previously been surgically prepared by placement of aortic catheters and implantation of chronic indwelling electro-magnetic and Doppler ultrasonic flow probes on the aorta and on mesenteric, renal, and iliac arteries. Meperidine, 2 mg/kg, produced mild renal vascular dilation (10% maximum decreases in resistances and 5% increases in blood flow), but did not alter the resistances and flows in the mesenteric or iliac vascular beds. Meperidine, 6 mg/kg, again resulted in renal dilation (maximum 22% decreases in resistance and 18% increase in blood flow). The iliac vasculature also dilated (maximum 39% decreases in resistance and 40% increases in blood flow). However, the mesenteric vasculature constricted (89% increases in resistance and 40% decreases in blood flow). Following 2 mg/kg of meperidine cardiac output and aortic pressure decreased significantly while total peripheral resistance increased significantly. Heart rate remained unchanged. Following 6 mg/kg of meperidine total peripheral resistance and aortic pressure decreased significantly while heart rate increased. Cardiac output increased during the first part of the observation period then subsequently decreased significantly. It is concluded that in unmedicated dogs meperidine has significant effects on total cardiovascular function and on regional blood flow.

Animals↗