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Biomedical subjects

S F Vatner

Publications and source records attributed to S F Vatner.

At least 181 records · Page 10Linked to original sources
PubMed1984

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs.

We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O2 contents. With heart rate held constant by electrical stimulation, and with respiration controlled or allowed to vary spontaneously, carotid chemoreceptor reflex activation (induced by intracarotid nicotine) elicited a striking biphasic coronary vascular response characterized by an early dilation (previously described) and a late constriction. For example, with respiration controlled and with the autonomic nervous system intact, carotid chemoreceptor reflex activation resulted in a late increase in arterial pressure (19 +/- 4%; P less than 0.002), absolute reductions in right main (24 +/- 4%; P less than 0.002), and left circumflex (12 +/- 2%; P less than 0.004) coronary blood flows, and increases in right (62 +/- 13%; P less than 0.002) and left (26 +/- 3%; P less than 0.0001) coronary resistances. This carotid chemoreceptor reflex activation-induced late coronary constriction was also associated with a concomitant increase in myocardial oxygen extraction, i.e., arterial oxygen content remained constant, while coronary sinus oxygen content decreased (19 +/- 6%; P less than 0.04). Neither propranolol nor atropine had any significant effect on the magnitude of the right coronary constriction. However, both the absolute reduction in right coronary blood flow and increase in right coronary resistance were abolished by phentolamine. Furthermore, either total cardiac denervation or adrenalectomy significantly attenuated (P less than 0.01) carotid chemoreceptor reflex activation-induced reductions in right coronary blood flow and increase in right coronary resistance. We conclude that, with autonomic nervous system activity intact, carotid chemoreceptor reflex activation can elicit an absolute reflexly mediated reduction in coronary blood flow in the normal, conscious dog, despite an increase in arterial pressure. The mechanism of this vasoconstriction involves alpha-adrenergic receptor stimulation mediated by both cardiac sympathetic nerves and circulating catecholamines.

Adrenalectomy↗
PubMed1984

Responses of renal hemodynamics and function to acute volume expansion in the conscious dog.

The renal vascular and functional responses to acute volume expansion were determined in conscious dogs with all reflexes intact, sinoaortic arterial baroreceptor denervation, arterial baroreceptor denervation plus bilateral stellectomy, and arterial baroreceptor denervation plus bilateral vagotomy. In the intact dogs, when an isotonic saline infusion increased right atrial pressure by 6 mm Hg, arterial pressure increased by 15 +/- 3 from 95 +/- 3 mm Hg (P less than 0.01) and heart rate rose from 87 +/- 4 to 135 +/- 6 beats/min (P less than 0.01), while renal blood flow rose only slightly (4 +/- 2%), and calculated renal resistance was not altered significantly. After arterial baroreceptor denervation, volume expansion with saline induced a greater rise in blood flow (16 +/- 2%), but did not alter arterial pressure, and calculated resistance fell by 19 +/- 3% from 0.72 +/- 0.05 mm Hg/ml per min (P less than 0.01), while heart rate still increased. After arterial baroreceptor denervation and either bilateral stellectomy or vagotomy, volume expansion reduced renal vascular resistance by similar amounts. When intact animals were volume expanded by 20% of estimated blood volume with isooncotic, isotonic 3% dextran in saline solution, and with renal perfusion pressure held constant, central venous pressure increased by 4.5 +/- 0.6 from 1.8 +/- 0.4 mm Hg (P less than 0.01), renal blood flow increased significantly by 16 +/- 5 ml/min (P less than 0.05) from 191 +/- 30 ml/min, while calculated renal vascular resistance decreased significantly by 0.08 +/- 0.02 from 0.62 +/- 0.09 mm Hg/ml per min (P less than 0.05). Average urine flow rate and sodium excretion 10-60 minutes after expansion increased markedly by 1.85 +/- 0.27 ml/min and 9.84 +/- 1.13 muEq/min per kg, respectively (P less than 0.01). After arterial baroreceptor denervation, volume expansion induced a similar rise in central venous pressure and renal blood flow. The diuretic and natriuretic responses were not attenuated by arterial baroreceptor denervation. After arterial baroreceptor denervation plus bilateral vagotomy, there was a significant and similar rise in renal blood flow, whereas diuretic (urine flow rate rose by only 0.50 +/- 0.10 from 0.35 +/- 0.08 ml/min) and natriuretic (sodium excretion rose by only 4.83 +/- 0.95 from 1.50 +/- 0.48 muEq/min per kg) responses were significantly attenuated (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1984

Effects of pressure overload, left ventricular hypertrophy on beta-adrenergic receptors, and responsiveness to catecholamines.

Pressure overload left ventricular (LV) hypertrophy was produced by banding the ascending aorta of puppies and allowing them to grow to adulthood. LV free wall weight per body weight increased by 87% from a normal value of 3.23 +/- 0.19 g/kg. Hemodynamic studies of conscious dogs with LV hypertrophy and of normal, conscious dogs without LV hypertrophy showed similar base-line values for mean arterial pressure, heart rate, and LV end-diastolic pressure and diameter. LV systolic pressure was significantly greater, P less than 0.01, and LV stroke shortening was significantly lss, P less than 0.01, in the LV hypertrophy group. In both normal and LV hypertrophy groups, increasing bolus doses of norepinephrine or isoproterenol produced equivalent changes in LV dP/dt. beta-adrenergic receptor binding studies with [3H]-dihydroalprenolol ( [3H]DHA) indicated that the density of binding sites was significantly elevated, P less than 0.01, in the hypertrophied LV plasma membranes (111 +/- 8.8, n = 8), as compared with normal LV (61 +/- 5.6 fmol/mg protein, n = 11). The receptor affinity decreased, i.e., disassociation constant (KD) increased, selectively in the LV of the hypertrophy group; the KD in the normal LV was 6.8 +/- 0.7 nM compared with 10.7 +/- 1.8 nM in the hypertrophied LV. These effects were observed only in the LV of the LV hypertrophy group and not in the right ventricles from the same dogs. The plasma membrane marker, 5' -nucleotidase activity, was slightly lower per milligram protein in the LV hypertrophy group, indicating that the differences in beta-adrenergic receptor binding and affinity were not due to an increase in plasma membrane protein in the LV hypertrophy group. The EC50 for isoproterenol-stimulated adenylate cyclase activity was similar in both the right and left ventricles and in the two groups. However, maximal-stimulated adenylate cyclase was lower in the hypertrophied left ventricle. Plasma catecholamines were similar in the normal and hypertrophied groups, but myocardial norepinephrine was depressed in the dogs with LV hypertrophy (163 +/- 48 pg/mg) compared with normal dogs (835 +/- 166 pg/mg). Thus, severe, but compensated LV hypertrophy, induced by aortic banding in puppies, is characterized by essentially normal hemodynamics in adult dogs studied at rest and in response to catecholamines in the conscious state. At the cellular level, reduced affinity and increased beta-adrenergic receptor number characterized the LV hypertrophy group, while the EC50 for isoproterenol-stimulated adenylate cyclase activity was normal. By these mechanisms, adequate responsiveness to catecholamines is retained in conscious dogs with severe LV hypertrophy.

Animals↗
PubMed1984

Alpha-adrenergic tone in the coronary circulation of the conscious dog.

To examine the role of neural factors in the control of coronary vasoactivity in conscious animals, dogs were supplied with miniature pressure gauges in the aorta and left ventricle (to measure aortic and left ventricular pressures, respectively and with a flow probe on the left circumflex coronary artery (to measure coronary blood flow). The experiments were conducted several weeks after recovery from operation. Stimulation of the carotid chemoreceptor and pulmonary inflation elicited a biphasic reflex response. Initially, coronary vasodilation was observed; coronary blood flow tripled even after changes in metabolic factors were minimized by pretreatment with propranolol. A similar response occurred after a spontaneous deep breath. The coronary vasodilation could be blocked by alpha-adrenergic receptor blockade. The second phase of the response involved an increase in coronary vascular resistance, associated with elevated arterial pressure and an absolute reduction in coronary blood flow and coronary sinus oxygen content. The secondary coronary vasoconstriction was also abolished by alpha-adrenergic blockade. Paradoxically, alpha-adrenergic receptor blockade with phentolamine (at constant heart rate and after beta-adrenergic receptor blockade) did not increase coronary blood flow and reduced coronary vascular resistance only slightly. Selective alpha 1-adrenergic receptor blockade with prazosin and trimazosin on different days induced progressively greater reductions in coronary vascular resistance. Trimazosin was the only alpha-adrenergic receptor blocker to elevate coronary blood flow significantly. It is conceivable, but speculative, that withdrawal of alpha-adrenergic tone may involve activation of an intermediate agent, which is a potent coronary vasodilator. Alternatively, withdrawal of alpha-adrenergic tone may be an important mechanism for immediate control of the coronary circulation, but under more chronic conditions it plays a lesser role as a result of suppression by metabolic factors.

Animals↗
PubMed1983

Reflex cardiovascular responses to chemoreceptor stimulation in conscious dogs with cardiac hypertrophy.

Carotid chemoreceptor reflex activation (CCRA) has been previously shown to result in intense alpha-adrenergic peripheral vasoconstriction, a biphasic coronary vascular response characterized by an early vasodilation and a late alpha-adrenergic vasoconstriction, and a cholinergic increase in cardiac cycle length in normal conscious dogs. In the present study, we investigated the extent to which these reflex cardiovascular responses to CCRA are modified after the development of pressure-overload right ventricular (RV) hypertrophy induced by chronic (9-12 mo) pulmonary arterial stenosis. With heart rate constant and respiration allowed to vary spontaneously, the magnitude of the late CCRA-induced (intracarotid nicotine) increase (P less than 0.01) in right coronary resistance was markedly attenuated (P less than 0.01) in conscious dogs with RV hypertrophy [0.29 +/- 0.07 (SE) mmHg X ml-1 X min] compared with normal dogs (1.87 +/- 0.36). When respiration was controlled to eliminate pulmonary inflation reflex activation, the late CCRA-induced increase (P less than 0.01) in right coronary resistance was still found to be depressed (P less than 0.01) in the RV hypertrophy group (1.11 +/- 0.20 mmHg X ml-1 X min) compared with normal dogs (3.65 +/- 0.75). This late CCRA-induced right coronary vasoconstriction was not potentiated by beta-adrenergic receptor blockade but was abolished (P less than 0.01) by alpha-adrenergic receptor blockade. In contrast to the depressed right coronary vasoconstriction, the CCRA-induced alpha-adrenergic constriction (P less than 0.01) of the iliac arterial vascular bed was similar in both groups, and the cholinergic increase (P less than 0.01) in cardiac cycle length was enhanced (P less than 0.01) in the RV hypertrophy group compared with normal dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Dipyridamole dilates large coronary arteries in conscious dogs.

The effects of 0.25 mg/kg dipyridamole on left ventricular (LV) pressures, LV dP/dt, heart rate, aortic pressures, left circumflex coronary blood flow, and left circumflex coronary arterial diameters and on calculations of late diastolic coronary resistance and large coronary cross-sectional area were studied in 15 conscious dogs. Injection of dipyridamole, a drug that has a mechanism of action dependent on myocardial adenosine production, caused sustained increases in mean coronary blood flow (244 +/- 28%), large coronary arterial cross-sectional area (28 +/- 3.2%), heart rate (32 +/- 3.6%), and LV dP/dt (23 +/- 3.0%) and reductions in late diastolic coronary resistance (73 +/- 2.4%) and mean arterial pressure (14 +/- 1.9%). Neither beta-adrenergic-receptor blockade alone nor in conjunction with constant heart rate affected the dilation of large coronary arteries to dipyridamole significantly. Ganglionic blockade with hexamethonium also had little effect on the response of large and small coronary vessels to dipyridamole. Surprisingly neither beta-adrenergic-receptor nor ganglionic blockade abolished the rise in LV dP/dt observed after dipyridamole. Aminophylline, however, effectively eliminated the dilation of large coronary arteries and resistance coronary vessels in response to dipyridamole. In summary, as long as dipyridamole does not induce severe sustained hypotension it exerts potent effects on both coronary arterial resistance and large coronary arteries in the conscious dog. The coronary dilation is independent of reflex adrenergic activation, but appears dependent on myocardial adenosine production.

Adenosine↗
PubMed1983

Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs.

The effects of coronary artery occlusion and reperfusion at 1 hour (1-hr group), 2 hours (2-hr group), and 3 hours (3-hr group) were compared with a permanently occluded group (P group) on measurements of overall left ventricular and regional endocardial function over a 4-week period. The studies were conducted in conscious dogs 1-2 weeks after recovery from instrumentation with solid state left ventricular pressure gauges, aortic, and left atrial catheters, hydraulic occluders, and Doppler flow transducers on the left anterior descending or left circumflex coronary arteries, and multiple pairs of ultrasonic transducers implanted in the endocardial third of the left ventricular free wall to measure endocardial segment shortening. During coronary artery occlusion, similar effects were observed in the four groups. At 1 hour after coronary artery occlusion, three classes of ischemia-induced dysfunction were observed; dyskinetic (systolic shortening completely lost and replaced by paradoxical bulging), severely hypokinetic (systolic shortening depressed by 65-95%), and moderately hypokinetic (systolic shortening depressed by 40-65%). Compared with the P group, significant (P less than 0.05) return of systolic shortening and velocity of shortening gradually occurred over the 4-week period following reperfusion in all classes of segments in the 1-hour group. In the 2-hour group, systolic shortening returned in the moderately and severely hypokinetic segments, but was slight and not significant in the dyskinetic segments. In the 3-hour group, significant systolic shortening returned only in the moderately hypokinetic segments. The effects of isoproterenol, 0.04 micrograms/kg per min, and exercise were compared on "salvaged" dyskinetic segments prior to and at 1, 2, 3, and 4 weeks after coronary artery occlusion and reperfusion. The responses to isoproterenol were significantly depressed at 1 week after reperfusion and gradually recovered over the 4-week period. At 3-4 weeks after reperfusion, severe exercise also increased shortening and velocity of shortening in "salvaged" segments. Thus, in the conscious dog, coronary artery reperfusion at 1 hour after coronary artery occlusion results in substantial return of endocardial function even in the most severely ischemic myocardium. The "salvaged" myocardium responds adequately to myocardial stress with increases in the extent and velocity of systolic shortening, as long as 3-4 weeks after reperfusion are allowed for recovery. However, after 3 hours of coronary artery occlusion, little salvage of regional myocardial function can be induced by acute reperfusion in this model.

Animals↗
PubMed1983

Comparison of effects of nifedipine and nitroglycerin on large and small coronary arteries and cardiac function in conscious dogs.

The effects of nifedipine, 20 micrograms/kg, iv, and nitroglycerin, 25 micrograms/kg, iv, were compared in conscious dogs, instrumented for instantaneous and continuous measurements of coronary arterial and left ventricular (LV) diameters, arterial and LV pressures, coronary blood flow, and cardiac output. The two drugs were administered to reduce arterial pressure initially by similar amounts, by approximately 30 mm Hg. The maximal increases in large coronary arterial dimensions occurred 2-4 minutes after the initial peak reductions in arterial pressure and increases in coronary blood flow. The maximal increase in large coronary arterial cross-sectional area with nifedipine (28 +/- 2.9%) and nitroglycerin (33 +/- 5.3%) were similar. At this time, nifedipine increased coronary blood flow (114 +/- 20%) and reduced late diastolic coronary vascular resistance (-61 +/- 3.1%), whereas nitroglycerin reduced coronary blood flow (-14 +/- 1.7%) and increased late diastolic coronary vascular resistance (15 +/- 6.6%). During the time of peak large coronary arterial dilation, nifedipine reduced mean arterial pressure (-13 +/- 2.1%) and total peripheral resistance (-30 +/- 2.6%), whereas, with nitroglycerin, arterial pressure was not different from control and total peripheral resistance was significantly increased (13 +/- 1.8%). At this time, LV end-diastolic diameter was reduced with nitroglycerin (-5.6 +/- 0.4%) but unaffected by nifedipine. Thus, in the conscious dog, nitroglycerin and nifedipine induced similar effects on large coronary arteries but differing effects on resistance coronary and peripheral vessels as well as preload. Nifedipine, in contrast to nitroglycerin, induced sustained vasodilation of both coronary resistance vessels and peripheral arterioles, whereas nitroglycerin, but not nifedipine, reduced preload.

Animals↗
PubMed1983

Effects of acetylcholine on large and small coronary arteries in conscious dogs.

The effects of acetylcholine, 10 microgram/kg i.v., were examined in nine conscious dogs on measurements of left ventricular pressure, dP/dt, aortic pressure, heart rate, coronary blood flow, left circumflex external coronary arterial diameter, arterial and coronary sinus O2 content and calculations of late diastolic coronary resistance and left circumflex internal coronary cross-sectional area. In conscious dogs in the absence of autonomic blockade, acetylcholine induced a rapid, transient response characterized by hypotension and peak increases in coronary blood flow (+135 +/- 14%) and coronary sinus O2 content (+5.0 +/- 0.5 volume percent) and decreases in late diastolic coronary resistance (-65 +/- 3%). The peak large coronary arterial effects were observed 60 sec later at a time when arterial pressure, left ventricular end-diastolic pressure, left ventricular dP/dt and heart rate were not significantly different from control. At this time, large coronary cross-sectional area was increased by 36 +/- 4%, whereas late diastolic coronary resistance was not significantly different from control. Beta adrenergic or combined alpha and beta adrenergic receptor blockade did not alter the responses significantly. However, the effects were abolished by muscarinic blockade with atropine methylbromide, 0.1 mg/kg. Thus, acetylcholine dilates large coronary arteries as well as coronary resistance vessels. These effects are independent of metabolic and adrenergic mechanisms, and are mediated by muscarinic receptors, inasmuch as the effects are abolished by prior muscarinic receptor blockade.

Acetylcholine↗
PubMed1982

Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs.

The effects of three alpha-adrenergic-receptor blocking agents (phentolamine, prazosin, and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 20%) and in the presence of beta-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the three drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 +/- 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 +/- 2 and 11 +/- 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 +/- 4%. The three drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 +/- 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 +/- 2%, which was significantly more than reductions in LDCR induced by prazosin (22 +/- 2%) and by phentolamine (11 +/- 3%). A test dose of phenylephrine (5.0 micrograms/kg) increased mean arterial pressure by 53 +/- 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 +/- 2.1, 14 +/- 1.6, and 1.9 +/- 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.

Adrenergic alpha-Antagonists↗
PubMed1982

Phylogenesis of the Bainbridge reflex.

The effects of volume loading were examined on measurements of left ventricular (LV) pressure and heart rate in patients undergoing cardiac catheterization. These data were compared to those collected in conscious dogs and subhuman primates (baboons). In man acute volume loading increased LV end-diastolic pressure by 14 mmHg, but did not increase LV systolic pressure significantly. Similar increases in LV end-diastolic pressure were observed in conscious dogs and baboons. LV systolic pressure also did not rise in baboons, but did increase (+32 mmHg) with volume loading in dogs. In man volume loading increased heart rate by 15 beats/min, significantly less (P less than 0.01) than observed in baboons (+37 beats/min), and which in turn was significantly less than that observed in dogs (+88 beats/min). Thus, the Bainbridge reflex, i.e., the tachycardia that occurs with volume loading, appears to exist in primates including man. However, the extent of utilization of this reflex decreases significantly from nonprimate mammals (dogs) to subhuman primates (baboons) to man.

Adolescent↗
PubMed1982

Effects of prazosin on coronary and left ventricular dynamics in conscious dogs.

The left ventricular (LV) and coronary vascular effects of prazosin, a drug that reduces peripheral vascular resistance by blocking postsynaptic alpha receptors, were examined in conscious dogs. Prazosin, 0.07 mg/kg/min i.v. for 7 minutes, induced sustained hypotensive effects for more than 12 hours. The peak effects occurred 30-45 minutes after administration. Prazosin increased heart rate by 28 +/- 9%, did not change mean coronary blood flow significantly, decreased mean arterial pressure by 15 +/- 4%, LV end-diastolic diameter by 10 +/- 2%, LV end-systolic diameter by 8 +/- 2%, late diastolic coronary resistance by 22 +/- 7%, and LV dP/dt by 9 +/- 4%. These effects of prazosin were not altered substantially by maintaining heart rate constant with electrical pacing or by pretreatment with beta-adrenergic blockade. However, after chronic reserpine treatment, prazosin did not reduce either mean arterial pressure or late diastolic coronary resistance. The alpha-blocking properties of the drug were established when prazosin attenuated pressure responses to phenylephrine, norepinephrine and bilateral carotid occlusion. Thus, in conscious dogs with heart rate constant, prazosin, by blocking alpha-adrenergic receptors, induces prolonged coronary vasodilation associated with reductions in the major determinants of myocardial oxygen consumption, e.g., arterial and LV pressures, LV end-diastolic diameter and LV dP/dt. However, the coronary vasodilation was not intense enough to increase coronary blood flow above control levels.

Animals↗
PubMed1982

Effects of a calcium-channel antagonist on large and small coronary arteries in conscious dogs.

The effects of i.v. nifedipine, 20 micrograms/kg, on left ventricular (LV) pressure, dP/dt, aortic pressure, heart rate, LV diameters, cardiac output, coronary blood flow and left circumflex coronary arterial diameter, and calculations of late diastolic coronary and total peripheral resistances and left circumflex coronary cross-sectional area were examined in 11 conscious dogs. In dogs with spontaneous rhythm, nifedipine induced an early, transient response characterized by hypotension and peak increases in coronary blood flow and decreases in total peripheral and late diastolic coronary vascular resistances. The peak effects on large coronary arteries were observed 2--5 minutes later, when mean arterial pressure was only 8.2 +/- 1.6 mm Hg below control and LV end-diastolic pressure and diameter were not significantly different from control. LV dP/dt was elevated by 7.1 +/- 1.1%, heart rate was elevated by 25 +/- 3.3 beats/min, and cardiac output remained elevated by 54 +/- 7.4%. At this time, coronary cross-sectional area was elevated by 26 +/- 3.0%, late diastolic coronary vascular resistance was reduced by 50 +/- 2.7%, and total peripheral resistance was 40 +/- 3.8% below control. The coronary sinus oxygen content was elevated by 3.4 +/- 0.8 vol% and the arteriovenous oxygen difference fell by 3.5 +/- 0.8 vol%. After beta-adrenergic blockade with propranolol and with heart rate constant or varying, the increases in coronary cross-sectional area and decreases in late diastolic coronary vascular resistance induced by nifedipine were still observed, but were significantly smaller (p less than 0.01). Thus, nifedipine dilates both large coronary arteries and coronary resistance vessels, effects that could be attributed in part to beta-adrenergic mechanisms. Nifedipine also exerts potent effects on coronary and peripheral arterial vessels, but has little effect on preload.

Adrenergic beta-Antagonists↗