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Biomedical subjects

H L Stone

Publications and source records attributed to H L Stone.

At least 37 records · Page 2Linked to original sources

Coronary vascular response to adrenergic stimulation in exercise-conditioned dogs.

The present study was designed to determine whether daily exercise alters adrenergic and muscarinic neural control of coronary blood flow during resting and exercising conditions in the conscious dog. Mean left circumflex artery blood flow (CBF), mean coronary blood pressure, and heart rate were measured during resting conditions (55 +/- 9 ml/min, 108 +/- 6 mmHg, and 93 +/- 2 beats/min, respectively) and during submaximal exercise (85 +/- 9 ml/min, 108 +/- 7 mmHg, and 210 +/- 15 beats/min). Injection of phentolamine into the left circumflex coronary artery during treadmill exercise resulted in a 10 +/- 1% increase in CBF before training (untrained, UT) and a 21 +/- 6% increase after 4-5 wk of daily exercise (partially trained, PT) (P less than 0.02 UT vs. PT). Intracoronary atenolol or propranolol caused a 15 +/- 6% reduction in CBF during exercise in dogs before and after PT. While the dogs were lying quietly at rest intracoronary injections of norepinephrine initially increased CBF 85%, followed by a prolonged 19 +/- 9% decrease in CBF. CBF decreased 16 +/- 3% after intracoronary injection of phenylephrine. After PT the coronary vasoconstriction following norepinephrine and phenylephrine injections was significantly potentiated (31 +/- 6 and 35 +/- 4%, respectively). These data suggest that exercise training caused significant changes in the coronary vascular response to alpha-receptor stimulation so that an alteration in the neural control of the coronary circulation occurred.

Animals↗

Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death.

The relationship between activity of the autonomic nervous system, myocardial ischemia, and malignant arrhythmias has been investigated in a new experimental preparation for sudden death. Fifty-seven dogs were chronically instrumented and studied under control conditions (n = 15) and 1 month after production of an anterior myocardial infarction (n = 42). The protocol consisted in occluding the left circumflex coronary artery for 2 min, commencing at the last minute of an exercise stress test and extending through the first minute after cessation of exercise. With this protocol, ventricular fibrillation was observed in 40% of normal dogs and 66% of dogs with infarction. In 14 dogs with infarction, left stellectomy reduced the incidence of ventricular fibrillation to zero (p less than .001). The reflex changes in heart rate elicited within the first minute of ischemia during exercise in the animals that survived (from 204 +/- 14 to 198 +/- 31 beats/min, -6) were opposite those in animals that had ventricular fibrillation (from 208 +/- 24 to 229 +/- 30 beats/min, +21) (p less than .05). The ischemia-induced reduction in heart rate despite continuation of exercise suggests the presence in the dogs that survived of active vagal reflexes that may have played an important role in the maintenance of cardiac electrical stability. This preparation has the potential to induce ventricular fibrillation consistently in conscious animals by the interaction of a few clinically relevant factors (acute myocardial ischemia, submaximal exercise and its cessation, sympathetic and vagal reflexes, and heart rate) and offers the possibility of acquiring further insights into the mechanisms of malignant arrhythmias and evaluating novel strategies for targeted prevention.

Animals↗

The effects of daily exercise on susceptibility to sudden cardiac death.

The purpose of this study was to investigate the effects of daily exercise on susceptibility to sudden cardiac death. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise in chronically instrumented dogs with a healed anterior wall myocardial infarction. Thirteen dogs developed ventricular fibrillation (VF; susceptible), while five did not (resistant). Before the exercise plus ischemia test, the baroreflex was evaluated with a bolus injection of phenylephrine (10 micrograms/kg). The changes in heart rate caused by a 30 mm Hg increase in systolic arterial pressure as well as the slopes of either heart rate or RR interval plotted against systolic arterial pressure were significantly lower in dogs that developed VR (resistant, -49.6 +/- 7.8; susceptible, -15.3 +/- 6.4 beats/min; p less than .001). Four resistant and eight susceptible animals were then placed on a 6 week daily exercise program, while eight susceptible dogs had an equal period of rest. At the end of the 6 week period the exercise plus ischemia test was repeated; no susceptible animal that performed daily exercise developed VF, and all but one of the rested animals did. Daily exercise improved baroreflex control of heart rate in the susceptible group but not in the resistant group. Rest did not alter baroreflex function (change in heart rate after 30 mm Hg increase in systolic arterial pressure: after 6 weeks of exercise, resistant -43.3 +/- 18.9 beats/min, susceptible -60.8 +/- 16.6 beats/min; after 6 weeks of rest, susceptible 27.4 +/- 11.0 beats/min). We conclude that daily exercise prevents VF induced by acute myocardial ischemia in a subpopulation of dogs that were previously identified as susceptible to sudden cardiac death. Exercise also altered the autonomic control of the heart, possibly decreasing sympathetic and/or increasing parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hormonal and renal response to plasma volume expansion in the primate Macaca mulatta.

The purpose of this study was to investigate the hormonal and renal response to plasma volume expansion in the ketamine-anesthetized rhesus monkey. The blood volume was determined in nine animals and found to be 6% of the body weight. Six monkeys received isoncotic isotonic fluid amounting to 25% of the blood volume. Plasma volume expansion led to significant decrease in the plasma concentrations of antidiuretic hormone (46.7%) and aldosterone (78.4%) as well as plasma renin activity (50.0%). The mean arterial pressure, plasma osmolality, and plasma concentrations of Na+ and K+ were unaffected by plasma volume expansion. However, renal plasma flow, glomerular filtration rate, the excretion of Na+ and K+, and urine flow increased. It was concluded that, in the ketamine-anesthetized rhesus monkey, circulating hormones contribute to blood volume homeostasis presumably through a neural mechanism similar to that observed in dogs and humans.

Aldosterone↗

Changes in diastolic coronary resistance during submaximal exercise in conditioned dogs.

Diastolic coronary resistance (DCR) was studied in 10 conscious dogs in the untrained (UT) and partially trained (PT) condition. The PT regime consisted of treadmill running 5 days/wk for 4-5 wk. Left circumflex coronary flow, aortic pressure, and heart rate were measured, and diastolic coronary resistance (DCR) was calculated. Adrenergic blockade was achieved with propranolol (1 mg/kg, iv) (beta B) and phentolamine (1 mg/kg, iv) (alpha B). During submaximal exercise in the UT condition, DCR fell from a resting value of 3.84 +/- 0.24 Torr . ml-1 . min with increasing work load to 1.57 +/- 0.12 Torr . ml-1 . min at 6.4 km/h (speed)/16% (grade). The decrease in DCR during submaximal exercise was greater in the PT than in the UT condition. DCR following alpha-adrenergic blockade was not significantly changed in the UT and PT conditions (e.g., at 6.4 km/h (speed)/16% (grade), 1.10 +/- 0.141 vs. 1.03 +/- 0.107 Torr . ml-1 . min, whereas following beta-adrenergic blockade, DCR was larger in the UT compared with the PT condition (e.g., at 6.4 km/h (speed)/16% (grade), 2.03 +/- 0.091 vs. 1.73 +/- 0.073 Torr . ml-1 X min). Myocardial oxygen consumption was not significantly different in the PT and UT conditions, indicating no difference in metabolism with partial training. The present study suggests that during submaximal exercise in the PT condition there is a change in the neurogenic control of the coronary vasculature by a reduction in sympathetic neural activity on the coronary resistance vessels.

Animals↗

Alteration of ischemic cardiac function in normal heart by daily exercise.

Myocardial function, tissue blood flow, and heart rate measurements were studied during control and a 2-min occlusion of the left circumflex coronary artery in conscious dogs. These measurements were made in the same dogs before exercise in the untrained state (UT) and after a 4-wk treadmill exercise program in the partially trained condition (PT). Ultrasonic segment length gauges were used to measure myocardial function in the ischemic zone, defined by staining the myocardial tissue. Microspheres (15 microns), labeled with different isotopes, were used to measure the myocardial tissue flow in the normal and ischemic zones. Myocardial function in the ischemic zone of 20 dogs was reduced 71 +/- 6% in the UT condition; however, after PT, the percent reduction in segment length function was only 33 +/- 4% during occlusion. During occlusion, an increase in heart rate of 46 +/- 7% in the UT condition was observed; yet after PT, heart rate increased only 19 +/- 5%. In 5 UT dogs with heart rate held constant (150 beats/min), the decrease from control in tissue blood flow to the ischemic zone in the subendocardium during occlusion was 60 +/- 7%. After PT, the decrease from control in tissue blood flow in the same dogs was 34 +/- 6%. These data indicate that the improved myocardial function during ischemia was a result of the improved coronary collateral blood flow into the ischemic zone after PT.

Animals↗

A comprehensive retraining program for inactive medical technologists.

Shortage of laboratory personnel appears to have created growing interest and activity in retraining inactive medical technologists. A recent three year program at the University of Wisconsin involving 63 individuals enrolled in one or more courses provides some results. Twenty-three are now employed, and nine are actively seeking employment. The development, presentation, evaluation and cost of the program are here reported.

Adolescent↗

Left stellectomy and denervation supersensitivity in conscious dogs.

The possibility that denervation supersensitivity might result from left stellectomy was investigated because of its potential clinical implications. The study was conducted in 12 conscious dogs by injecting norepinephrine as a bolus dose or as an infusion before and 2 to 4 weeks after left stellectomy. The variables analyzed were the first derivative of left ventricular pressure (dP/dt max) and the number of premature ventricular complexes. Under control conditions dP/dt max was unaffected by left stellectomy (3,572 +/- 280 versus 3,549 +/- 235 mm Hg/s). Bolus injections and infusions produced the same results and showed no difference in the increases in dP/dt max produced by norepinephrine observed before and after left stellectomy. For example, with the largest dose of norepinephrine, 1.25 microgram/kg, the changes from the control value were 4,533 +/- 269 and 5,032 +/- 668 mm Hg/s, respectively (difference not significant). The number of premature ventricular complexes resulting from the two largest doses of norepinephrine was significantly decreased after left stellectomy (85 +/- 12 versus 46 +/- 14, P less than 0.05), and ventricular tachycardia, which occurred in three dogs under control conditions, was never observed after left stellectomy. This study reveals another aspect of the antiarrhythmic effect of left stellectomy and demonstrates that it does not produce denervation supersensitivity.

Animals↗

Coronary blood flow changes following activation of adrenergic receptors in the conscious dog.

The role of coronary vascular adrenergic receptors in changing coronary flow was studied in dogs instrumented to measure left circumflex artery blood flow (CBF), mean coronary artery blood pressure (CBP), and heart rate (HR). Norepinephrine (NE), isoproterenol (IP), and phenylephrine (PH) were injected into the left circumflex artery before and after selective intracoronary alpha- and beta 1- or combined beta 1- and beta 2-receptor blockade. NE, IP, and PH did not alter CBP (112 +/- 6 mmHg). In addition, IP and PH did not affect HR (103 +/- 4 beats/min). NE increased HR to 150 +/- 6 beats/min, which was eliminated by blocking beta 1-receptors with atenolol and by removing the left stellate ganglion. IP increased CBF from 65 +/- 9 to 115 +/- 16 ml/min (mediated by both beta 1- and beta 2-receptors). PH caused an alpha-receptor-mediated coronary vasoconstriction (42 +/- 5 ml/min), which was potentiated by beta 1- and beta 2-receptor blockade. NE caused a biphasic flow response. CBF initially increased to 117 +/- 14 ml/min (mediated predominantly by beta 1-receptors) followed by a prolonged decrease to 54 +/- 7 ml/min (mediated by alpha-receptors). Removing the left stellate ganglion did not affect the CBF response to NE. These data indicate that PH directly stimulates coronary alpha-receptors and IP stimulates myocardial beta 1- and coronary beta 2-receptors. NE also stimulates myocardial cells causing a reflex that increases HR and indirectly increases CBF. The vasoconstriction to NE and PH was not evident after pentobarbital anesthesia, whereas the coronary vasodilation and increase in HR to NE was still present.

Animals↗

Effects of horizontal body casting on the baroreceptor reflex control of heart rate.

The purpose of this study was to investigate the effects of long-term horizontal body position on baroreceptor reflex control of heart rate. Six male rhesus monkeys (6.2-9.4 kg) were given bolus injections of 4.0 micrograms/kg phenylephrine during each of the following conditions: awake, anesthetized (10 mg/kg ketamine HCl), and after beta-blockade (1 mg/kg propranolol HCl) before, 7, 14, and 28 days after being placed in a horizontal body cast. R-R interval vs. systolic arterial pressure was plotted, and the slope was determined by least-squares-fit linear regression. Baroreceptor slope was significantly reduced by 7 days of horizontal body position and remained attenuated throughout the 28-day restraint period both before and after beta-receptor blockade. These data are consistent with the thesis that prolonged exposure to a zero-gravity environment impairs autonomic reflex regulation of the cardiovascular system.

Animals↗

Effect of exercise conditioning on coronary resistance.

Diastolic coronary resistance (DCR) was determined in seven conscious dogs in the untrained state and after 4-5 wk of daily exercise conditioning (partial training). The conditioning regime consisted of treadmill running 5 days/wk. The dogs were instrumented to measure aortic pressure and left circumflex coronary flow during atrial pacing with implanted electrodes. Heart rate was varied from the resting value to 240 beats/min before and after adrenergic blockade with propranolol (beta B, 1 mg/kg) or phentolamine (alpha B, 1 mg/kg); myocardial oxygen consumption (MVO2) was measured in three dogs under the same condition in both the untrained (UT) and partially trained (PT) condition. DCR decreased with increasing heart rate [from 4.75 +/- 0.56 (SE) to 2.48 +/- 0.22 Torr . ml-1 . min at 240 beats/min]; alpha B reduced DCR, whereas beta B increased DCR. In the PT condition, DCR decreased to 4.02 +/- 0.40 Torr . ml-1 . min at rest and was decreased to 1.82 +/- 0.16 Torr . ml-1 . min at 240 beats/min (P less than 0.05 compared with UT). alpha-Adrenergic and beta-adrenergic blockade in the PT condition resulted in parallel reduction in DCR compared with the UT condition. MVO2 was unaffected by either PT or adrenergic blockade but increased as heart rate increased with atrial pacing. These data suggest a change in caliber of the coronary resistance vessel because of the parallel shift in the relationship between DCR and heart rate.

Animals↗

The effect of metoclopramide and dopamine on plasma aldosterone concentration in normal man and rhesus monkeys (Macaca mulatta): a new model to study dopamine control of aldosterone secretion.

Metoclopramide, a dopamine receptor antagonist, increases plasma aldosterone concentration in man, suggesting that dopamine regulates the secretion of aldosterone. In the current study, we administered metoclopramide to rhesus monkeys and normal subjects and compared the time-course and dose-response characteristics of plasma aldosterone. We also examined the effect of dopamine on the plasma aldosterone response to metoclopramide in both species. Six male rhesus monkeys and several normal subjects (five women and two men) were studied on diets providing an estimated daily sodium intake of 70 mg/kg. In both species the peak increase in plasma aldosterone occurred 15 min after metoclopramide was injected. The peak plasma aldosterone value was 3-fold higher than control values. There were no significant changes in PRA, cortisol or potassium, whereas plasma PRL increased 7-fold in the monkeys and 11-fold in the normal subjects. After 0.04 mg/kg metoclopramide, there was no change in plasma aldosterone concentration in the monkeys, whereas aldosterone increased significantly (delta = 3.7 +/- 0.68 ng/dl) in the human subjects. The half-maximal dose of metoclopramide was also higher in the monkeys than in the normal subjects. A dopamine infusion at 4.0 to 8.0 micrograms/kg . min partially suppressed the plasma aldosterone response to metoclopramide in both the human subjects and the monkeys. This study demonstrates that metoclopramide produces dose-related increases in plasma aldosterone concentration in the nonhuman primate that are similar to those in normal man and that the increases can be inhibited by dopamine. We conclude that aldosterone secretion may be under dopamine control and that the rhesus monkey should be an excellent model in which to study further the regulation of aldosterone by dopamine.

Adult↗