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Biomedical subjects

D C Randall

Publications and source records attributed to D C Randall.

At least 55 records · Page 3Linked to original sources
PubMed1988

Control of left ventricular function during acceleration-induced blood volume shifts.

Peripheral pooling of blood was produced in chronically instrumented, sedated dogs (n = 7) by subjecting them to a +2 Gz force (along their spinal axis) for 3 min. The acceleratory force was then quickly removed, thereby mobilizing blood toward the thoracic cavity. Left ventricular volume, calculated from ultrasound measurements of major and minor axes and wall thickness, increased (p less than 0.05) from 21.7 +/- 3.6 ml (diastolic, mean +/- S.E.M.) and 14.1 +/- 3.3 ml (systolic) during the peripheral pooling of blood to 28.2 +/- 4.1 ml (diastolic) and 16.0 +/- 2.9 ml (systolic) as measured at 2 min after release of the acceleratory force. The d(LVP)/dt was essentially unchanged (i.e., from 3415 +/- 482 mm Hg.s-1 to 3536 +/- 249 mm Hg.s-1). The experiment was repeated after total pharmacologic autonomic blockade (propranolol, atropine, phenoxybenzamine). Left ventricular volumes during +2 Gz after blockade were 27.7 +/- 2.5 ml (diastolic) and 21.2 +/- 2.9 (systolic). The acceleration-induced changes in cardiovascular function, including the changes in ventricular volume, were not significantly different from those of the reflexive state. These results, therefore, do not reveal a substantial role for the autonomic nervous system in the regulation of left ventricular volume responses to the sudden cessation of G-induced peripheral blood pooling. Since the cessation of the G force induced essentially identical increases in left ventricular volumes and stroke volumes both before and after the autonomic blockade, it is concluded that the heart relied mainly upon the Frank-Starling mechanism to adapt to the changes in load.

Acceleration↗
PubMed1985

A comparison of the autonomic nervous control of the heart during classical aversive vs appetitive conditioning in dog.

Dogs were trained in either classical (i.e. Pavlovian) appetitive (n = 7) or aversive (n = 7) conditioning by presenting a tone (the conditional stimulus, CS +) that was followed by either food or shock delivery, respectively. In the first case, dog food was given to the animals during the last 30 s of a 1 min CS+. Aversive conditioning was accomplished by giving a 1 s shock at the end of a 30 s CS+. The control consisted of a different tone (CS-) which was never followed by food or shock. A chronically implanted transducer was used to record left ventricular pressure from which its first time derivative was calculated; d(LVP)/dt was used as an index of myocardial inotropic state. Heart rate (HR) was also determined. These data were averaged over the 30 s prior to the CS+, the 30 s of the conditional stimulus tone itself, and the 30 s following shock or during food delivery. Well-trained animals evidenced changes in cardiac inotropism and chronotropism during the CS+ and also in response to unconditional shock or food; these are referred to as the conditional and unconditional cardiovascular responses, respectively. No statistically significant HR or d(LVP)/dt changes were observed during the CS-. The conditional response to food was small: relative to the pre-CS+ interval, average HR increased 11 bpm (P less than 0.05) and average d(LVP)/dt increased 309 mm Hg/s (P less than 0.01). During food delivery, HR increased by additional 23 bpm (P less than 0.01) and d(LVP)/dt increased by another 232 mm Hg/s (P less than 0.01). Beta-adrenergic blockade virtually eliminated the conditional HR and d(LVP)/dt response to food, indicating that both the chronotropic and inotropic changes during CS+ were due to elevated sympathetic drive. beta-blockade did not eliminate the unconditional HR response (+17 bpm, P less than 0.01), indicating that parasympathetic withdrawal has a mediating role in this persisting tachycardia. The conditional response to shock consisted of a 26 bpm increase in HR (P less than 0.01), while d(LVP)/dt increased 998 mm Hg/s (P less than 0.01). The beta-blockade reduced the HR conditional response to +8 bpm (NS) and essentially eliminated the increase in d(LVP)/dt. These data indicate that increases in cardiac sympathetic tone play a primary role in mediating the conditional cardiovascular response for both paradigms. Parasympathetic withdrawal, on the other hand, figures critically in mediating the unconditional response to food.

Animals↗
PubMed1985

Behaviorally conditioned changes in atrio-ventricular transmission in awake dog.

The purpose of this study was to examine the effects of behaviorally conditioned changes in autonomic activity on atrio-ventricular (AV) transmission in dog. To produce consistent activation of the cardiac nerves in the awake animal (n = 7), a classical appetitive conditioning paradigm was used. A conditioning trial consisted of a 30 s control period followed by one of two differing situations: (1) a 60-s conditional stimulus (CS+) tone wherein food (i.e. 'UCS' or unconditioned stimulus) was given during the last 30 s; or (2) at 30-s discriminative stimulus (CS-) tone which was never followed by food reward. Eight of each type trial were given daily until a stereotypic cardiovascular response was developed for the CS+ but not the CS-. The hemodynamic conditional response (i.e. 'CR', the response to the CS+) consisted of a moderate tachycardia (+14.5%, P less than or equal to 0.05), a small pressor response (+6.7%, P less than or equal to 0.01), and a moderate increase in the first time derivative of left ventricular pressure (+14.9%, P less than or equal to 0.01) reflecting an increase in inotropic state. The unconditional response (i.e., 'UCR', the response to the food reward) consisted of a substantial increase in HR (25.7%, P less than or equal to 0.01) above CR values while left ventricular pressure (LVP) and d(LVP)/dt increased 5.0% and 10.0% (P less than or equal to 0.01 for both) above their CR values. The effect of the conditioned changes in neural activity on the AV node was observed by pacing the atrium from 110 to 180 bpm during the first 15 s of each trial period (i.e. control, CS+, UCS). The discrepancy between the atrial pace rate and the transmitted ventricular rate is expressed as a 'mean difference score' and serves as an index of the fidelity of the AV transmission process: the smaller the difference, the closer a 1:1 ratio of atrial vs ventricular beats is approached. The relatively large mean difference score for the control periods (46.0 +/- 9 bpm) indicates that the paced atrial impulse did not faithfully precede ventricular contraction during these periods. The mean difference significantly decreased (34.6%, P less than or equal to 0.05) during the CS+, and approached an almost 1:1 ratio (75.6% decrease from CS+ values, P less than or equal to 0.01) during food delivery. beta-Adrenergic blockade (propranolol, 1 mg/kg, i.v.) eliminated the changes in mean difference during the CS+ but not during food delivery. There were no statistically significant physiological changes during CS-.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Prevention of sudden death after repair of tetralogy of Fallot: treatment of ventricular arrhythmias.

The majority of sudden deaths after repair of tetralogy of Fallot have been presumed to be due to ventricular arrhythmia; however, it remains to be demonstrated that antiarrhythmic medication reduces the incidence of sudden death. Since 1978, ventricular arrhythmias have been treated aggressively; these include any ventricular arrhythmia on routine electrocardiogram and more than 10 uniform premature ventricular complexes per hour on 24 hour electrocardiogram. A review was undertaken of 488 patients followed up for more than 1 month after repair of tetralogy of Fallot (mean follow-up time 6.1 years); 13.5% had ventricular arrhythmia on routine electrocardiogram. Ventricular arrhythmia appeared from 2 months to 21 years postoperatively (mean 7.3 years). Ventricular arrhythmias were significantly (p less than 0.01) related to: longer follow-up duration, older age at follow-up, older age at operation and higher postoperative right ventricular systolic and end-diastolic pressures. Ventricular arrhythmia on routine electrocardiogram occurred in 100% of those who later died suddenly compared with 12% of those who did not die (p less than 0.01). Treatment for ventricular arrhythmia was given to 46 patients and considered "successful" if there were fewer than 10 uniform premature ventricular complexes per hour on 24 hour electrocardiogram. A successful drug was found in 44 of the 46: 30 of 34 given phenytoin, 6 of 9 given propranolol, 1 of 7 given quinidine, 1 of 2 given disopyramide, 8 of 9 given mexiletine and 4 of 5 given amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Hibernation "trigger": opioid-like inhibitory action on brain function of the monkey.

A hibernation "trigger" factor derived from the blood of the hibernating woodchuck acts to suppress vital physiological processes in the primate. When infused into the cerebral ventricle of the conscious monkey, the factor induced hypothermia, behavioral depression, bradycardia and aphagia. The opiate antagonists, naloxone and naltrexone, either reverse or retard these behavioral and physiological signs. We hypothesize that the "trigger" molecule is an endogenous opioid-like peptide which may be unique to the hibernator. Moreover, the non-hibernating primate apparently possesses receptor sites in the brain that are capable of responding to this potent molecule.

Animals↗
PubMed1982

Cardiovascular regulation in canines during low-frequency acceleration.

Integrated, reflex, cardiovascular regulation in unanesthetized (tranquilized), chronically-instrumented dogs was studied using sinusoidal whole-body spinal-axis acceleration (+/- 2 Gz) at frequencies below 0.25 Hz. The participation of neurally mediated cardiac and vascular control mechanisms was examined by comparing the responses of the same animal in a normal (reflexive) state and ina pharmacologically blockaded (nonreflexive) state. Integrated neural mechanisms were found to be the most effective in minimizing acceleration-induced, arterial pressure disturbances for frequencies below 0.012 Hz; became progressively out of phase with the disturbances between 0.012 and 0.052 Hz, resulting in decreased effectiveness; and failed to significantly participate in the regulatory process for frequencies between 0.052 and 0.25 Hz, where "protection" was provided by the hydraulic and intrinsic biomechanical characteristics of the circulatory system. An analysis of the relative contribution of peripheral vascular and cardiac mechanisms indicated that 1) neurally mediated, systemic vascular responses were largest for frequency; 2) heart rate oscillations were large for frequencies below 0.052 Hz (corner frequency) and then decreased rapidly with increasing frequency; and 3) neurally mediated stroke volume oscillations were the largest for the lowest frequencies and decreased with increasing frequency.

Animals↗
PubMed1982

Heart rate adaptation to exercise training in cardiac-denervated dogs.

To determine the effect of cardiac denervation on the development of a training-induced decrease in heart rate at rest and during submaximal exercise, six cardiac-denervated (CD) and six sham-operated (SO) dogs were exercise trained by means of a 6-wk treadmill running program. Gastrocnemius citrate synthase activity increased significantly to the same degree in CD and SO dogs indicating that both groups were equally trained. Resting heart rates (RHR) for SO dogs decreased significantly from 64 +/- 4.8 to 51 +/- 3.2 beats/min (mean +/- SE) from pre- to posttraining. CD dogs showed no changes in RHR (95 +/- 3.5 to 96 +/- 5.3 beats/min). Heart rate responses of SO dogs to a standardized, submaximal exercise test decreased significantly from pre- to posttraining. However, CD dogs displayed no decrease in heart rate responses to the standardized, submaximal exercise test. Additionally, at pre- and posttraining, as heart rates rose in response to exercise test intensity, they increased to a significantly greater degree in SO dogs compared with CD dogs. The results indicate that in dogs, cardiac denervation prevents the decreases in resting heart rate and heart rate during submaximal exercise normally associated with endurance exercise training.

Adaptation, Physiological↗
PubMed1981

Neural, hormonal and intrinsic mechanisms of cardiac control during acute coronary occlusion in the intact dog.

Three basic mechanisms may be involved in the control of cardiac function during acute coronary occlusion: (1) neural; (2) hormonal (circulating catecholamine); and (3) intrinsic (e.g. Frank--Starling law). The response of intact, sedated (Innovar-Vet, 0.08 cc/kg), chronically instrumented dogs to a 5 min left circumflex coronary occlusion was tested to delineate the relative roles of each of the above mechanisms. First, 6 innervated and 6 cardiac denervated dogs were examined. The major difference between groups was that the occlusion-induced tachycardia was significantly smaller in the denervated dogs than in the normally innervated animals (+10 +/- 7 vs +27 +/- 4/min, respectively, (mean +/- S.D.)). Changes in the first time derivative of left ventricular pressure (d(LVP)/dt) were similar (--898 +/- 556 vs --796 +/- 274 mm Hg/sec, denervated vs innervated). Decreases in stroke volume and mean arterial pressure were also similar in the two groups. The occlusion-induced tachycardia was compared in a second group of denervated dogs (n = 5) before and after administration of propranolol to examine the role of circulating catecholamines, and, by exclusion, to observe the response of the heart per se, independently of extrinsic control factors. The heart rate response was similar in both cases (+8 +/- 4 vs +6 +/- 4/min, unblocked vs blocked). Finally, blood pressure was prevented from falling during coronary occlusion in 3 normally innervated dogs by coupling the femoral artery to a reservoir of saline suspended above the animals. Blunting the input to the baroreceptors in this manner did not significantly change the size of the occlusion-induced tachycardia. We conclude that during acute coronary occlusion in dog: (1) the major role of the cardiac nerves involves modulating changes in the chronotropic state of the heart; (2) changes in d(LVP)/dt result principally from intrinsic phenomena linked to ischemia-induced alterations in myocardial performance; (3) changes in circulating catecholamines play only a minor role in controlling the heart during acute coronary occlusion in denervated dog; and (4) receptors located within the heart figure significantly in the etiology of the occlusion-induced tachycardia.

Acute Disease↗
PubMed1981

Mechanisms mediating the coronary vascular response to behavioral stress in the dog.

Left circumflex coronary blood flow (CBF) was measured in eight mongrel dogs with 8 MHz continuous wave Doppler flow transducers during classical aversive conditioning. The cardiovascular condition response consisted of significant (P less than 0.01) increases in: (1) mean aortic pressure (16.1%), (2) d(left ventricular pressure)/dt (64.2%), and (3) heart rate (63.2%). The coronary vascular response to behavioral stress consisted of an initial late diastolic decrease in CBF (12.5%) between 5 and 10 seconds after conditional stimulus onset, followed by a significant increase in CBF (96.8%). Concurrently, late diastolic coronary vascular resistance (CVR) first significantly increased (21.9%), then significantly decreased (39.8%). The increase in CVR was attenuated by cardiac pacing and converted into a significant decrease after alpha-receptor blockade. The decrease in CVR was reduced either by cardiac pacing or cardioselective beta-receptor blockage and eliminated by the combination of alpha- and beta-receptor blockade. Thus, these data indicate that the coronary vascular response to stress consisted of two components: an initial alpha-adrenergic coronary vasoconstriction, followed by a more complex vasodilation which was probably mediated by metabolites released secondarily to increases in heart rate and inotropic state.

Adrenergic alpha-Antagonists↗
PubMed1976

Response of primate heart to emotional stress before and after cardiac denervation.

Eleven chair-restrained rhesus monkeys were classically conditioned to a 1-min, 900-Hz tone (CSf) followed by food and a 1-min, 3.4-5Hz tone (CSs) followed by shock. Each conditional stimulus produced large, sudden, and highly significant (P less than .01) increases in left ventricular systolic pressure (LVP), its first time derivative (d(LVP)/dt), and heart rate (HR). The animal's hearts were sugically denervated following control studies of the conditional responses. Two to four weeks later, these responses were reexamined by again presenting CSf and CSs to five surviving monkeys following a format identical to that used in the control experiments. Complete cardiac denervation virtually eliminated the sudden increases in each of the measured variables. Denervation also "unmasked" small-magnitude, delayed chronotropic and inotropic responses during CSs (but not CSf). These effects were ascribed to the action of circulating catecholamines known to be secreted during "emotional" stress. Four monkeys studied for 6 mo or more postoperatively showed evidence for varying degrees of cardiac reinnervation. Loss of nervous control of the nonhuman primate heart greatly compromises the cardiovascular response to these environmental and behavioral stress situations.

Animals↗