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R S Tuttle

Publications and source records attributed to R S Tuttle.

At least 37 records · Page 2Linked to original sources

Pharmacology of the hemodynamic and myocardial response to occlusion of the mesenteric artery in the cat.

Occlusion of the superior mesenteric artery in the cat produces increases in heart rate, systemic pressure, cardiac output and muscle blood flow. Total peripheral resistance is reduced and regional resistance in skin increased. Blockade of the right and left cardiac nerves with xylocaine lowered basal heart rate and reduced cardiac output. The increase in heart rate produced by occlusion of the artery (MAO) was prevented by blockade of the stellate ganglia and cardiac nerves. Propranolol lowered basal heart rate and cardiac output and subsequently blocked the increase in both parameters during MAO. The increase in muscle blood flow was also blocked resulting in an increase in total resistance. We conclude that, in the cat, MAO reflexly increases myocardial tone and enhances venous return from muscle, the latter by a reflex beta adrenergic vasodilation. Both factors provide for the increase in cardiac output. A reflex beta adrenergic vasodilation in muscle, evoked by vasoconstriction in the mesenteric bed, may contribute to survival in the hemorrhaged animals, since capillary exchange in muscle may be increased by this reflex and fluid shifted from the extra--to the intravascular compartment.

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Hemodynamic reflex in muscle in response to brief occlusion of the mesenteric artery.

Brief occlusion of the superior mesenteric artery in the cat produces increases in systemic pressure and in muscle blood flow. Capillary filtration in muscle, measured during occlusion of the superior mesenteric artery, exceeds that of the controls. Propranolol, which blocks the evoked increase in muscle blood flow, reduces capillary filtration during occlusion to less than the control. Cutting the mesenteric nerve returns capillary filtration to the control level. Passive redistribution of blood, such as might follow occlusion of a large vascular region, is not the basis for the evoked changes in muscle hemodynamics. They are abolished by cutting the mesenteric nerve and by propranolol, and are demonstrable during constant pressure perfusion of muscle. The evidence suggests that occlusion of the mesenteric artery produces an increase in capillary filtration by balancing a reflex sympathetic beta-adrenergic vasodilation in pre-capillary resistance vessels with an increase in resistance in the precapillary sphincters.

Animals↗

Mesenteric baroreceptors.

Occlusion of the mesenteric vessels in the cat and injection of catecholamines produced significant changes in skin and muscle blood flows. These were abolished by cutting the mesenteric nerves. The occurrence of systemic pressure and peripheral resistance changes in cross-perfused mesenteric preparations indicates that hemodynamic factors alone, such as might result from occlusion of a large vascular region, were not initiating the reflex. This also excludes extramesenteric receptors within the heart and large vessels from the reflex. Since both intravascular pressure and catecholamines have been shown to modify Pacinian receptor discharge in vivo, the evidence suggests that the mesenteric Pacinian corpuscle is the baroreceptor probably initiating the vasomotor reflexes in skin and muscle. The net effect of mesenteric receptor activity appears to be an inhibition of vasomotor neurons supplying skin and muscle.

Animals↗

Cardiovascular effects of 1-benzylimidazole.

A derivative of imidazole, 1-benzylimidazole [(1-phenylmethyl)-H-imidazole], was found to have strong cardiotonic activity. In isolated ventricular strips of rabbits, 6.3 times 10(-5) M 1-benzylimidazole (BI) increased contractile force by 100%, and in the intact cat, 0.5 mg/kg of BI increased cardiac output by 30 to 40%. The increase was maintained in both preparations for 5 to 30 minutes. Heart rate was not changed in the atropine-pretreated cat. Basic cycle length, recorded intracellularly in rabbit sinoatrial nodal cells, was increased by 8%. Since BI had many actions similar to the cardiac glycosides, including the absence of effects on rate and resistance to adrenergic beta blockers, it was of interest to determine whether BI and ouabain could interact and modify, or enhance their respective actions. In combination, it was found that ouabain and BI had summative effects on contractility and maintained the frequency-force relationships. In this respect, the action of BI is similar to that of glucagon and Ca++, but not to that of the catecholamines.

Animals↗

Separation of antihypertensive from ganglioplegic effects of felodipine in the cat.

The effects of felodipine on sympathetic ganglionic transmission and on the effector responses of two muscle models were studied. In anesthetized cats we established what injected dose and plasma levels of this selectively vasodilating dihydropyridine were necessary for the neural and for the primary hypotensive effects on arterial blood pressure in vivo. Felodipine in cats reduced mean arterial pressure at a dose of 0.010 mumol/kg i.v., corresponding to a plasma concentration of 10 nmol/L. A 15-25-fold higher dose, or plasma concentration, was required to produce a significant reduction in the amplitude of the sympathetic postganglionic action potential (PAP). The latencies of the PAPs remained constant. Felodipine in vitro did not attenuate the neurogenic response of the nictitating membrane. However, the spontaneous activity, as well as the neurogenic response of the portal vein, was inhibited by felodipine in nanomolar concentrations. Felodipine at the highest dose caused a small but significant attenuation of the postganglionic nictitating membrane response in vivo. This reduction was of insufficient magnitude to account alone for the diminution of the response to preganglionic stimulation. We conclude that felodipine in low concentrations reduces blood pressure by a direct relaxation of vascular smooth muscle, while, in addition, at high concentrations a partial ganglionic blockade may be induced.

Action Potentials↗