Title

Factors Retarding Death Of Adult Rat Ventricular Myocytes In Conditions Approximating Ischemia

Date of Award

1984

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmacology

Abstract

Myocardial cell responsiveness to ionic and energy conditions approximating ischemia was evaluated in the presence and absence of selective Ca('++) antagonists.Individual cells were isolated from adult rat ventricle; viability was assessed over time. Cell decline was accelerated by both elevated K('+)(,o) and decreased Na('+)(,o) in a concentration-dependent manner in the presence of 1 mM Ca('++)(,o) under limited energy conditions (N(,2) + glucose). In the absence of added Ca('++), cell decline was diminished by both elevated K('+)(,o) and decreased Na('+)(,o) in a concentration-dependent manner. Altered pH had no observable effect on K('+)(,o) or Na('+)(,o)-induced changes in cell viability.Verapamil and diltiazem inhibited high K('+)-induced increases in cell decline in the presence of 1 mM Ca('++); nisoldipine and nitrendipine had no effect. None of the these drugs affected Na('+)-induced increases in cell decline in the presence of 1 mM Ca('++).(')Verapamil and diltiazem did not affect the frequency of induced oscillations in skinned heart cells. Their effects on cell viability were additive to those of caffeine.A cardioplegic formulation was devised to maximally protect heart cells in low energy conditions by reducing ion gradients and including selective Ca('++) antagonists to control free Ca('++).

Keywords

Health Sciences, Pharmacology

Link to Full Text

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