Characterization of the electromechanical effects of the ionophore salinomycin on isolated mammalian ventricular muscle

CHARACTERIZATION OF THE ELECTROMECHANICAL EFFECTS OF THE IONOPHORE SALINOMYCIN ON ISOLATED MAMMALIAN VENTRICULAR MUSCLE. M.S. Gaide, Department of J. Lehr, H. Gelband, B.C. Pressman and A.L. Bassett. Pharmacology, University of Miami Medical School, Miami, Florida, U.S.A. The carboxylic ionophore salinomycin (S) enhances cardiac contractility in the intact dog by an unelucidated mechanism; it also selectively transThe inotropic effect of S was ports I? > Na+ in bulk-phase model systems. studied in isometrically contracting dog and rabbit ventricular muscle (1) repetitively superfused with Tyrode's solution at 36O and stimulated (0.5 Hz) and (2) by sudden exposure to 133 mM Kf. S (0.1 - 10 PM) produced no significant positive inotropic effect and invariably active force was unchanged force (P) and dP/dt decreased within 15 min; resting (1-2 hr). These effects persisted in the presence of B-adrenergic blockade (nadolol 10 i.lM). Pretreatment (30 min) with S (l-10 nM) prior to Intra133 mM K+ did not alter force developed during I<+-contracture. cellular microelectrode recordings revealed that l-50 nM S shortened action potential duration (APD) < 10% at 50, 70 and 100x repolarization. Resting potential and AP rate of rise were reduced by 50 nM S. Our data suggest that S does not significantly enhance intracellular ~1 Ca2+ its inotropic directly nor favorably affects the AP, and consequently (Supported by NIH HL 19044, action --in situ is due to other mechanisms. HL T32 07188 and Heart Assoc. of Greater Miami.)

AN EXPLANATION FOR THE LOSS OF VASCULAR COMPETENCE IN ISCHEMIC MYOCARDIUM. Gavin, J.B., Seelye, R.N. and T.J. Nevalainen. Department of Pathology, University of Auckland School of Medicine, Auckland, New Zealand. To investigate the reasons for the "no reflow" phenomenon which develops in early rnyocardial infarcts, the circumflex branch of the left coronary artery was ligated in anesthetised, heparinised dogs. Sodium fluorescein (1%) was injected distal to the ligatures at intervals after ligation. Standard 5rmn thick transmural sections through the posterior papillary muscle (PPM) were then examined to determine the ability of the ischemically injured blood vessels to conduct tracer. Up to 30 minutes, tracer was evenly distributed across the ventricular wall, between 30-60 minutes, flow to the subendocardium was patchy, beyond 60 minutes the PPM was not perfused. Studies of the compressibility of the myocardium demonstrated that this loss of blood flow was associated with the development of "rigor mortis" in the affected muscle. That this was a cause and effect relationship was demonstrated by perfusing the vessels with an isotonic solution containing 5&4/L iodoacetate to accelerate the development of rigor. The early onset of rigor was paralleled by the premature development of "no flow" in the myocardial vessels supplying the subendocardial myocardium. (Supported by the Medical Research Council of New Zealand).