The effects of extracellular ions on beta-blocker cardiotoxicity

Toxicology and Applied Pharmacology
W KernsR Raymond

Abstract

The mechanism of beta-blocker induced cardiotoxicity is poorly understood. One possible explanation is that beta-blockers induce ion dyshomeostasis, resulting in cardiac hyperpolarization. The intent of this study was to determine if modifying extracellular ions would reverse cardiotoxicity from two beta-blockers: propranolol (PROP) and atenolol (ATEN). Two treatments were studied: low extracellular K+ and high extracellular Na+. Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit- Bicarbonate buffer (KHB) solution. Toxicity (Tox) was induced by perfusing hearts for 30 min with KHB + PROP [5 microgram/ml] or KHB + ATEN [2.5 mg/ml]. Subsequently, hearts were perfused with KHB containing either PROP or ATEN, but modified by lowering K+ [2.3 mM] or raising Na+ [160 mM] for a 30-min treatment (Tx) period. Hearts were paced near the end of treatment. Cardiodynamics were monitored via a balloon-tipped catheter in the left ventricle. The first derivative of LV pressure (dP/dt) with respect to time served as our index of myocardial performance. Tx groups were as follows: (1) KHB only, (2) PROP only, (3) PROP + K, (4) PROP + Na, (5) ATEN only, (6) ATEN 4 K, and (7) ATEN + Na. PROP induced negative chronotro...Continue Reading

Citations

Aug 10, 2000·Journal of Toxicology. Clinical Toxicology·J N LoveK J Henderson
Aug 26, 2014·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·C William HeiseKimberlie Graeme
Jun 1, 1997·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·W KernsR Raymond
Jan 21, 2012·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Jeanna M MarraffaMary Ann Howland
May 19, 2005·Toxicological Reviews·Christopher R DeWitt, Javier C Waksman

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