The effects of extracellular ions on βblocker cardiotoxicity

William Kerns, Mary Ransom, Christian Tomaszewski, Jeffrey Kline, Richard Raymond

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The mechanism of β-blocker induced cardiotoxicity is poorly understood. One possible explanation is that β-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 β-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 ug/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 + ↓K, and (7) ATEN + ↑Na. PROP induced negative chronotropic effects and rendered the hearts refractory to pacing. ATEN demonstrated similar chronotropic toxicity plus decreased myocardial contractility. Tx with low extracellular K+ and high extracellular Na+ increased HR and restored the ability to pace, thereby reversing toxicity. These data suggest that β-blocker toxicity is mediated via hyperpolarization.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalToxicology and Applied Pharmacology
Volume137
Issue number1
DOIs
StatePublished - Mar 1996
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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