Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium

John S. Cameron, Linda S. Miller, Shinichi Kimura, Charles J. Kaiser, David R. Campbell, Patricia L. Kozlovskis, Marion S. Gaide, Robert J. Myerburg, Arthur L. Bassett

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pressure overload brought about by renal hypertension on (1) papillary muscle electrophysiology and (2) regional sensitivity to verapamil, LV were isolated from cats subjected to unilateral nephrectomy and contralateral kidney wrapping. After 3 months, systemic hypertension (mean increase=60.2±1.4 mmHg) was associated with moderate LV hypertrophy of ≈18% (LV weight/body weight). Transmembrane action potentials recorded from the endocardial surface (including anterior papillary muscle) in pressure overloaded LV in vitro (800 ms stimulus cycle length) showed increased action potential duration at 25, 75 and 90% of repolarization (APD25, APD75 and APD90, respectively) relative to controls (LV from normal and sham operated cats). With respect to the anterior papillary muscle in pressure overloaded LV, APD25, APD75 and APD90 were increased to a greater extent in cells at the base of the muscle compared to those increases observed at the tip (P<0.05). In contrast to its effects in controls, verapamil (2 μg/ml) significantly reduced APD25 at both the base and the tip of the papillary muscle in pressure overloaded preparations, but particularly at the base; also, the disparities between the APD75 or APD90 at tip and base were decreased. Thus, (1) regional electrophysiologic disparities were induced in systemic hypertension, and (2) these differences were subsequently reduced by verapamil. Highly localized disparate effects of verapamil in normal and pressure overloaded LV myocardium indicate the need to assess drug action in diseased preparations.

Original languageEnglish (US)
Pages (from-to)169-175
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume18
Issue number2
DOIs
StatePublished - Feb 1986

Keywords

  • Action potential duration
  • Anterior papillary muscle
  • Cardiac electrophysiology
  • Cat
  • Left ventricular pressure overload
  • Microelectrodes
  • Renal hypertension
  • Verapamil

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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