Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures

J. E. Heavner, B. Shi, K. Inners-McBride, G. Asimakis, M. J. Wang, D. C. McIntyre

Research output: Contribution to journalArticlepeer-review

Abstract

Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vive differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5X10-6, 1X10-5, 5X10-5, 1X10-4, and 5X10- 4 M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vive observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5X10-5M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10-4M cocaine: Arrest in Fast hearts occurred only with 5X10-4M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.

Original languageEnglish (US)
Pages (from-to)625-633
Number of pages9
JournalLife Sciences
Volume63
Issue number8
DOIs
StatePublished - Jul 17 1998
Externally publishedYes

Keywords

  • Cocaine cardiotoxicology
  • Coronary artery
  • Differential sensitivity
  • Kindling
  • Langendorff preparation
  • Rats

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

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