Use of the isolated perfused heart for evaluation of cardiac toxicity

P. G. Anderson, S. B. Digerness, J. L. Sklar, P. J. Boor

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mM allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mM allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 ± 0.6 ml/min/g wet heart weight vs 16.0 ± 0.7, p < 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 ± 8 mm Hg vs 103 ± 9, p < 0.01), but by 2 hr was decreased compared to controls (89 ± 6 vs 105 ± 5, p < 0.05). End diastolic pressure was markedly increased at 2 hr (58 ± 3 vs 4 ± 0.8, p < 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.

Original languageEnglish (US)
Pages (from-to)497-510
Number of pages14
JournalToxicologic Pathology
Volume18
Issue number4 I
StatePublished - 1990
Externally publishedYes

Fingerprint

Allylamine
Toxicity
Rats
Blood Pressure
Latex
Sarcoplasmic Reticulum
Ventricular Pressure
Cardiotoxicity
Heart Ventricles
Balloons
Perfusion
Swelling
Pressure
Weights and Measures
Wounds and Injuries
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Anderson, P. G., Digerness, S. B., Sklar, J. L., & Boor, P. J. (1990). Use of the isolated perfused heart for evaluation of cardiac toxicity. Toxicologic Pathology, 18(4 I), 497-510.

Use of the isolated perfused heart for evaluation of cardiac toxicity. / Anderson, P. G.; Digerness, S. B.; Sklar, J. L.; Boor, P. J.

In: Toxicologic Pathology, Vol. 18, No. 4 I, 1990, p. 497-510.

Research output: Contribution to journalArticle

Anderson, PG, Digerness, SB, Sklar, JL & Boor, PJ 1990, 'Use of the isolated perfused heart for evaluation of cardiac toxicity', Toxicologic Pathology, vol. 18, no. 4 I, pp. 497-510.
Anderson PG, Digerness SB, Sklar JL, Boor PJ. Use of the isolated perfused heart for evaluation of cardiac toxicity. Toxicologic Pathology. 1990;18(4 I):497-510.
Anderson, P. G. ; Digerness, S. B. ; Sklar, J. L. ; Boor, P. J. / Use of the isolated perfused heart for evaluation of cardiac toxicity. In: Toxicologic Pathology. 1990 ; Vol. 18, No. 4 I. pp. 497-510.
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