Contrasting effects of anoxia and graded hypoxia on single cardiac myocyte function

H. S. Silverman, M. D. Stern, E. G. Lakatta

Research output: Contribution to journalArticle

Abstract

The hypoxic cardiac myocyte has been used as a simplified model of myocardial ischemia. Precise control of oxygen tension is possible in a system with limited diffusion barriers offering an advantage over tissue preparations. This system was employed to study the effects of graded reductions in oxygen tension on cell morphology, spontaneous and electrically stimulated mechanical activity, and [Ca2+](i) in single adult rat cardiac myocytes. All of 10 resting myocytes exposed to glucose-free anoxia (pO2 < .02 torr) abruptly underwent rigor contracture, retaining a clear sarcomere pattern, following a lag period of 22.6 ± 2.8 minutes. These cells relengthened at reoxygenation 5 minutes following rigor onset. In contrast, 5 of 12 cells exposed to graded hypoxia (1-3 torr) were partially rounded and displayed a disorganized sarcomere pattern during hypoxic exposure and further shortened at reoxygenation (p = .03). Spontaneous mechanical oscillations thought to result from spontaneous sarcoplasmic reticulum calcium cycling only developed in those cells exposed to hypoxia, and their frequency was markedly enhanced in 6 of the 12 exposed cells. None of the 10 cells exposed to anoxia showed an increase in spontaneous activity. When spontaneous mechanical activity and underlying Ca2+(i) oscillations were induced by raising buffer [Ca2+] in 3 indo-1 loaded myocytes, anoxia abolished these as well. Cells stimulated at 0.2 Hz demonstrated spontaneous calcium oscillations and a significant rise in [Ca2+](i) (indo-1 fluorescence ratio) prior to rigor onset only when exposed to graded hypoxia. Thus moderate hypoxia may cause earlier calcium loading and more progressive cell destruction than occurs during anoxia. These findings may in part explain the differences in arrhythmogenecity and in myocardial damage seen in different models of ischemia.

Original languageEnglish (US)
Pages (from-to)256-264
Number of pages9
JournalAmerican Journal of Cardiovascular Pathology
Volume4
Issue number3
StatePublished - Dec 1 1992

Keywords

  • Calcium
  • Hypoxia
  • Myocyte

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Contrasting effects of anoxia and graded hypoxia on single cardiac myocyte function'. Together they form a unique fingerprint.

  • Cite this