title: Contrasting effects of anoxia and graded hypoxia on single cardiac myocyte function.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland 21205.
authors.forename: H S
authors.initials: HS
authors.lastname: Silverman
authors.forename: M D
authors.initials: MD
authors.lastname: Stern
authors.forename: E G
authors.initials: EG
authors.lastname: Lakatta
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002469:Cell Separation; D004558:Electric Stimulation; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology