缺氧(环境)
心肌细胞
收缩性
内科学
灌注
生物
内分泌学
无氧运动
医学
化学
氧气
生理学
有机化学
作者
Howard S. Silverman,Shao-kui Wei,Mark C. Haigney,Christopher Ocampo,Michael D. Stern
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:1997-05-01
卷期号:80 (5): 699-707
被引量:80
标识
DOI:10.1161/01.res.80.5.699
摘要
Abstract Studies in animal models and humans suggest that myocardium may adapt to chronic or intermittent prolonged episodes of reduced coronary perfusion. Stable maintenance of partial flow reduction is difficult to achieve in experimental models; thus, in vitro cellular models may be useful for establishing the mechanisms of adaptation. Since moderate hypoxia is likely to be an important component of the low-flow state, isolated adult rat cardiac myocytes were exposed to 1% O 2 for 48 hours to study chronic hypoxic adaptation. Hypoxic culture did not reduce cell viability relative to normoxic controls but did enhance glucose utilization and lactate production, which is consistent with an anaerobic pattern of metabolism. Lactate production remained transiently increased after restoration of normal O 2 tension. Myocyte contractility was reduced (video-edge analysis), as was the amplitude of the intracellular Ca 2+ transient (indo 1 fluorescence) in hypoxic cells. Relaxation was slowed and was accompanied by a slowed decay of the Ca 2+ transient. These changes were not due to alterations in the action potential. Tolerance to subsequent acute severe hypoxia occurred in cells cultured in 1% O 2 and was manifested as a delay in the time to full ATP-depletion rigor contracture during severe hypoxia and enhanced morphological recovery of myocytes at reoxygenation. The latter was still seen after normalization of the data for the prolonged time to rigor, suggesting a multifactorial basis for tolerance. An intervening period of normoxic exposure before subsequent acute severe hypoxia did not result in loss of tolerance but rather increased the delay to subsequent ATP depletion rigor. Cellular glycogen was preserved during chronic hypoxic exposure and increased after the restoration of normal O 2 tension. As mitochondrial cytochromes should be fully oxygenated at levels well below 1% O 2 , hypoxic adaptation may be mediated by a low-affinity O 2 -sensing process. Thus, adaptations that occur during prolonged periods of moderate hypoxia are proposed to poise the myocyte in a better position to tolerate impending episodes of severe O 2 deprivation.
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