Intermittent hypoxia improves calcium homeostasis in rat cardiomyocytes and confers cardioprotection against ischemia-reperfusion injury

Abstract

Calcium (Ca2+) handling is central to cardiac function and may be involved in the cardioprotection induced by intermittent hypoxia (IH). We hypothesized that IH ameliorates the impaired Ca2+ handling during ischemia/reperfusion (I/R). Male Sprague-Dawley rats were exposed to normobaric IH (10% oxygen, 6 hours/day, 7 days). Isolated perfused hearts from the IH and control (in room air) rats were subjected to 30 minutes ischemia and 2 hours reperfusion. The I/R injuries reflected by lactate dehydrogenase (LDH) activity and infarct size (IS) were significantly reduced in the IH group (LDH: 116.0±20.5 U/ml vs. control 273.2±29.5 U/ml, P < 0.01, n=9 per group; IS: 22.2±2.6 % of risk zone vs. control 31.4±3.1 % of risk zone, P < 0.05, n=8 per group). Spectrofluorometric measurement of cytosolic Ca2+ ([Ca2+]i ) in isolated fura-2- loaded ventricular myocytes showed a decrease in the amplitude of electrically induced [Ca2+]i transients with an elevated diastolic [Ca2+]i level during metabolic inhibition and anoxia (MI/A). The MI/A-induced changes in the amplitude of [Ca2+]i transients and diastolic [Ca2+]i level were significantly less in the IH group. Also, the IH group had greater recovery in the amplitude of [Ca2+]i transients (83.3±6.0 % vs. control 66.7±4.7 %, P < 0.05, n=8 per group) and faster decay rate (τ) of the caffeine-induced [Ca2+]i transients (2.3±0.3 second vs. control 4.5±0.4 second, P < 0.01, n=6 per group). Results suggest that IH improves the [Ca2+]i handling in the cardiomyocytes and enhances tolerance against I/R injury. (supported by research grants from the RGC and URC)