Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar-Kyoto rats.

rationaleChronic intermittent hypoxia (CIH) is thought to induce several cardiovascular effects in patients with obstructive sleep apnoea (OSA). However, the effects of CIH on patients with long-standing hypertension are unknown. PURPOSE: This prospective study aimed to investigate the influence of combined OSA and hypertension on cardiomyocyte death.

methodsWistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to repetitive hypoxia-reoxygenation cycles (30 s of 5% O(2); 45 s of 21% O(2)) or room air for 6 h/day during the light phase (10 a.m.-4 p.m.) for 10, 20, or 30 days, and the levels of necrosis and apoptosis induced in their left ventricular cardiomyocyte were examined.

resultsCIH increased the accumulation of reactive oxygen species, which induced cardiomyocyte necrosis in WKY and SHR (both p < 0.05). Cardiomyocyte oxidative stress levels by CIH were higher in SHR than in WKY (p < 0.05); therefore, cardiomyocyte necrosis was amplified (p < 0.05). Notably, if a superoxide-scavenging agent is injected beforehand, cardiomyocyte necrosis can be effectively inhibited (p < 0.05). When WKY and SHR are exposed to CIH, increases in mitochondria-released cytochrome c and activation of caspase-3 are found in the cytosolic fraction only in WKY.

conclusionsCIH causes cardiomyocyte loss in SHR mainly through cardiomyocyte necrosis. In WKY however, CIH simultaneously induces apoptosis and necrosis of cardiomyocytes.