The Sex Difference Of Cardioprotection Induced By Chronic Intermittent Hypobaric Hypoxia

Objective: Evidence shows that there are significant sex difference in incidence, pathological manifestation and prognosis of coronary heart disease (CHD). The incidence of CHD in adult female is much lower than that in adult male, which may be related with the protective effect of estrogen on heart. A lot of experimental researches showed that chronic intermittent hypobaric hypoxia (CIHH) conferred a protective effect on heart against ischemia/reperfusion injury and anti-arrhythmia in adult male rat. So far, however, we don't know if there is a sex difference in CIHH-induced cardio- protection and there is no report on the cardiac protection of CIHH in adult female animals. The aim of present study was to explore the sex difference of CIHH-induced cardioprotection through observing the effect of two kinds of CIHH on isolated ischemia/reperfusion hearts in male, female adult rats.Methods: Adult male and female sprague-Dawley rats were randomly divided into eight groups: male control group (CON-M), male 28-day 3000m CIHH group (MIH3000-28), male 42-day 3000m CIHH group (MIH3000-42), male 28-day 5000m CIHH group (MIH5000-28), female control group (CON-F), female 28-day 3000m CIHH group (FIH3000-28), female 42-day 3000m CIHH group (FIH3000-42), and female 28-day 5000m CIHH group (FIH5000-28). CIHH animals were put into a hypobaric chamber to get 28 days or 42 days CIHH mimicking 3000m, 5 hrs/day or 5000m altitude, 6 hrs/day, respectively. The control animals were kept in the same environment as CIHH rats with free access to water and food except hypoxic exposure.The chest was open and heart was removed under anesthesia condition. Langendorff technique was used to record the left ventricular function, including left ventricular develop pressure (LVDP), maximum change rate of left (±LVdP/dtmax), left ventricular end diastolic pressure (LVEDP) and coronary flow(CF)under basic and ischemia/reperfusion conditions.Results: (1) There was no significant difference of cardiac function between each group under basic condition. The CF in CIHH rats excepting MIH3000-28 rats was increased compared with corresponding CON rats.(2) After ishchemia/ reperfusion, the rats in FIH3000-28, FIH3000-42 and FIH5000 -28 displayed an obvious cardiac protection against ishchemia/ reperfusion injury. The recovery of LVDP after ishchemia/ reperfusion in FIH3000-28, FIH3000-42 and FIH5000-28 was 45%, 42% and 53% ,respectively, much higher than 23% in CON-F(P<0.05); The recovery of +LVdp/dtmax was 49%, 45% and 58%,respectively, much higher than 20% in CON-F(P<0.05); The recovery of - LVdp/dtmax was 50%, 44% and 58%,respectively, much higher than 23% in CON-F(P<0.05). The recovery of CF in FIH3000-28, FIH3000-42 and FIH5000-28 was 44%, 43%and 47%,respectively, much higher than 32% in CON-F (P<0.05). There were no differences of all parameters among rats in FIH3000-28, FIH3000-42 and FIH5000-28.(3) After ishchemia/ reperfusion, the rats in MIH3000-42 and MIH5000-28 displayed an obvious cardiac protection against ishchemia/ reperfusion injury. The recovery of LVDP after ishchemia/ reperfusion in MIH3000-42 and MIH5000-28 was 46% and 51%,respectively, much higher than 29% in CON-M(P<0.05); The recovery of +LVdp/dtmax was 46% and 46%,respectively, much higher than 23% in CON-M(P<0.05); The recovery of -LVdp/dtmax was 49% and 50%,respectively, much higher than 24% in CON-M(P<0.05);The recovery of CF after ishchemia/ reperfusion in MIH3000-42 and MIH5000-28 was 45% and 30%,respectively, much higher than 25% in CON-M(P<0.05); The recovery of LVDP, +LVdp/dtmax, -LVdp/dtmax and CF in MIH3000-42 and MIH5000-28 were significant higher than those in MIH3000-28 (P<0.5).(4) The parameters of cardiac function were increased in FIH3000-28 compared with those in MIH3000-28. And there were no difference of parameters of cardiac function between other male and female CIHH animals.Conclusion: CIHH can enhance resistance of myocardium against ischemia/reperfusion injury, which might be related with increasing of CF. The protective effect of CIHH is influenced by animal sex, CIHH duration and intensity.