| Objective: Many experimental researches showed chronic intermittent hypobaric hypoxia (CIHH) conferred a protective effect on heart: enhancing the resistance to heart against ishchemia/reperfusion injury, relieving the decrease of cardiac function induced by ishchemia/reperfusion and anti-arrhythmia. There were much difference on morphous and function between adult rats and developing rats, but the researches on effect of CIHH on ishchemia/reperfusion injury in developing rat heart were very limited. So the aim of the present study was to explore the protective effect of CIHH against ischemia/reperfusion in developing rat hearts and assess the role of mitochondrial permeability transition pore (MPTP) and ATP sensitive potassium channels (KATP channel).Methods: Postnatal male Sprague-Dawley rats (n=84) were divided randomly into three groups: control group (CON), CIHH 28 days group (CIHH28) and CIHH 42 days group (CIHH42). The CON was divided into CON28 and CON42 according to the match of body weight with CIHH28 and CIHH42. CIHH animals were put into a hypobaric chamber to get 28days and 42 days CIHH mimicking 3000 m altitude (PB = 525 mmHg, PO2 = 108.8 mmHg), 5 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. Both CIHH and CON rats were raised at room temperature with a natural light: dark cycle (12 h: 12 h). The body weight and physical activity were recorded in fixation time weekly.The rats were anesthetized with sodium pentobarbital (45 mg/kg i.p) administered intraperitoneally. After chest and pericardium opened, arterial and venous blood samples of CON and CIHH were collected from left ventricle and right ventricle respectively for blood gas analysis. The isolated hearts were perfused in the langendorff apparatus, undergoing 30min global ischemia and 60min reperfusion. Cardiac function was recorded at different time of reperfusion. The heart weight was measured at the end of the experiment. Ventricles were frozen in liquid nitrogen quickly and stored at -70oC to determine superoxide dismutase (SOD) and total antioxidation capacity (TAC). Transmission electron microscope was used to observe the change of myocardiac ultrastructure.Glybendamide (GLY), an non-specific inhibitor of ATP sensitive potassium channel (KATP), 5-hydroxydecanoate (5-HD), an inhibitor of mitochondrial ATP sensitive potassium channel (mitoKATP), and Atractyloside (ATRA), an inhibitor of MPTP opening were used in CIHH rats as well as Cyclosporin A (CSA), an opener of MPTP, and Diazoxide (DIZA), an opener of mitoKATP channel, were used in CON rats during different time of experiment. Results: The basic coronary flow (CF) in CIHH rats was significant higher than that in CON rats, while other parameters of cardiac function didn't change. The cardiac function and ultramicrostructure were damaged during hypoxia/reperfusion, but there was a significant different between CIHH and CON rats. The recovery of cardiac function in CIHH rats was much better than that in CON, including the increase of the left ventricular developed pressure (LVDP) and the maximum first derivative of left ventricular pressure (±LVdP/dt), the decrease of left ventricular end-diastolic pressure (LVEDP) (P<0.05). In CIHH rats, antioxygenation and CF were increased and ultramicrostructure damage was much slighter.GLY, 5-HD and ATRA,inhibited the recovery of left ventricular function in CIHH rats, including the decrease of LVDP and±LVdp/dtmax, while the increase of LVEDP during reperfusion. On the other hand, DIAZ and CSA induced a cardioprotection in CON rats, including the increase of LVDP and±LVdp/dtmax, while decrease of LVEDP during reperfusion.Conclusion: CIHH can enhance the resistance to developing heart against ishchemia/reperfusion injury; the protective mechanism of CIHH was related with increasing in CF and the antioxidant capacity of myocardium, the opening of KATP channels and the closing of MPTP.
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