Intermittent Hypobaric Hypoxia Decreases Reactivity Of Right Ventricular Papillary Muscle In Rat To Isoproterenol

Objective: Intermittent hypobaric hypoxia (IHH) has been provided a clear cardiac protection against ischemia/reperfusion or hypoxia/reoxygenation injury and arrhythmia. Recently, more people pay close attention to mechanism of intermittent hypobaric hypoxia of cardiac protective, but the underlying mechanism is not clear yet. Further studies indicated that KATP channels contributed to the cardiac protection induced by IHH against ischemia/reperfusion injury; the elimination of calcium overloading during ischemia/reperfusion by IHH might underlie the mechanism of protection. IHH hypoxia may preserve Ca2+ homeostasis and contraction by preserving RyRs and SERCA2 proteins as well as NCX activity during I/R. IHH upregulated the baseline level of iNOS mRNA and protein expression leading to an increase in NO production, which may play an important role in the cardiac protection of IHH against I/R injury. Increasing resistance of rat heart to ischemia/reperfusion injury after intermittent hypoxia exposure may be related to the amount of HSP70 induced. Recently, in the same experimental condition with us, Chen, L. et al reported intermittent hypobaric hypoxia can decrease Ca2+ overloading during ischemic, the mechanism is relevant toα1B-adrenergic receptor. In the physiological condition, the sympathetic nervous system is one of the most important extrinsic mechanisms regulating the cardiac function throughβ-adrenergic receptor stimulation. Little is known, however, aboutβ-adrenergic receptor in intermittent hypobaric hypoxia cardiac protection. The purpose of present study is to investigate the effect of IHH on the electric and mechanic response induced by isoproterenol (ISO) in right ventricular papillary muscle of rat. As a result, we investigate the effect of ISO on AP and contraction in rat right papillary muscle, in order to discuss the effect of intermittent hypobaric hypoxia onβ-adrenergic receptor.Method: Male Sprague-Dawley rats were anesthetized with pentobarbital sodium (1 mg/kg, i.p.). The hearts were quickly removed and rinsed in cold modified Tyrode's solution (4℃) gassed with 100% oxygen. Papillary muscles were taken from the right ventricles and one end of the muscles was fixed in the small chamber, the other was connected with a tension transducer (JZ100, XINHANG, CHINA) to record the contraction. The preparations were pinned down on a thin silicon disc on the base of perfusing chamber and equilibrated in modified Tyrode's solution for 1h, stable temperature (36.0±0.5℃) and stable speed (12ml/min). Parameters of action potential and contraction were recorded simultaneously using intracellular microelectrode technique and contraction recording. The transmembrane action potentials were recorded by means of 3 mol/L KCl-filled micropipettes (a tip resistance of 10²0M?), coupled to a high input impedance amplifier (MEZ 8201, Nihon Kohden). The amplified signals were fed to the A/D converter and processed by a microcomputer. The parameters of action potential included: the resting potential (RP), the amplitude of AP (APA), overshot of AP (OS), maximal rate of phase 0 depolarization (Vmax), prolongation of duration of 50% and 90% repolarization of AP (APD50 and APD90). The parameters of contraction included: the maximal isometric tension (Pmax) and velocity of tension development (PdT/dt).Results: The results of study showed: (1) Action potential duration (APD) in IHH rats was prolonged significantly compared with that in Con rats. APD50 in IHH14, IHH28 and IHH42 was 35.0±7.6, 31.7±6.0 and 48.3±3.4 ms, respectively, significantly longer than 23.2±5.5 ms in Con. APD90 in IHH14, IHH28 and IHH42 was 100.2±5.9, 99.2±9.0 and 133.8±21.2 ms, respectively, significantly longer than 72.5±9.8 ms in Con. (2) ISO changed parameters of AP and contraction significantly in a dose-dependent manner, including increase of the amplitude of AP (APA), overshot of AP (OS) and maximal rate of phase 0 depolarization (V_max), prolongation of duration of 50% and 90% repolarization of AP (APD50 and APD₉₀), as well as increase of the maximal isometric tension (P_max) and velocity of tension development (P_dT/dt). (3) The response of AP and contraction on ISO in IHH rats were decreased significantly compared with that in Con animals. Conclusion: The result of our study suggests that IHH decrease reactivity of right ventricular papillary muscle in rat to ISO, meaning of inhibition ofβ-adrenergic receptor function, which might be one of mechanisms for cardiac protection of IHH.