Effects Of Chronic Intermittent Hypobaric Hypoxia On Heart Rate Variability In Conscious Rats

Objective: In recent years, chronic intermittent hypobaric hypoxia (CIHH) has been approved to have a cardiac protection and a great attention is drawn to it. It was proved by a great number of researches that CIHH have a cardiac protective effect against ischemia/reperfusion or hypoxia/reoxygenation injury, including increasing the tolerance of myocardium to ischemia/reperfusion injury, limiting infarction size and and morphologic damage, inhibiting apoptosis of cardiomyocytes, enhancing the recovery of myocardiac function from ischemia/reperfusion, and antiarrhythmia. The proposed mechanisms include oxygen transportation, energy metabolism, neurohumoral regulation, antioxidation, stress protein, adenosine, ATP-sensitive potassium channel, mitochondrion, calcium homeostasis, NO and protein kinase. The cardiac protection of CIHH was affected by the protocol of hypoxia, the age and sex of experiment. The precise mechanisms underlying the protective effects of CIHH, however, are far from clear. The heart is innervated by cardiac sympathetic and parasympathetic nerves. Both cardiac sympathetic and parasympathetic nerves play an important role in normal cardiac function, and involved in pathophysiology of some cardiovascular diseases. However, the little is known about the effects of CIHH on the regulation of cardiac autonomic nerve or whether cardiac autonomic nerve involving in the cardioprotective effects of CIHH. The aim of present study is to investigate the effects of CIHH on autonomic nerve function in conscious rats through the HRV analytic technique.Methods: Twelve male healthy Sprague–Dawley rats, weighting 260~320 g, were randomly divided into control group (CON, n = 6) and CIHH treating group (CIHH, n = 6). The CIHH rats were exposed to simulated high-altitude hypoxia mimicking 5000 m altitude (O2:11.1%) in a hypobaric chamber, 6 hrs per day for 42 days. The control animals lived in the same environment as the CIHH animals with free access to food and water, except that they breathed normal room air. The body weight of rats was recorded in the fixed time each week.The limbsⅡlead electrocardiogram (ECG) in conscious rats was recorded for 20 minutes under basic normoxia and for 13 minutes under acute hypoxia (about 10~11% O2) condition at before, 14days, 28 days and 42 days during whole experimental course, respectively.The dynamic ECG during the last 5 minutes recording under normoxia and acute hypoxia condition was selected and analyzed by HRV program (PowerLab, Australia). Heart rate was calculated from original ECG and heart rate power spectrum was gained with the fast Fourier transform. The parameters of HRV included the total power (TP), the low- frequency component (LF), the high- frequency component (HF) and LF/HF.All data were expressed as mean±SE. Sigma Stat 3.1 and Origin 6.0 were used for data processing and analyzing. ANOVA was used for comparison of data among the multi- groups and t-test was used for comparison of data between two groups. P <0.05 was taken as a significant difference.Results: (1) There were no significant difference of general states like physical activity and body weight between CON and CIHH rats; (2) In the basic normoxia condition, there was no statistics difference on heart rate,TP,LF,HF and LF/HF at the beginning or the end of experiment between the two groups (P>0.05). Following experiment, however, the basic LF and HF, but not the ratio of LF/HF, showed an increasing tendency (P>0.05) in the two groups; (3) The heart rate of rats increased (P<0.05), but TP of rats decreased (P<0.05) obviously during acute hypoxia and there was no difference of the increasing of HR and deceasing of TP during acute hypoxia between CON rats and CIHH rats without CIHH treatment (P>0.05). After 14, 28 and 42 days'CIHH treatment, the increasing of HR and decreasing of TP during acute hypoxia in CIHH rats were significant smaller than that in CON rats (P<0.05). During acute hypoxia the LF and HF in rats were decreased, and the change of LF and HF was slightly attenuated following the rat grow in both groups. After 14days CIHH, the reductions of LF and HF during acute hypoxia were significant smaller in CIHH rats than that in CON rats (P<0.05). After 28 days CIHH, there were no differences of LF and HF in CIHH rats between acute hypoxia and basic normoxia. LF/HF in both groups was not changed during acute hypoxia (P<0.05).Conclusion: Chronic intermittent hypobaric hypoxia has no effects on the basic HR and HRV in rats under normoxia environment but could effectively prevent the increasing of HR and decreasing of HRV during acute hypoxia, through antagonizing depression of vagal tone, which might be involved in the cardioprotection of CIHH.