| Ischemic heart disease is one of the major diseases which seriously threaten the people's physical and mental health nowadays. The most common kind of Ischemic heart disease is the coronary heart disease (CHD) whose morbidity and mortality is increasing year by year. In recent years, the coronary interventional treatment and coronary artery bypass graft have been used and achieved great effects in improving symptoms and prognosis for the patients. Because the complexities of risk factors and rapid progress, the limits of patients physical status, family conditions and other factors, the further seeking for the medicines to protect the ischemic and hypoxic myocardium effectively is still an urgent issue.Aralosides (AS) is the effective ingredients which extracted from the root and stem bark of Aralia elata. It has anti-inflammatory , inhibiting allergy , anti-autoimmunity , cardiotonic , anti-ischemic , anti-aging and other pharmacological effects. During the current clinical practices, AS is used for treatments of rheumatoid arthritis, neurasthenia, nephritis, edema, kidney disease, impotence, hepatitis, chronic diseases such as Qi weakness. There have been some studies on AS protection against myocardial ischemia and hypoxia, but have not been analyzed from the ion channel level. In this experiment, we have explored the AS protection mechanism through observing the AS effects on the myocardial contractility, action potentials and L-type calcium current in simulated myocardial ischemic and hypoxic Guinea pigs.1. Effects of AS on heart papillary muscle contractility in ischemic and hypoxic Guinea pigKilled the Guinea pig through hitting the head and get the right ventricular anterior papillary muscles. With the optimal stimulation voltage and initial length, the Guinea pigs were treated with ischemic and hypoxic solution of 10 min,+ AS 1μg ? ml-1 solution,+ AS 10μg ? ml-1 solution and + AS 100μg ? ml-1 solution in turn of 3 min internals. The results showed that the papillary muscle contraction range decreased from 100% to (70.52±5.15) % for ischemic and hypoxic solution group. Compared with the control group, the difference was significant. The papillary muscle contraction range of ischemic and hypoxic + AS 1μg ? ml-1 group increased from (70.52±5.15) % to (73.53±5.07) %, the difference was not significant. The papillary muscle contraction rate of ischemic and hypoxic + AS 10μg ? ml-1 group increased to (89.25±4.36) %, ischemic and hypoxic + AS 100μg ? ml-1 group increased to (95.41±3.11) %. For the two groups, the differences were significant compared with the ischemic and hypoxic solution group. These results indicated that AS can enhance the hypoxic heat papillary muscle contractility.2.Effects of AS on papillary muscle action potential in ischemic and hypoxic Guinea pigInserted the KCl-filling micro-electrode tip into papillary muscle cells and observed the APA, APD50 and APD90 changes by oscilloscope followed the electrical stimulation of posterior papillary muscle after perfusion of solution. The results showed that normal guinea pig papillary muscles APA was 101.45±7.73 mV, the APD50 was 186.72±12.86 ms, the APD90 was 240.8±17.8 ms, For the ischemic and hypoxic solution group, the APA was 79.79±7.43 mV, the APD50 was 152.56±12.69 ms, the APD90 was 195.56±15.96 ms. Compared with the control group, the differences were significant. For the ischemic and hypoxic + AS 1μg ? ml-1 group, the APA was 81.93±7.31 mV, the APD50 was 160.18±13.37 ms, the APD90 was 205.88±17.78 ms. The differences were not significant compared with the ischemic and hypoxic solution group. For the ischemic and hypoxic +AS 10μg·ml-1 group, the APA was 88.83±7.21 mV. The differences were significant compared with the ischemic and hypoxic solution group. The APD50 was 178.14±12.02 ms and the APD90 was 232.03±22.14 ms, the differences were significant compared with the ischemic and hypoxic solution group. For the Ischemic and hypoxic + AS 100μg ? ml-1 group, the APA was 94.04±7.3 mV, the APD50 was 180.02±12.39 ms, the APD90 was 234.2±22.11 ms. The differences were significant compared with the ischemic and hypoxic solution group. These results indicated that AS can prolonged the APD of hypoxic papillary muscle.3. Effects of AS on ventricular myocardiocytes membrane L-type calcium current in ischemic and hypoxic Guinea pigRapid isolated the guinea pig ventricular myocardiocytes and refused calcium. Recorded the ICa-L by whole-cell patch clamping. The results showed that the ICa-L changed from -0.218±0.029 nA to -0.227±0.025nA,-0.267±0.019 nA,-0.276±0.016nA with the 1μg ? ml-1, 10μg ? ml-1 and 100μg ? ml-1 final concentration AS respectively. For the ischemic and hypoxic + AS 100μg ? ml-1 and+ AS 100μg ? ml-1 groups, the differences were significant compared with the ischemic and hypoxic solution group. I-V curves shifted down significantly. The difference of the Ischemic and hypoxic + AS 100μg ? ml-1 group compared with the ischemic and hypoxic solution group was not significant. These results indicated that AS can increase ischemic and hypoxic ventricular myocardiocytes ICa-L.In summary, AS can improve the calcium-overload-induced myocardial stunning by increasing myocardial contractility for the ischemic and hypoxic myocardiocytes. AS can reduce the incidence of arrhythmia under the condition of ischemia and hypoxia which complete through stabilizing the cardiac electrophysiology by the prolonging of APD50 and APD90 and increasing of ICa-L. And thus make protective effects on ischemic and hypoxic myocardium. |
PDF Full Text Request