| Summary: | 碩士 === 國防醫學院 === 藥理學研究所 === 98 === Sepsis, the systemic inflammatory response syndrome to infection, is the leading cause of death in the critically ill patients, predominantly as a consequence of multiple organ failure. Furthermore, myocardial dysfunction is a recognized manifestation of this syndrome and contributes to the high mortality of sepsis. Changes of the action potential (AP) may cause the change of cardiac contractility. The transient outward K+ current (Ito) is a major repolarizing ionic current on phase 1 of action potentials in cardiac myocytes. Under many phathological conditions, the Ito may be altered. The aim of this study was to evaluate the changes of transient outward potassium channels in septic rat ventricle. Animals were divided into two groups: sham and sepsis. The sepsis was induced by cegal ligation and puncture (CLP) in male Wistar rats. At 0, 3, 9 and 18 hr after CLP, the changes of hemodynamics (mean arterial pressure, heart rate, systolic pressure, diastolic pressure and pulse pressure) were examined. At 18 hr after laparotomy, animals were sacrificed and heart was exercised for electrophysiology study and measurement of Kv 4.2/Kv 4.3 protein level expression. Results showed that mean arterial pressure, systolic pressure and diastolic pressuer in septic rats were significantly lower than sham groups and heart rate were higher. In vitro, action potential amplitude of 乳頭肌s from septic rat was decreased and resting membrane potential was more positive than that of sham group, but action potential durations (APD20, APD50 and APD90) were not different between two groups. From single cell study, transient outward K+ current of septic rat ventricular myocytes were decreased when compared to the sham group (6.03 ± 0.80 pA/pF, n=6; 9.26 ± 0.44 pA/pF, n=6; at +45 mV). The decay time constants, steady state inactivation and activation curves of Ito were not different between two groups. From immunofluorescence staining, Kv 4.2 and Kv 4.3 protein expression were decreased in both epicardium and endocardium of CLP group. From Western blot study, Kv 4.3 protein level was not altered, though Kv 4.2 was significantly decreased in septic rat ventricle. In conclusion, the down regulation of transient outward potassium channel proteins in CLP, may not be the same for Kv 4.2 and Kv 4.3.
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