Protective Effects And Mechanisms Of Pravastatin Sodium On Impaired Myocardium Induced By LPC

Objectives To study LPC induced myocardial damage and the protective effects of pravastatin sodium in vitro and in vivo.Methods According To the objectives mentioned above, this study was divided into two parts.First part To observe the myocardial damages on isolated rat hearts induced by LPC and the protective effects of pravastatin sodium, 40 Sprague-Dawley (SD) healthy male rats, 300-400g weight, were divided into 2 groups (Group L and Group P) randomly. Isolated hearts perfusion model was constructed by Langendorff's methods. In group L, firstly, after heart stabilized, normal Krebs-Henseleit was perfused to the arteriae aorta continuously for 30 minutes, then Krebs-Henseleit containing exogenous LPC (5 micromole per liter) for 5 minutes, finally, normal Krebs-Henseleit for 30 minutes again. In group L, all the procedures were the same except containing pravastatin sodium (400 nanogram per milliliter). During the whole processes, we observed the follow parameters: 1.haemodynamics: including Left ventricular systolic pressure(LVSP), Maximum elevation or depression rate of left ventricular pressure(±dp/dt_max), Left ventricular end diastolic pressure (LVEDP), heart rate(HR) and coronary flow(CF), the incidence of arrhythmia; 2. biochemistry indexes: the concentration of lactic acid dehydrogenase(LDH), creatine kinase(CK) and creatine kinase isoenzyme (CK-MB) in the effluent from coronary artery; 3.histological character istics of left ventricular myocardium stained with hematoxylin and eosin.Second part To observe the myocardial damages in vivo rats' hearts induced by LPC and the protective effects of pravastatin sodium, and their possible mechanisms. 40 SD healthy male rats, 300-400g weight, were divided into 2 groups (Group L and Group P) randomly. Arterial catheters were intubated into left ventricle through right carotid artery. And then they were connected to the multichannel physiology recording systems (BIOPAC), the changes of haemodynamics and the electrocardiogram of the second limb lead were monitored. In group L, after heart stabilized, the SD rats were given exogenous LPC (0.01 millimol per kilogram) intravenously. In group P, all the rats were given pravastatin sodium (3.6 milligram kilogram per kilogram) 2 weeks prior to LPC induction. The following procedure was the same as the L group. Haemodynamics, incruding LVSP,±dp/dtmax, LVEDP, HR, the changes of biochemistry indexes, such as high sensitivity C reactive protein (hs-CRP) and endothelin(ET), the incidence of arrhythmia, and myocardium apoptosis detecting by TUNEL staining were observed.Results1. After exogenous LPC were given, the rats' haemodynamics in group L were affected obviously.±dp/dtmax, HR and CF decreased, LVEDP elevated, the incidence of arrhythmia and the persistence time of arrhythmia increased markedly(P<0.05). Compared with group L, the rats' haemodynamics in group P improved significantly (P<0.05).2. The level of LDH, CK and CK-MB in the effluent from coronary artery in both groups stepped up after exogenous LPC given (P<0.05). Compared with group L, all of them were decresed in group P (P<0.05).3. HE staining showed that myocardium arranged disorderly. Myocardial interstitium edema could be seen around the blood vessels. Inflammatory cells infiltrated and intromyocardium hemorrhage were more in group L. compared with group L, the myocardial cells arranged more orderly, swell, inflammatory cells and hemorrhage were light in group P.4. The blood concentration of hs-CRP and ET stepped up obviousely after given exogenous LPC (P<0.05). Compared with group L, both were significantly decreased in group P (P<0.05).5. Apoptotic cells could be detected easily by TUNEL staining after LPC was given. But the apoptotic indexes of group P were smaller than that of group L.ConclusionsExogenous LPC can induce myocardium damage. However the pravastatin sodium can relieve myocardial damage and improve cardiac function. The underground mechanisms may lie in: improving haemodynamics, extenuating the inflammatory reaction and myocardium apoptosis, improving endothelial function.