Studies On The Myocardial Protection Of Propofol And Fentanyl Preconditioning In Acute Hemorrhagic Shock Rabbits

Acute hemorrhagic shock as a common urgent and serious condition mainly occurs in various kinds of wounds and operations. Positive and effective management will directly determine patient's prognosis. ischemic and anoxic damage is the key feature of hemorrhagic shock. Myocardial ischemia will result in irreversible organ damages even death. Although myocardium is tolerant to ischemia to some extent, its systolic function still decreased significantly during acute hemorrhagic shock, which can cause other organs filling defect and aggravate organ damages. Therefore, it is very important clinically to lessen ischemic damage and enhance myocardial function under low volume status. Myocardial protection effects and mechanisms of ischemic preconditioning have been widely investigated. In the meanwhile, pharmacological preconditioning is causing our more attention because of its better feasibility. In this study, acute hemorrhagic shock animal model was established according to Wigger's method. The changes of myocardial systolic function, serum cardiac Troponin I (cTn-I) and myocardial morphological structure were observed to explore the protective effects of propofol and fentanyl preconditioning on myocardial injury and provide experimental basis for myocardial protection in acute hemorrhagic shock.AIM:To observe the myocardial protective effects of propofol and fentanyl preconditioning in acute hemorrhagic shock rabbits.METHODS:Twenty-four healthy white rabbits weighing 2.0-2.5kg either sex were randomly divided into control group (group C), propofol preconditioning group (group P) and fentanyl preconditioning group(group F). Rabbits were anesthetized with pentobarbital sodium (30 mg.kg-1) by marginal ear vein administration. Following tracheostomy, trachea was intubated and spontaneous breathing was remained. Right femoral artery was dissociated for bloodletting. The right carotid artery was dissociated and catheterized with a polyethyene tube into left ventricle for hemodynamic monitoring. Then, three groups were all perfused with heparin (3 mg.kg-1).15min before bloodletting, the same volume of saline, propofol (5 mg.kg-1) and fentanyl (25μg.kg-1) were given to group C, group P and group F respectively. Acute hemorrhagic animal model was established according to the Wigger's method. Briefly, blood was withdrawn over a 10 min period to reduce mean arterial pressure (MAP) to 40 mmHg. HR,MAP, LVP, +dp/dtmax ,-dp/dtmax and electrocardiogram (ECG) were monitored continuously during 90 min of hemorrhagic shock. Arterial blood samples (2 ml) were taken at before bloodletting, 60 min and 90 min after bloodletting for detecting serum cardiac Troponin I (cTn-I) by chemiluminescence method. Myocardial samples (1mm×1mm×1mm) were taken after 90 min shock for observing morphological structures by JEM-2000EX electron microscopy.RESULTS:Left ventricle functional parameters: There was no significant difference in hemodynamics before bloodletting among the groups (P> 0.05). There was no statistics significance of HR among three groups before 60min-point of shock (P> 0.05). At 75 min and 90 min HR of C group is lower than F and P group (P< 0.05). During the period of shock, hemodynamic indexes in three groups all recovered gradually. But compared with control group, the hemodynamic indexes in group F and group P were higher at each time-point of shock (P< 0.05). There was no significant difference between group F and group P (P> 0.05). All hemodynamic indexes during the period of hemorrhagic shock were lower than those before bloodletting in three groups (P< 0.05).Biochemical indicators of myocardial damage: There was no significant difference in the serum concentrations of cTn-I among three groups before bloodletting (P> 0.05). The level of serum concentrations of cTn-I increased significantly in all groups after bloodletting compared with that of before bloodletting (P< 0.05). But cTn-I values in group P and group F were lower than those of group C (P< 0.05). There was no difference between group P and group F (P> 0.05).Electron microscope observation of myocardium: There were different anoxic myocardial injuries in three groups after 90 min of hemorrhagic shock. Group C:Myocardium were broken and distorted and there were plenty of lower electron density zones. Sarcomeres decurtated and H-band disappeared; mitochondrial cristae were disrupted and edema and electron dense deposites were observed within mitochondria. Group F and P: The myocardial myofilament arrayed in order. Chromatin in nucleus was uniformly dispersed. Sarcomeres were normal on the whole. H-band and M-line were clear . Mitochondria swelled while the cristae remained in order.CONCLUSIONS:Propofol and fentanyl preconditioning can attenuate myocardial injury in acute hemorrhagic shock, decrease the serum level of cTn-I, maintain the normal myocardial structure and enhance systolic and diastolic function of left ventricle. Propofol and fentanyl preconditioning is an effective method to relieve myocardial damage in acute hemorrhagic shock.