The Study Of The Effect Of Glucose-insulin-potassium(GIK) Infusion On Myocardial Energy Metabolism After Brain Death

Objective:Heart transplantation is one of the most effective methods in the treatment of end-stage heart diseases.Since the1990s,the patients who was need for organ transplantation had been increasing by22.4%per annum,but the shortage of donor had always restrict the development of heart transplantation.At present,the brain death donor heart is the main source of heart transplantation.A series of pathophysiological changes after Brain death will cause damage to the myocardium,thus affecting the quality of donor and transplant survival rate.Therefore it is critical to the protection of the donor heart.As the unique organ of the human body,the heart,the power unit of the blood circulatory system,is quite strong to energy’s dependence.This study aims to increase slowly intracranial pressure method to establish the pig brain dead model and GIK solution for injection intervention treatment, Watch the indexes brain death of pig which include the level of glycogen,ATP,ADP,AMP,COX,SDH in cardiac muscle,and the level of FFA in serum,electron microscope ultrastructural changes of heart and to evaluate the effects of GIK solution brain death of myocardial cell energy metabolism and explore the protective effect of GIK solution on brain death heart donors.Methods:12pigs of healthy banna xiaoerzhu were divided randomly into two groups(n=6),the control group(group A) and the experimental group(group B).Both groups are done intravenous general anesthesia trachea intubation lookahead,then breathing machine helps to breathe,internal jugular vein catheterization,foley catheter was placed after craniotomy and Foley balloon catheter line intracranial pressure,then brain death model was set up and maintained10h,the control group was limited to import0.9%saline and dopamine(10-20mg/Kg) maintain CVP for6-10cmH20,MAP for60mmHg.If the collapse in urine disease applicate arginine vasopressin,all of the above and time and urine output there are detailed records.Experimental animals after intravenous anesthesia inject GIK solution((25%glucose500ml,26U insulin,80mmol/l kalium chloratum,1.5ml/kg/hours),application0.9%saline and dobutamine maintain for CVP6-10cmH2O,MAP for60mmHg.If the collapse in urine disease application arginine vasopressin,quantity and time and urine output also detailed records.Both groups in the experimental process in the drug intervention outside,other are the same.Application of intracranial pressure slowly discontinuous method to establish the brain dead model, through the respiration,circulation support experimental animal brain dead state10hours,after10hours remove respiration,circulation support. Both groups were in experimental animals brain death within1Oh took arterial blood6ml saved(0、1、5、10hours),at the end of experiment took ventricular myocardial tissue6pieces respectively saved.Results1.Through the slow intracranial pressure method to establish the pig brain dead model,12pigs intraoperative the success rate for100%,postoperative10h model80%survival rate,made in the process of two death model,he end of10pig.The reason for failure in1May because brain dead experimental process the midbrain tissue destruction serious cause death.Another example of experimental animal appears circulatory failure with unknown reason in the course of the experiment.2.The control group through the slow intracranial pressure method to establish the pig brain death model,with cardiac function in the late fall gradually,mean arterial pressure (MAP) reduce,central vein pressure (CVP) increase,a low blood pressure state,need blood vessels activity dopamine drugs to maintain the basic blood pressure.Even2of them at the end of the experiment use epinephrine.The group with GIK solusion for Injection intervention, mean arterial pressure (MAP),central vein pressure (CVP) than the control group improved obviously and dopamine dosage for significantly less.No experimental group using the adrenaline.The dosage of vasoactive drugs were significantly different between the two groups (P<0.01).It is show that GIK solusion for injection play an important role in improving heart function obviously after pig brain death heart.3.Myocardial tissue glycogen,ATP,ADP,AMP levels:the glycogen,ATP,ADP, AMP levels of two groups which in myocardial tissue have no significant difference(P>0.05).There are no statistical significance.There are differences in EC between the two groups(P<0.05).Blood free fatty acid (FFA) changes:FFA when1and5hours after brain death was different between the control group and the experimental group(P=0.05),there was statistical significance.0,10hours after brain death ate no differences(P>0.05).The level of FFA in blood were different between experimental group and control group(P<0.05),there is statistical significance.4.Activity of SDH and CCO:activity of SDH and CCO in myocardial tissue are no significant differences between the control group and experimental group(P>0.05).5.Myocardial by light microscope showed:myocardial muscle fiber of two groups fracture significantly,cell gap is big,cytoplasm was loose,myocardial fiber swelling, interstitial edema significantly,myocardial striations are not clear,apoptosis obviously.6. Myocardial by electron microscopy showed:the two group myocardial cell perform myocardial cell nucleus deformation,chromatin pyknosis,chromatin marginalization. Cell volume change,mitochondria swelling,or even disappear dissolved,part of the muscle fibers of fuzzy fusion,arranged in disorder.Conclusions1.By the way of using slow discontinuous increasing intracranial pressure,brain death model of12pigs were successfully established.The application of the continuous improvement of intracranial pressure slowly law and monitoring the pig brain dead model,the success rate and repeatability high,more in line with the development of clinical brain death process,the effective breathing and circulation support,brain death can maintain stable state.2.The cardiovascular active drug dosage of the experimental group is significantly lower than the control group,indicating that GIK has a protective effect on brain death donor heart.3.From the photoelectric microscope results of cardiac tissue can be seen that the state of brain death idamnify myocardium.4.The overall level of FFA in experimental group is lower than the control group,but the results of1,5hours after brain death are different,0,10hours after brain death have no difference.It indicate that GIK liquid is useful to energy metabolism in brain death donor heart,but there are not obvious at the beginning and the end of brain death.5. There are no differences in the level of SDH,CCO between the control group and the experimental group.lt point out that the state of brain death make strong injury to myocardial cells and mitochondrial respiratory enzyme inactivation is serious.At the end of research,The impact of GIK solution on metabolic effect of donor heartis not obvious.6. ATP, ADP, AMP, glycogen,proved by the statistics,are not different between the two groups.However,it can be seen ATP、glycogen levels of the experimental group generally higher than the control group.EC is different between the two groups.This suggests that GIK may be beneficial in terms of energy metabolism on brain death donor heart,by optimizing the energy metabolism of myocardial,but its protective effect has certain timeliness.