| Background: The prevalence and death rate of cardiovascular diseases are still on the rise in China.It is estimated that there are 290 million people suffering from cardiovascular diseases,and the death rate of cardiovascular diseases still ranks the first,accounting for more than 40% of the total number of residents dying from diseases.Sudden cardiac death,which accounts for more than 50% of all cardiovascular deaths,has a survival rate of only 5% to 10% due to its sudden and unpredictable occurrence,making it an important challenge in the prevention and treatment of cardiovascular diseases in the 21 st century.Sudden cardiac death is mainly caused by malignant arrhythmia,especially ventricular arrhythmia,such as ventricular tachycardia and ventricular fibrillation.Hibernation myocardium is widely existed in patients with ischemic cardiomyopathy,and it has acquired the susceptibility to sudden cardiac death by reducing the adaptability of function and metabolism to maintain survival.Therefore,it is necessary to study the mechanism of sudden cardiac death caused by hibernation myocardium,so as to provide a theoretical basis for the prevention and treatment of malignant arrhythmia.Objective:To elucidate the difference of plasma flow between hibernating myocardium and normal myocardium and to explore its relationship with sudden cardiac death.Method:16 healthy adult beagles were divided into group A(hibernation group,8)and group B(sham operation group,8).In group A,thoracotomy ligation was used to cause left anterior descending branch stenosis(75%),and outdoor activities were maintained daily for 4 h after surgery.Chronic ischemia was observed in the blood supply area of the target blood vessel,and the myocardial model of chronic hibernation was prepared.Group B will cross the silk thread under the anterior descending branch,but not ligation,the rest with group A.Both groups were terminated 12 weeks after surgery.All groups were matched in age and weight,and were kept in the same environment for 12 weeks.Cardiac tissue was obtained for HE staining and masson staining,and the morphology of cardiac cells and the distribution of collagen fibers in each group were observed.Thewhole cell patch clamp technique was used to determine the IKs and AP of Epi,M and Endo cell membranes separated by enzymatic hydrolysis.Results1.In this experiment,there were 16 beagle dogs in group A and group B,all of which successfully completed the experiment,and the modeling in group A was successful.All the data basically met the expected requirements,and there were no anesthesia accidents,myocardial infarction,infection and other postoperative complications.2.Results of echocardiography:2.1 echocardiography dobutamine stress test(dobutamine stress test)in group A,the anterior wall of the left ventricle(the hibernating myocardium area)was compared with the posterior wall of the left ventricle(the normal myocardium area)during the dobutamine stress test.With the increase of dobutamine dose,the thickening rate(WT%)of the anterior wall of the left ventricle(the hibernating myocardium)in systolic period significantly decreased,and two-way movement was observed,that is,with the increase of dobutamine dose,the wall movement was first enhanced,and then weakened(all P < 0.01).With the increase of dobutamine dose,the ventricular wall motion of the posterior wall of the left ventricle(the normal myocardial area)continued to increase(all P < 0.01),and the hibernating myocardial model was successful.2.2 results of wall movement analysis at rest,there were more segments with abnormal wall movement in group A,and no abnormal wall movement in group B,the difference was statistically significant(P < 0.01).2.3 Measurement of left ventricular global systolic function the postoperative systolic function of the left ventricle decreased in group A,which was manifested as A significant decrease in ejection fraction;the preoperative systolic function of the left ventricle in group B showed no significant change compared with the postoperative systolic function(P < 0.01).3.Pathological examination results of group A and group B3.1 HE staining of myocardial tissueIn group A,the cardiomyocyte volume increased,the cardiomyocyte edema and fracture,the disorganized arrangement presented the shape of whirlpool or wavy or disordered,and the fissure between the myocardium was significantly widened and disordered.In group B,the myocardial cells were arranged in bundles in a compact and orderly manner,and there was no obvious proliferation in the extracellular stroma.3.2 Masson staining of myocardial tissueIn group A,the blue-stained areas of cardiac cells increased,and the collagen fibers were arranged in A disordered and crisscrossed manner.In group B,collagen fibers of cardiac myocytes were evenly distributed and neatly arranged,and the number was less than that of group A.4.Electrophysiological recording results of cardiomyocytes4.1 changes in Iks current density of three-layer cardiomyocytes:Changes in Iks current density of inner myocardial cells: when the membrane voltage was60 mv,the current density of Iks in group A decreased compared with group B(3.011±0.772 vs4.232±1.645),but there was no statistical significance(P>0.05).Changes of Iks current density in middle myocardial cells: when the membrane voltage was 60 mv,the current density of Iks in group A decreased compared with that in group B(2.622±0.842 vs 5.045±1.680),which was statistically significant(P < 0.01).Changes in Iks current density of outer myocardial cells: when the membrane voltage was60 mv,the current density of Iks in group A decreased compared with that in group B,showing A statistical difference(4.475±2.831 vs 9.804±5.903)(P < 0.05).Intra-group comparison:In the sham operation group,the current density of IKs in m-layer was lower than that in Endo layer and Epi layer,which was statistically significant(P < 0.05).There was a statistical difference between Endo layer and Epi layer(P < 0.05).In the hibernating myocardium group,the current density of IKs in m-layer decreased compared with that in Endo layer and Epi layer,with no statistical difference(P > 0.05).There is no significant difference between Endo layer and Epi layer4.2 differences in action potential time history(APD)of three-layer cardiomyocytesStimulated by the base circumference of 800 ms,The changes of APD90 in the inner myocardial cells:Group A was longer than group B(245.14±44.447 vs 289.76±53.360),but there was no statistical significance(P>0.05).The changes of APD90 in the middle myocardial cells: Group A was longer than group B(307.34±36.116 vs 580.75±8.553),The difference was statistically significant(P < 0.05).The changes of APD90 in the middle myocardial cells: Group A was longer than group B(275.70±78.022 vs 481.38±1.720),but there was no statistical significance(P>0.05).Intra-group comparison:In the sham operation group(control):M>Endo,M>Epi(P<0.05)?In the hibernating myocardium group,(model):M>Epi>Endo(P<0.05)TDR: Compared with the sham operation group,TDR was significantly increased in thehibernation groupconclusion1.The method of thoracotomy and ligation,followed by regular outdoor exercise after the operation,is a simple and feasible method for the preparation of hibernating myocardial model in dogs.The method is simple,with high success rate,low technical requirements for experimenters,and no radiation in the experiment.2.during cardiac hibernation,the IKs of three-layer cardiomyocytes were significantly reduced and APD was prolonged,and the changes of cardiomyocytes presented heterogeneity,which further increased the dispersion of trans-ventricular repolarization,provided the electrophysiological basis for the occurrence of malignant arrhythmia,and may make the hibernating myocardium an independent risk factor of sudden cardiac death. |
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