| Background and objectsWith the improvement of people's living standards,the global morbidity rate of diabetes mellitus(DM) increases rapidly.And DM is a major risk factor for coronary heart disease.People with DM are at higher risk of myocardial infarction(MI) than non-diabetic patients.The risk of ventricular arrhythmias and sudden cardiac death following myocardial infarction is significantly increased in patients with DM.During the last decade,a series of studies demonstrated that there was sympathetic nerve sprouting and hyperinnervation after MI,namely neural remodeling,which was responsible for ventricular arrhythmogenesis and sudden cardiac death in chronic phase after MI.However,whether there is neural regeneration or remodeling in diabetics after MI,and the association with the higher incidence of ventricular arrhythmias(VAs) are rarely reported.The main objects of this study are:1) To establish a diabetic animal model with myocardial infarction.2) To investigate the characteristics of cardiac nerves after myocardial infarction in diabetic rabbits.3) To approach the relationship between the changes of sympathetic nerves and the incidence of ventricular arrhythmias induced by programmed electrical stimulation(PES).MethodsNew Zealand rabbits were randomized to two groups:group A(fed with high-fat/high-sucrose diet in the first two months and then injected with 80mg/kg wt alloxan via the marginal ear vein to make diabetes mellitus) and group B(fed with normal rabbit feed),then each was divided into myocardial infarction subgroup and sham operation subgroup,means DM,DM with MI,Sham,MI four groups.After electrophysiological recordings,immunocytochemical staining of cardiac nerves was performed using anti-tyrosine hydroxylase(TH) and anti-growth associated protein 43 (GAP43) antibodies.And real-time RT-PCR was used to examine the TH mRNA expression at the infarct border.ResultsIn group A,3 rabbits didn't meet the diabetic criteria and were ruled out.Two died during the induction phase of diabetes mellitus.Two from MI and 2 from DM with MI groups died during the surgical induction of MI.Programmed electrical stimulation:Electrophysiological studies:The incidence of inducible ventricular arrhythmias in the Sham,DM,MI and DM with MI were 14.3%,50%*,64.3%# and 85.7%#§,respectively(*P＜0.05 vs.Sham,#P＜0.01 vs. Sham,§P＜0.05 vs.DM).Immunohistochemical studies:1) TH positive nerve fibers:In the Sham group, the nerve fibers were evenly distributed,mainly in the perivascular regions with a high density.In the DM group,the location of nerve fibers was similar to that of the Sham group but with less density.In the MI group,nerve fibers were mainly distributed at the periphery of infarcted tissues and at the perivascular regions,with a disorderly distribution.In the DM with MI group,nerve fibers were also present at the peri-infarct zone and the distribution was more chaotic.2) GAP43 positive nerve fibers:GAP43 positive nerve fibers' distribution was slender or absent in the Sham group,and the circumstance was similar to the DM group.However,in the MI group the distribution and shape of GAP43 positive nerve fibers were more diverse and abundant comparing with the Sham group,some nerve fibers clustered together around the infarct border.Similarly,in the DM with MI group heterogeneous distribution of nerve fibers was easily observed in the peri-infarct zone.Real-time RT-PCR:Compared with the Sham group,the expression level of TH mRNA decreased in the DM group and increased significantly the MI group(P＜0.05), at the infarct border and the left ventricular free wall.In the DM with MI group,the expression of TH mRNA was higher than that of the DM group(P＜0.05).Conclusion1 There were different extents of impairment to myocardial sympathetic innervation in diabetic rabbits.2 Neural remodeling was observed 8 weeks after myocardial infarction,especially at the peri-infarct zone.3 The influence of MI on cardiac sympathetic nerves in diabetic rabbit increases the incidence of inducible ventricular arrhythmias.
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