Changes Of Systolic And Diastolic Function Of Left Ventricular Cardiomyocytes In Diabetic Rats With And Without Early Insulin Treatment

Objective1. To investigate the changes of systolic and diastolic function that occurred in leftventricular cardiomyocytes during the early stage of diabetes rats and their intrinsiclinks with myocardial ultrastructure and the whole cardiac function.2. To explore the effect of early treatment of insulin at lower doses on systolic anddiastolic function of left ventricular cardiomyocytes, myocardial ultrastructure and thewhole cardiac function in diabetes rats.Methods1. Rats were randomly divided into the following three groups: diabetes mellitus (DM)group, insulin treatment (INS) group and control (CN) group. Rats in INS group werehypodermically injected with insulin since the DM models were established throughintraperitoneal injection of streptozotocin.2. Echocardiography, transmission electron microscope and video-based edge-detectorsystem were used to explore the experiment.3. At the point of which DM model was established and2,4,8weeks, we observed the changes of whole cardiac function and myocardial ultrastructure as well as changes ofsystolic and diastolic function of cardiomyocytes of left ventricle (LV) in part1.4. At the point of8weeks after DM model being established, we observed the changes ofmyocardial ultrastructure of left ventricle, systolic and diastolic function ofcardiomyocytes as well as changes of whole cardiac structure and function in part2.ResultsPart11. Echocardiography is as follows: There was no difference in CN group. And there wereslight differences between DM group at the point of which DM model was established,2and4weeks (all P>0.05). Compared with CN group, DM group showed larger leftventricular cavity and thinner interventricular septum with decreased left ventricularfraction shortening (LVFS) and left ventricular ejection fraction (LVEF) at8weeks (allP<0.05).2. Transmission electron microscope results are as follows: DM group was observedmyocardial ultrastructure abnormal very mildly at week2, obviously at week4andthese abnormalities deteriorated at week8. At week2, DM group showed minorityswollen and aggregated mitochondria; At week4, fractured and dissolved myofilament,swollen and aggregated mitochondria and deposited collagen fibers and glycogengranules were observed in DM group; At week8, DM group showed vacuolardegeneration of mitochondria and capillary basement membrane thickened slightly.3. Left ventricular cardiomyocyte function assessments are as follows: Compared withthe same time point of CN group, time from peak to90%relaxation (TR90) in the DMgroup slightly prolonged at2weeks, while reduction of cell length, peak shorteningvalue (PS%) and maximal velocity of shortening and relengthening (±dL/dt) alongwith prolongation of time to peak shortening (TPS) and TR90occurred at4,8weeks(all P<0.05).Part21. Echocardiography suggested that in contrast to CN group, DM group showed largerLV end-systolic and end-diastolic diameters (LVEDD and LVESD, respectively), thinner systolic interventricular septum (IVSs) and LV posterior wall (LVPWs), anddecreased LVFS,LVEF (all P<0.05). Compared to DM group, INS group indicatedsmaller LVESD and increased LVFS, LVEF (all P<0.05).2. Furthermore, transmission electron microscope revealed that DM group showedfractured and dissolved myofilament, swollen and aggregated mitochondria，thickenedslightly capillary basement membrane and deposited collagen fibers and glycogengranules. But myocardial ultrastructure abnormality in INS group was amelioratedcompared with DM group.3. Moreover, single cardiomyocyte function assessments demonstrated that cell lengthshortened, PS%,+dL/dt and-dL/dt reduced, and TPS and TR90prolonged in the DMgroup compared with CN group (all P<0.05). While INS group amelioratedabnormalities of cell length, PS%,+dL/dt,-dL/dt, TPS and TR90compared with DMgroup (all P<0.05).Conclusions1. Decrease of diastolic function of single cardiomyocytes in diabetic rats was earlierthan changes of systolic function.2. Cellular level damage already occured in left ventricular myocardium of diabetic ratsbefore the whole heart became malfunctional.3. Early treatment of insulin at lower dose could ameliorate the reduction of diastolicand systolic function of single cardiomyocytes in left ventricular caused by diabeticcardiomyopathy.4. Early treatment of insulin at lower dose could ameliorate the abnormalities ofmyocardial structure and function and moderate diabetic myocardial lesion that showa cardioprotective effective role of insulin in diabetic mellitus.5. The experiment suggests clinicians that early diagnosis and early treatment is crucialfor diabetic cardiomyopathy.