Diabetes and Myocardial Ischaemia Sensitivity of the diabetic heart to ischemic injury
Diabetes and Myocardial Ischaemia - Sensitivity of the diabetic heart to ischemic injury
888. ●●●●● ●●●● ●Diabetes Insulin-dependent Diabetes mellitus (Type D) Non-Insulin-dependent Diabetes mellitus (Type ID) ●Ischemia Coronary artery disease Impairment of ventricular performance
⚫ Diabetes ⚫ Insulin-dependent Diabetes mellitus (Type I) ⚫ Non-Insulin-dependent Diabetes mellitus (Type II) ⚫ Ischemia ⚫ Coronary artery disease ⚫ Impairment of ventricular performance
●●● Sensitivity of the diabetic heart to ●● ischemic injury ●Controversy Epidemiological and clinical studies .↑Susceptibility Framingham Heart Study CVD Events in Diabetics Experimental studies 2 10 ·↑or↓sensitivity 2 0
⚫ Sensitivity of the diabetic heart to ischemic injury ⚫ Controversy ⚫ Epidemiological and clinical studies ▪ Susceptibility ⚫ Experimental studies ▪ or sensitivity
Clinical studies Coronary artery disease (Atherosclerosis) ●Major complication ·Angina ·Acute myocardial infarctions(AM⑩ .Congestive heart failure Cause of death in more than half of all patients
Clinical studies ⚫ Coronary artery disease (Atherosclerosis) ⚫ Major complication ⚫ Angina ⚫ Acute myocardial infarctions(AMI) ⚫ Congestive heart failure ⚫ Cause of death in more than half of all patients
888 ●●●●● ●●●● Clinical studies Long-term mortality rate after AMI ·2-3 times higher CAD Mortality in Type 2 Diabetes Men Women Diabetes Diabetes No Diabetes 1 Frstninghsmn -94-7多-1112-1形1892028 0-94-7B-1112-1518-9920-28 Duration of Follow-Up (yr) Duration of Follow-Up (yr)
Clinical studies ⚫ Long-term mortality rate after AMI ⚫ 2-3 times higher
●●● Experimental studies ●●● The sensitivity of the heart from experimental animal models of diabetes to ischemia Controversy 。More Less 。Similar
Experimental studies ⚫ The sensitivity of the heart from experimental animal models of diabetes to ischemia ⚫ Controversy ⚫ More ⚫ Less ⚫ Similar
888 ●●●●● ●0●0 Less sensitive to ischemic injury 889 ●First evidence Tani M,Neely JR.Hearts from diabetic rats are more resistant to in vitro ischemia.Possible role of altered calcium metabolism.Circ Res 1988,62:931-940
Less sensitive to ischemic injury ⚫ First evidence ⚫ Tani M,Neely JR. Hearts from diabetic rats are more resistant to in vitro ischemia. Possible role of altered calcium metabolism. Circ Res 1988, 62:931-940
888. ●●●●● ●●●● Less sensitive to ischemic injury 889 ●Diabetic model .Induced by streptozotocin (STZ) .Duration:or=6 weeks Isolated perfused heart .Global zero-flow ischemia:5~60 min Exogenous substrates ●Glucose ·Glucose+pyruvate .HR,SP,LVP,CO,arrhythmias In vivo zero-flow regional ischemia Smaller infarcts
Less sensitive to ischemic injury ⚫ Diabetic model ⚫ Induced by streptozotocin (STZ) ⚫ Duration: < or = 6 weeks ⚫ Isolated perfused heart ⚫ Global zero-flow ischemia: 5 ~ 60 min ⚫ Exogenous substrates ⚫ Glucose ⚫ Glucose +pyruvate ⚫ HR, SP,LVP,CO, arrhythmias ⚫ In vivo zero-flow regional ischemia ⚫ Smaller infarcts
●●● Less sensitive to ischemic injury ● ●Mechanisms pHi control during and following ischemia Diabetic heart Less lactate accumulation at the end of ischemia Smaller H+load during ischemia ·SLNa+/H+exchange
Less sensitive to ischemic injury ⚫ Mechanisms ⚫ pHi control during and following ischemia ⚫ Diabetic heart ▪ Less lactate accumulation at the end of ischemia ▪ Smaller H+ load during ischemia ▪ SL Na+/H+ exchange
888。 ●●●●● ●0●0 Less sensitive to ischemic injury 889 ●Mechanisms Metabolic changes in diabetic heart Energy substrate use ·Glucose:↓ Fatty acids:1(90-99%)
Less sensitive to ischemic injury ⚫ Mechanisms ⚫ Metabolic changes in diabetic heart ⚫ Energy substrate use ▪ Glucose: ▪ Fatty acids:(90~99%)