MYOCARDIAL MECHANICS AND TITIN IN EXPERIMENTAL INSULIN-RESISTANT RATS

We investigated the intrinsic cardiac mechanics of myocardium and chan ges in titin in insulin-resistant rats. Microsonometry and micromanome try were used to evaluate the maximal elastance (Emax) and myocardial stiffness constant (Km) of the left ventricle, in addition to the trad itional systolic and diastolic cardiac function, with an isolated work ing heart preparation. Thirty 150 g Wistar rats were divided into thre e groups of 10. Group A was fed rat chow, while groups B and C were fe d a 66% fructose diet for 7-8 months. Group C also received clonidine. Group B rats developed insulin resistance, as well as elevated plasma glucose and blood pressure. Group C rats also had insulin resistance and elevated plasma glucose, but not higher blood pressure. Group B ra ts had decreased Emax, decreased peak-dp/dt, prolonged Tau and increas ed Km compared to normal control rats. Group C rats, which mimicked th e clinical condition of diabetic cardiomyopathy, maintained normal glo bal left ventricular function as revealed by cardiac output, peak + dp /dt, peak - dp/dt and Tau of relaxation. However, they had a lower Ema x slope (355 +/- 51 vs 535 +/- 56 mmHg . mm than group A rats, p < 0.0 5) and increased Km (81.6 +/- 9.9 vs 25.5 +/- 4.8 in group A, p < 0.00 1), even though the extent of elevation of plasma glucose was only mil d (71.3 +/- 2.0 to 108.9 +/- 4.4 mg/dl, p < 0.001). Their left ventric ular mass, myocyte size, interstitial fibrosis and vascular picture di d not change. However, the content of myocardial titin decreased signi ficantly (intensity ratio of titin/actin was 0.23 +/- 0.01 and 0.29 +/ - 0.02 in group C and group A rats respectively, p < 0.05). These find ings suggest that changes in titin play a role in the change in myocar dial functional characteristics and may be one of the causes of diabet ic cardiomyopathy.