PROTECTION AGAINST MYOCARDIAL DYSFUNCTION AFTER A BRIEF ISCHEMIC PERIOD IN TRANSGENIC MICE EXPRESSING INDUCIBLE HEAT-SHOCK-PROTEIN-70

Brief ischemic periods lead to myocardial dysfunction without myocardi al infarction, It has been shown that expression of inducible HSP70 in hearts of transgenic mice leads to decreased infarct size, but it rem ains unclear if HSP70 can also protect against myocardial dysfunction after brief ischemia, To investigate this question, we developed a mou se model in which regional myocardial function can be measured before and after a temporary ischemic event in vivo, In addition, myocardial function was determined after brief episodes of global ischemia in an isolated Langendorff heart, HSP70-positive mice and transgene negative littermates underwent 8 min of regional myocardial ischemia created b y occlusion of the left descending coronary artery, followed by 60 min of reperfusion, This procedure did not result in a myocardial infarct ion, Regional epicardial strain was used as a sensitive indicator for changes in myocardial function after cardiac ischemia, Maximum princip al strain was significantly greater in HSP70-positive mice with 88+/-6 % of preischemic values vs, 58+/-6% in transgene-negative mice (P < 0. 05), Similarly, in isolated Langendorff perfused hearts of HSP70-posit ive and transgene-negative littermates exposed to 10 min of global isc hemia and 90 min of reperfusion, HSP70 transgenic hearts showed a bett er-preserved ventricular peak systolic pressure, Thus, we conclude tha t expression of HSP70 protects against postischemic myocardial dysfunc tion as shown by better preserved myocardial function.