CARDIAC MYOCYTE FUNCTION AND LEFT-VENTRICULAR STRAINS AFTER BRIEF ISCHEMIA AND REPERFUSION IN RABBITS

Background After a brief episode of ischemia, myocardial function may be depressed for prolonged periods despite reperfusion. The mechanisms of postischemic dysfunction differ depending on the experimental mode l. Regional ischemia and reperfusion in the intact animal provide a cl inically relevant model, but experimental variables are difficult to c ontrol. Experimental conditions can be well controlled in isolated car diac muscle and myocyte preparations, but these models are limited by the assumptions used to mimic ischemia and reperfusion. This study com bines the unique advantages of both preparations. We characterized in vivo alterations in regional two-dimensional finite strains with ische mia and reperfusion produced in the intact animal, then isolated cardi ac myocytes from the region with postischemic dysfunction to character ize in vitro function of postischemic myocytes. Methods and Results In seven anesthetized rabbits, three piezoelectric crystals were inserte d in a triangular array to measure two-dimensional finite strains arou nd the large coronary artery in the left ventricular anterior free wal l. After 15 minutes of ischemia and reperfusion, strains were depresse d at a stable level approximate to 30% to 40% below control values bet ween 1 and 6 hours after reperfusion. The direction of maximal shorten ing deformations was midway between circumferential and longitudinal d irections during control and did not shift after reperfusion. In a sec ond group of five rabbits, cardiac myocytes were isolated from the reg ion with postischemic dysfunction after 15 minutes of ischemia and 45 minutes of reperfusion. We compared in vitro function in 45 postischem ic myocytes with 48 cardiac myocytes isolated from five normal rabbits . Each rabbit (postischemic and control) contributed 9+/-1 (SD) myocyt es to the study. All myocytes were studied within 1 hour after myocyte isolation (approximate to 3 to 5 hours after reperfusion for postisch emic myocytes). Myocytes were stimulated at 0.5 Hz and perfused with 2 mmol/L [Ca2+] Tyrode's solution to measure unloaded cell shortening. There was significantly less shortening in postischemic myocytes (12.4 +/-2.1%) than control myocytes (16.2+/-1.2%). Maximal cell length (L(m ax)) was significantly longer in postischemic (134+/-7 mu m) than cont rol myocytes (122+/-7 mu m), as was minimum cell length (L(min)) (118/-8 versus 103+/-9 mu m, respectively). The duration of shortening (ti me from stimulation co L(min)) was significantly shorter in postischem ic (279+/-56 milliseconds) than control myocytes (405+/-44 millisecond s). Peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) di d not differ. Conclusions In rabbits, 15 minutes of ischemia produced a stable depression in finite strains for 1 to 6 hours after reperfusi on, with shortening deformations reduced by approximate to 30% to 40% without a shift in direction. Cardiac myocytes isolated from postische mic myocardium display functional impairments in vitro similar to thos e measured in vivo, with an approximate to 25% reduction in unloaded m yocyte shortening and decreased contraction duration. This indicates t hat ischemia and reperfusion induce intrinsic impairments in contracti lity independently of external loading conditions. This model may be u seful for examining cellular mechanisms of postischemic myocardial dys function.