Reduction of regional contractile function by preconditioning ischemia does not play a permissive role in the infarct size-limitation by the preconditioning.
Although previous studies have shown that preconditioning cannot be explained by concurrent myocardial stunning alone, it remains unclear whether reduction of contractile function by preconditioning ischemia is required for its cardioprotective effect. The present study examined whether preconditioning occurs in the absence of regional contractile dysfunction. In the first series of experiments, rabbits received two cycles of 2-min coronary occlusion separated by 5-min reperfusion, with or without dobutamine infusion (10 micrograms/kg/min, i.v.) commencing before the onset of ischemia. Regional thickening fraction measured by epicardial Doppler sensor was 72.8 +/- 4.7% of baseline (mean +/- SEM) in the untreated group and 102.9 +/- 3.1% in the dobutamine group at the end of the second cycle of ischemia/reperfusion. In the second series of the study, four groups of rabbits underwent 30-min coronary occlusion and reperfusion. The control group was untreated, and the PC group was preconditioned with two cycles of 2-min ischemia/5-min reperfusion before the 30-min ischemia. The PC-DOB group received both preconditioning and dobutamine infusion (10 micrograms/kg/min, i.v.), which was started 5 min before the preconditioning and continued for 19 min. The DOB group was given dobutamine infusion like the PC-DOB group, but was not preconditioned. After 72-h reperfusion, infarct size and area at risk were determined by histology and fluorescent particles, respectively. Infarct sizes in the PC and PC-DOB groups (25.0 +/- 3.4% and 22.7 +/- 3.3% of area at risk, respectively) were significantly smaller than that in the control group (48.2 +/- 2.6%). In the DOB groups, infarct size (43.5 +/- 4.0%) was similar to the control value. Infusion of dobutamine at a dose sufficient to abolish the contractile dysfunction which would have been induced by ischemic preconditioning did not attenuate the infarct size-limiting effect of preconditioning. Thus, it is unlikely that reduction of contractile function plays a permissive role in the appearance of the cardioprotective effect of preconditioning.
Goto
M
M
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine.
Miura
T
T
Itoya
M
M
Sakamoto
J
J
Iimura
O
O
D000818:Animals; D004280:Dobutamine / Q000494:pharmacology; D006439:Hemodynamics; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology*; D017682:Myocardial Stunning; D009206:Myocardium / Q000473:pathology; D011817:Rabbits
D004280:Dobutamine