The myocardial protective effect of ischemic preconditioning is well known. However, the mechanism is remains unclear. The purpose of this study is to determine the role of adenosine, protein kinase C, KATP channel and the change of monophasic action potential duration on cardioprotective effect of ischemic preconditioning in cat.

In this experiment, 66 cats were allocated into 7 groups:control (n=10), ischemic preconditioning (n=10), adenosine pre-treated (n=10), SPT (8-p-sulfophenyl theophylline) pre-treated (n=9), polymyxin B pre-treated (n=9), glibenclamide pre-treated (n=9) and nicorandil pre-treated (n=9) groups. Ischemic preconditioning was performed in ischemic preconditioning, SPT pre-treated, polymyxin B pre-treated and glibenclamide pre-treated groups by 3 episodes of 5 minutes ischemia and 10 minutes reperfusion. All animals were subjected to 40 minutes of ischemia and 40 minutes reperfusion. Monophasic action potential duration at 50% repolarization (MAP50) was measured in the ischemic and non-ischemic area respectively by epicardial probe throughout the experiment. The effect of ischemic preconditioning was determined by infarct size (% area at risk).

Ischemic preconditioning, adenosine pre-treatment and nicorandil pre-treatment groups demonstrated a significant reduction in infarct size (26±4%, 25±4% and 34±8% infarction of the risk zone, respectively, p<0.01, p<0.01 and p<0.05 vs. control) with respect to control (41±8% infarction of the risk zone). However, pretreatment with SPT, polymyxin B or glibenclamide abolished the effect of ischemic preconditioning. Ischemic preconditioning group exhibited a significant reduction of MAP50 duration in the ischemic area during preconditioning;at the first preconditioning 128±11 msec vs. 144±10 msec control, at the second preconditioning 110±10 msec vs.147±10 msec control (p<0.01), at the third preconditioning 114±10 msec vs. 145±11 msec control (p<0.05). But, pretreatment with SPT, polymyxin B and glibenclamide prevented the reduction of MAP50 in the ischemic area during ischemic preconditioning. During 40 minutes ischemia, the shortening of MAP50 was more pronounced in the preconditioned group than in control group;at 5 minutes 112±13 msec vs. 124±10 msec control, at 10 minutes 89±12 msec vs. 133±11 msec control (p<0.05 ), at 20 minutes 93±12 msec vs. 136±11 msec control (p<0.05), and at 30 minutes 107±19 msec vs. 144±14 msec control (p<0.05). In adenosine pre-treated group, the MAP50 was significantly shortened than control group throughout 40 minutes occlusion period;at 5 minutes 90±8 msec (p<0.05), at 10 minutes 77±9 msec (p<0.05), at 20 minutes 92±8 msec (p<0.05), and at 30 minutes 103±8 msec (p<0.05). Nicorandil pretreatment pronounced the ischemic shortening of MAP50 in ischemic area and the effect was significant during early ischemic period;at 10 minutes 98±22 msec (p<0.05 vs. control). In pretreatment groups with SPT, polymyxin B or glibenclamide, the ischemic preconditioning of MAP50 measured in non-ischemic area was not significantly different compared with control group. MAP50 measured in ischemic area during reperfusion was not significantly different between groups.

Based on this study, adenosine receptor-protein kinase C-KATP channel activation and monophasic action potential duration shortening during ischemia play an important role in myocardial protection during ischemic injury.