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The results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.

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Purpose. It seems controversial whether or not neutrophil elastase inhibitors are effective in attenuating the myocardial ischemia/reperfusion injury. We thus investigated possible protective effects of sivelestat, a neutrophil elastase inhibitor, against myocardial stunning-i.e., prolonged myocardial dysfunction following a brief episode of ischemia.Methods. Swine were divided into control group (group C), low-dose sivelestat group (group L), and high-dose sivelestat group (group H) (n=7 for each group). All the swine were subjected to myocardial ischemia through ligation of the left anterior descending coronary artery (LAD) for 12-min, followed by 90-min reperfusion. Sivelestat was infused intracoronally at concentrations of 6 and 60 mg/ml throughout the reperfusion period in the group L and H, respectively, while saline in the group C. Heart rate (HR), left ventricular developed pressure (LVdP), maximum rate of LVdP (LVdP/dtmax), LV end-diastolic pressure (LVEDP), percentage of segment shortening (%SS, an index of regional myocardial contractility), and coronary venous interleukin-6 concentration in LAD perfusion area were measured before ischemic induction and during reperfusion. Results. The ischemia-reperfusion insult did not cause any significant changes in the HR, LVdP, LVdP/dtmax, and LVEDP in all groups. However, it significantly decreased %SS in the LAD perfusion area, while increased the interleukin-6 concentration in the group C. Those changes in %SS and the interleukin-6 concentration were both greatly attenuated, but not prevented, in the group L and group H. Conclusion.Sivelestat presumably attenuates myocardial contractile dysfunction due to myocardial stunning by inhibiting neutrophil-derived elastase and thereby suppressing the production of interleukin-6 in activated neutrophils.(250 words) 4

We conclude that milrinone administered before ischemia or just after reperfusion attenuates myocardial stunning.