Protective effect of α -1, 6-glucosidase inhibitors against ischemia-reperfusionjury

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I.It was examined whether α-1, 6-glucosidase inhibitor, miglitol, has an anti-anginal effect * dog anginal model with stenosis of coronary artery. An epicardial electrode and a microdialysis probe was implanted into the myocardium to measure ST change and interstitial lactate accumulation. Anginal attack was induced for 10 minutes by a combination of atrial pacing and phenylephrine infusion. Double product at the first and second anginal attack were increased to a similar degree in each of the groups (approximately 240% compared to the baseline). There was no significant difference in the regional blood flow between the first and the second anginal attack both in the miglitol and control groups. At the first and second anginal attack, the ST segment was decreased from 2.2±0.4 to 1.3±0.4 mV in the miglitol group (P<0.05), but was similar in the control group (2.3±0.3 and 2.2±0.4 mV). The lactate increment(△lactate) at the risk area was 1.2±0.3 and 0.3±0.1 mg/ml (p<0.05) in the mislitol … More group and 1.1±0.3 and 1.3±0.4 mg/ml in the control group, respectively. The lactate increment at the second anginal attack in the miglitol group was significantly smaller than the control. Miglitol has an anti-anginal effect through the inhibition of glycogenolysis during effort-induced ischemia.II.It was examined whether pharmacolonical inhibition of glycogenolysis by α-1, 6-glucosidase inhibitor, MOR-14, can protect the heart against post-ischemic left ventricular dysfunction (stunning). The hearts of rats were excised and perfused on a Langendorff apparatus with Krebs-Henseleit solution. The hearts were paced at 320 beats/min except during ischemia. Left ventricular developed pressure (LVDP, mmHg), ±dP/dt (mmHg/sec) and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min consisting of a 30 min pre-ischemic period followed by a 30 min global ischemia and 60 min reperfusion with or without 2 mM of MOR-14 during a 30 min pre-ischemic period or during a 30 min reperfusion period. In another sereies of experiments, myocardial glycogen content and lactate were neasured at 30 min of ischemia in groups treated with and without 2 mM of MOR-14. Pre-ischemic but not post-ischemic treatment with MOR-14 significantly improved LVDP, ±dP/dt without altering coronary flow during reperfusion. MOR-14 significantly preserved the glycogen content and significantly attenuated the lactate accumulation during 30 min ischemia. Pre-ischemic treatment with MOR-14 is protective asainst stunning through the inhibition of glycogenolysis in the isolated rat heart. Less