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Preischaemic treatment with N-methyl-1-deoxynojirimycin (MOR-14), an alpha-1,6-glucosidase inhibitor, attenuates glycogenolysis and lactate accumulation during ischaemia and markedly reduces infarct size in rabbit hearts. In the present study, we have investigated whether protein kinase C (PKC), a principal mediator of ischaemic preconditioning, is also involved in the cardioprotective effect of MOR-14. To assess the effect of PKC inhibition on infarct size in MOR-14-treated hearts, 38 rabbits were subjected to 30 min of ischaemia followed by 48 h of reperfusion. Infarct size, as a per cent of area at risk, was significantly smaller in rabbits administered 100 mg kg(-1) of MOR-14 10 min before ischaemia (17+/-2%, n=10), than in a control group (46+/-5%, n=10). This beneficial effect of MOR-14 was abolished when 5 mg kg(-1) of chelerythrine, a PKC inhibitor, was given 10 min prior to MOR-14 injection (39+/-4%, n=10), although chelerythrine alone did not alter infarct size (43+/-4%, n=8). Further, chelerythrine had no effect on MOR-14-induced attenuation of glycogen breakdown and lactate accumulation in hearts excised at 30 min of ischaemia. Immunoblot analysis of PKC in homogenates of Langendorff-perfused rabbit hearts revealed that MOR-14 significantly increased levels of PKC-epsilon in the particulate fraction at 20 and 30 min of ischaemia and in the cytosolic fraction at 30 min of ischaemia. Taken as a whole, our data suggest that PKC acts downstream of the inhibition of glycogenolysis by MOR-14 to reduce infarct size. Thus, activation of PKC is a more direct mediator of the cardioprotection afforded by MOR-14 than is inhibition of glycogenolysis.

Purpose: To evaluate the long-term survival and cardiac performance in the patients who underwent percutaneous coronary intervention(PCI) or coronary artery bypass graft surgery(CABG) to the chronic total occluded(CTO) lesions in their main coronary arteries. Subjects: Consecutive 317 patients who had CTO lesions (TIMI 0) in their main coronary arteries were treated with PCI (PTCA,DCA,STENT,PTCRA) or CABG between June 1991 and 2000. CTO lesion was excluded when CABG was formerly performed. Methods: These patients were compared by survival rate,LVEF,EDVI,ESVI at pre PCI/CABG and LVEF,EDVI,ESVI in the chronic phase i.e., mean followed-up interval of four years, between successfully revasculized group(Y) and unsuccessful group(N). Results: In the cardiac death group(n = 16), chronic LVEF,EDVI,ESVI were significantly worse (35vs56,124vs87,84vs41), compared with survived group(n = 280). In the Y group, LVEF and ESVI were significantly improved after revasculazation of CTO, although there was no improvement in N group. Furtheremore, when patients were limited to have less than 100ml/m 2 of LVESV before PCI/CABG, improvement of LVEF and ESVI was found much more clear. Summary: Better LVEF and LVESV before PCI/CABG predicts much more improvement of cardiac function after revasculization of CTO. In addition, Lower LVEF (35%) and Larger LV volume (LVEDV;124ml/m 2 ,LVESV;84ml/m 2 ) in chronic phase indicates higher mortality in spite of the recanalization of CTO.