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

观察α-1，6-葡萄糖苷酶抑制剂米格列醇对犬冠状动脉狭窄心绞痛模型的抗心绞痛作用。心外膜电极和微透析探头植入心肌内，测量ST段改变和间质乳酸蓄积。心房起搏加苯肾上腺素注射诱导心绞痛发作10min。在第一次和第二次心绞痛发作时，每组患者的双倍乘积都有类似程度的增加(与基线相比约为240%)。米格列醇组和对照组在第一次和第二次心绞痛发作时的局部血流量均无显著差异。在第1次和第2次心绞痛发作时，米格列醇组的ST段由2.2±0.4 mV降至1.3±0.4 mV(P&lt；0.05)，而对照组为2.3±0.3 mV和2.2±0.4 mV。危险区域的乳酸增量(乳酸)分别为1.2±0.3和0.3±0.1毫克/毫升(p&lt；0.0 5)…。More组和对照组分别为1.1±0.3和1.3±0.4 mg/ml。米格列醇组第二次心绞痛发作时的乳酸增量明显小于对照组。米格列醇通过抑制努力诱导的缺血时的糖原分解而具有抗心绞痛的作用。II.研究了α-1，6-葡萄糖苷酶抑制剂MOR-14抑制糖原分解的药理学效应是否能保护心脏免受缺血后左心功能不全(眩晕)的影响。取大鼠心脏，在含有Krebs-Henseleit溶液的朗宁多夫装置上灌流。心脏起搏速度为320次/分钟，除缺血期间外。连续监测左心室发展压(LVdP，mm Hg)、±dp/dt(mm Hg/s)和冠脉流量(ml/min)。缺血前30min，全心缺血30min，再灌注60min，在缺血前30min或再灌流30min期间加或不加2 mM的MOR-14。在另一系列实验中，在缺血30min时，测定了使用和不使用2 mM MOR-14组的心肌糖原含量和乳酸含量。缺血前而非缺血后应用MOR-14可显著改善再灌流期间的LVdP、±dp/dt，而不改变冠脉流量。MOR-14可显著保留缺血30min时的糖原含量，显著抑制乳酸蓄积。缺血前应用MOR-14可通过抑制大鼠离体心的糖原分解来保护心脏的抗晕厥作用。较少

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