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  • 1
    Electronic Resource
    Electronic Resource
    The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog (2005)
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 32 (2005), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an α-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown.2. In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50–100 µg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres.3. There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 ± 0.4 vs 2.2 ± 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area.4. In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.2005.04269.x
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  • 2
    Electronic Resource
    Electronic Resource
    N-Methyl-1-deoxynojirimycin (MOR-14), an α-glucosidase inhibitor, markedly improves postischemic left ventricular dysfunction (2000)
    Springer
    Heart and vessels 15 (2000), S. 268-273 
    Details
    ISSN: 1615-2573
    Keywords: Key words Left ventricular dysfunction ; Ischemia ; Reperfusion ; α-Glucosidase inhibitor ; Glycogen ; Glycogenolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined whether pharmacological inhibition of glycogenolysis by N-methyl-1-deoxynojirimycin (MOR-14), a new compound which reduces the glycogenolytic rate by inhibiting the α-1,6-glucosidase activity of the glycogen-debranching enzyme, can protect the heart against postischemic left ventricular dysfunction. The hearts of male Sprague-Dawley rats were excised, and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were paced at 320 beats/min except during the ischemia. Left ventricular developed pressure (LVDP, mmHg), ±dP/dt (mmHg/s), and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min including a 30-min preischemic period followed by a 30-min episode of global ischemia and 60 min reperfusion, with or without 0.5 or 2 mM of MOR-14 during the 30-min preischemic period or the first 30 min of reperfusion. In another series of experiments, the myocardial content of glycogen and lactate was measured during the 30-min episode of ischemia in groups treated with and without 2 mM of MOR-14. Preischemic but not postischemic treatment with MOR-14 significantly improved LVDP and ±dP/dt without altering coronary flow during reperfusion in a dose-dependent manner. MOR-14 significantly preserved the glycogen content and significantly attenuated the lactate accumulation during the 30-min episode of ischemia. Preischemic treatment with MOR-14 is protective against postischemic left ventricular dysfunction through the inhibition of glycogenolysis in the isolated rat heart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003800070004
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    Paper (German National Licenses)
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