[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of ischemic preconditioning (IP) on reperfusion arrhythmias in type 2 diabetic rats as well as the effects of the insulin sensitizer pioglitazone. Thirty-week-old OLETF rats with or without pioglitazone (10 mg/kgBW, orally) were used as a model for type 2 diabetes. LETO rats served as controls. The incidences and durations of reperfusion ventricular tachyarrhythmias (RVT) were evaluated using a working heart method. After 5 minutes of initial perfusion, the rats were divided into the following groups: 1) control rats without IP (CIP(-)), 2) control rats with IP (CIP(+)), 3) diabetic rats without IP (DIP(-)), 4) diabetic rats with IP (DIP(+)), 5) pioglitazone-treated diabetic rats without IP (TDIP(-)), and 6) pioglitazone-treated diabetic rats with IP (TDIP(+)). Three 2-minute cycles of global diastolic ischemia and 5 minutes of reperfusion before long ischemia were performed as IP. The incidence and duration of RVT in CIP(+) were significantly lower than in CIP(-). There was no significant difference in the duration of RVT between DIP(+) and DIP(-). However, the duration of RVT in TDIP(+) was significantly shorter than TDIP(-). These results suggested that the effects of IP on reperfusion arrhythmias are deteriorated in type 2 diabetic rats. The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats.
No preview · Article · Oct 2007 · International Heart Journal
[Show abstract][Hide abstract] ABSTRACT: Acute myocardial infarction (MI) sometimes occurs without painful symptoms and in such cases, prognosis is worsened by delays in diagnosis and revascularization. Renal insufficiency induces many types of neuropathy, but the relation between renal insufficiency and painless MI remains unclear.
Patients with MI and elevated creatine kinase levels were retrospectively analyzed. Renal insufficiency (serum creatinine concentration > or =1.5 mg/dl) and other characteristics (age, sex, body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia, history of stroke, previous MI, hemodialysis, and atrial fibrillation) were compared between patients who had MI with painful symptoms (painful MI, n=131) and patients who had MI without painful symptoms (painless MI, n=18). Other variables compared were the time from symptom onset to admission, peak creatine kinase concentration, Killip class, site of MI, emergency coronary angiography, postprocedural Thrombolysis In Myocardial Infarction grade III flow, and in-hospital death. Univariate analysis identified older age, renal insufficiency, and previous MI as predictors of painless MI. Patients with painless MI showed higher rates of Killip class > or =II and in-hospital death and a longer time from symptom onset to admission. However, multivariate analysis identified only renal insufficiency as an independent predictor of painless MI.
MI without painful symptoms frequently develops in patients who have renal insufficiency, so the possibility of painless MI should be evaluated in such patients to ensure early diagnosis and treatment.
No preview · Article · Sep 2007 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: Diabetic patients often have manifestation of coronary heart disease. As a consequence, therapeutic strategies for diabetes should pay more attention to hypoglycemic agents which do not have adverse effects on myocardium. Mitiglinide is considered to have little or no impact on the cardioprotective effect of ischemic preconditioning (IP) because of its high selectivity for blocking sulfonylurea receptor1 (SUR1). However, glibenclamide, a nonselective SUR blocker, attenuates this beneficial effect. In the present study, we tested the hypothesis that mitiglinide preserves the protective action of IP evaluated by ischemia/reperfusion ventricular tachyarrhythmia (rVT) in isolated perfused rat hearts. After initial perfusion, the hearts were assigned to one of the following groups: 1) non-IP with control perfusion buffer (non-IP group); 2) IP with control perfusion buffer (IP-C group); 3) IP with perfusion buffer containing glibenclamide (IP-G group); and 4) IP with perfusion buffer containing mitiglinide (IP-M group). The protocol for the non-IP group consisted of 21 minutes of aerobic perfusion before 10 minutes of ischemia. In the other 3 groups (IP groups), there were 3 cycles of 2-minute ischemia followed by 5 minutes of reperfusion before 10 minutes of ischemia. The IP-C group had a significantly shorter rVT duration than the non-IP group (4.4 +/- 1.8 minutes versus 14.3 +/- 2.5 minutes; P < 0.05). rVT duration was the shortest in the IP-M group (3.9 +/- 1.0 minutes), but among the longest in the IP-G group (14.0 +/- 2.6 minutes). In conclusion, mitiglinide preserved the cardioprotective effect of IP, however, glibenclamide abolished this beneficial effect. Therefore, mitiglinide may offer a long-term benefit for myocardial ischemia in diabetic patients.
No preview · Article · May 2007 · International Heart Journal