Effect of insulin and glucose infusion on myocardial infarction size in uraemic rats

• Published in: Basic research in cardiology 2009-09, Vol.104 (5), p.571-579
• Main Authors: Dikow, Ralf, Wasserhess, Caroline, Zimmerer, Katrin, Kihm, Lars Philipp, Schaier, Matthias, Schwenger, Vedat, Hardt, Stefan, Tiefenbacher, Christiane, Katus, Hugo, Zeier, Martin, Gross, Lisa Marie
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Cardiology; Disease Models, Animal; Glucose - administration & dosage; Glucose Transporter Type 4 - metabolism; Infusions, Parenteral; Insulin - administration & dosage; Insulin Receptor Substrate Proteins - metabolism; Insulin Resistance; Male; Medicine; Medicine & Public Health; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardium - metabolism; Myocardium - pathology; Nephrectomy; Original Contribution; Rats; Rats, Sprague-Dawley; Time Factors; Uremia - complications; Uremia - drug therapy; Uremia - pathology; Uremia - physiopathology
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-009-0018-2

The post myocardial infarction (MI) mortality rate is high in renal patients. One possible explanation is the reduced ischemia tolerance caused by uraemia. Previous investigations showed larger MI size in uraemic rats when compared with sham-operated controls. To explore a possible link between uraemic insulin resistance syndrome and MI size in uraemia, we studied an intervention model with administration of insulin and glucose during acute MI in subtotally nephrectomized (SNX) rats and sham-operated controls. In 16 SNX rats and 16 sham-operated controls, the left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. To visualize the perfused myocardium, lissamine-green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (TTC stain) were assessed in sections of the left ventricle (LV) using image analysis. While eight SNX rats and eight sham-operated controls were treated with a placebo during the procedure, the other animals received an insulin bolus of 85 mU/kg and then a continuous insulin infusion of 8 mU/kg per minute. Blood glucose levels were clamped to baseline levels with an infusion of 25% glucose. Insulin receptor substrates (IRS-1 and IRS-2) and glucose transporter (GLUT 4) were studied by western blot in another seven SNX and seven sham-operated controls without further intervention. The infarcted area, given as a proportion of the nonperfused risk area, was not different in sham-operated controls treated with a hyperinsulinaemic clamp versus untreated (0.55 ± 0.07 vs. 0.51 ± 0.13, p  = 0.477). The eight SNX animals treated with the hyperinsulinaemic clamp utilized significantly less glucose to stabilize baseline glucose levels when compared with the sham-operated controls (5,637 vs. 3,207 μl Glc 25%, p  = 0.007). The infarcted area was significantly lower in SNX rats treated with the hyperinsulinaemic clamp compared to non-treated SNX animals (0.56 ± 0.06 vs. 0.79 ± 0.09, p