An Experimental Series Investigating the Effects of Hyperinsulinemic Euglycemia on Myocardial Blood Flow Reserve in Healthy Individuals and on Myocardial Perfusion Defect Size following ST-Segment Elevation Myocardial Infarction

Abstract

Background: Incomplete restoration of myocardial blood flow is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularisation. Experimental hyperinsulinemic euglycemia (HE) increases myocardial blood flow reserve (MBFR). If fully exploited, this effect may also improve myocardial blood flow to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine: a) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and b) the effect of an insulin-dextrose infusion given immediately following revascularisation of STEMI on myocardial perfusion.Methods: MBFR was determined using myocardial contrast echocardiography (MCE). Experiment 1 [Insulin duration]: twelve participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 [Insulin dose]: twenty-two participants received one of three insulin doses (0.5, 1.5, 3.0mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFR's were determined. Experiment 3 [Insulin resistance]: five metabolic syndrome (MetS) and six type-2 diabetes (T2DM) participants received 1.5mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFR's were determined. Experiment 4 [STEMI]: following revascularisation for STEMI, twenty patients were randomised to receive either 1.5mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. MCE was performed at four time intervals to quantify percentage contrast defect length.Results: Experiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared to baseline, MBFR increased in the 1.5 (2.42±0.39 to 3.25±0.77, p=0.002), did not change in 0.5, and decreased in 3.0 (2.64±0.25 to 2.16±0.33, p=0.02) mU/kg/minute groups. Experiment 3: compared to baseline, MBFR increase was only borderline significant in MetS and T2DM participants (1.98±0.33 to 2.59±0.45, p=0.04, and 1.67±0.35 to 2.14±0.21, p=0.05). Experiment 4: Baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than control at 60 minutes (2.8±5.7 vs 13.7±10.6, p=0.02).Conclusions: Presence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. HE may improve MBF following ischemia, but further studies are needed to clarify this.