Background Glucagon-like Peptide-1 (GLP-1), an incretin hormone, has been shown to promote myocardial glucose uptake and protect against ischaemia in animal models. Glucose metabolism provides more energy per oxygen molecule than fatty acid oxidation. Therefore, changing myocardial metabolism from using free fatty acids (FFA) to glucose could improve myocardial efficiency to maintain normal function despite the constrained oxygen supply that occurs in coronary artery disease. We assessed the hypothesis that GLP-1 infusion would protect the heart from ischaemic dysfunction during dobutamine stress echocardiography (DSE) in patients with stable angina and coronary artery disease.
Methods Twelve patients (age 64±10 years) with coronary artery disease and good left ventricular (LV) function awaiting elective revascularisation were studied. Two DSE scans were conducted in a randomised order following an overnight fast. GLP-1 (7–36) amide was infused intravenously at 1.2 pmol/kg/min during one of the scans and the other acted as a control. Blood samples were taken for glucose, insulin, FFA and GLP-1 (7–36). Tissue Doppler imaging was acquired in three apical views at rest, peak stress and 30 min into recovery. Regional wall function was assessed by peak systolic velocity (Vs), strain and strain rate averaged from 12 non-apical segments, and global LV function was assessed using mitral annular Vs averaged over six sites. Myocardial segments considered to be ischaemic were assigned to the perfusion territories of vessels with >50% stenoses.
Results There was no difference in rate pressure product between the GLP-1 and control scans (21 151±4476 vs 21 652±3467 mm Hg.bpm; p=0.66). GLP-1 infusion increased plasma GLP-1 (7–36) (186.6±67.0 vs 8.0±7.6 pg/ml; p<0.0001) and decreased glucose (4.4±1.0 vs 5.2±1.0 mmol/l; p<0.0001) at peak stress compared to control. GLP-1 infusion did not affect cardiac function at rest but improved both global and regional wall LV function at peak stress and in recovery (Abstract 49 Table 1). There was a reduction in function in recovery compared to baseline in the control scan (stunning) which did not occur with GLP-1 infusion. The improvement in function at peak stress was greater in ischaemic (Vs: 8.92±2.42 vs 7.62±2.69 cm/s; p<0.0001) than non-ischaemic segments (Vs: 11.26±3.52 vs 10.78±3.76 cm/s; p=0.28).
Conclusion Infusion of GLP-1 improved global and regional wall LV function during dobutamine stress in patients with coronary artery disease. This was predominantly driven by a cardioprotective effect on ischaemic segments.
- glucagon-like peptide-1