Sophie J Clarke

Pre-treatment with glucagon-like Peptide-1 protects against ischemic left ventricular dysfunction and stunning without a detected difference in myocardial substrate utilization.

OBJECTIVES This study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention. BACKGROUND GLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear. METHODS Twenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients. RESULTS BO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, -4.3 vs. -19.0%, p = 0.02; delta stroke volume, -7.8 vs. -26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups. CONCLUSIONS Pre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023).

Optimising cardioprotection during myocardial ischaemia: targeting potential intracellular pathways with glucagon-like peptide-1

Coronary heart disease and type-2 diabetes are both major global health burdens associated with an increased risk of myocardial infarction (MI). Following MI, ischaemia-reperfusion injury (IRI) remains a significant contributor to myocardial injury at the cellular level. Research has focussed on identifying a strategy or intervention to minimise IRI to optimise reperfusion therapy, with the aim of delivering a superior clinical outcome. The incretin hormone glucagon-like peptide-1, already an established basis for the treatment of type-2 diabetes, also has the potential to protect against IRI. We explain the physiology and cellular processes involved in IRI, and the intracellular pathways activated by GLP-1, which could intercept IRI and deliver cardioprotection. The review also examines the current preclinical and clinical evidence for GLP-1 in cardioprotection and future directions for research as we look for an effective adjunctive treatment to minimise IRI.

Glucagon-Like Peptide-1: A Promising Agent for Cardioprotection During Myocardial Ischemia

Summary Glucagon-like peptide-1-(7-36) amide (GLP-1) is a human incretin hormone responsible for the release of insulin in response to food. Pre-clinical and human physiological studies have demonstrated cardioprotection from ischemia-reperfusion injury. It can reduce infarct size, ischemic left ventricular dysfunction, and myocardial stunning. GLP-1 receptor agonists have also been shown to reduce infarct size in myocardial infarction. The mechanism through which this protection occurs is uncertain but may include hijacking the subcellular pathways of ischemic preconditioning, modulation of myocardial metabolism, and hemodynamic effects including peripheral, pulmonary, and coronary vasodilatation. This review will assess the evidence for each of these mechanisms in turn. Challenges remain in successfully translating cardioprotective interventions from bench-to-bedside. The window of cardioprotection is short and timing of cardioprotection in the appropriate clinical setting is critically important. We will emphasize the need for high-quality, well-designed research to evaluate GLP-1 as a cardioprotective agent for use in real-world practice.

TCT-214 GLP-1 cardioprotection against ischemic dysfunction in humans is not mediated by a mitochondrial K-ATP dependent pathway in left ventricular conductance catheter studies

Unknown; Seoul National University Hospital, Seoul, Korea, Republic of; Seoul National University Hospital, Seoul, Korea, Republic of; Brest University, Brest, France; Institut Cardiovasculaire Paris Sud, Massy, France; Emory, Atlanta, Georgia, United States; Policlinico Umberto I University, Rome, Italy; Saint Luke’s Mid America Heart Institute; Columbia University Medical Center/Hôpital du Sacré-Coeur de Montréal, New York, New York, United States; CRF, New York, New York, United States; NewYorkPresbyterian Hospital/Columbia University Medical Center, New York, New York, United States; Brigham and Women’s Hospital, Boston, Massachusetts, United States; Columbia University Medical Center/ NewYork-Presbyterian Hospital, New York, New York, United States; Columbus Hospital/San Raffaele Hospital, Milan, Milan, Italy

TCT-318 Cardioprotection with Glucagon-like Peptide-1 (GLP-1) may occur independent of coronary collaterals and metabolic substrate utilisation

Withdrawn