Author + information
- Joel Giblett1,
- Richard Axell2,
- Paul White3,
- Sophie Clarke4,
- Philip Read5,
- Liam McCormick6,
- Adam Brown7,
- Michael O'Sullivan8,
- Nick West9,
- David Dutka10 and
- Stephen Hoole11
- 1Papworth Hospital, Cambridge, United Kingdom
- 2Papworth Hospital
- 3Addenbrooke's Hospital
- 4University of Cambridge
- 5Papworth Hospital, Huntingdon, United Kingdom
- 6MonashHeart, Melbourne, Victoria, Australia
- 7Papworth Hospital, Cambridge, United Kingdom
- 8Unknown, Cambridge, United Kingdom
- 9Papworth Hospital, Cambridge, United Kingdom
- 10Addenbrookes, Cambridge, United Kingdom
- 11Papworth Hospital, Cambridge, United Kingdom
Glucagon-like Peptide-1 (GLP-1) protects against left ventricular (LV) stunning but the mechanism of cardioprotection is unclear. Subcellular pathways responsible for ischaemic conditioning have been implicated in animal studies. We investigated whether blockade of mitochondrial K-ATP channels (mKATP) with glibenclamide would abrogate GLP-1 cardioprotection in humans.
Non-diabetic patients with normal LV function attending for elective percutaneous coronary intervention to their left anterior descending (LAD) artery (n=32) were assigned to 4 equal groups: saline control, GLP-1, Glibenclamide and GLP-1 & Glibenclamide. Glibenclamide 5mg orally was administered at least 60 minutes prior to the procedure. Pressure-volume loops were recorded using a conductance catheter placed in the LV at baseline (BL1) and after a 1-minute LAD balloon occlusion (BO1). GLP-1 or saline infusion was initiated after BO1. After 30 minutes, loops were repeated before and after a further balloon occlusion (BL2 & BO2). Data were analyzed for measures of systolic (dP/dtmax) and diastolic (dP/dtmin) LV function.
BO1 caused LV dysfunction in all groups. Recovery from stunning (BL2) and cumulative LV dysfunction (BO2) were improved with GLP-1, either alone or in combination with glibenclamide. Glibenclamide alone matched the control group (Figure).
Glibenclamide did not abrogate GLP-1-mediated cardioprotection against myocardial stunning, suggesting that it does not occur via a KATP-dependent pathway in humans.