Thorac Cardiovasc Surg 2012; 60 - PP32
DOI: 10.1055/s-0031-1297679

GLP-1 improves survival and preserves diastolic function and cardiac glucose oxidation in rats with pressure overload

TD Nguyen 1, Y Shingu 2, PA Amorim 2, M Schwarzer 1, T Doenst 1
  • 1Klinik für Herz- und Thoraxchirurgie, Friedrich-Schiller-Universität Jena, Jena, Germany
  • 2Herzzentrum Leipzig, Universität Leipzig, Leipzig, Germany

Objectives: The incretin hormone GLP-1 has been associated with protective effects in diabetes and ischemic heart disease. We investigated the role of GLP-1 treatment in rats subjected to chronic pressure overload (PO) with the aim to detect a novel metabolic mechanism to improve ventricular function.

Methods: Rats underwent transverse aortic constriction (TAC) to induce PO or sham operation. Two weeks after TAC, osmotic pumps were implanted for intravenous infusion of rGLP-1. Six weeks after TAC, we evaluated hypertrophy and heart function in vivo by echocardiography, pulmonary congestion by lung weight-to-body weight index (LW/BW), left ventricular stiffness by pressure-volume relationship ex vivo and measured glucose oxidation (GO) and fatty acid oxidation (FAO) in the isolated working heart.

Results: Oder of results: Sham; TAC; TAC+GLP-1; *: p<0.001

Six weeks of untreated TAC increased left ventricular posterior wall thickness in diastole (LVPWd). Whereas fractional shortening was unchanged at this time point, LW/BW was dramatically increased and survival was reduced compared to sham indicating impaired diastolic function. Compared to untreated TAC, GLP-1 treatment did not ameliorate hypertrophy, but improved survival (100%; 38%; 70%;*), reduced LW/BW (5.2±0.1; 12.5±0.7; 8.0±1.1g/kg;*) and left ventricular stiffness (stiffness constant k: 4.8±0.1; 9.6±0.5; 6.8±0.5;*). Untreated TAC resulted in decreased FAO and GO. Compared to untreated TAC, GLP-1 treatment substantially increased GO (0.56±0.04; 0.28±0.06; 0.47±0.09µmol/min/gdry) and significantly increased GO/FAO ratio (0.5±0.1; 0.8±0.1; 1.7±0.3;*). While GLP-1 may boost insulin secretion, there were no differences in serum insulin levels suggesting insulin-independent mechanisms.

Conclusions: Chronic GLP-1 treatment improves survival, reduces ventricular stiffness and pulmonary congestion in rats with PO suggesting preserved diastolic function. These effects were independent of insulin and associated with preserved GO. GLP-1 treatment may be a new therapeutic option also for patients undergoing cardiac surgery.