Objectives: Phosphodiesterase-5 inhibitors and elevated myocardial cyclic guanosine monophosphate levels can induce potent cardioprotection-like effects against ischaemia-reperfusion injury. We investigated the effects of vardenafil, a selective phosphodiesterase-5 inhibitor on myocardial and endothelial functions during reperfusion in a canine model of cardioplegic arrest and extracorporal circulation. Methods: Vehicle-treated (control, n = 8) and vardenafil-treated (30 μg kg-1 intravenous (IV); n = 8) anaesthetised dogs underwent hypothermic cardiopulmonary bypass with 60 min of hypothermic cardiac arrest. Left and right ventricular end-systolic pressure volume relationship (Ees) was measured by a combined pressure-volume conductance catheter at baseline and after 60 min of reperfusion. Left anterior descending coronary blood flow and endothelium-dependent vasodilatation to acetylcholine were determined. Isolated coronary arterial rings were investigated for vasomotor function using an in vitro organ bath system. Results: Pharmacological preconditioning with vardenafil led to significantly higher plasma cyclic guanosine monophosphate levels and myocardial adenosine triphosphate content to a better recovery of left and right ventricular Ees (Δ left ventricular Ees given as percent of baseline: 74.2 ± 4.5% vs 50.4 ± 5.0%, p < 0.05) and to a higher coronary blood flow (58 ± 12 vs 24 ± 7 ml min-1, p < 0.05). Endothelium-dependent vasodilatory responses to acetylcholine - measured both in vivo and in vitro - were improved in the vardenafil group. Conclusions: Application of vardenafil improves myocardial and endothelial functions after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that phosphodiesterase-5 inhibition could be a novel therapeutic option in the protection against ischaemia-reperfusion injury in cardiac surgery.
- Cardiopulmonary bypass
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine