Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass.
OBJECTIVE
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 microgkg(-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 (E(es)) 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 E(es) (Delta left ventricular E(es) 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 mlmin(-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.
Szabó
Gábor
G
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. dzsi@hotmail.com
Radovits
Tamás
T
Veres
Gábor
G
Krieger
Nelli
N
Loganathan
Sivakkanan
S
Sandner
Peter
P
Karck
Matthias
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004730:Endothelium, Vascular / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011229:Preanesthetic Medication; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
D002316:Cardiotonic Agents; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000255:Adenosine Triphosphate; D006152:Cyclic GMP