Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass.

Abstract

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 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.

• Authors: Gábor Szabó, Tamás Radovits, Gábor Veres, Nelli Krieger, Sivakkanan Loganathan, Peter Sandner, Matthias Karck
• Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (Eur J Cardiothorac Surg) Vol. 36 Issue 4 Pg. 657-64 (Oct 2009) ISSN: 1873-734X [Electronic] Germany
• PMID: 19523842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Imidazoles
• Phosphodiesterase 5 Inhibitors
• Phosphodiesterase Inhibitors
• Piperazines
• Sulfones
• Triazines
• Vardenafil Dihydrochloride
• Adenosine Triphosphate
• Cyclic GMP

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Cardiopulmonary Bypass (adverse effects)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Cyclic GMP (blood)
• Disease Models, Animal
• Dogs
• Drug Evaluation, Preclinical (methods)
• Endothelium, Vascular (physiopathology)
• Hemodynamics (drug effects)
• Imidazoles (pharmacology, therapeutic use)
• Ischemic Preconditioning, Myocardial (methods)
• Myocardial Reperfusion Injury (etiology, prevention & control)
• Phosphodiesterase 5 Inhibitors
• Phosphodiesterase Inhibitors (pharmacology, therapeutic use)
• Piperazines (pharmacology, therapeutic use)
• Preanesthetic Medication
• Sulfones (pharmacology, therapeutic use)
• Triazines (pharmacology, therapeutic use)
• Vardenafil Dihydrochloride
• Ventricular Function, Left (drug effects)
• Ventricular Function, Right (drug effects)