Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass

G. Szabó, T. Radovits, Gábor Veres, Nelli Krieger, Sivakkanan Loganathan, Peter Sandner, Matthias Karck

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)657-664
Number of pages8
JournalEuropean Journal of Cardio-thoracic Surgery
Volume36
Issue number4
DOIs
Publication statusPublished - Oct 2009

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Cardiopulmonary Bypass
Wounds and Injuries
Phosphodiesterase 5 Inhibitors
Cyclic GMP
Heart Arrest
Reperfusion Injury
Acetylcholine
Reperfusion
Endothelium
Type 5 Cyclic Nucleotide Phosphodiesterases
Baths
Vasodilation
Stroke Volume
Thoracic Surgery
Canidae
Catheters
Adenosine Triphosphate
Vardenafil Dihydrochloride
Pharmacology
Dogs

Keywords

  • Cardiopulmonary bypass
  • Contractility
  • Endothelium
  • Ischaemia-reperfusion
  • Vardenafil

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass. / Szabó, G.; Radovits, T.; Veres, Gábor; Krieger, Nelli; Loganathan, Sivakkanan; Sandner, Peter; Karck, Matthias.

In: European Journal of Cardio-thoracic Surgery, Vol. 36, No. 4, 10.2009, p. 657-664.

Research output: Contribution to journalArticle

Szabó, G. ; Radovits, T. ; Veres, Gábor ; Krieger, Nelli ; Loganathan, Sivakkanan ; Sandner, Peter ; Karck, Matthias. / Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass. In: European Journal of Cardio-thoracic Surgery. 2009 ; Vol. 36, No. 4. pp. 657-664.
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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 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.",
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T1 - Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass

AU - Szabó, G.

AU - Radovits, T.

AU - Veres, Gábor

AU - Krieger, Nelli

AU - Loganathan, Sivakkanan

AU - Sandner, Peter

AU - Karck, Matthias

PY - 2009/10

Y1 - 2009/10

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AB - 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.

KW - Cardiopulmonary bypass

KW - Contractility

KW - Endothelium

KW - Ischaemia-reperfusion

KW - Vardenafil

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