Effects of selective phosphodiesterase-5-inhibition on myocardial contractility and reperfusion injury after heart transplantation.
Recently, the infarct reducing and cardioprotective effects of phosphodiesterase-5-inhibitors were described. In this study, we investigated these effects on ischemia/reperfusion injury in a rat model of heart transplantation. Three groups were assigned for our study: a vardenafil preconditioning group, an ischemic control, and a nonischemic control. Hemodynamic parameters were significantly increased in the vardenafil group (Pmax: 82+/-4 vs. 110+/-12 vs. 127+/-13 mm Hg; dP/dtmax: 1740+/-116 vs. 3197+/-599 vs. 4397+/-602 mm Hg/sec; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Furthermore, we recorded increased ATP levels and significantly less apoptosis in the treatment group after terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (apoptosis index: 27.23%+/-1.54% vs. 16.77%+/-1.42% vs. 18.86%+/-1.07%; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Our current results support the concept that the cGMP-PKG-pathway plays an important role in ischemia/reperfusion injury. We could show that up-regulating this pathway has a preconditioning-like effect and can effectively reduce ischemia/reperfusion injury.
Loganathan
Sivakkanan
S
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
Radovits
Tamás
T
Hirschberg
Kristóf
K
Korkmaz
Sevil
S
Barnucz
Eniko
E
Karck
Matthias
M
Szabó
Gábor
G
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D016027:Heart Transplantation / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D013450:Sulfones / Q000627:therapeutic use; D013599:Systole / Q000187:drug effects; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic; D014227:Triazines / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride; D014682:Vena Cava, Inferior / Q000601:surgery; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP