Suppressing apoptosis with milrinone simulating extracorporeal circulation: a pilot study.
BACKGROUND
After cardioplegia, ischemia/reperfusion injury can induce apoptosis. The aim of this study was to evaluate our ex vivo microperfusion model on human myocardium during simulated cardioplegia (cp) and reperfusion (rep). In addition, the aim was to verify the anti-apoptotic properties of the phosphodiesterase 3 inhibitor milrinone.


METHODS
Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG prior to induction of cardiopulmonary bypass. Biopsies were exposed to ex vivo conditions with varying periods of cp/rep (30/10, 60/20, 120/40 min). Group I consisted of untreated controls (n=15), Group II of treated controls who had cp/rep (n=15) while Group III had cp/rep+milrinone (n=15). For the detection of apoptosis, anti-activated caspase-3 and PARP-1 cleavage immunostaining were used.


RESULTS
The percentage of apoptotic cardiomyocytes in Group I was significantly (P<0.05) lower compared to Group II, revealing a time-dependent increase. In Group III with milrinone treatment, apoptosis was significantly suppressed (P<0.05).


CONCLUSIONS
Milrinone significantly suppressed apoptosis in our ex vivo setting. This finding warrants further study aiming to evaluate the potential beneficial effects of milrinone on the suppression of ischemia/reperfusion injury in a clinical setting.
Usta
E
E
Department of Thoracic-, Cardiac- and Vascular Surgery, Tübingen University Hospital, Tübingen, Germany. engin.usta@gmx.de
Mustafi
M
M
Scheule
A M
AM
Ziemer
G
G
D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D053148:Caspase 3 / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000187:drug effects*; D005112:Extracorporeal Circulation; D005260:Female; D006324:Heart Arrest, Induced; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000494:pharmacology*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010865:Pilot Projects; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors
D010726:Phosphodiesterase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C505407:CASP3 protein, human; D053148:Caspase 3; D020105:Milrinone