Donor heart preservation with pinacidil: the role of the mitochondrial K ATP channel.
BACKGROUND
Pinacidil solutions have been shown to have significant cardioprotective effects. Pinacidil activates both sarcolemmal and mitochondrial potassium-adenosine triphosphate (K(ATP)) channels. This study was undertaken to compare pinacidil solution with University of Wisconsin (UW) solution and to determine if the protective effect of pinacidil involved mitochondrial or sarcolemmal K(ATP) channels.


METHODS
Thirty-two rabbit hearts received one of four preservation solutions in a Langendorff apparatus: (1) UW; (2) a solution containing 0.5 mmol/L pinacidil; (3) pinacidil with Hoechst-Marion-Roussel 1098 (HMR-1098), a sarcolemmal channel blocker; and (4) pinacidil with 5-hydroxydecanote, a mitochondrial channel blocker. Left ventricular pressure-volume curves were generated by an intraventricular balloon. All hearts were placed in cold storage for 8 hours, followed by 60 minutes of reperfusion.


RESULTS
Postischemic developed pressure was better preserved by pinacidil than by UW. This cardioprotective effect was eliminated by 5-hydroxydecanote and diminished by HMR-1098. Diastolic compliance was better preserved by pinacidil when compared with UW. This protection was abolished by the addition of 5-hydroxydecanote and moderately decreased by HMR-1098.


CONCLUSIONS
Our results support the superiority of pinacidil over UW after 8 hours of storage. The cardioprotective role of pinacidil is mediated primarily by the mitochondrial K(ATP) channel.
Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Michael D
MD
Diodato
Nirav R
NR
Shah
Sunil M
SM
Prasad
Sydney L
SL
Gaynor
Jennifer S
JS
Lawton
Ralph J
RJ
Damiano
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D006880:Hydroxy Acids / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels; D011312:Pressure; D011817:Rabbits; D011887:Raffinose / Q000494:pharmacology; D011897:Random Allocation; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D020858:Tissue and Organ Harvesting / Q000379:methods; D016277:Ventricular Function, Left / Q000187:drug effects
D001549:Benzamides; D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007328:Insulin; D008565:Membrane Proteins; D019188:Organ Preservation Solutions; D015221:Potassium Channels; C055206:University of Wisconsin-lactobionate solution; C500600:Washington University solution; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D000493:Allopurinol; D020110:Pinacidil; C410297:HMR 1098; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose