Donor heart preservation with the potassium channel opener pinacidil: comparison with University of Wisconsin and St. Thomas' solution.
BACKGROUND
Hyperpolarized arrest with the potassium channel opener pinacidil has been shown to provide effective myocardial protection during short-term global ischemia. This study tested the hypothesis that pinacidil may provide effective long-term protection for heart transplant preservation.


METHODS
Four concentrations of pinacidil (50 microM, 100 microM, 0.5 mM, 1.0 mM) mixed in Krebs-Henseleit solution were compared with University of Wisconsin and St. Thomas' Hospital solutions in a Krebs-Henseleit perfused rabbit Langendorff model (n = 6 for each group). Hearts underwent 4 hours of hypothermic (4 degrees C) storage. Over a wide range of volumes, left ventricular systolic function, diastolic compliance, and coronary flow were measured prior to and following storage. Time to mechanical and electrical arrest, and post-ischemic percent tissue water were also measured.


RESULTS
Pinacidil 0.5 mM provided the best preservation of post-ischemic systolic function and coronary flow compared with the other pinacidil concentrations and was statistically equivalent to St. Thomas' solution in terms of post-ischemic systolic, diastolic, and flow properties. However, hearts protected with University of Wisconsin solution had significantly better preservation of systolic function and coronary flow.


CONCLUSIONS
This investigation demonstrated that pinacidil in Krebs-Henseleit solution possesses efficacy in long-term donor heart preservation. Pinacidil was equivalent to St. Thomas' solution but inferior to University of Wisconsin solution. Hyperpolarized arrest with potassium channel openers may be a novel strategy to improve donor heart preservation.
Hoenicke
E M
EM
Penn State Geisinger Health System, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. ehoenicke@psghs.edu
Peterseim
D S
DS
Ducko
C T
CT
Sun
X
X
Damiano
R J
RJ
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D003080:Cold Temperature; D003326:Coronary Circulation; D005978:Glutathione / Q000494:pharmacology; D016027:Heart Transplantation; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011887:Raffinose / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D016277:Ventricular Function, Left
D001639:Bicarbonates; D007328:Insulin; D019188:Organ Preservation Solutions; D015221:Potassium Channels; C041711:St. Thomas' Hospital cardioplegic solution; C055206:University of Wisconsin-lactobionate solution; D012965:Sodium Chloride; D000493:Allopurinol; D011189:Potassium Chloride; D020110:Pinacidil; D005978:Glutathione; D008274:Magnesium; D000241:Adenosine; D002122:Calcium Chloride; D011887:Raffinose