Donor heart preservation with a novel hyperpolarizing solution: superior protection compared with University of Wisconsin solution.
OBJECTIVE
A donor heart preservation solution was designed to use hyperpolarized arrest with the adenosine triphosphate-sensitive potassium-channel opener pinacidil. This solution contained concentrations of potassium, sodium, calcium, magnesium, lactobionate, and the buffer histidine specifically chosen to minimize intracellular calcium accumulation associated with prolonged ischemia.


METHODS
Twenty-four rabbit hearts were randomly assigned to receive 1 of 3 preservation solutions in a crystalloid-perfused Langendorff model: (1) prototype solution containing a 0.5 mmol/L concentration of pinacidil, (2) prototype solution without pinacidil as control, and (3) University of Wisconsin solution. Thirty minutes of initial perfusion preceded baseline data acquisition. Data comprised left ventricle pressure-volume curves generated by inflating an intraventricular latex balloon. After cardioplegic administration, hearts underwent 4 hours of hypothermic storage, followed by 60 minutes of reperfusion and postischemic data acquisition.


RESULTS
Postischemic developed pressure was better preserved by pinacidil solution (92.4% +/- 4.5%) than by the control (74.9% +/- 3.4%, P =.01) and University of Wisconsin solutions (66.7% +/- 5.1%, P =.001). Diastolic negative dP/dT was better preserved by pinacidil solution (104.4% +/- 10.2%) than by the control (80.2% +/- 4.2%, P =.034) and University of Wisconsin solutions (71.7% +/- 7.0%, P =.015). Diastolic compliance, expressed as baseline/postischemic diastolic slope ratios, was more poorly preserved by University of Wisconsin solution (0.67 +/- 0.07) than by the pinacidil (0.88 +/- 0.05, P =.041) and control solutions (0.87 +/- 0.05, P =.021). Postischemic coronary flow was higher in hearts exposed to pinacidil solution (77.8% +/- 3.0%) than in those exposed to the control (66.8% +/- 2.4%) and University of Wisconsin solutions (70.9% +/- 4.0%, P =.07).


CONCLUSIONS
The superiority of the pinacidil solution in this experiment demonstrated that hyperpolarized arrest with potassium-channel openers improves donor heart preservation when administered in a novel histidine-buffered lactobionate-enriched vehicle.
Hoenicke
E M
EM
Department of Surgery, Division of Cardiothoracic Surgery, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, USA.
Sun
X
X
Strange
R G
RG
Damiano
R J
RJ
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D016027:Heart Transplantation; D007328:Insulin / Q000494:pharmacology; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D020110:Pinacidil / Q000494:pharmacology*; D011817:Rabbits; D011887:Raffinose / Q000494:pharmacology; D012815:Signal Processing, Computer-Assisted; D014665:Vasodilator Agents / Q000494:pharmacology*
D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D014665:Vasodilator Agents; D000493:Allopurinol; D020110:Pinacidil; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose