Abstract 15629: Superior Myocardial Protection With Adenosine - Triphosphate - Sensitive Potassium Channel Opener Diazoxide in a Novel Mouse Langendorff Model
Introduction: Adenosine triphosphate - sensitive potassium (KATP) channel openers are cardioprotective via an unknown mechanism. Mouse models allow genetic manipulation of KATP channel components for investigation of this mechanism. Mouse Langendorff models utilizing 30 min of global ischemia are known to induce myocardial infarction. In such models, the benefit of a KATP channel opener over traditionally utilized hyperkalemic cardioplegia solutions has not been demonstrated.
Hypothesis: Prolongation of global ischemia in a mouse Langendorff model will allow demonstration of superior protection with KATP channel opener diazoxide when added to traditional hyperkalemic cardioplegia solutions.
Methods: Wild type mouse hearts underwent 30 min baseline perfusion with Krebs-Henseleit solution (KH), 1.5 hours global ischemia following infusion of test solution, followed by 30 min reperfusion with KH solution. Test solutions were hyperkalemic cardioplegia (CPG) (N=11) or CPG + KATP channel opener diazoxide (CPG + DZX) (N=12). Pressure measurements were taken at baseline, during ischemia, and following reperfusion via a left ventricular balloon, and coronary flow was measured.
Results: CPG + DZX group had improved recovery of developed pressure and coronary flow, although this did not reach statistical significance (Table). Ischemic end diastolic pressure (EDP) was similar between groups at 30 mins. At a mean of 74 min (CPG) or 77 min (CPG+ DZX), an additional increase in EDP was noted (plateau) (Figure) and was higher in the CPG group. Similarly, EDP at reperfusion and end of experiment were higher in the CPG group.
Conclusions: Prolongation of global ischemia in a mouse Langendorff model demonstrated additional benefit when DZX was added to hyperkalemic cardioplegia. This model allows investigation of KATP channel components and their role in DZX cardioprotection as well as translation to prolonged ischemic episodes associated with cardiac surgery.
Author Disclosures: C. Makepeace: None. E. Kanter: None. R. Schuessler: None. C. Nichols: None. J. Lawton: None.
- © 2016 by American Heart Association, Inc.