HYPERPOLARIZED CARDIAC-ARREST WITH A POTASSIUM-CHANNEL OPENER, APRIKALIMD

Cardioplegic solutions that arrest the heart at or near the resting me mbrane potential may provide better myocardial protection than standar d depolarizing hyperkalemic cardioplegia by reducing both metabolic de mand and harmful transmembrane ion fluxes. This hypothesis was investi gated in an isolated, blood-perfused, rabbit heart Langendorff model d uring 30 minutes of normothermic global ischemia. Hyperpolarized cardi ac arrest induced by aprikalim, an opener of adenosine triphosphate-de pendent potassium channels, was compared with hyperkalemic depolarized arrest and with unprotected global ischemia, Left ventricular pressur e was recorded over a wide range of balloon volumes before ischemia an d 30 minutes after reperfusion, End-diastolic pressure versus balloon volume data were fitted to a two-coefficient exponential relationship, Changes in the diastolic compliance of the left ventricle were assess ed by comparison of preischemic and postischemic coefficients within e ach cardioplegia group. Postischemic recovery of developed pressure wa s used to assess changes in left ventricular systolic function, The ti ssue water content of each heart was also determined, Myocardial prote ction with aprikalim resulted in better postischemic recovery of devel oped pressure (90% +/- 9%) than either protection with hyperkalemic ca rdioplegia (73% +/- 11%) or no protection (62% +/- 9%). Myocardial tis sue water content in hearts protected with hyperkalemic cardioplegia ( 77.4% +/- 1.4%) was less than the tissue water content of either unpro tected hearts (79.4% +/- 1.2%)'or hearts protected with aprikalim (78. 7% +/- 0.9%), Despite these differences, neither hyperkalemic cardiopl egia (p = 0.15) nor aprikalim cardioplegia (p = 0.30) was associated w ith a significant postischemic decrease in ventricular compliance, By contrast, unprotected global ischemia was associated with a significan t decrease in ventricular compliance (p < 0.001).