title: Hyperpolarized cardiac arrest with a potassium-channel opener, aprikalim.
abstract: Cardioplegic solutions that arrest the heart at or near the resting membrane potential may provide better myocardial protection than standard depolarizing hyperkalemic cardioplegia by reducing both metabolic demand and harmful transmembrane ion fluxes. This hypothesis was investigated in an isolated, blood-perfused, rabbit heart Langendorff model during 30 minutes of normothermic global ischemia. Hyperpolarized cardiac arrest induced by aprikalim, an opener of adenosine triphosphate-dependent potassium channels, was compared with hyperkalemic depolarized arrest and with unprotected global ischemia. Left ventricular pressure was recorded over a wide range of balloon volumes before ischemia and 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 assessed by comparison of preischemic and postischemic coefficients within each cardioplegia group. Postischemic recovery of developed pressure was used to assess changes in left ventricular systolic function. The tissue water content of each heart was also determined. Myocardial protection with aprikalim resulted in better postischemic recovery of developed pressure (90% +/- 9%) than either protection with hyperkalemic cardioplegia (73% +/- 11%) or no protection (62% +/- 9%). Myocardial tissue water content in hearts protected with hyperkalemic cardioplegia (77.4% +/- 1.4%) was less than the tissue water content of either unprotected hearts (79.4% +/- 1.2%) or hearts protected with aprikalim (78.7% +/- 0.9%). Despite these differences, neither hyperkalemic cardioplegia (p = 0.15) nor aprikalim cardioplegia (p = 0.30) was associated with a significant postischemic decrease in ventricular compliance. By contrast, unprotected global ischemia was associated with a significant decrease in ventricular compliance (p < 0.001).
mesh_terms: D000255:Adenosine Triphosphate; D000818:Animals; D001834:Body Water / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000503:physiopathology; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D011817:Rabbits; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; D000255:Adenosine Triphosphate