Sevoflurane mimics ischemic preconditioning effects on coronary flow and nitric oxide release in isolated hearts

Background: Like ischemic preconditioning, certain volatile anesthetics hav e been shown to reduce the magnitude of ischemia/ reperfusion injury via ac tivation of K+ adenosine triphosphate (ATP)-sensitive (K-ATP) channels. The purpose of this study was (1) to determine if ischemic preconditioning (IP C) and sevoflurane preconditioning (SPC) increase nitric oxide release and improve coronary vascular function, as well as mechanical and electrical fu nction, if given for only brief intervals before global ischemia of isolate d hearts; and (2) to determine if K-ATP channel antagonism by glibenclamide (GLB) blunts the cardioprotective effects of IPC and SPC. Methods: Guinea pig hearts were isolated and perfused with Krebs-Ringer's s olution at 55 mmHg and randomly assigned to one of seven groups: (1) two 2- min total coronary occlusions (preconditioning, IPC) interspersed with 5 mi n of normal per fusion; (2) two 2-min occlusions interspersed with 5 min of perfusion while perfusing with GLB (IPC+GLB); (3) SPC (3.5%) for two 2-min periods; (4) SPC+GLB for two 2-min periods; (5) no treatment before ischem ia (control [CON]); (6) CON+GLB; and (7) no ischemia (time control). Six mi nutes after ending IPC or SPC, hearts of ischemic groups were subjected to 30 min of global ischemia and 75 min of reperfusion. Left-ventricular press ure, coronary now, and effluent NO concentration ([NO]) were measured. Flow and NO responses to bradykinin, and nitroprusside were tested 20-30 min be fore ischemia or drug treatment and 30-40 min after reperfusion. Results: After ischemia, compared with before (percentage change), left-ven tricular pressure and coronary flow, respectively, recovered to a greater e xtent (P < 0.05) after IPC (42%, 77%), and treatment with SPC (45%, 76%) th an after CON (30%, 65%), IPC+GLB (24%, 64%), SPC+GLB (20%, 65%), and CON+GL B (28%, 64%). Bradykinin and nitroprusside increased [NO] by 30 +/- 5 (mean s +/- SEM) and 29 +/-4 nM, respectively, averaged for all groups before isc hemia. [NO] increased by 26 +/- 6 and 27 +/- 7 nM, respectively, in SPC and IPC groups after ischemia, compared with an average [NO] increase of 8 +/- 5 nM (P < 0.01) after ischemia in CON and each of the three GLB groups. Fl ow increases to bradykinin and nitroprusside were also greater after SPC an d IPC. Conclusions: Preconditioning with sevoflurane, like IPC, improves not only postischemic contractility, but also basal now, bradykinin and nitroprussid e-induced increases in flow, and effluent [NO] in isolated hearts. The prot ective effects of both SPC and IPC are reversed by K-ATP channel antagonism .