MECHANISM OF MYOCARDIAL PROTECTION BY ISOFLURANE - ROLE OF ADENOSINE TRIPHOSPHATE-REGULATED POTASSIUM (K-ATP) CHANNELS

Background: The mechanism of the protective actions of volatile anesth etics in ischemic myocardium has not been clearly elucidated. The role of myocardial adenosine triphosphate-regulated potassium (K-ATP) chan nels in isoflurane-induced enhancement of recovery of regional contrac tile function after multiple brief occlusions and reperfusion of the l eft anterior descending coronary artery (LAD) was studied in dogs anes thetized with barbiturates. Methods: Dogs (n = 32) were instrumented t o measure left ventricular and aortic blood pressure, cardiac output, LAD coronary blood flow velocity, and subendocardial segment length. R egional myocardial perfusion was measured using radioactive microspher es. Hemodynamics and percentage segment shortening (%SS) in the LAD pe rfusion territory were evaluated after instrumentation was complete; a fter pretreatment with the K-ATP channel antagonist, glyburide (0.05 m g/kg(-1)) or drug vehicle (polyethylene glycol in ethyl alcohol; contr ol experiments); and in the presence or absence of 1 MAC isoflurane ad ministered for 30 min before and during five 5-min occlusions and repe rfusion of the LAD in four experimental groups. Isoflurane was discont inued at the onset of the final reperfusion period. Measurements of he modynamics, %SS, and myocardial perfusion were repeated at several int ervals during 180 min after reperfusion of the LAD. Results: Left ante rior descending coronary artery occlusion caused regional dyskinesia d uring each 5-min occlusion in each dog. Control and glyburide-pretreat ed dogs demonstrated poor recovery of %SS by 180 min after reperfusion (2 +/- 10 and 7 +/- 6% of baseline, respectively). In contrast, dogs anesthetized with isoflurane exhibited complete recovery of function ( %SS) by 180 min after reperfusion (82 +/- 8% of baseline). Enhanced re covery of regional contractile function by isoflurane was abolished by pretreatment with glyburide 180 min after reperfusion (16 +/- 10% of baseline). Improvement of functional recovery of stunned myocardium by isoflurane, and the blockade of this action by glyburide, was not ass ociated with changes in hemodynamics or regional myocardial perfusion. Conclusions: The results indicate that isoflurane prevents decreased systolic shortening caused by multiple episodes of ischemia and reperf usion. These actions result in improved recovery of contractile functi on of postischemic, reperfused myocardium and are mediated by isoflura ne-induced activation of K-ATP channels.