Y Toyoda1, S Khan, W Chen, R A Parker, S Levitsky, J D McCully. 1. Division of Cardiothoracic Surgery and Biometrics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract
BACKGROUND: Cardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity during ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection afforded by K/Mg cardioplegia was unknown. METHODS: Rabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minutes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts received cardioplegia 5 minutes before ischemia. Separate groups of GI and K/Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642-I), at the immediate start of reperfusion (HOE-642-R), or both before ischemia and at the immediate start of reperfusion (HOE-642-IR). RESULTS: Left ventricular peak developed pressure was significantly increased in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all groups, but was significantly increased in HOE-R as compared with HOE-IR (p < 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decreased left ventricular peak developed pressure after 90 minutes of reperfusion (p < 0.05 versus K/Mg), with no significant effect on infarct size. CONCLUSIONS: NHE-1 inhibition used alone provides cardioprotection with optimal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardioplegia decreases postischemic functional recovery during late reperfusion.
BACKGROUND: Cardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity during ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection afforded by K/Mg cardioplegia was unknown. METHODS:Rabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minutes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts received cardioplegia 5 minutes before ischemia. Separate groups of GI and K/Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642-I), at the immediate start of reperfusion (HOE-642-R), or both before ischemia and at the immediate start of reperfusion (HOE-642-IR). RESULTS:Left ventricular peak developed pressure was significantly increased in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all groups, but was significantly increased in HOE-R as compared with HOE-IR (p < 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decreased left ventricular peak developed pressure after 90 minutes of reperfusion (p < 0.05 versus K/Mg), with no significant effect on infarct size. CONCLUSIONS:NHE-1 inhibition used alone provides cardioprotection with optimal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardioplegia decreases postischemic functional recovery during late reperfusion.
Authors: J L Lequerica; J E O'Connor; L Such; A Alberola; I Meseguer; M Dolz; M Torreblanca; A Moya; F Colom; B Soria Journal: J Physiol Biochem Date: 2006-12 Impact factor: 4.158