Search

Toyoda, Yoshiya, Ingeborg Friehs, Robert A. Parker, Sidney Levitsky, and James D. McCully. Differential role of sarcolemmal and mitochondrial [K.sub.ATP] channels in adenosine-enhanced ischemic preconditioning. Am J Physiol Heart Circ Physiol 279: H2694-H2703, 2000.--Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. The purpose of this study was to determine whether APC is modulated by ATP-sensitive potassium ([K.sub.ATP]) channels and to determine whether this modulation occurs before ischemia or during reperfusion. The role of [K.sub.ATP] channels before ischemia (I), during reperfusion (R), or during ischemia and reperfusion (IR) was investigated using the nonspecific [K.sub.ATP] blocker glibenclamide (Glb), the mitochondrial (mito) [K.sub.ATP] channel blocker 5-hydroxydecanoate (5-HD), and the sarcolemmal (sarc) [K.sub.ATP] channel blocker HMR-1883 (HMR). Infarct size was significantly increased (P [is less than] 0.05) in APC hearts with Glb-I, Glb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treatment significantly decreased APC functional recovery (P [is less than] 0.05 vs. APC), whereas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR significantly decreased postischemic functional recovery (P [is less than] 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size reduction is modulated by mito[K.sub.ATP] channels primarily during ischemia and suggest that functional recovery is modulated by sarc[K.sub.ATP] channels during ischemia and reperfusion. stunning; myocardial protection; ATP-sensitive potassium channels

Presents a study which determined whether adenosine-enhanced ischemic preconditioning is modulated by adenosine triphosphate (ATP)-sensitive potassium channels. Mechanism of action of sarcolemmal and mitochondrial ATP-sensitive potassium channels during myocardial ischemia and reperfusion; Methodology; Results and discussion.

Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use microarray and proteomic analyses to identify pathways modulated by LV-aortic banding (AOB) and RV-pulmonary artery banding (PAB) in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta [LV-AOB; n = 6]. RV-PAB was achieved by banding the pulmonary artery (n = 6). Controls (n = 6 each) were sham-manipulated. After 4 (LV-AOB) and 6 (RV-PAB) wk recovery, the hearts were removed and matched RNA and proteins samples were isolated for microarray and proteomic analysis. Microarray and proteomic data demonstrate that in LV-AOB there is increased transcript expression levels for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium, and protein kinase-A signaling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also an increased transcript expression levels for cardiac oxidative phosphorylation but increased protein expression levels for structural constituents of muscle, cardiac muscle tissue development, and calcium handling. These results identify divergent transcript and protein expression profiles in LV-AOB and RV-PAB and provide new insight into the biological basis of ventricular specific hypertrophy. The identification of these pathways should allow for the development of specific therapeutic interventions for targeted treatment and amelioration of LV-AOB and RV-PAB to ameliorate morbidity and mortality.