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AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic [alpha]-subunits and regulatory [beta]- and [gamma]-subunits with multiple isoforms. Mutations in the cardiac [[gamma].sub.2]-isoform have been associated with hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological regulation of AMPK complexes containing different subunit isoforms is not well defined and is important for an understanding of the function of this signaling pathway in the intact heart. We evaluated the kinase activity associated with heart AMPK complexes containing specific or- and y-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated [[alpha].sub.1]-isoform (6-fold, P < 0.01) and [[alpha].sub.2]-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of a-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory [[gamma].sub.1]- and [[gamma].sub.2]-isoforms were expressed in the heart. The [[gamma].sub.1]- and [[gamma].sub.2]-isoforms coimmunoprecipitated with [[alpha].sub.1]- and [[alpha].sub.2]-isoforms in proportion to [alpha]-subunit content, [[gamma].sub.1]-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation ([Thr.sup.172]) in hearts. Ischemia similarly increased AMPK activity associated with the [[gamma].sub.1]- and [[gamma].sub.2]-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic [[alpha].sub.1]-and [[alpha].sub.2]-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory [[gamma].sub.1]- or [[gamma].sub.2]-isoforms to which they are complexed. Despite the pathophysiological importance of [[gamma].sub.2]-isoform mutations, [[gamma].sub.1]-isoform complexes account for most of the AMPK activity in the ischemic heart. adenosine monophosphate-activated protein kinase; ischemia; subunits; isoforms

AMP-activated protein kinase (AMPK) is emerging as a key signaling pathway that modulates cellular metabolic processes. In skeletal muscle, AMPK is activated during exercise. Increased myocardial substrate metabolism during exercise could be explained by AMPK activation. Although AMPK is known to be activated during myocardial ischemia, it remains uncertain whether AMPK is activated in response to the physiological increases in cardiac work associated with exercise. Therefore, we evaluated cardiac AMPK activity in rats at rest and after 10 min of treadmill running at moderate (15% grade, 16 m/min) or high (15% grade, 32 m/min) intensity. Total AMPK activity in the heart increased in proportion to exercise intensity (P < 0.05). AMPK activity associated with the [[alpha].sub.2]-catalytic subunit increased 2.8 [+ or -] 0.4-fold (P < 0.02 vs. rest) and 4.5 [+ or -] 0.6-fold (P < 0.001 vs. rest) with moderate- and high-intensity exercise, respectively. AMPK activity associated with the [[alpha].sub.1]-subunit increased to a lesser extent. Phosphorylation of the [Thr.sup.172]-regulatory site on AMPK [alpha]-catalytic subunits increased during exercise (P < 0.001). There was no increase in Akt phosphorylation during exercise. The changes in AMPK activity during exercise were associated with physiological AMPK effects (GLUT4 translocation to the sarcolemma and ACC phosphorylation). Thus cardiac AMPK activity increases progressively with exercise intensity, supporting the hypothesis that AMPK has a physiological role in the heart. energy metabolism; signal transduction; glucose

AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic α-subunits and regulatory β- and γ-subunits with multiple isoforms. Mutations in the cardiac α2-isoform have been associated with hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological regulation of AMPK complexes containing different subunit isoforms is not well defined and is important for an understanding of the function of this signaling pathway in the intact heart. We evaluated the kinase activity associated with heart AMPK complexes containing specific α- and γ-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated α1-isoform (6-fold, P < 0.01) and α2-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of α-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory γ1- and γ2-isoforms were expressed in the heart. Theγ1 and α2-isoforms coimmunoprecipitated with α1- and α2-isoforms in proportion to α-subunit content. γ1-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation (Thr172) in hearts. Ischemia similarly increased AMPK activity associated with the γ1- and γ2-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic α1- and α2-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory γ1- or γ2-isoforms to which they are complexed. Despite the pathophysiological importance of γ2-isoform mutations, γ1-isoform complexes account for most of the AMPK activity in the ischemic heart. [ABSTRACT FROM AUTHOR]

Background: Arteriotomy closure device (ACD) use has increased following percutaneous transfemoral coronary procedures (PTCP). However, their safety in patients with chronic kidney disease (CKD) is not known. Therefore, we evaluated the complication rates of ACD among patients with CKD., Methods: Six-hundred ten consecutive patients who underwent PTCP and ACD were retrospectively studied. Patients were grouped according to their creatinine clearance (CrCl in ml/min/1.73 m2) calculated by the Cockcroft-Gault formula using the National Kidney Foundation classification system; Stage I (CrCl > or = 90); Stage II (60-89); Stage III (30-59); Stage IV (15-29); and Stage V (< or = 15). The primary endpoint was the combined incidence of pseudoaneurysm, retroperitoneal hematoma, femoral artery thrombosis, surgical vascular repair, and groin infection., Results: Among 610 patients 283 (46%) underwent PCI. The primary endpoint was seen in 66 (10.8%) patients. Univariate predictors of primary outcome were lower CrCl (p < 0.001), and presence of peripheral vascular disease (p = 0.03). There was an inverse relationship between CrCl and complication rate. CKD was the strongest independent multivariate predictor for the primary endpoint (OR 1.032; 95% CI 1.019-1.046; p < 0.0001), driven by higher infection (p < 0.0001), thrombosis (p = 0.003) and hematoma (p = 0.007)., Conclusions: Renal function appears to be significantly associated with vascular access-site complications. Worsening renal function is associated with higher vascular access site complications, largely driven by an increased infection rate.