BACKGROUND: Glucocorticoids can reduce myocardial dysfunction associated with ischemia and reperfusion injury following cardiopulmonary bypass (CPB) and circulatory arrest. The hypothesis was that maintenance of cardiac function after CPB with methylprednisolone therapy results, in part, from preservation of myocyte calcium cycling. METHODS: Piglets (5-7 kg) underwent CPB and 120 min of hypothermic circulatory arrest with (CPB-GC) or without (CPB) methylprednisolone (30 mgkg(-1)) administered 6h before and at CPB. Controls (No-CPB) did not undergo CPB or receive glucocorticoids (n=6 per treatment). Myocardial function was monitored in vivo for 120 min after CPB. Calcium cycling was analyzed using rapid line-scan confocal microscopy in isolated, fluo-3-AM-loaded cardiac myocytes. Phospholamban phosphorylation and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a) protein levels were determined by immunoblotting of myocardium collected 120 min after CPB. Calpain activation in myocardium was measured by fluorometric assay. RESULTS: Preload recruitable stroke work in vivo 120 min after reperfusion decreased from baseline in CPB (47.4±12 versus 26.4±8.3 slope of the regression line, P<0.05), but was not different in CPB-GC (41±8.1 versus 37.6±2.2, P=0.7). In myocytes isolated from piglets, total calcium transient time remained unaltered in CPB-GC (368±52.5 ms) compared with controls (434.5±35.3 ms; P=0.07), but was prolonged in CPB myocytes (632±83.4 ms; P<0.01). Calcium transient amplitude was blunted in myocytes from CPB (757±168 nM) compared with controls (1127±126 nM, P<0.05) but was maintained in CPB-GC (1021±155 nM, P>0.05). Activation of calpain after CPB was reduced with glucocorticoids. Phospholamban phosphorylation and SERCA2a protein levels in myocardium were decreased in CPB compared with No-CPB and CPB-GC (P<0.05). CONCLUSIONS: The glucocorticoid-mediated improvement in myocardial function after CPB might be due, in part, to prevention of calpain activation and maintenance of cardiac myocyte calcium cycling.
BACKGROUND: Glucocorticoids can reduce myocardial dysfunction associated with ischemia and reperfusion injury following cardiopulmonary bypass (CPB) and circulatory arrest. The hypothesis was that maintenance of cardiac function after CPB with methylprednisolone therapy results, in part, from preservation of myocyte calciumcycling. METHODS: Piglets (5-7 kg) underwent CPB and 120 min of hypothermic circulatory arrest with (CPB-GC) or without (CPB) methylprednisolone (30 mgkg(-1)) administered 6h before and at CPB. Controls (No-CPB) did not undergo CPB or receive glucocorticoids (n=6 per treatment). Myocardial function was monitored in vivo for 120 min after CPB. Calciumcycling was analyzed using rapid line-scan confocal microscopy in isolated, fluo-3-AM-loaded cardiac myocytes. Phospholamban phosphorylation and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a) protein levels were determined by immunoblotting of myocardium collected 120 min after CPB. Calpain activation in myocardium was measured by fluorometric assay. RESULTS: Preload recruitable stroke work in vivo 120 min after reperfusion decreased from baseline in CPB (47.4±12 versus 26.4±8.3 slope of the regression line, P<0.05), but was not different in CPB-GC (41±8.1 versus 37.6±2.2, P=0.7). In myocytes isolated from piglets, total calcium transient time remained unaltered in CPB-GC (368±52.5 ms) compared with controls (434.5±35.3 ms; P=0.07), but was prolonged in CPB myocytes (632±83.4 ms; P<0.01). Calcium transient amplitude was blunted in myocytes from CPB (757±168 nM) compared with controls (1127±126 nM, P<0.05) but was maintained in CPB-GC (1021±155 nM, P>0.05). Activation of calpain after CPB was reduced with glucocorticoids. Phospholamban phosphorylation and SERCA2a protein levels in myocardium were decreased in CPB compared with No-CPB and CPB-GC (P<0.05). CONCLUSIONS: The glucocorticoid-mediated improvement in myocardial function after CPB might be due, in part, to prevention of calpain activation and maintenance of cardiac myocyte calciumcycling.
Authors: V Brix-Christensen; T K Petersen; H B Ravn; V E Hjortdal; N T Andersen; E Tønnesen Journal: Acta Anaesthesiol Scand Date: 2001-04 Impact factor: 2.105
Authors: Jeffrey M Pearl; David P Nelson; Steven M Schwartz; Connie J Wagner; Steven M Bauer; Elizabeth A Setser; Jodie Y Duffy Journal: Ann Thorac Surg Date: 2002-09 Impact factor: 4.330
Authors: Steven M Schwartz; JodieE Y Duffy; Jeffrey M Pearl; Semin Goins; Connie J Wagner; David P Nelson Journal: Pediatr Res Date: 2003-03-19 Impact factor: 3.756
Authors: Valerie A Schroeder; Jeffery M Pearl; Steven M Schwartz; Thomas P Shanley; Peter B Manning; David P Nelson Journal: Circulation Date: 2003-05-19 Impact factor: 29.690
Authors: Jodie Y Duffy; Kelly M McLean; Jefferson M Lyons; Adam J Czaikowski; Connie J Wagner; Jeffrey M Pearl Journal: Crit Care Med Date: 2009-02 Impact factor: 7.598
Authors: Jodie Y Duffy; Orlando Petrucci; R Scott Baker; Christopher T Lam; Casey A Reed; Danielle J Everman; Pirooz Eghtesady Journal: J Thorac Cardiovasc Surg Date: 2010-09-29 Impact factor: 5.209
Authors: Meshe Chonde; Katharyn L Flickinger; Matthew L Sundermann; Allison C Koller; David D Salcido; Cameron Dezfulian; James J Menegazzi; Jonathan Elmer Journal: Biomed Res Int Date: 2019-06-11 Impact factor: 3.411
Authors: Michael Wester; Anton Heller; Michael Gruber; Lars S Maier; Christian Schach; Stefan Wagner Journal: PLoS One Date: 2019-09-09 Impact factor: 3.240