title: Glucocorticoids preserve calpastatin and troponin I during cardiopulmonary bypass in immature pigs.
abstract: Degradation of troponin I (TnI) by calpain occurs with myocardial stunning in ischemia-reperfusion injury. Glucocorticoids attenuate myocardial ischemia-reperfusion injury, but their effect on TnI degradation is unknown. A piglet model was used to test the hypotheses that cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are associated with TnI degradation and that TnI alterations could be prevented by glucocorticoid treatment. Piglets were cooled to 18 degrees C, subjected to 2 h of circulatory arrest, rewarmed to 37 degrees C, and allowed to recover for 2 h. Methylprednisolone was administered 6 h before surgery (3 0 mg/kg) and at initiation of CPB (30 mg/kg). The untreated group received saline. Left ventricular tissue was collected after recovery and analyzed by Western blot for TnI, calpain, and calpastatin (the natural inhibitor of calpain). CPB/DHCA animals had 27.4 +/- 0.2% of total detected TnI present in degraded form. Glucocorticoid treatment significantly decreased the percentage of degraded TnI (12.0 +/- 0.1%, p < 0.05). Calpain I and calpain II increased after CPB/DHCA compared with non-CPB/DHCA controls (p < 0.05), with or without glucocorticoid treatment. Calpastatin significantly decreased in untreated CPB/DHCA animals compared with non-CPB/DHCA controls (p < 0.05), but levels were preserved by glucocorticoids. Glucocorticoids were associated with preservation of maximum rate of increase of left ventricular pressure at 95 +/- 10% of baseline, whereas maximum rate of increase of left ventricular pressure decreased to 62 +/- 12% of baseline without steroids. TnI degradation occurs after CPB/DHCA in neonatal pigs. Reduction in reperfusion injury by glucocorticoids may depend partly on preservation of calpastatin activity and intact TnI.
authors.affiliation: Division of Cardiology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. schws0@chmcc.org
authors.forename: Steven M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: JodieE Y
authors.initials: JY
authors.lastname: Duffy
authors.forename: Jeffrey  M
authors.initials: J
authors.lastname: Pearl
authors.forename: Semin
authors.initials: S
authors.lastname: Goins
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Wagner
authors.forename: David P
authors.initials: DP
authors.lastname: Nelson
mesh_terms: D000367:Age Factors; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002302:Cardiac Output; D002315:Cardiopulmonary Bypass; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology*; D013552:Swine; D019210:Troponin I / Q000378:metabolism*; D014655:Vascular Resistance
chemical_list: D002135:Calcium-Binding Proteins; D005938:Glucocorticoids; D019210:Troponin I; C033668:calpastatin; D002154:Calpain