title: Oxidative stress-induced leaky sarcoplasmic reticulum underlying acute heart failure in severe burn trauma.
abstract: Burn trauma causes cardiac dysfunction. However, much of the underlying cellular and molecular mechanisms remain elusive. In the present study, we demonstrate the roles of excessive sarcoplasmic reticulum (SR) Ca(2+) leakage and oxidative stress in burn-associated acute heart failure. In cardiomyocytes from failing rat hearts 12 h after full-thickness cutaneous burn of about 40% of the total body surface area, we found that Ca(2+) transients and contractility were impaired, but the triggering L-type Ca(2+) channel current density was unaltered, giving rise to a significantly reduced gain of excitation-contraction coupling. This deficiency in SR Ca(2+) release was accompanied by a reduction in Ca(2+) content in the SR. Surprisingly, the frequency of spontaneous Ca(2+) sparks was increased by 1.4-fold; Ca(2+) tolerance test (10 mM extracellular Ca(2+)) further showed 2.0- and 1.5-fold more frequent Ca(2+) waves and Ca(2+) sparks, respectively. Myofilament sensitivity to Ca(2+), however, seemed to be unaffected. These results suggest hyperactivity of the ryanodine receptor (RyR) Ca(2+) release channel and a leaky SR in burn. Importantly, pretreatment with antioxidant vitamins C and E seemed to prevent burn-induced RyR hypersensitivity and SR leakage and thereby normalize Ca(2+) transients and contractility. Concomitantly, the in vivo cardiac functions were also more tolerant of traumatic burn. Collectively, our findings suggest that SR leakage due to oxidative stress is likely a major candidate mechanism underlying burn-associated acute heart failure. Antioxidant therapy in burn trauma provides cardioprotection, at least in part, by protecting RyR's from oxidative stress-induced hypersensitivity.
authors.affiliation: Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Deng
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yan
authors.forename: Kaitao
authors.initials: K
authors.lastname: Li
authors.forename: Wenchang
authors.initials: W
authors.lastname: Tan
authors.forename: Chunhua
authors.initials: C
authors.lastname: Jin
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000200:Action Potentials; D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002056:Burns / Q000150:complications*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium