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Am J Physiol Heart Circ Physiol 292: H2475-H2484, 2007. First published January 19, 2007; doi:10.1152/ajpheart.01164.2006
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Cellular mechanisms of burn-related changes in contractility and its prevention by mesenteric lymph ligation

Kentaro Kawai, Tomoko Kawai, Justin T. Sambol, Da-Zhong Xu, Zhiqiang Yuan, Francis J. Caputo, Chirag D. Badami, Edwin A. Deitch, and Atsuko Yatani

Department of Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey

Submitted 23 October 2006 ; accepted in final form 9 January 2007

Major burn injury results in impairment of left ventricular (LV) contractile function. There is strong evidence to support the involvement of gut-derived factor(s) transported in mesenteric lymph in the development of burn-related contractile dysfunction; i.e., mesenteric lymph duct ligation (LDL) prevents burn-related contractile depression. However, the cellular mechanisms for altered myocardial contractility of postburn hearts are largely unknown, and the cellular basis for the salutary effects of LDL on cardiac function have not been investigated. We examined contractility, Ca2+ transients, and L-type Ca2+ currents (ICa) in LV myocytes isolated from four groups of rats: 1) sham burn, 2) sham burn with LDL (sham + LDL), 3) burn ({approx}40% of total body surface area burn), and 4) burn with LDL (burn + LDL). Myocytes isolated from hearts at 24 h postburn had a depressed contractility ({approx}20%) at baseline and blunted responsiveness to elevation of bath Ca2+. Myocyte contractility was comparable in sham + LDL and sham burn hearts. LDL completely prevented burn-related changes in myocyte contractility. Mechanistically, the decrease in contractility in myocytes from postburn hearts occurred with a decrease in the amplitude of Ca2+ transients ({approx}20%) without changes in resting Ca2+ or Ca2+ content of the sarcoplasmic reticulum. On the other hand, ICa density was decreased ({approx}30%) in myocytes from postburn hearts, with unaltered voltage-dependent properties. Thus burn-related myocardial contractile dysfunction is linked with depressed myocyte contractility associated with a decrease in ICa density. These findings also provide strong evidence that mesenteric lymph is involved in the onset of burn-related cardiomyocyte dysfunction.

burn injury; L-type calcium current; cardiac myocyte



Address for reprint requests and other correspondence: A. Yatani, Dept. of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Ave., C-506, Newark, NJ 07103 (e-mail:yataniat{at}umdnj.edu)




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J. T. Sambol, M. A. Lee, F. J. Caputo, K. Kawai, C. Badami, T. Kawai, E. A. Deitch, and A. Yatani
Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction
J Appl Physiol, January 1, 2009; 106(1): 57 - 65.
[Abstract] [Full Text] [PDF]




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