Cellular mechanisms of burn-related changes in contractility and its prevention by mesenteric lymph ligation.
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, Ca(2+) transients, and L-type Ca(2+) currents (I(Ca)) in LV myocytes isolated from four groups of rats: 1) sham burn, 2) sham burn with LDL (sham + LDL), 3) burn ( approximately 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 ( approximately 20%) at baseline and blunted responsiveness to elevation of bath Ca(2+). 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 Ca(2+) transients ( approximately 20%) without changes in resting Ca(2+) or Ca(2+) content of the sarcoplasmic reticulum. On the other hand, I(Ca) density was decreased ( approximately 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 I(Ca) density. These findings also provide strong evidence that mesenteric lymph is involved in the onset of burn-related cardiomyocyte dysfunction.
Kawai
Kentaro
K
Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Kawai
Tomoko
T
Sambol
Justin T
JT
Xu
Da-Zhong
DZ
Yuan
Zhiqiang
Z
Caputo
Francis J
FJ
Badami
Chirag D
CD
Deitch
Edwin A
EA
Yatani
Atsuko
A
D000818:Animals; D002056:Burns / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control*; D002478:Cells, Cultured; D008196:Lymph / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000378:metabolism*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*