title: Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction.
abstract: Clinical and experimental studies have shown that trauma combined with hemorrhage shock (T/HS) is associated with myocardial contractile dysfunction. However, the initial events triggering the cardiac dysfunction are not fully elucidated. Thus we tested the hypothesis that factors carried in intestinal (mesenteric) lymph contribute to negative inotropic effects in rats subjected to a laparotomy (T) plus hemorrhagic shock (HS; mean arterial blood pressure of 30-40 Torr for 90 min) using a Langendorff isolated heart preparation. Left ventricular (LV) function was assessed 24 h after trauma plus sham shock (T/SS) or T/HS by recording the LV developed pressure (LVDP) and the maximal rate of LVDP rise and fall ( +/- dP/dt(max)) in five groups of rats: 1) naive noninstrumented rats, 2) rats subjected to T/SS, 3) rats subjected to T/HS, 4) rats subjected to T/SS with mesenteric lymph duct ligation (T/SS+LDL), or 5) rats subjected to T/HS+LDL. Cardiac function was comparable in hearts from naive, T/SS, and T/SS+LDL rats. Both LVDP and +/- dP/dt(max) were significantly depressed after T/HS. The T/HS hearts also manifested a blunted responsiveness to increases in coronary flow rates and Ca(2+), and this was prevented by LDL preceding T/HS. Although electrocardiograms were normal under physiological conditions, when the T/HS hearts were perfused with low Ca(2+) levels ( approximately 0.5 mM), prolonged P-R intervals and second-degree plus Wenckebach-type atrioventricular blocks were observed. No such changes occurred in the control or T/HS+LDL hearts. The effects of T/HS were similar to those of the Ca(2+) channel antagonist diltiazem, indicating that an impairment of cellular Ca(2+) handling contributes to T/HS-induced cardiac dysfunction. In conclusion, gut-derived factors carried in mesenteric lymph are responsible for acute T/HS-induced cardiac dysfunction.
authors.affiliation: Dept. of Surgery, Univ. of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Sambol
authors.forename: Marlon A
authors.initials: MA
authors.lastname: Lee
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Caputo
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kawai
authors.forename: Chirag
authors.initials: C
authors.lastname: Badami
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawai
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yatani
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003326:Coronary Circulation; D004110:Diltiazem / Q000494:pharmacology; D004195:Disease Models, Animal; D004562:Electrocardiography; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate; D008026:Ligation; D008196:Lymph / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000601:surgery*; D008297:Male; D008643:Mesentery; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure
chemical_list: D002121:Calcium Channel Blockers; D004110:Diltiazem; D002118:Calcium