title: Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction.
abstract: Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30-35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1-2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca²⁺ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/dt(max)) were decreased and inotropic response to Ca²⁺ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction.
authors.affiliation: Dept. of Surgery, UMDNJ-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: Mingshan
authors.initials: M
authors.lastname: Jiang
authors.forename: Garima
authors.initials: G
authors.lastname: Dosi
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yatani
mesh_terms: D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D004195:Disease Models, Animal; D008196:Lymph / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D008643:Mesentery; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure