Pharmacological preconditioning with monophosphoryl lipid a improves post ischemic diastolic function and modifies TNF-alpha synthesis

• Published in: European journal of cardio-thoracic surgery 2005-03, Vol.27 (3), p.501-507
• Main Authors: SHARONY, Ram, FROLKIS, Inna, FROYLICH, Dvir, WILDHIRT, Stephan M, SHAPIRA, Itzhak, REICHART, Bruno, NESHER, Nahum, URETZKY, Gideon
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary Circulation - drug effects; Gene Expression Regulation - drug effects; Hemodynamics - drug effects; Ischemic Preconditioning, Myocardial - methods; Lipid A - analogs & derivatives; Lipid A - therapeutic use; Male; Medical sciences; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Organ Culture Techniques; Pneumology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Ventricular Function, Left - drug effects
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1016/j.ejcts.2004.11.033

Pharmacologic preconditioning represents an attractive myocardial protection strategy. Tumor necrosis factor-alpha plays an important role in myocardial ischemia-reperfusion injury. We aimed to determine the effect of Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic left ventricular function and tumor necrosis factor-alpha synthesis during ischemia and reperfusion. Rats (n=10) were pretreated with Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later, the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic measurements, tumor necrosis factor-alpha mRNA expression and protein content were studied after stabilization (baseline), after 35 min of global ischemia and at 40 min of reperfusion. Left ventricular developed pressure and peak rate of left ventricular developed pressure (dP/dt) rise were comparable between the animals in the control and Monophosphoryl lipid A treated groups during baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4 vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P