Aprotinin Modifies Left Ventricular Contractility and Cytokine Release After Ischemia-Reperfusion in a Dose-Dependent Manner in a Murine Model

被引:8
作者
McEvoy, Matthew D. [2 ]
Sabbagh, Michel J. [2 ]
Taylor, Anna Greta [2 ]
Zavadzkas, Juozas A.
Koval, Christine N.
Stroud, Robert E.
Ford, Rachael L.
McLean, Julie E.
Reeves, Scott T. [2 ]
Mukherjee, Rupak
Spinale, Francis G. [1 ,3 ]
机构
[1] Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, Charleston, SC 29403 USA
[2] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29403 USA
[3] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA
关键词
RISK; METAANALYSIS; NEUTROPHIL; SURGERY; INJURY; BYPASS; VOLUME;
D O I
10.1213/ane.0b013e31818cdb13
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
BACKGROUND: Periods of ischemia-reperfusion (I/R) during cardiac surgery are associated with transient left ventricular (LV) dysfunction and an inflammatory response. In this study, we examined the potential dose-dependent effects of aprotinin (APRO) on LV contractility and cytokine release in the setting of I/R. METHODS: An index of LV contractility, LV maximal elastance (E-max), was measured at baseline, 30 min of ischemia, and 60 min of reperfusion by microtransducer volumetry. Mice were randomized as follows: (a) APRO 20,000 kallikrein-inhibiting units (KIU)/kg (n = 11); (b) APRO 4 x 10(4) KIU/kg (n = 10); (c) APRO 8 x 10(4) KIU/kg (n = 10); and (d) vehicle (saline; n = 10). APRO doses were calculated to reflect half, full, and twice the clinical Hammersmith closing schedule. After I/R, plasma was collected for cytokine measurements. RESULTS: After I/R, E-max decreased from the baseline value by more than 40% in the vehicle group as well as in the APRO 4 x 10(4) KIU/kg and APRO 8 x 10(4) KIU/kg groups (P < 0.05). However, E-max returned to near baseline values in the APRO 2 x 10(4) KIU/kg group. Tumor necrosis factor (TNF) increased 10-fold after I/R, but it was reduced with higher APRO doses. CONCLUSIONS: This study demonstrated that a low dose of APRO provided protective effects on LV contractility, whereas higher doses suppressed TNF release. These unique findings suggest that there are distinct and independent mechanisms of action of APRO in the context of I/R.
引用
收藏
页码:399 / 406
页数:8
相关论文
共 27 条
[1]  
Beath SM, 2000, ANESTH ANALG, V91, P257
[2]   Systemic inflammation and reperfusion injury in patients with acute myocardial infarction [J].
Blancke, F ;
Claeys, MJ ;
Jorens, P ;
Vermeiren, G ;
Bosmans, J ;
Wuyts, FL ;
Vrints, CJ .
MEDIATORS OF INFLAMMATION, 2005, (06) :385-389
[3]   Aprotinin and preservation of myocardial function after ischemia-reperfusion injury [J].
Bull, DA ;
Maurer, J .
ANNALS OF THORACIC SURGERY, 2003, 75 (02) :S735-S739
[4]   Aprotinin preserves myocardial biochemical function during cold storage through suppression of tumor necrosis factor [J].
Bull, DA ;
Connors, RC ;
Albanil, A ;
Reid, BB ;
Neumayer, LA ;
Nelson, R ;
Stringham, JC ;
Karwande, SV .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2000, 119 (02) :242-249
[5]   Effects of food restriction on systolic mechanical behavior of the ventricular pump in middle-aged and senescent rats [J].
Chang, KC ;
Peng, YI ;
Lee, FC ;
Tseng, YZ .
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2001, 56 (03) :B108-B114
[6]   Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals [J].
Feldman, MD ;
Erikson, JM ;
Mao, Y ;
Korcarz, CE ;
Lang, RM ;
Freeman, GL .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 279 (04) :H1698-H1707
[7]   A comparison of aprotinin and lysine analogues in high-risk cardiac surgery [J].
Fergusson, Dean A. ;
Hebert, Paul C. ;
Mazer, C. David ;
Fremes, Stephen ;
MacAdams, Charles ;
Murkin, John M. ;
Teoh, Kevin ;
Duke, Peter C. ;
Arellano, Ramiro ;
Blajchman, Morris A. ;
Bussieres, Jean S. ;
Cote, Dany ;
Karski, Jacek ;
Martineau, Raymond ;
Robblee, James A. ;
Rodger, Marc ;
Wells, George ;
Clinch, Jennifer ;
Pretorius, Roanda .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (22) :2319-2331
[8]   Myocardial and lung injury after cardiopulmonary bypass: Role of interleukin (IL)-10 [J].
Giomarelli, P ;
Scolletta, S ;
Borrelli, E ;
Biagioli, B .
ANNALS OF THORACIC SURGERY, 2003, 76 (01) :117-123
[9]   Modifying risk for extracorporeal circulation: Trial of four antiinflammatory strategies [J].
Gott, JP ;
Cooper, WA ;
Schmidt, FE ;
Brown, WM ;
Wright, CE ;
Merlino, JD ;
Fortenberry, JD ;
Clark, WS ;
Guyton, RA .
ANNALS OF THORACIC SURGERY, 1998, 66 (03) :747-753
[10]  
Greilich PE, 2001, CIRCULATION, V104, pI265