Thoughts and Progress It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future. Effect of Variation in Systemic Blood Flow on Plasma TNF- in a Pig Model with Left Ventricular Assist Device *Yasuhiro Uozaki, †Walid C. Dihmis, †Hidetoshi Yamauchi, †Madeleine Moczar, †Masatoshi Miyama, †Fabien Pasteau, †Denis Tixier, †Sektiari L. Bambang, and †Daniel Y. Loisance, *First Department of Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan; and †Centre de Recherches Chirurgicales, Association Claude Bernard, Cre ´teil, France Abstract: Tumor necrosis factor- (TNF-) release has been implicated in a sepsis-like syndrome following car- diopulmonary bypass (CPB). This also may be important in patients who have had a left ventricular assist device (LVAD) implanted. This report investigates the effect of reducing systemic blood flow on hemodynamic response, mixed venous oxygen saturation (SvO 2 ), and the release of TNF-. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF- in the femoral artery (FA) and superior mesenteric vein (SMV) was measured at baseline and following systemic blood flow changes. Si- multaneously, hemodynamic parameters and oxygen satu- ration in the pulmonary artery (SvO 2 ) were measured. Fol- lowing reductions in systemic blood flow, plasma TNF- increased gradually to a maximum level at a systemic blood flow of 20%. There was no significant difference between TNF- levels in the SMV and the FA. There was a significant (p < 0.05) correlation between cardiac index, stroke volume index, and TNF-. The SvO 2 decreased sig- nificantly (p < 0.05) at a systemic blood flow of 30 and 20%. A rise in TNF- occurred when the SvO 2 was less than 75%. The data demonstrate that a reduction in sys- temic blood flow causes an increase in plasma TNF-. This can lead to the development of a sepsis-like syndrome in a group of patients who already are hemodynamically com- promised. While weaning short-term LVAD support, rapid diminution of the cardiac output and the pump flow must be avoided. Key Words: Left ventricular assist de- vice—Tumor necrosis factor-—Sepsis-like syndrome— Hemodynamic parameters—Mixed venous oxygen satura- tion. The use of left ventricular assist devices (LVADs) has increased in recent years (1–6). There are a num- ber of LVAD-related complications, including bleeding, thromboembolism, and infection (3–6). Tumor necrosis factor- (TNF-) has been shown to be an important mediator of inflammation in hu- mans and animals. Jansen and others reported that the release of endotoxin, associated with the production of TNF-, plays an additional role in the development of the inflammatory reaction during cardiopulmonary bypass (CPB) (7–10). However, there are no reports related to the measurement of TNF- during LVAD use. TNF--induced hemodynamic changes include el- evated cardiac output (CO), tachycardia, and de- creased systemic vascular resistance (11). Mixed ve- nous oxygen saturation (SvO 2 ) also helps to address the metabolic status (12–14). To understand further the hemodynamic responses and Sv O 2 during LVAD, we employed a pig model and provided evi- dence of TNF- production by lowering LVAD flow. Materials and Methods Operative procedures Nine adult pigs (weight 60.0 ± 3.3 kg) were used. All animals received humane care in compliance with the Principles of Laboratory Animal Care for- mulated by the National Society for Medical Re- search and the Guide for the Care and Use of Labo- ratory Anima1s published by the National Institutes of Health (NIH publication No. 85–23, Revised 1985). All pigs were anesthetized with intravenous pen- tobarbitone (30 mg/kg), mechanically ventilated through an endotracheal tube, and maintained with 1% to 2% halothane and 40% oxygen. An arterial catheter was inserted in the right femoral artery (FA) for continuous measurements of arterial blood pressure and for measurements of TNF-. A pulmo- Received September 1999; revised October 2000. Address correspondence and reprint requests to Dr. Yasuhiro Uozaki, First Department of Surgery, Toyama Medical and Phar- maceutical University, 2630 Sugitani, Toyama 930-0194, Japan. E-mail: suginouo@pa.cff.nr.jp Artificial Organs 25(2):146–153, Blackwell Science, Inc. © 2001 International Society for Artificial Organs 146