Effect of free radical scavenger on cardiovascular system in sepsis

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591562
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Keio University
• Principal Investigator: SERITA Ryohei Keio University, Anesthesiology, instructor, 医学部, 助手 (50245594)
• Co-Investigator(Kenkyū-buntansha): MORISAKI Hiroshi Keio University, Anesthesiology, Associate professor, 医学部, 助教授 (60182226)
• Project Period (FY): 2004 – 2005
• Keywords: sepsis / cardiac function / free radical scavenger / nicaraven / cytokine

Research Abstract

The purposes of present study were to determine the effects of nicaraven on cardiac function and cytokine production in lipopolysaccharide (LPS) induced sepsis.
This protocol was approved by our institutional committee. Following arterial and venous cannulation and tracheostomy, rats (330-350 g) were anesthetized with pentobarbital, and mechanically ventilated with a control mode (TV = 12 ml/kg, RR = 40 rpm). After baseline measurements, rats (n = 20) were administrated with LPS (10 mg/kg, intravenously) and randomly assigned to following two groups : the nicaraven group treated with nicaraven (3 mg/kg/min, intravenously) and the control group treated with saline. The left ventricular, pressure and volume were measured with the pressure and conductance catheter every one hour. Cardiac function, including cardiac output (CO), ejection fraction (EF), and maximal elastance of left ventricle (E_<max>) were analyzed with a computer soft. Blood was collected, centrifuged (2000g, 15 min, x 2), and stored (-80 c) from rats every 2 hours after operation to measure plasma concentration of TNF-α, IL1-β and macrophage migration inhibitory factor (MIF) using enzyme-linked immunosorbent assays kits. Arterial blood gas analysis and lactate concentration were also measured. Data were analyzed by repeated measure ANOVA.
The CO in the nicaraven group was kept significantly higher than the control group (p < 0.05). The EF and E_<max> in the nicaraven group were also kept significantly higher than the control group (p < 0.05). Arterial lactate, TNF-α, IL1-β and MIF were significantly lower in the nicaraven group versus the control group (P < 0.05).
In conclusion, the current study indicates that the treatment with nicaraven preserves cardiac function and reduces plasma concentration of cytokine, and improves lactic acidosis in septic model.