Influence of propofol on blood pressure spectrum in sepsis and the role of inducible nitric oxide synthase.
BACKGROUND
Sepsis is characterized by an increase in nitric oxide (NO) production, hemodynamic dysfunction and multiple organ failure. Propofol, a commonly used anesthetic in the intensive care unit for sedation and hypnosis, is thought to exert a protective effect on NO overproduction by inhibiting the expression of inducible NO synthase (iNOS) in sepsis. The aim of this study was to examine the influence of propofol on the temporal changes in the power density of frequency components of systemic arterial pressure (SAP) variability in rats subject to Escherichia coli lipopolysaccharide (LPS)-induced endotoxemia and to delineate the role of iNOS.


METHODS
Twenty-four Sprague-Dawley rats were used in this study. Arterial catheters were inserted for direct SAP monitoring, and SAP signals were subjected to online real-time power spectral analysis via fast Fourier transformation. Animals were divided into four groups to receive different dosages of propofol infusion (15 or 30 mg/kg/hr) with or without the iNOS synthase inhibitor, S-methylisothiourea (SMT, 2 mg/kg). Changes in the power density of high-frequency (BHF), low-frequency (BLF) or very-low-frequency (BVLF) components of the SAP spectrum in each group were analyzed.


RESULTS
Systemic injection of LPS resulted in a transient decrease, followed by a rebound increase and a second-phase decrease in the power density of BHF, BLF and BVLF of the SAP spectrum. Compared with low dose (15 mg/kg/hr), high-dose (30 mg/kg/hr) propofol anesthesia profoundly suppressed the power density of BHF, BLF and BVLF of SAP signals during LPS-induced endotoxemia. Such suppression was not affected by SMT pretreatment. SMT treatment, on the other hand, augmented the rebound increase in the power density of BHF and BLF, and ameliorated the second phase decrease in the power density of BHF in the endotoxemic rats that were maintained under low dose propofol anesthesia.


CONCLUSIONS
We concluded that iNOS-induced NO might be involved in the manifestation of the BHF and BLF components of the SAP spectrum during endotoxemia when low-dose propofol is used, and this effect of NO is blunted when high-dose propofol is administered.
Liu
Yen-Chin
YC
Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan, R.O.C.
Chan
Julie Y H
JY
Tsai
Yu-Chuan
YC
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000503:physiopathology; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*
D018686:Anesthetics, Intravenous; D007550:Isothiuronium; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium; D015742:Propofol