title: The cardioprotective effect of hypertonic saline is associated with inhibitory effect on macrophage migration inhibitory factor in sepsis.
abstract: Sepsis can cause myocardial dysfunction, which contributes to the high mortality of sepsis. Hypertonic saline (HS) has been reported to increase myocardial contractility in sepsis. In the present study, mechanisms of action of HS resuscitation (4 mL of 7.5% NaCl per kilogram) on cardiac function have been evaluated in septic rats. HS was administered 1 h after LPS (10 mg/kg, i.v.) challenge. The mean arterial blood pressure significantly decreased 4 h after LPS challenge, and septic shock was observed at the end of experiment (6 h). Posttreatment with HS prevented hypotension caused by LPS and significantly improved cardiac function, evidenced by increases in left ventricular developed pressure, mean +dP/dt and -dP/dt. The amplitude of electrical-stimulated intracellular Ca(2+) transient in isolated single cardiomyocytes was significantly reduced after 6 h LPS insult, which was recovered by HS. In addition, LPS resulted in significant increases in neutrophil myeloperoxidase activity, macrophage migration inhibitory factor (MIF), and NF-κB phospho-p65 protein levels in myocardium at 6 h, which were significantly attenuated by HS. In conclusion, HS improved myocardial contractility and prevented circulatory failure induced by endotoxemia, which may attribute to improvement of intracellular calcium handling process and inhibitory effects on neutrophil infiltration and MIF production in hearts.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Taipei Medical University, Taipei, Taiwan ; Department of Anesthesiology, Catholic Mercy Hospital, Hsinchu, Taiwan.
authors.forename: Kwok-Keung
authors.initials: KK
authors.lastname: Lam
authors.affiliation: Department of Physiology & Biophysics, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Pao-Yun
authors.initials: PY
authors.lastname: Cheng
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Kung
authors.affiliation: Department of Nursing, HungKuang University, Taichung, Taiwan.
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, National Defense Medical Center, 160 Min-Chuan E. Road, Taipei 114, Taiwan.
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Chao
authors.affiliation: Division of Cardiology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Hwong-Ru
authors.initials: HR
authors.lastname: Hwang
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Chi-Mei Medical Center, 901 Chung Hwa Road, Tainan 710, Taiwan ; Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Ming-Ting
authors.initials: MT
authors.lastname: Chung
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan ; Department of Pharmacology, National Defense Medical Center, 160 Min-Chuan E. Road, Taipei 114, Taiwan.
authors.forename: Yen-Mei
authors.initials: YM
authors.lastname: Lee
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D012462:Saline Solution, Hypertonic; D002118:Calcium