A novel nonanticoagulant heparin prevents vascular endothelial cell dysfunction during hyperdynamic sepsis.
Although a novel nonanticoagulant heparin (i.e., GM1892) produces various beneficial effects after hemorrhage and resuscitation, it remains unknown whether this agent has any salutary effects on the depressed vascular endothelial cell function during sepsis. To determine this, rats were subjected to sepsis by cecal ligation and puncture (CLP). At 1 h after CLP, GM1892 (7 or 14 mg/kg body wt), conventional heparin (7 or 14 mg/kg), or an equal volume of saline was administered intravenously. At 5 h after CLP (i.e., hyperdynamic sepsis), the thoracic aortae were isolated and placed in organ chambers. Dose-response relaxation curves were determined for acetylcholine (ACh; 10(-8) to 10(-5) M), which stimulates endothelial nitric oxide production, and for nitroglycerine (10(-9) to 10(-6) M), which directly provides nitric oxide in vivo. ACh-induced relaxation was depressed at 5 h after CLP while there was no significant alteration in nitroglycerine-induced relaxation. Treatment with 14 mg/kg GM1892 or 14 mg/kg heparin (but not with 7 mg/kg GM1892 or 7 mg/kg heparin), however, prevented the decrease of ACh-induced relaxation. Thus, GM1892 (which does not possess any significant anticoagulant properties) at the higher dosage appears to be useful for maintaining vascular endothelial cell function during hyperdynamic sepsis.
Morrison
A M
AM
Department of Surgery, Michigan State University, East Lansing 48824, USA.
Wang
P
P
Chaudry
I H
IH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D002432:Cecum; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006495:Heparin, Low-Molecular-Weight / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018805:Sepsis / Q000503:physiopathology*; D014661:Vasoconstriction; D014664:Vasodilation
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C094917:GM 1892; D005996:Nitroglycerin; D000109:Acetylcholine; D009638:Norepinephrine