Pentoxifylline attenuates the depressed endothelial cell function and vascular muscle contractility following trauma and hemorrhagic shock.
Although pentoxifylline (PTX) produces various beneficial effects following adverse circulatory conditions, it is not known whether this agent attenuates the depressed vascular endothelial cell function [i.e., the reduced release of endothelium-derived nitric oxide (EDNO)] and smooth muscle contractility after trauma and hemorrhage. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximal shed volume was returned in the form of lactated Ringer's solution. The animals were then resuscitated with 4 times the volume of maximal bleedout with lactated Ringer's solution, following which PTX (50 mg/kg body weight), or an equivalent volume of normal saline, was infused intravenously over 95 minutes. At 1.5 hours after resuscitation, the aorta was isolated and studied in vitro. Norepinephrine-induced vascular contraction and dose responses for acetylcholine (ACh), an endothelium-dependent vasodilator, were then determined. The results indicate that the decreased ACh-induced relaxation in hemorrhaged animals was restored with PTX treatment. Moreover, the increased ACh IC50 values (ACh concentration that causes half-maximum relaxation) after hemorrhage were reduced by PTX. In contrast, there was no significant difference in the relaxation induced by an endothelium-independent vasodilator, nitroglycerine, in the tested groups. Thus, PTX restores a hemorrhage-induced decrease in endothelium-derived nitricoxide production. In addition, the depressed smooth muscle contractile function was also attenuated by PTX treatment. Because PTX restored the depressed endothelial cell function and smooth muscle contractility, this agent appears to be a useful adjunct to fluid resuscitation for the management of trauma and hemorrhage.
Wang
P
P
Department of Surgery, Michigan State University, East Lansing 48824-1315, USA.
Ba
Z F
ZF
Stepp
K J
KJ
Chaudry
I H
IH
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism*
D009569:Nitric Oxide; D010431:Pentoxifylline; D009638:Norepinephrine