Hepatosplanchnic and peripheral tissue oxygenation during treatment of hemorrhagic shock: the effects of pentoxifylline administration.
OBJECTIVE
To evaluate the effects of pentoxifylline (PF) administration on liver, gut, and peripheral oxygenation during crystalloid resuscitation of hemorrhagic shock.


BACKGROUND
Hypoperfusion of the hepatosplanchnic vascular bed and hypoxia of vital organs may be prolonged despite adequate therapy of hemorrhagic shock. Vasoconstriction, leukostasis, platelet aggregation, and red blood cell plugging could be the underlying causes. PF has been shown to counteract these effects, but its effects in a large animal shock model have been less studied.


METHODS
Thirteen anesthetized piglets (mean weight 19.6 kg) were bled steadily to a mean arterial pressure (MAP) of 40 to 50 mmHg and a 70% reduction in cardiac output during 1 hour. These levels were maintained for an additional hour. The animals were resuscitated with acetated Ringer's solution according to MAP and cardiac output values and followed for 80 minutes (total 3 hours and 20 minutes). Seven piglets were given PF boluses (12.5 mg/kg) and infusion (0.2 mg/kg x min), and the rest (n = 6) served as controls. Hemodynamic and systemic oxygen transport variables were recorded. Liver parenchymal and peripheral tissue (subcutaneous, transcutaneous, conjunctival) oxygen tensions (PO2) were measured continuously with polarographic electrodes. Jejunal intramucosal pH (pHi) was calculated every hour by the luminal PCO2, obtained with a balloon tonometer, and arterial bicarbonate concentration.


RESULTS
Cardiac output decreased by a mean of 76% during shock and was restored during resuscitation in both groups. MAP decreased from 110 to 40 mmHg but remained at 70 to 80 mmHg during resuscitation in both groups despite remarkable volume load (2.6 ml/min per kg). Liver parenchymal PO2 decreased from 29+/-1 to 15+/-1 mmHg during shock and increased to 36+/-2 mmHg in the PF group, whereas in control group it remained at 26 mmHg. The difference between groups was significant, but at the end of follow-up the liver PO2 decreased to 21 mmHg in both groups. Gut pHi, peripheral tissue oxygen tensions, and the plasma adrenaline and noradrenaline concentrations did not differ between the groups.


CONCLUSIONS
Pentoxifylline improved specifically, although only transiently, liver tissue oxygenation. Perhaps the microvascular abnormalities after resuscitation of hemorrhagic shock are more prominent in the hepatic vascular bed, rendering PF specifically effective in that area. The lack of any effect of PF on gut and peripheral tissue oxygenation may have resulted from the persistent vasoconstriction and inadequate restoration of blood volume with crystalloid solution.
Nordin
A
A
Fourth Department of Surgery, Helsinki University Hospital, Finland.
Mildh
L
L
Mäkisalo
H
H
Härkönen
M
M
Höckerstedt
K
K
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D010431:Pentoxifylline / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D013552:Swine; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014781:Viscera / Q000098:blood supply / Q000378:metabolism
D014665:Vasodilator Agents; D010431:Pentoxifylline