The effects of extended perioperative pentoxifylline on random skin flap survival.
OBJECTIVE
This study was designed to determine the effects of long-term perioperative pentoxifylline administration on random skin flap survival in an appropriate animal model. A secondary objective was to document bioavailability of pentoxifylline in the animal model by measuring blood levels of parent compound and metabolites at regular intervals and comparing these to levels measured in humans.


METHODS
A randomized control study of the effects of oral pentoxifylline on the survival of "random" skin flaps was conducted at the animal care facility of an academic tertiary referral center on six randomly selected Yorkshire pigs. Oral pentoxifylline was administered daily to four pigs for 3 months, and two pigs received placebo. Pentoxifylline blood levels for each experimental animal were measured after 4, 8, and 12 weeks of daily dosing. Blood viscosity, fibrinogen, and hematocrit were measured for each of the six animals on day 1, day 30, day 60, and day 91. On day 91, 12 surgical random skin flaps were elevated on each of the six animals and immediately sewn back in the donor bed. Pentoxifylline dosing was continued for 2 weeks, and placebo was continued in control animals. On postoperative day 15, all animals were killed and all flaps were measured individually for area of viability. The outcome measure was the detection of statistically significant increase in survival area in skin flaps of those animals administered perioperative pentoxifylline.


RESULTS
No significant augmentation of flap survival was noted in experimental animals when compared with those in the control group; no significant difference was noted between or within groups of experimental animals. Pentoxifylline and metabolite blood levels in all experimental animals at every interval were noted to be comparable to those documented in human studies; metabolite concentrations conformed to expected patterns as observed in humans. No significant alterations of blood viscosity, fibrinogen, or hematocrit were measured in the experimental animals when compared with those in the control group. The only animal showing mean flap survival outside the 95% confidence interval was one in the control group.


CONCLUSIONS
No augmentation of random skin flap survival could be shown in the pig model after a 3 month regimen of daily oral pentoxifylline. Blood levels of pentoxifylline in experimental animals were compared with those documented in humans. No alteration of blood viscosity, fibrinogen, or hematocrit was noted in any of the experimental animals when compared with each other or with those in the control group.
Department of Otolaryngology, West Virginia University, Morgantown 26506-9200.
J P
JP
Pickens
S M
SM
Rodman
S J
SJ
Wetmore
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001809:Blood Viscosity / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006085:Graft Survival / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D010431:Pentoxifylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010919:Placebos; D011292:Premedication; D012039:Regional Blood Flow / Q000187:drug effects; D016038:Skin Transplantation / Q000379:methods / Q000473:pathology / Q000502:physiology*; D013552:Swine
D010919:Placebos; D005340:Fibrinogen; D010431:Pentoxifylline