Michael F. Angel

The Critical Relationship Between Free Radicals and Degrees of Ischemia: Evidence for Tissue Intolerance of Marginal Perfusion

UNLABELLED Skin-flap ischemia has been associated with the presence of free radicals. In this study, two enzyme systems involved in free-radical metabolism were used to compare a distal skin flap to a skin graft. Forty-two rats were divided into several test groups. A 10 X 3 cm dorsal rat flap was used, and tissue biopsies for xanthine oxidase and malonyldialdehyde (MDA) were obtained 2.5, 5.5, and 8.5 cm from the base of the flap at the hours given. In group I (control), the flap was outlined but not elevated, and biopsies were obtained. In group II, the flap was elevated, and biopsies were obtained at 6 hours. In group III, the flap was elevated, the distal 4 X 3 cm was amputated and replaced as a full-thickness skin graft, and biopsies were obtained at 6 hours. In group IV, the flap was elevated, and biopsies were obtained at 12 hours. In group V, the flap was treated as in group III, and biopsies were obtained at 12 hours. In group VI, the flap was elevated, and biopsies were obtained at 24 hours. In group VII, the flap was treated as in group III, and biopsies were obtained at 24 hours. RESULTS Xanthine oxidase was significantly higher in all distal biopsies compared to proximal biopsies. Xanthine oxidase also increased with time. Malonyldialdehyde increased over time as well as with distance from the flap base. Distal flap biopsies at 24 hours had greatly increased levels of malonyldialdehyde compared to skin grafts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Free radicals: basic concepts concerning their chemistry, pathophysiology, and relevance to plastic surgery

This paper is an attempt to present important concerns in the rapidly expanding field of free radicals to a plastic surgical audience. Mechanisms and a systematic approach to free-radical pathology are presented, with several illustrative areas discussed more deeply.

Secondary ischemia time in rodents : contrasting complete pedicle interruption with venous obstruction

The current study investigated the effect of secondary ischemic insults on ultimate flap survival. Rodent skin flaps subjected to 8 hours of secondary ischemia with total pedicle obstruction had 56 percent survival (7 of 12) compared with primary ischemic flaps of the same time, which all survived. At 10 hours of ischemia, only 42 percent of secondary ischemic flaps survived compared with 67 percent (8 of 12) of primary ischemic flaps. When the secondary ischemia was caused by venous obstruction, the results were even more striking. Ninety-two percent (11 of 12) of primary venous obstruction flaps survived 3 hours of ischemia and 75 percent (9 of 12) survived 5 hours of ischemia, while only 56 percent (7 of 12) and 8 percent (1 of 12) of flaps subjected to secondary venous obstruction survived at the same times, respectively. The explanation of these observations on the basis of tissue pathophysiologic changes will require further study. The results support the need for close monitoring of clinical flaps to ensure optimal survival.

Deferoxamine increases skin flap survival: additional evidence of free radical involvement in ischaemic flap surgery

This study presents further evidence of free radical involvement in skin flap necrosis in a dorsal rat flap model. Rats receiving deferoxamine, a free radical scavenger and iron chelator had significantly less necrosis (p less than 0.001) than saline treated rats. In a separate experiment, tissue determinations for malonyldialdehyde (MDA) were consistent with the survival results in showing a significant decrease in MDA in all biopsy sites (p less than 0.05 or less), indicative of reduced lipoperoxidation in the deferoxamine treated rats.

Injuries associated with mandible fractures sustained in motor vehicle collisions.

Motor vehicle collisions are second only to altercations as the most common cause of mandible fractures. This article details in a retrospectively studied group the incidence of isolated mandible fractures and associated injuries in patients who were involved in motor vehicle collisions. This group consisted of 148 patients with mandible fractures listed in the University of Mississippis trauma registry during the past 5 years. In almost all patients, associated injuries occurred with mandible fractures that were caused by motor vehicle collisions, with an incidence of 99.3 percent. Facial and head lacerations and facial fractures were the leading associated injuries, occurring in more than half of the patients who had a mandible fracture. Closed head injury is the major life‐threatening associated injury and cause of mortality. The life‐threatening injuries occurred in 64.8 percent of patients in this study. The mortality rate in this group of patients was 8.1 percent. These data suggest that mandible fractures from motor vehicle collisions should never be viewed as an isolated injury but rather as part of a spectrum of significant and sometimes life‐threatening injuries that require thorough trauma evaluation at the time of presentation. (Plast. Reconstr. Surg. 108: 328, 2001.)

The effect of thromboxane synthetase inhibition on tolerance of skin flaps to secondary ischemia caused by venous obstruction

The harmful effects of the no-reflow phenomenon on skin flaps were modified by using the thromboxane synthetase inhibitor UK-38,485. Sprague-Dawley rats (N = 134) were subjected to either 3 or 5 hours of secondary venous occlusion occurring 24 hours after a primary ischemic episode of 1 1/2 hours. Within each time period, rats received either saline or UK-38,485 at the primary ischemic episode and/or at the secondary ischemic episode. Flaps treated with UK-38,485 in relation to the period of secondary ischemia had a higher survival rate than control ischemic flaps (p < 0.01). Those treated only at the end of the primary ischemic episode but prior to the secondary ischemic episode had improved survival rates, but these were not statistically significant. These effects may be explained by the lower throm-boxane: prostacyclin ratios at the time of revascularization. The possible interrelationship of the prostanoids with free-radical mechanisms in the no-reflow phenomenon is also discussed.

Augmentation of skin flap survival with allopurinol.

Although allopurinol is primarily known as an effective medication for gout, it has been shown to enhance tissue survival in a wide range of ischemic conditions. The study reported here investigated the effects of allopurinol on flap survival in a dorsal rat model. In a preliminary study, animals were given varying doses of allopurinol (0 to 400 mg per kilogram). A clinically efficacious dose was established upon conclusion of the test period by laboratory determinations and necropsy data. Other animals were divided into 3 groups: 1 (saline control), N = 11; 2 (50 mg per kilogram of allopurinol daily), N = 10; 3 (100 mg per kilogram of allopurinol qd), N = 11. Flaps were raised and necrosis assessed at 8 days. Flaps treated with allopurinol 100 mg per kilogram had significantly better survival than the controls (p < 0.001) and 50 mg per kilogram (p < 0.01). Allopurinol 50 mg per kilogram had no effect on flap survival.

The effect of deferoxamine on tolerance to secondary ischaemia caused by venous obstruction

The current study investigated the efficacy of deferoxamine for treating secondary ischaemia due to venous obstruction in a rodent epigastric pedicle flap model. Rats receiving one dose of the free radical scavenger and iron chelator deferoxamine (150 mg/kg) intravenously prior to reperfusion had a mild improvement in flap survival: 46% in controls, 77% in deferoxamine-treated. This was statistically significant at p less than 0.05 (chi 2 = 5.2). This suggests that free radicals are partly involved in the mechanism of ischaemia/reperfusion injury in secondary ischaemia, as has been previously demonstrated for primary ischaemia (Angel et al., 1986b). Supporting biochemical evidence will be necessary to understand better the mechanisms involved in secondary ischaemia.

Immediate and delayed use of arteriovenous fistulae in microsurgical flap procedures: a clinical series and review of published cases.

In microsurgical flap procedures, creation of an arteriovenous fistula (AVF) is a technique of vein grafting where the vein graft is connected to recipient vessels as a flow-through loop prior to harvest and inset of the flap. Controversy exists whether this technique can be used as a 2-stage procedure with the loop and flap transfer accomplished in sequential operations or if the loop and flap transfer should be performed in a single operation. We performed 12 consecutive 1-stage AVF-flap procedures, with 1 flap failure. We combined this series with previously published reports to compare outcomes of 1-stage and 2-stage procedures. We found no significant difference in flap outcomes or complication rates between the 2 strategies. We conclude from our experience and this analysis that single-stage AVF-flap procedures are the optimum application of this technique.

Avoiding free nipple grafting with the inferior pedicle technique.

Abstract:In cases of severe macromastia, the free nipple graft technique has been the traditional alternative to pedicle transposition. Distress over nipple survival in large reduction mammaplasty and long pedicle transposition is largely responsible for this. A retrospective investigation of the records of 142 reduction mammaplasty patients was carried out to determine whether nipple survival or overall complication rates were significantly different in patients undergoing larger (>1500 g per side) as compared with smaller reductions (<1500 g per side). The 2 patient groups were compared with respect to mild or severe complications. Data were analyzed using Fisher exact test and 2-sample t tests. A P value of <0.05 was considered statistically significant. No patient in either group had total nipple loss. There were no statistically significant differences in major or minor complications between the 2 groups. In our experience, the inferior pedicle, Wise pattern reduction is a reliable and predictable method of reduction, appropriate for all breast sizes and pedicle lengths.