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Biomedical subjects

M F Angel

Publications and source records attributed to M F Angel.

At least 55 records · Page 3Linked to original sources

Metastatic melanoma to the facial nerve.

Isolated metastatic malignant melanoma to the facial nerve has never been reported. This presentation illustrates a primary melanoma of the helix of the ear that was treated by excisional biopsy and then wedge resection in 1983. The primary melanoma was Clark's level IV and 1.3 mm in thickness. In 1985, a facial paresis slowly developed. There was no gross evidence of recurrent melanoma in the ear or neck, but CT scan showed a mass in the region of the stylo mastoid foramen. A reoperation of the primary site revealed metastatic melanoma in the facial nerve, expanding it to approximately 10 times its normal size. A composite resection was done for the melanoma, and the paralyzed face was immediately rehabilitated by a masseter muscle transfer. The patient received 6000 rads to this area postoperatively and has remained free of disease to date, having returned to his profession as a dentist. A detailed study of all the specimens indicated that this represented a primary metastasis to the facial nerve.

Adult↗

Interaction between thromboxane and free radical mechanisms in experimental ischaemic rabbit skin flaps.

The possible relationship between increased blood levels of thromboxane (TXA2) and tissue levels of free radicals during ischaemia was investigated. Rabbit epigastric skin flaps were subjected to 4 h of body temperature ischaemia, then infused with either the TXA2 synthetase inhibitor UK-38,485, the free radical scavenger superoxide dismutase (SOD), or both immediately prior to reperfusion. After 30 min of reperfusion, increases in the tissue levels of xanthine oxidase (XO) and malonyldialdehyde (MDA), both of which are indices of free radical generation and decreases in the tissue levels of SOD were found. SOD treatment completely restored XO, MDA and SOD levels to normal, whereas UK-38,485 only partially improved all three parameters. None of these changes was statistically significant. Effluent blood thromboxane B2 (TXB2) levels from the flap increased significantly (P less than 0.01) after ischaemia and were reduced significantly by both UK-38,485 and SOD (P less than 0.05). Combined UK-38,485 and SOD treatment was no better than treatment with either agent alone. ATP levels and oedema, which decreased and increased respectively due to ischaemia, were not significantly altered by drug infusion. These results suggest that free radical damage may be related to TXA2-generated thrombosis in ischaemia/reperfusion injury.

Adenosine Triphosphate↗

The anatomy of the subscapular artery and its effects on flap design in the rabbit.

The course of the subscapular artery was studied in 20 rabbits. Its course was constant, giving two branches to the latissimus dorsi muscle after which the vessel sent a branch (S1) that perforated the panniculus carnosus to supply a large territory of skin. In a separate experiment, the contribution of the S1 branch to the viability of the rabbit latissimus dorsi musculocutaneous flap was evaluated. From this experiment it can be concluded that, first, it is possible in a rabbit to elevate a large skin flap based solely on a muscle perforator (S1), which survives completely. Second, in the rabbit latissimus dorsi musculocutaneous flap, S1 is the major blood supply to the skin component. Damage to it severely diminishes skin flap survival, even if the vascular supply to the underlying muscle is completely intact.

Animals↗

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 less than 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 thromboxane: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.

Animals↗

Effect of a thromboxane synthetase inhibitor UK-38,485 on the tolerance of skin flaps of primary ischaemia.

The harmful effects of ischaemia or skin flaps were modified using the thromboxane synthetase inhibitor UK-38,485. The epigastric island flaps of Sprague-Dawley rats (n = 288) were subjected to 10, 12 or 14 h of total pedicle occlusion, or 3, 5 or 7 h of venous occlusion of the sole vascular pedicle. Within each time period, rats received intravenous doses of either physiological saline (controls) or UK-38,485 at the beginning or end of the ischaemic episode. Flaps treated with UK-38,485 overall had a higher survival rate than control ischaemic flaps (P less than 0.001). This applied both to total (arterial) ischaemia (P less than 0.001) and partial (venous) ischaemia (P less than 0.01). There was no significant difference between treatment given at the beginning or at the end of the ischaemic episode. These results may be explained by reduced platelet aggregation and thrombosis in the microvasculature due to the lower thromboxane/prostacyclin ratios for treated flaps. The possible inter-relationship of the prostanoids with free radical mechanisms in the no-reflow phenomenon is also discussed.

Animals↗

The dorsal rat flap: a discussion of the model and the salutary effect of cimetidine on flap survival.

Failure of skin flaps remains a significant clinical problem. The dorsal rat flap, a reliable experimental model, was used to test the efficacy of cimetidine in treating a failing flap. Flaps were elevated in 45 rats divided into three equal groups. Group 1 was a saline control group, Group 2 received cimetidine 250 mg/kg three times a day for 7 days postoperatively, and Group 3 received cimetidine for 1 day before surgery, and then as in Group 2. Necrosis was assessed on the seventh postoperative day. Group 2 had 31.1 +/- 1.3 (mean % +/- SEM) necrosis, significantly better than saline control animals (p less than 0.01) and pretreated animals (p less than 0.05). These results suggest the usefulness of cimetidine in ischemic flap surgery.

Animals↗

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.

Animals↗

Effect of phosphoenolpyruvate and adenosine triphosphate on rabbit skeletal muscle after ischaemia: preliminary biochemical study.

The present study examined the effect of phosphoenolpyruvate (PEP) and adenosine triphosphate (ATP) on rabbit skeletal muscle flap survival after warm ischaemia. Two muscle flap models, rectus femoris pedicle flap and latissimus dorsi free flap, were subjected to a total ischaemia of 4 hours at 37 degrees C and 20 degrees C, respectively. Immediately prior to revascularisation, the muscles were infused with either Hanks' balanced salt solution (BSS) or Hanks' BSS containing 200 mumol PEP and 6.6 mumol ATP. Quantification of muscle damage was determined by measuring the plasma levels of creatinine kinase (CK), lactate dehydrogenase (LDH), lactate, potassium, and phosphate at 0, 2, 24, and 96 hours after revascularisation. Infusion of PEP/ATP compared with Hanks' BSS alone significantly decreased the efflux of CK in both rectus femoris (P less than 0.025) and latissimus dorsi muscles (P less than 0.05) and of LDH in the rectus femoris muscle (P less than 0.01). No significant changes were observed, however, for the plasma levels of lactate, potassium, and phosphate. From this study it was concluded that PEP and ATP partially protect skeletal muscle from ischaemia and reperfusion injury.

Adenosine Triphosphate↗

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.

Animals↗

Prior elevation of vascular island skin flaps: intolerance to ischemia caused by venous obstruction.

Previous experiments in our laboratory have shown that prior elevated flaps, those elevated 24 hr prior to complete ischemia, are more tolerant of the ischemic insult than acutely ischemic flaps that have had no prior elevation. In the current study, the effect of prior elevation was observed on tolerance to ischemia caused by venous occlusion alone. Under these conditions, limited blood flow may be possible via the unclamped artery, so a state of partial ischemia exists. After seven hours of venous obstruction, acutely elevated flaps had a 50 percent survival rate at postoperative day 7. This was significantly better (p less than 0.005, chi 2 test) than the 0 percent survival rate for prior elevated flaps for the same period of venous obstruction. It is speculated that the more rapid generation of cytotoxic free radicals during the period of partial ischemia is more detrimental to the prior elevated flaps that have greater blood flow, than to the controls.

Animals↗

The use of split metatarsal osteocutaneous free flaps in palatal and alveolar defects.

A series of seven osteomucosal defects of the palate were closed by split metatarsal osteocutaneous free flaps. All seven patients had successful closure of their defects with minimal facial scarring and insignificant donor site morbidity. This procedure, performed in one stage, avoids the use of previously compromised local tissues and improves the blood supply to the area, thereby enhancing the subsequent indicated reconstruction of other damaged structures.

Adult↗

The deleterious effect of arteriovenous flow reversal during experimental free muscle transfer.

Arteriovenous flow reversal (AVR) has been used experimentally to salvage ischemic limbs and to create novel skin flaps with some success. The clinical applicability of AVR in muscle by way of two arteriovenous anastomoses in the rabbit was investigated. Twenty-four rabbits were divided into two groups. In Group 1 (control), the rectus femoris muscle was harvested and transplanted in the opposite thigh, anastomosing the donor femoral artery to the recipient femoral artery, and the donor rectus femoris vein to the recipient femoral vein. In Group 2 (flow reversal), the same procedure was done except the donor artery was anastomosed to the recipient vein and vice versa. Six and 24 hr postoperatively, specimens were compared macroscopically and by weight and histology. Reversed flow muscles were significantly heavier than control muscles at 6 hr and at 24 hr. Histologically, 6 hr of AVR caused edema, intramuscular hemorrhage, neutrophil infiltration, and thrombosis of most vessels. By 24 hr muscle cell degeneration was well advanced. All control muscles were viable, with only mild edema and slight peripheral necrosis. Possible reasons for the failure of AVR in muscle are discussed. On the basis of these results, AVR in free muscle transfer is not advocated.

Animals↗

The effect of time of vascular island skin flap elevation on tolerance to warm ischemia.

The effect of time of vascular island skin flap elevation on tolerance to a subsequent 12-hour period of warm ischemia was studied. Sixty rats were separated into five equal groups; the rat epigastric island flap was used as the model. In group 1 flaps were elevated and immediately subjected to 12 hours of complete ischemia by application of microvascular clamps to both artery and vein of the pedicle. In group 2 the flap was elevated, and after 12 hours of recovery ischemia was induced for 12 hours. Groups 3 to 5 were similar to group 2 except that the time interval between initial elevation and subsequent ischemia varied: 24 hours for group 3; 72 hours for group 4; 144 hours for group 5. Necrosis was evaluated on postoperative day 7. Those flaps elevated 24 hours before ischemic insult (group 3) had significantly better survival than all other groups (p less than 0.025 at least). There were no significant differences between the other groups. Flap elevation 24 hours before a complete ischemic episode significantly increased tolerance to ischemia. Elevating a flap earlier or later than 24 hours did not have any significant benefit.

Animals↗

The effect of prior elevation of skin flaps and ischemia on blood thromboxane levels.

The physiological factors that allow for the survival of ischemic skin flaps have not been clearly elucidated. Previous work by others has shown that elevation of a flap 24 hours before an episode of complete ischemia significantly improved survival, presumably by delaying the onset of the no-reflow phenomenon. The current study, using an epigastric flap, investigated the role of thromboxane in these events by observing postischemic plasma levels of thromboxane B2, the stable metabolite of the short-lived thromboxane A2. Acutely ischemic flaps were compared with those elevated 24 hours before ischemia. After the ischemic insult, blood was drawn from the venous effluent of the flaps. Thromboxane levels after 4 hours of ischemia were significantly decreased (p less than 0.001) in the postischemic period in those flaps elevated 24 hours before ischemia compared with flaps that had undergone ischemia acutely. Moreover, acutely ischemic flaps had significantly more thromboxane than nonischemic controls (p less than 0.001). These results confirm the importance of thromboxane metabolism in the no-reflow phenomenon.

Animals↗

Hydrostatic distention and pharmacological treatment of epinephrine-induced microarterial spasm.

The efficacy of using hydrodistention and vasodilatory drugs to relieve spasm in arteries was investigated. The femoral arteries of 64 rabbits (divided into five groups) were placed in spasm by the topical application of epinephrine (1 mg/ml). In group A (controls) vasospasm was induced without further treatment. In group B vasospasm was induced, and the arteries were hydrodistended with normal saline. In three additional groups vasospasm was induced and either 10% lidocaine hydrochloride (group C), verapamil hydrochloride (group D), or chlorpromazine hydrochloride (group E) was applied. Thirty minutes later the vessels were hydrodistended. All vessels were measured at set intervals, and some specimens were retained for light and electron microscopy. All methods of spasm relief were successful, although to varying degrees. Hydrodistention alone produced the widest dilation for the longest time. Lidocaine was the most successful drug treatment alone. Verapamil followed by hydrodistention was the most successful combination regimen, but did not produce better results than hydrodistention alone. Hydrodistention alone produced significant arterial wall damage, resulting in permanent structural modifications. Prior vasodilatory drug treatment reduced but did not eliminate hydrodistention damage. Although hydrodistention dilates for longer periods than vasodilatory drugs, the arterial wall damage associated with hydrodistention indicates that it should be used only when all other methods of vasodilation have failed.

Animals↗

The beneficial effect of chlorpromazine on dorsal skin flap survival.

A 3 x 10-cm dorsal rat skin flap contains a distal portion that is poorly perfused. The dorsal flap served as a useful model to test hemodynamic properties of the vasodilatory drug chlorpromazine. A control group of flaps were treated with saline and the test group with chlorpromazine (15 mg/kg intraperitoneally). Eight days postoperatively, the surface area of the flaps that necrosed was 27.3% for the treated group and 36.5% for the controls. Using Student's t-test this difference was significant (p less than 0.001). Nutrient blood flow determined by the penetration of fluorescein dye into the flap was consistently greater in the chlorpromazine-treated group compared with the control group in the first 24 hours postoperatively. The adenosine triphosphate (ATP) levels measured at 0 and 24 hours postoperatively were consistently lower in the distal parts of the flap, treated or control, compared with proximal parts of the flap (p less than 0.001, analysis of variance). However, there were no significant differences in ATP levels between treated and control biopsies at any one site on the flap. In conclusion, chlorpromazine had a beneficial effect on rat skin survival, and increased blood flow appears to be one of the major reasons.

Animals↗