JOURNAL
OF SURGICAL
19, 83-87 (1975)
RESEARCH
The Effect
of Phenoxybenzamine,
6-Hydroxydopamine M. R. WEXLER,
Phentolamine
on Skin Flap Survival
M. KALISMAN,
R. YESCHUA,
AND
and
in Rats Z. NEUMAN
Department of Plastic Surgery, Hadassah University Hospital, Jerusalem, Israel Submitted for publication
INTRODUCTION
treated by 2.5 mg/kg of 6-hydroxydopamine in 0.0001 N hydrochlorid acid in saline. Group F was treated like Group E 8 days before separation. Because the 6-hydroxydopamine is rapidly oxyidized this solution was prepared immediately before use. The animals were not anesthetized for the injections, all the injections were administered 4 hr before separation (except Group E), all materials were injected in 1 cc of volume, and all were injected at the base of the flap. All animals were killed on the 8th postoperative day and the surviving part of the flap was measured.
The assumption that catecholamines are, at least partially, responsible for skin flap necrosis raised the question whether the use of alpha-adrenergic blocking agents or of catecholamine depleting agents will overcome this harmful effect. We describe our experimental work using three compounds (phentolamine (Regitine), phenoxybenzamine (Dibenzyline), and 6-hydroxydopamine) on flap survival in rats. The mechanism of their action is discussed. MATERIAL
AND
METHODS
Seventy five male and female albino rats (SpragueeDawley, approximate 200-g body weight) were divided into six groups (A, B, C, D, E, F), each consisting of 15 rats. Under thiopentone anesthesia their backs were shaved with an electric clipper and a flap based cranially was designed. The width of the flap was 1 cm and the length of the flap was 12 cm. The flaps were dissected at the level of the penniculus carnosus above the muscles of the back, and were handled with great care. Due to the fact that meticulous suturing of the skin edges resulted in complete survival of many flaps, in a control group of 20 rats, it was decided to use seven stitches for one flap only, three sutures on either side of the flap, 3 cm apart from each other, and one suture at the distal end of the flap. All animals were operated on by the authors (Fig. I). Group A served as control and received no treatment. Group B was treated by normal saline. Group C was treated by 2.5 mg/kg of phenoxybenzamine. Group D was treated by 2.5 mg/kg of phentolamine. Group E was
RESULTS All groups treated with either phenoxybenzamine, . phentolamine, or 6hydroxydopamine showed better survival compared to the control Groups A and B. (The results are shown in Table 1.) The best flap survival was obtained in the group that received 6-hydroxydopamine 8 days before separation. The results were statistically evaluated by Student’s t test. The improvement in survival in Groups C, D, E, F were statistically significant (0.0 1
OF SURGICAL
19, 83-87 (1975)
RESEARCH
The Effect
of Phenoxybenzamine,
6-Hydroxydopamine M. R. WEXLER,
Phentolamine
on Skin Flap Survival
M. KALISMAN,
R. YESCHUA,
AND
and
in Rats Z. NEUMAN
Department of Plastic Surgery, Hadassah University Hospital, Jerusalem, Israel Submitted for publication
INTRODUCTION
treated by 2.5 mg/kg of 6-hydroxydopamine in 0.0001 N hydrochlorid acid in saline. Group F was treated like Group E 8 days before separation. Because the 6-hydroxydopamine is rapidly oxyidized this solution was prepared immediately before use. The animals were not anesthetized for the injections, all the injections were administered 4 hr before separation (except Group E), all materials were injected in 1 cc of volume, and all were injected at the base of the flap. All animals were killed on the 8th postoperative day and the surviving part of the flap was measured.
The assumption that catecholamines are, at least partially, responsible for skin flap necrosis raised the question whether the use of alpha-adrenergic blocking agents or of catecholamine depleting agents will overcome this harmful effect. We describe our experimental work using three compounds (phentolamine (Regitine), phenoxybenzamine (Dibenzyline), and 6-hydroxydopamine) on flap survival in rats. The mechanism of their action is discussed. MATERIAL
AND
METHODS
Seventy five male and female albino rats (SpragueeDawley, approximate 200-g body weight) were divided into six groups (A, B, C, D, E, F), each consisting of 15 rats. Under thiopentone anesthesia their backs were shaved with an electric clipper and a flap based cranially was designed. The width of the flap was 1 cm and the length of the flap was 12 cm. The flaps were dissected at the level of the penniculus carnosus above the muscles of the back, and were handled with great care. Due to the fact that meticulous suturing of the skin edges resulted in complete survival of many flaps, in a control group of 20 rats, it was decided to use seven stitches for one flap only, three sutures on either side of the flap, 3 cm apart from each other, and one suture at the distal end of the flap. All animals were operated on by the authors (Fig. I). Group A served as control and received no treatment. Group B was treated by normal saline. Group C was treated by 2.5 mg/kg of phenoxybenzamine. Group D was treated by 2.5 mg/kg of phentolamine. Group E was
RESULTS All groups treated with either phenoxybenzamine, . phentolamine, or 6hydroxydopamine showed better survival compared to the control Groups A and B. (The results are shown in Table 1.) The best flap survival was obtained in the group that received 6-hydroxydopamine 8 days before separation. The results were statistically evaluated by Student’s t test. The improvement in survival in Groups C, D, E, F were statistically significant (0.0 1
