Effect of a prostaglandin I2 analogue, beraprost sodium, on burn-induced gastric mucosal injury in rats.

Stress ulcers still have a high mortality in critically burned patients and the pathophysiology remains relatively unknown. Impaired gastric mucosal perfusion is one of the factors contributing to gastric mucosal ulceration. Burn injury causes thrombosis and vascular occlusion by increasing the blood viscosity, resulting in decreased organ perfusion. Reduced blood flow is one of the most important factors in gastric mucosal ulceration. Beraprost sodium is a chemically stable prostaglandin I2 (PGI2) analogue with antiplatelet, vasodilator and cytoprotective actions. In the present study, we examined the effects of a PGI2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn-induced gastric mucosal changes in rats. Twenty male Sprague-Dawley rats weighing an average of 400 g were burned with hot water (90 degree C) and then divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Gastric mucosal blood flow was measured with a laser Doppler flowmeter and the area of mucosal necrosis was also determined macroscopically and histologically. Gastric mucosal damage was significantly reduced in the beraprost sodium-treated rats and gastric mucosal blood flow was significantly improved (p < 0.05). These findings demonstrate that PGI2 plays a very important role in the pathophysiology of burn-induced Curling's ulcer and that beraprost sodium can improve gastric mucosal blood flow and reduce mucosal damage.

A new experimental model of a true myocutaneous flap in the rat: the gluteus maximus myocutaneous flap.

Rat myocutaneous flap models are relatively rare. The authors describe the development of a new myocutaneous flap model using the gluteus muscle in rats. A description of the anatomy of the gluteus maximus is included, along with a method of producing skin-island gluteus maximus myocutaneous flaps that can be pedicled or free. This flap model may serve as a useful tool in laboratory studies of the physiologic or pathologic changes in myocutaneous flaps, and may help to narrow the gap between experimental and clinical applications.

Reduction of progressive burn injury by using a new nonselective endothelin-A and endothelin-B receptor antagonist, TAK-044: an experimental study in rats.

Endothelins are well-known vasoconstrictor peptides produced by vascular endothelial cells that have been reported to have a fundamental role in regulation of the systemic blood circulation. Plasma levels of endothelins are increased by burn injury, which also causes thrombosis and occlusion of vessels in the dermis as well as a vascular response in the adjacent uninjured dermis. Diminished blood flow leads to progressive ischemia and necrosis of the dermis beneath and around the burn (zone of stasis). If blood flow could be restored in this zone, secondary tissue damage would be minimized. In this study we examined the effects of a new nonselective endothelin receptor antagonist, TAK-044 (Takeda Chemical Industries, Ltd., Osaka, Japan), on burn trauma in rats. Fifty male Sprague-Dawley rats weighing an average of 450 gm were burned with a brass probe that produced a row of three burns 10 x 30 mm in size and two intervening unburned areas 5 x 30 mm in size. Rats were divided into five groups of 10 animals. Four groups received 0.01, 0.1, 1 or 10 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Skin blood flow was measured with a laser-Doppler flowmeter, and the development of edema and the area of necrotic tissue also were determined. Inhibition of endothelin activity by TAK-044 after burn injury improved microvascular perfusion in the zone of stasis and prevented the progression of tissue damage in this zone. This supports the role of endothelins in the progression of burn injury in the zone of stasis. TAK-044 was most effective in preventing progressive burn damage at a dose of 1 mg/kg. The extent of necrosis and edema was reduced significantly, and blood flow in the zone of stasis was increased in the treated rats.

Two cases of Merkel cell carcinoma cured by intratumor injection of natural human tumor necrosis factor.

Two patients were treated with intratumor injection of natural human tumor necrosis factor for recurrent or primary Merkel cell carcinoma. In both patients, local chemotherapy achieved complete tumor regression without causing ulceration or scarring. These results suggest that intratumor injection of natural human tumor necrosis factor may be very effective for the treatment of Merkel cell carcinoma.

Reduction of progressive burn injury by a stable prostaglandin I2 analogue, beraprost sodium (Procylin): an experimental study in rats.

Beraprost sodium is a chemically stable prostaglandin I2 analogue with antiplatelet and vasodilator actions. Burn injury causes thrombosis and vessel occlusion by increasing the blood viscosity and by thermal damage to the vascular network in the dermis. A vascular response also occurs in the uninjured dermis surrounding the site of injury. Diminished blood flow and spreading tissue oedema lead to progressive ischaemia and necrosis around the burn site (zone of stasis), with the final necrotic tissue area being larger than the initial one. If blood flow could be restored in the zone of stasis, secondary tissue damage would be minimized. In this study, we examined the effects of a prostaglandin I2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn injury in rats. Twenty male Sprague-Dawley rats weighing an average of 450 g were burned with a comb-shaped brass probe that produced a row of three burns measuring 10 x 30 mm each and two intervening unburned areas measuring 5 x 30 mm each. The rats were divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Skin blood flow was measured with a laser Doppler flowmeter, and the development of oedema as well as the area of necrotic tissue were also determined. The extent of skin necrosis and oedema were significantly reduced in the beraprost sodium-treated rats, and blood flow in the zone of stasis was increased. These findings demonstrate that prostaglandin I2 plays an important role in burn injury and that beraprost sodium can reduce secondary necrosis in the zone of stasis.

Treatment of nevus Ota: combined skin abrasion and carbon dioxide snow method.

Thirty-seven patients with nevus Ota were treated by skin abrasion-carbon dioxide snow therapy. Data obtained from 24 patients (including 5 infants) who completed treatment were analyzed to determine the number of treatment courses and to assess the outcome by color and histologic type. The 5 infants completing treatment received a mean of 10 courses of carbon dioxide snow therapy. Excluding these infants, the mean number of treatment courses was 3 for skin abrasion and 16 for carbon dioxide snow therapy. The therapeutic outcome was satisfactory, being graded as "excellent" in 6 patients, "excellent to good" in 6 patients, "good" in 10 Patients, and "fair" in 2 patients. None of the patients had a "poor" outcome. Darker lesions were generally less responsive to treatment. Lesions with melanocytes in the superficial dermis showed a better response with fewer courses of treatment. Those with melanocytes throughout the whole dermis generally had a poorer outcome. The results confirm that the benefits of this procedure are limited by the associated pain and the need for great skill and a long treatment duration.

Effect of beraprost sodium (Procylin), a stable prostaglandin I2 analogue, on a dorsal skin flap model in rats.

Beraprost sodium, a chemically stable prostaglandin I2 analogue with antiplatelet vasodilator actions, was tested by comparing the extent of viability of random pattern skin flaps in control rats and rats treated with beraprost sodium. An isolated tail based 2 x 7 cm flap was constructed in 50 Sprague-Dawley rats. In group 1 (beraprost sodium treated group, n = 25) 0.015 mg beraprost sodium were injected intraperitoneally immediately after the flap had been raised. In group 2 (control group, n = 25) the animals were injected intraperitoneally with the same volume of saline immediately after the flap had been raised. At the end of the seventh day the flap survival area was documented using digital planimetry. The difference between the results showed that beraprost sodium had significantly beneficial effect on skin flap survival (p < 0.01, Welch's test).

The effect of Beraprost sodium on the survival of subcutaneous transferred jejunum after vascular pedicle interruption in a rat model.

Beraprost sodium, a stable PGI2 analog, having antiplatelet aggregation and vasodilating actions, was tested in a rat subcutaneous heterotopic jejunal model for its ability to improve survival after vascular pedicle interruption. Forth Sprague-Dawley rats were divided into four groups: Group 1 (control, ligation of pedicle on postoperative day 5); Group 2 (Beraprost sodium, ligation on day 5); Group 3 (control, ligation on day 7); and Group 4 (Beraprost sodium, ligation on day 7). The resulting viability rates were: Group 1 = 0 percent, Group 2 = 40 percent, Group 3 = 30 percent, Group 4 = 90 percent. These results indicate that the administration of Beraprost sodium facilitates the neovascularization of the transferred intestine and shortens the time required for viability of the transferred tissue, after interruption of the vascular pedicle.

Pectoralis major myocutaneous flaps in rats.

A new neurovascular, island, myocutaneous flap, including the pectoralis major, was created in a rat model. This model is useful for the observation of muscle degeneration and skin changes due to ischemia or denervation. Although this model requires a delay procedure, it allows the flap, that can be used as a free myocutaneous flap, to be raised reliably.

Morphometric characteristics of cryptotia.

In this study, we measured the normal and affected auricles of patients with cryptotia by the Martin method, quantitatively analyzed the data, and conducted a comparative study. On the basis of auricular measurements, cryptotia is defined as a deformity of the upper one third of the auricle, which develops as a result of the sum total of vectors operating inferiorly and medially. Furthermore, these data showed that the deformity occurring along the vertical axis is greater and that the inferiorly directed vector is stronger than the medially directed vector. A helical adhesion-like deformity was observed in the normal side auricles of 3 patients with unilateral cryptotia, and the hypothesis that the upper portion of the auricle became embedded secondary to a deformity of the cartilage appeared to be valid.

Intestinal tissue pH monitoring in microsurgery: an experimental study in rats.

We monitored the pH of ischemic intestine in rats to determine whether such measurements were a useful method of postoperative monitoring. Measurement of intestinal pH was found to be useful in detecting vascular occlusion, in distinguishing arterial from venous occlusion, and in estimating the time of occlusion. This method of monitoring can be recommended after free intestinal grafting.

Time limits for intestinal ischemia and congestion: an experimental study in rats.

We investigated to determine the time limits for intestinal ischemia and congestion. The experimental models were produced by clamping both ends and the intended feeder vessels of an approximately 1-cm length of rat jejunum. The results showed that in arteriovenous occlusion, the time required for the recovery rate to reach 50% was 7.03 hours. The time required for the recovery rate to reach 50% was 6.81 hours when arterial occlusion alone was performed and 3.70 hours when venous occlusion alone was performed. The difference between the two was statistically significant (p < 0.01). Consequently, it was found that the degree of intestinal damage due to venous occlusion was greater than the damage resulting from arteriovenous and arterial occlusion.

Effects of washing with a neutralizing agent on alkaline skin injuries in an experimental model.

In this report a skin alkaline injury model was constructed using experimental rats and 2 N NaOH. We observed the effects of washing with a neutralizing agent on the subcutaneous tissue pH at 1, 10 and 30 min after injury and compared it with water-washing groups. In comparison with the water washing group, the peak pH values following the use of the neutralizing agent were significantly higher in the 1-min washing group, and significantly lower in the 10-min and 30-min washing groups. Changes in the pH values of the subcutaneous tissue after reaching a peak showed a similar course in the 1-min washing group, whereas in the 10 and 30 min washing groups there was a significantly different rate of decrease of pH. These results indicate that although treatment with a neutralizing agent directly after injury causes harmful effects due to the neutralizing reaction with a highly concentrated alkali. Subsequently with prolonged washing there is an effective reduction of the high pH.

Comparative study of auricular dimensions for the normal auricles of microtia patients, their parents, and normal individuals.

We measured the dimensions of the normal auricle in microtia patients and those of both auricles in their parents, and compared the findings with data obtained in normal individuals. The physiognomical auricular length and width dimensions of the normal auricles in microtia patients were significantly smaller than those in normal individuals. The auricular length of the parents of microtia patients was also significantly smaller than in normal individuals. The auricles of the parents on the same side as those affected by microtia in the patients tended to be smaller than those on the contralateral side.

Epidermal cell viability in rat skin preserved at 4 degrees C.

To determine the longest storage period for the clinical application of epidermal cells and a better method of preservation at 4 degrees C, we stored skin in various fluids and assessed the changes in epidermal cell viability. The time course of changes in the viability of epidermal cells from skin in various preservation fluids was similar to the results obtained with whole skin in previous studies. The best preservation fluid was found to be RPMI 1640 medium, and the best method of preservation was immersion in RPMI 1640 at 4 degrees C with a medium change every 3 days.

Experimental study on alkaline skin injuries--periodic changes in subcutaneous tissue pH and the effects exerted by washing.

A skin alkaline injury model was constructed using rats and 2N-NaOH. The changes over time, paying special attention to subcutaneous tissue pH, were recorded and included a comparative study of the effect on subcutaneous tissue pH of washing with water at 1, 10 and 30 min after injury. After inflicting alkaline injury, the subcutaneous tissue pH reached its peak value at the 32nd minute and had not recovered to the pre-experimental level by the 90th minute. The peak pH values of the 1-, 10- and 30-min delays before washing groups were 7.97, 10.57 and 12.17, respectively. When washing was started within 1 min of injury the tissue pH values did not exceed 8.00. Washing had virtually no effect on lowering the raised pH levels when the delay between injury and the start of washing was 10 and 30 min.

Experimental study of subcutaneously transferred intestine: effect of the presence of serous membrane on acceptance rate.

The serous membrane is considered suspect as one of the obstacles responsible for delaying the acceptance of free jejunal grafts. A model was created of subcutaneous transfer of jejunum from which the serous membrane had been experimentally removed and the authors compared acceptance rates for intestine with and without a serous membrane. Results showed acceptance rates of 0 percent, 37.5 percent, 87.5 percent, and 100 percent respectively, for intestine devoid of serous membrane in which the vascular pedicle had been ligated 4, 5, 7 and 14 days after transfer. When these findings were compared with the results of an experiment on intestine with an intact serous membrane, statistically significant differences were detected between the acceptance rates of the groups ligated 5 and 7 days after transfer. The acceptance time required for intestine devoid of serous membrane was shown to be shorter.

An experimental study of ischemia following subcutaneous heterotopic intestinal graft: influence of arterial or venous occlusion.

A subcutaneously transferred intestinal model was prepared in the rat and experimental observations were conducted of serial histologic changes in the intestine and of acceptance rates, when the artery or vein in the pedicle was ligated at various times after transfer. Results showed 50 percent take in the artery-ligated group and 12.5 percent in the vein-ligated group, when performed 5 days after transfer; 87.5 percent take in the artery-ligated group and 50 percent in the vein-ligated group, when performed 7 days after transfer; and 100 percent take for both groups, when ligation was performed 14 days after transfer. Consequently, it was concluded that venous occlusion constitutes a greater danger to successful transfer of intestine than arterial occlusion.

Treatment of chronic facial palsy by transplantation of the neurovascularized free rectus abdominis muscle.

We performed neurovascularized free rectus abdominis muscle transplantations in two patients with chronic facial palsy. In one patient, the postoperative course was uneventful, but the patient died from rupture of esophageal varices. In the other patient, both morphologic and functional results were satisfactory. Therefore, the rectus abdominis muscle is considered to be a suitable donor for muscle transplantation for the treatment of chronic facial palsy. The rectus abdominis muscle is advantageous in that (1) simultaneous operations by two teams are possible with the patient in the supine position, (2) it is supplied by long nerves and long and large vessels, (3) it is flat and consists of segments with appropriate lengths, (4) the force and distance of contraction are appropriate, and (5) the tendinous intersections are suitable for anchoring sutures.