Wil J. Kort

The effect of cigarette smoking on the survival of free vascularized and pedicled epigastric flaps in the rat

&NA; Microsurgeons suspect that cigarette smoking reduces the survival of free vascularized flaps and replantations, but this has never been proven. This experimental study investigates the effect of smoking on free‐flap survival. A fasciocutaneous epigastric flap was used in 30 rats as a free flap and in 30 rats as a pedicled flap. Of each group, 10 rats were smoked 6 weeks before and 2 weeks after surgery, 10 rats were smoked only 6 weeks before surgery, and 10 rats underwent the sham smoking procedure. Also, a distally based dorsal skin flap was cut in all rats, representing a random vascularized flap. Vitality and size of both flaps and patency of the vascular anastomoses were assessed 14 days after surgery. The epigastric flaps were monitored by laser Doppler flowmetry and thermometry during the experiment. Survival of the free vascularized epigastric flaps was significantly lower in smoking rats. All pedicled flaps except one survived. The epigastric flaps only necrosed or survived completely, exactly correlating to the patency of the vascular anastomoses. The mean surviving area of the dorsal flaps was best for nonsmoking rats, worse for only preoperatively smoking rats, and worst for preoperatively and postoperatively smoking rats. The differences were statistically significant. Postoperative laser Doppler flow differed significantly between surviving and dying flaps, affirming the value of laser Doppler flow monitoring in microvascular surgery. In conclusion, this study proves that smoking of cigarettes is detrimental to the survival of free vascularized flaps. (Plast. Reconstr. Surg. 97: 86, 1996.)

Healing of ischemic colonic anastomosis: Fibrin sealant does not improve wound healing

Fibrin adhesives have been advocated as a protective sealant in high-risk colonic anastomoses to prevent leakage. To assess the effect of fibrin glue sealing on the healing ischemic anastomosis, we compared the healing of sutured colonic anastomoses in the rat, with and without fibrin adhesive (Groups IA and IB), and ischemic anastomoses with and without fibrin adhesive (Groups IIA and IIB). On days two, four, and seven, 10 animals in each group were sacrificed. Adhesion formation was scored, and thein situbursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was more prominent in Groups IB, IIA, and IIB on day four only; abscesses were noted in the ischemic group in four rats. Anastomotic bursting pressure was significantly lower in sealed (IB) and ischemic anastomoses (IIA) than in normal anastomoses (IA) on day four. Sealing of ischemic anastomoses did not change bursting pressures on days two, four, and seven. The relative decrease of collagen in the sealed anastomoses is significantly higher on day four only. It is concluded that sealing of normal colonic anastomoses in the rat has a negative effect on wound healing. Ischemia at the anastomotic site results in weaker anastomotic strength on day four postoperatively. Also in ischemic anastomoses, fibrin sealant does not improve wound healing during the first seven days. Adhesion formation on ischemic intestinal anastomoses was not prevented by fibrin sealing.

Clinical application of transcutaneous oxygen measurements in replantation surgery and free tissue transfer

In 65 replantations and 18 free tissue transfers (6 toe-to-thumb and 12 free flaps) transcutaneous oxygen levels were used as a postoperative monitoring system of the microcirculation. In successful replants and successful free tissue transfers an identical pattern of oxygen levels was observed. In failing replants or free tissue transfer, PO2 levels react immediately to changes in microcirculation and these changes in PO2 appear several hours earlier than the clinical symptoms or changes in temperature. This enables salvage operations after circulatory failure caused by thrombosis to be performed before irreversible tissue damage occurs.

Raised Plasma Thromboxane B2 Levels in Experimental Acute Necrotizing Pancreatitis in Rats: The Effects of Flunarizine, Dazoxiben, and Indomethacin

The possible role of thromboxane A2 (TXA2) in acute necrotizing pancreatitis (ANP) was investigated in rats. After ANP was induced by injecting sodium taurocholate (5% w/v) into the pancreatic duct, the thromboxane B2 (TXB2) levels in plasma increased significantly. The effects of indomethacin, a general blocker of prostaglandin synthesis, on survival time and on plasma TXB2 levels were compared with those of dazoxiben, a more specific blocker of TXA2 synthesis, and Flunarizine, a calcium entry blocker known to inhibit the effects of TXA2. In a test group without any treatment, all animals died within 30 h of ANP induction. Although TXB2 levels were lowered by the administration of indomethacin, dazoxiben, and Flunarizine, survival times were not significantly altered. Indomethacin pretreatment had no beneficial effect, whereas 30% and 40% of the animals survived for 36 h after treatment with Flunarizine and dazoxiben, respectively. The results of the present study indicate that inhibition of TXA2 synthesis alone does not dramatically alter survival time. However, a potential role for other arachidonate metabolites in ANP cannot be ruled out by this study.

Effects of long-acting somatostatin analog (SMS 201-995) on eicosanoid synthesis and survival in rats with acute necrotizing pancreatitis

The effects of a long-acting somatostatin analog (SMS 201-995) were studied in an established model of acute necrotizing pancreatitis in rats. SMS 201-995, when given prior to induction of pancreatitis, decreased the mortality rate from 100% to 40% (P=0.0001). When treatment was given after induction of pancreatitis, the mortality rate was 75% (P =0.2). Administration of SMS 201-995 did not influence the serum concentrations of amylase markedly, but the lipase levels were significantly lowered (P<0.05). The low levels of serum insulin and the glucose level in whole blood were not influenced. The volume of ascitic fluid was reduced (P<0.01). Moreover, less peritoneal fat necrosis was seen, suggesting a reduction in toxic factors in the ascitic fluid. Treatment with SMS 201-995 prior to induction of pancreatitis caused a significant increase in the levels of circulating 6-keto-PGF1α, the stable metabolite of prostaglandin I2 (P<0.01). The levels of thromboxane B2 and prostaglandin E2 did not change significantly. The present data support the hypothesis that SMS 201-995 is an activator of prostaglandin I2, thereby modifying the course of the disease.

Significance of prostaglandin E2 in acute necrotising pancreatitis in rats.

Acute necrotising pancreatitis in rats was induced by injecting 5% sodium taurocholate into the pancreatic duct. Prostaglandin E2 (100 micrograms/kg subcutaneously twice) decreased the mortality rate from 100% to 60% (NS). When treatment with prostaglandin E2 was combined with simultaneous administration of either dazmegrel (UK 38,485, 50 mg/kg bodyweight) or Sibelium (Flunarizine R 14,950, 0.2 mg/kg body weight) a significant decrease in the mortality rate (p less than 0.05) was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and prevents the formation of thromboxane A2. Flunarizine (a calcium entry blocker) decreases thromboxane A2 formation and also inhibits the effects of raised thromboxane A2 concentrations. As plasma thromboxane B2 (the stable metabolite of thromboxane A2) concentrations increase and the plasma prostaglandin E2 concentrations decrease in acute necrotising pancreatitis in rats, the results of the present study indicate that these prostaglandins play a role in the pathophysiology of the disease. It is suggested that restoration of the balance in prostanoid concentrations will have a beneficial effect on the course of acute necrotising pancreatitis.

Prostanoid Imbalance in Experimental Acute Necrotizing Pancreatitis in Rats

In an investigation of the pathogenesis of acute necrotizing pancreatitis (ANP) the plasma levels of TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in rats. After induction of ANP by injection of 5% sodium taurocholate into the pancreatic duct, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF 1 alpha levels were found. PGE2 levels decreased. Mortality was 100% within 30 h. Pretreatment with chloroquine, a phospholipase A2 inhibitor, led to a inhibition of TXB2 production, whereas 6-keto-PGF1 alpha and PGE2 levels showed a surprising slight elevation in the first 6 h. Pretreatment with chloroquine decreased mortality by 30%. Pretreatment with FPL 55712, a leukotriene synthesis blocker, caused an increase in TXB2 and PGE2 levels, whereas the formation of 6-keto-PGF1 alpha remained unaltered. Two out of nine animals survived after pretreatment with FPL 55712. The results of the present study indicate that arachidonate end products are involved in ANP. The significance of the high TXB2 levels, decreased PGE2 levels, and only slightly elevated 6-keto-PGF1 alpha levels during ANP requires further investigation. The thromboxane A2 to prostacyclin ratio may be important.

Significance of thromboxane A2 and prostaglandin I2 in acute necrotizing pancreatitis in rats

Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5% sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100% to 50%. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14 950, 0.2 mg/kg body weight) or dazmegrel (UK 38 485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P<0.05); with dazmegrel and iloprost it was 10% (P<0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis.

Improvement in Blood Flow and Diameter of the Postanastomotic Rat Tail Artery by Topical Application of Lidocaine in Varying Concentrations

Prolonged spasm in small vessels is a major problem after microsurgical procedures. Topical agents applied to resolve these spasms have been the subject of many experimental studies. In this model we studied the effectiveness of various concentrations of lidocaine in resolving microvascular spasms induced by anastomosing the ventral rat tail artery.

Dietary Fatty Acids and Kidney Transplantation in the Rat

In five groups of 15 rats allogeneic kidney transplantations were performed. Four groups received pre- and postoperatively a semisynthetic diet, isocalorically but differing in quantity and quality of fatty acids: group I received a diet high in saturated fat; group II, a diet high in linoleic acid; group III, a diet containing fish oil; group IV, a diet high in monoenoic acid. Finally, the fifth group of rats was fed a standard commercial chow and served as a control for the procedure of technique and immunological regimen. All groups received the same immunosuppressive regimen of immunological enhancement induced by pretreatment with complete donor blood. Survival and several parameters of graft function were studied. The results showed that the technical mortality, i.e. animals dying in the first week after transplantation, was substantially higher in rats on the semisynthetic diets in comparison with the group of rats on the commercial diet. A statistically significant better graft function could be observed in the group of rats on the diet high in linoleic acid in the first period after kidney transplantation, compared to the other groups on semisynthetic diets. This difference disappeared in the course of the study when a number of animals was lost due to graft rejection. Furthermore, in the same diet group mortality due to rejection was significantly decreased as well.