Increased experience with free-tissue transfer has minimized flap loss secondary to microvascular thrombosis, yet pharmacologic antithrombotic prophylaxis continues to be used routinely. Currently there is no consensus on the ideal pharmacologic agent, dosing, or efficacy. Low-molecular-weight dextran has been widely used for prophylaxis due to its properties of volume expansion and enhanced microrheology. Significant systemic morbidity (pulmonary morbidity, cardiac morbidity, anaphylaxis) is known to occur with use of low-molecular-weight dextran. The purpose of this study was to evaluate morbidity associated with postoperative low-molecular-weight dextran and aspirin prophylaxis in head and neck microsurgery patients. This study was a randomized prospective analysis of 100 consecutive patients undergoing microvascular reconstruction for head and neck malignancy during a 2-year period. Patients were randomized into one of three postoperative antithrombotic prophylaxis treatment groups: low-molecular-weight dextran 20 cc/hour for 48 hours (n = 35), low-molecular-weight dextran 20 cc/hour for 120 hours (n = 32), or aspirin 325 mg/day for 120 hours (n = 27). Six patients were excluded intraoperatively due to the need for systemic heparin therapy. Treatment groups were compared for age, sex, prior medical problems, duration of anesthesia, and intraoperative fluid intake. Flap outcome and the incidence of local and systemic complications were evaluated in the treatment groups. Patient ages ranged from 12 to 84 years (mean age, 58 years). No significant difference was found among the treatment groups with respect to age, sex, prior medical problems, duration of anesthesia, intraoperative fluid intake, and the distribution of donor and recipient sites. There were no total flap losses and two partial flap losses in this series. Three flaps were reexplored and all were salvaged. The incidence of systemic complications (congestive heart failure, myocardial infarction, pulmonary edema, pleural effusion, and pneumonia) was as follows: low-molecular-weight dextran 120 hours, 51 percent; low-molecular-weight dextran 48 hours, 29 percent; and aspirin, 7 percent. Analysis of these data suggests that the method of prophylaxis had no effect on overall flap survival. However, the incidence of systemic complications was significantly related to the method of prophylaxis, with patients receiving low-molecular-weight dextran 120 hours and 48 hours at a 7.2 and 3.9 times greater relative risk, respectively, of developing a systemic complication compared with patients receiving aspirin. The results of this study have eliminated the routine use of low-molecular-weight dextran prophylaxis at our institution in an effort to reduce morbidity in head and neck microsurgical reconstruction.

To establish a successful model of heterotopic total small intestinal transplantation (SIT) in rats in order to reduce the complications and increase the survival rate.

A total of 196 Wistar rats underwent heterotopic SIT with microsurgical technique. Technical modifications included shortening fasting time and supplying energy before surgery, administering optimal volume of crystalloid fluid to the donor and recipient during surgical procedures, reducing mechanical and ischemic injuries to donor intestine, revascularizing small intestinal graft with a combination of conventional aorta to aorta anastomosis and a cuffed portal vein to left renal vein anastomosis which resulted in an acceptably short warm ischemic time, and also an adequate blood supply and drainage of the graft.

The average time for the donor surgery was 86 min +/- 20 min, the mean operative time for the recipient was 115 min +/-20 min and warm ischemia time was shortened to 40 min +/- 5 min. There was a shorter revascularizing time of the graft, the abdominal aorta (AA) to AA anastomosis being 21 min +/- 10 min, and the cuffed portal vein (PV) to the renal vein anastomosis being 5 min +/- 5 min. The one-week survival rate of 98 rats with SIT was 88.78% (87/98), without thrombosis and stenosis of anastomosis. The longest survival time of recipient rats was more than 389 days after SIT, the rats were maintaining normal weight, with perfect intestinal function and intact intestinal histology.

These modified techniques for SIT would remarkably reduce the complications and improve survival rate in rats, which provided a potentially more consistent and practical model for experimental and clinical studies.

In free flap/replantation surgery, failure is usually associated with thrombotic occlusion of a microvascular anastomosis (risk zone I) or, on occasion, flow impairment in the microcirculation of the transferred or replanted tissue (risk zone II). The objective of this study is to describe the effect of low dose aspirin on blood flow at both risk zones in microvascular surgery. Risk zone I: In rat femoral arteries and veins, thrombus formation was measured at the anastomoses using transillumination and videomicroscopy. Forty male Wistar rats were assigned in equal numbers to four groups: either arterial or venous injury with either aspirin (5 mg/kg systemically) or saline treatment. We found that aspirin significantly reduces thrombus formation at the venous anastomosis (p = 0.001). Risk zone II: In the isolated rat cremaster muscle downstream from an arterial anastomosis, we measured capillary perfusion, arteriolar diameters, and the appearance of platelet emboli for 6 hours in the muscle microcirculation. Sixteen male Wistar rats in two equal groups received either aspirin (5 mg/kg systemically) or saline. We found that in aspirin-treated animals, capillary perfusion is significantly (p = 0.002) improved, whereas arteriolar diameters and emboli only slightly increased. In conclusion, low dose aspirin inhibits anastomotic venous thrombosis and improves microcirculatory perfusion in our rat model. These studies provide quantitative data confirming and clarifying the beneficial effects of low dose aspirin in microvascular surgery.

A common cause of free flap and replant failure is thrombotic occlusion of the anastomosed pedicle vessel(s). Clinical observations and subsequent experimental studies showed that platelet emboli generated at the arterial anastomosis caused significant alterations in the downstream microcirculation. To study both the thrombogenic arterial (anastomosis) site and the downstream microcirculation, we developed an animal model (the isolated rat cremaster) in which we could directly view and quantitatively analyze thrombus formation and the appearance of emboli in the downstream microcirculation. Using this model we studied the effect that reducing blood flow across the arterial anastomotic site had on thrombus formation at the anastomotic site and the appearance of emboli in the downstream microcirculation. In 40 male Sprague-Dawley rats we found that reducing blood flow velocity to approximately half of normal during reperfusion nearly eliminated emboli appearing in the downstream microcirculation compared with controls, 43.9 +/- 31.5 vs. 259.5 +/- 117.8 emboli, respectively. We also found that the same low flow had no effect on thrombus size at the pedicle artery injury site yet significantly decreased the rate at which thrombus formation occurred (time to maximum thrombus size; low flow = 25.3 +/- 8 minutes, normal flow = 6.6 +/- 3 minutes). From these studies we conclude that reducing pedicle artery blood flow in our rat model during reperfusion can protect the down-stream microcirculation from platelet emboli-induced injury; however, the same reduction in flow does not affect thrombus formation in the pedicle artery. Further studies using direct observation/measurement techniques are needed for a better understanding of the mechanisms regulating free flap and replant failure.

The ultimate goal in microvascular surgery is to achieve improved patency rates while reducing complications of systemic antithrombotic agents. Using a described model of microarterial thrombosis, the antithrombotic effects of oral aspirin (ASA) were assessed in rats. ASA-treated animals (30 mg/kg orally) exhibited significantly prolonged mean bleeding times 1 h and 24 h after dosing when compared to controls (p < 0.01). Platelet aggregation profiles also displayed an inhibition of platelet aggregation in the ASA group relative to controls. In the thrombosis model, however, patency rates were significantly improved at 20 min, but all vessels were thrombosed at 24 h.

Ketorolac tromethamine (Toradol), a potent nonsteroidal anti-inflammatory drug used for postoperative pain, also strongly inhibits platelet aggregation. The anti-thrombotic effects of intramuscular ketorolac were assessed with a described rat model of microarterial thrombosis. After a single dose of ketorolac mean bleeding times were significantly prolonged (p < 0.01) and platelet aggregation was markedly reduced. Patency rates at 20 min were significantly higher in ketorolac groups compared to controls (p < 0.005). However, all vessels were thrombosed at 24 h. Scanning electron microscopy demonstrated decreased platelet aggregation and decreased thrombus formation in ketorolac treated animals at 20 min. The prolonged bleeding time and reduction in platelet aggregation add support to concerns of bleeding complications reported in patients treated with ketorolac perioperatively. Thus, ketorolac should probably not be used for pain relief in patients in whom postoperative haematoma formation is a particular concern. In addition, in this model, ketorolac as a single agent was ineffective for long-term prevention of microarterial thrombosis.

The use of heparinised irrigation solutions has become common in microvascular surgery, but the concentration of heparin has been determined empirically. A laboratory model of microvascular thrombosis, employing a crush injury, intimal abrasion, and stasis to the rat superficial femoral artery was used to compare heparinised saline irrigation solutions of various concentrations. The solutions included normal saline (Group I, controls) and heparinised normal saline in concentrations of 10 U/ml (Group III), 250 U/ml (Group IV), and 500 U/ml (Group V). Group I animals had a patency rate of 25% at 20 min and 0% at 24 h. Group II showed a patency rate of 75% at 20 min but fell to 37.5% at 24 h. Patency in Group III was 87.5% at 20 min and at 24 h. Group IV had a 100% patency rate at 20 min and at 24 h. Group V animals were 100% patent at 20 min and 87.5% patent at 24 h. The activated partial thromboplastin time was prolonged in animals exposed to 250 U/ml and 500 U/ml of heparinised saline. Patency was significantly improved in animals exposed to 100 U/ml, 250 U/ml and 500 U/ml when compared to the control group (p less than 0.001). These results suggest that topical heparinised saline administration is of benefit in the prevention of microvascular thrombosis. Higher concentrations tested in this study resulted in a significant increase in patency, but also prolonged the activated partial thromboplastin time. 100 U/ml is the ideal concentration of heparinised saline irrigation because it significantly improved patency but did not produce detectable systemic effects in this model.