Endothelin receptor blockade improves oxygenation in contralateral TRAM flap tissue in pigs

Partial skin and fat necrosis is the most common complication occurring in TRAM flaps. It is related to disturbances of the microcirculation and oxygenation in the contralateral part of the flap. It may be hypothesised that the development of necrosis is promoted by the vasoconstrictor endothelin, the production of which is enhanced in ischaemic flap tissues. The purpose of this study was to evaluate the effect of tezosentan, a new endothelin receptor blocker, on microcirculation and oxygenation in experimental TRAM flaps. The administration of tezosentan began preoperatively (3 mg/kg body weight) and then continued at a rate of 1.5 mg/kg/h. A TRAM flap with a skin island measuring 16 x 8 cm was raised in the middle of the epigastrium in minipigs. The flap was pedicled on the right superior epigastric vessels. Microcirculatory blood flow was measured with laser Doppler flowmetry and tissue oxygen tension was measured with a Clark-type microprobe. Dominant subcutaneous veins were cannulated in both the ipsilateral and the contralateral parts of the flap. Subdermal tissue oxygen tension in the contralateral part of the flap was significantly reduced 4h after surgery to 5 mmHg (ca. 48 mmHg in normal tissue) in the control group, but to only 12 mmHg in the group that had been administered tezosentan (P< 0.05). Furthermore, tezosentan significantly attenuated venous hypertension (14 mmHg versus 24 mmHg), as well as lactate (4.0 mmol/l versus 5.6 mmol/l) and haemoglobin (10.2 g/dl versus 11.4 g/dl) concentrations in the venous effluent of the contralateral part of the flap, although microcirculatory blood flow remained virtually unchanged. Our findings suggest that tezosentan improves oxygenation and metabolism in the jeopardised contralateral flap tissue, probably as a result of a decrease in venous vascular resistance and fluid extravasation.