Carvedilol reduces ischaemic skeletal muscle necrosis

Carvedilol is an alpha, and nonselective beta-adrenergic receptor antagonis t with antioxidative properties known to protect against reperfusion injury in the heart, brain, and kidneys. The aim of this study was to test the hy pothesis that carvedilol improves postischaemic reperfusion and tissue surv ival in skeletal muscle. Sixteen Wistar rats underwent tourniquet ischaemia of the left hindlimb for 3 hours and 15 minutes at 27 degrees C. Single-fi ber laser Doppler probes were inserted in the left and right anterior tibia l muscles, and microvascular perfusion was measured until 2 hours after rem oval of the tourniquet. Perfusion indices for each 15-minute interval were calculated for the left hindlimb (tourniquet ischaemia) by dividing the pos tischaemic by the pre-ischaemic laser Doppler flowmetry values, and the geo metrical areas under the curves representing a plot of perfusion index rela tive to time, measured in arbitrary units, were compared. Laser Doppler flo wmetry values for the right anterior tibial muscle were compared. Tissue da mage was measured by histomorphometry of necrotic areas and no-reflow zones in cross sections from the anterior tibial muscle 72 hours after ischaemia . Neutrophils were counted in the same sections. The treatment group receiv ed I mg carvedilol/kg body weight before ischaemia and 1 mg/kg immediately before removal of the tourniquets, The areas under the curves representing the plot of perfusion index relative to time were larger for the rats treat ed with carvedilol: 9.5 compared with 3.0 arbitrary units (p = 0.0003). Tre atment did not change the laser Doppler flowmetry values for the right hind limbs. The histomorphometric areas of necrosis in cross sections from the m uscles were reduced from 88% (38-96%) in the control animals to 41% (7-85%) in those treated with carvedilol (p = 0.01), and the area of no-reflow was reduced from 20% (2-52%) to 0% (0-7%) (p = 0.006). The number of neutrophi ls did not differ between groups. The study supports the hypothesis that ca rvedilol improves early reperfusion and protects skeletal muscle subjected to 3 hours and 15 minutes of ischaemia.