Transvascular protein movement in the intact ischemic hindlimb

Postischemic limb swelling following reperfusion may be related to microvascular changes associated with ischemia. We used lymph-to-plasma total protein concentration ratios ( L P) and lymph flow (Q_L) as an index of transvascular exchange in the intact dog hindlimb during steady state (C) (1 hr), ischemia (I) (6 hr), and reperfusion (R) (3 hr). Central pressures, femoral arterial and venous pressures (P_A, P_V), and Q_L were recorded every 15 min. Lymph was collected from a femoral lymphatic in the passively flexed leg (50 cycles/min). Three groups of animals were studied: GI, sham-operated (N = 5); GII, moderate ischemia (N = 7, P_A = 30-45% C); and GIII, severe ischemia (N = 7, P_A = 5-20% C). In GI, Q_L gradually increased over 10 hr without change in L P. Moderate ischemia produced a decrease in Q_L, 3.55 ± 2.02 mg/hr to 0.92 ± 0.53 mg/hr (P < 0.0001), and Q_L remained below baseline during R with no change in L P over the 10 hr. Severe ischemia produced a similar decrease in Q_L, 1.91 ± 2.05 mg/hr to 0.15 ± 0.1 mg/hr (P < 0.01); however, an increase to 2.56 ± 2.14 mg/hr occurred during R. Severe ischemia increased L P 0.42 ± 0.08 to 0.64 ± 0.23 (P < 0.001) and remained elevated during R at 0.63 ± 0.18 (P < 0.001). An increase in the wet-to-dry weight ratio of ischemic to nonischemic muscle after reperfusion was noted only in GIII, 3.82 ± 1.17 vs 2.60 ± 0.45 (P < 0.04). Severe ischemia produces changes in vascular integrity which augment protein flow. Prevention of these vascular changes may help to minimize the muscle swelling of reperfusion.