Microvascular transport is associated with TNF plasma levels and protein synthesis in postischemic muscle

To better understand the mechanisms of ischemia-reperfusion (I/R) injury, we tested the hypothesis that protein synthesis is involved in the production of tumor necrosis factor (TNF) and in the microvascular transport changes in I/R. To evaluate the hypothesis, we inhibited protein synthesis with topically applied actinomycin D (AMD), measured I/R-induced changes in microvascular transport, and bioassayed the venous plasma levels of TNF. The rat cremaster muscle I/R model consisted of 4 h of ischemia followed by 2 h of reperfusion. Changes in transport were determined by integrated optical intensity (IOI) using FITC-Dextran 150 as tracer. Animals were separated into four groups:1) control (C),2) control treated with AMD (C + AMD), 3) I/R, and4) I/R treated with AMD (I/R + AMD). The mean (±SE) maximal IOI in C and C + AMD were 3.0 ± 1.0 and 3.7 ± 0.7 units, respectively. I/R elevated mean maximal IOI to 21.8 ± 1.9 units (P < 0.05 vs. C, C + AMD, I/R + AMD). Treatment with AMD reduced the I/R-induced mean m...