MICROVASCULAR TRANSPORT IS ASSOCIATED WITH TNF PLASMA-LEVELS AND PROTEIN-SYNTHESIS IN POSTISCHEMIC MUSCLE

To better understand the mechanisms of ischemia-reperfusion (I/R) inju ry, we tested the hypothesis that protein synthesis is involved in the production of tumor necrosis factor (TNF) and in the microvascular tr ansport changes in I/R. To evaluate the hypothesis, are inhibited prot ein 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 o f 4 h of ischemia followed by 2 h of reperfusion. Changes in transport were determined by integrated optical intensity (IOI) using FITC-Dext ran 150 as tracer. Animals were separated into four groups: I) control (C), 2) control treated with AMD (C + AMD), 3) I/R, and 4) I/R treate d with AMD (I/R + AMD). The mean +/-SE) maximal IOI in C and C + AMD w ere 3.0 +/- 1.0 and 3.7 +/- 0.7 units, respectively. IIR 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 maximal IOI to 9.7 +/- 2.0 units (P < 0.05 vs. I/R). In I/R group, plasma TNF levels incr eased (relative to preischemia baseline) immediately after the release of the vascular occlusion to 250 pg/ml and reached a peak value of 34 2 pg/ml at 60 min of reperfusion. in the I/R + AMD group, AMD reduced TNF increase to 44 pg/ml. The C and C + AMD groups showed no differenc es in TNF values during the 6 h of observation. We conclude that prote in synthesis and TNF generation are at least partially involved in YR- induced changes in microvascular transport.