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

Hiroaki Takenaka, Hidemi Oshiro, David D. Kim, Peter N. Thompson, Atsushi Seyama, Robert W. Hobson, Walter N. Durán

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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, and 4) 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 maximal IOI to 9.7 ± 2.0 units (P < 0.05 vs. I/R). In I/R group, plasma TNF levels increased (relative to preischemia baseline) immediately after the release of the vascular occlusion to 250 pg/ml and reached a peak value of 342 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 differences in TNF values during the 6 h of observation. We conclude that protein synthesis and TNF generation are at least partially involved in I/R-induced changes in microvascular transport.

Original languageEnglish (US)
Pages (from-to)H1914-H1919
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume274
Issue number6 43-6
DOIs
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • Actinomycin D
  • Deoxyribonucleic acid transcription
  • Ischemia-reperfusion injury
  • Skeletal muscle
  • Tumor necrosis factor

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