Calcium entry blockade prevents leakage of macromolecules induced by ischemia-reperfusion in skeletal muscle

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Abstract

Calcium kinetics and its intracellular mobilization are important in all biological processes. We used verapamil to examine the effect of calcium entry blockade on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate-conjugated dextran (FITC-dextran 150) was measured as an index of microvascular transport. After determination of baseline data (clearance of FITC-dextran 150, 3.0 ± 0.5 μl/5 min/g), the muscle was made ischemic for 2 hours by clamping its vascular pedicle and subsequently was reperfused for 2 hours. Ischemia-reperfusion produced a marked increase in FITC-dextran clearance. After a peak of 12 ± 2-fold increase observed in the first 15 minutes into reperfusion, FITC-dextran 150 clearance decreased in magnitude and stabilized at about sixfold above baseline. Verapamil did not change the baseline clearance values. Importantly, verapamil inhibited the ischemia-induced increase in clearance and maintained the values at or near the baseline levels. We simultaneously determined the rate of release of 6-ketoprostaglandin F(1α) (6-keto-PGF(1α)) and thromboxane B2 (TXB2) into the suffusate. Verapamil decreased the baseline values of 6-keto-PGF(1α) and increased those of TXB2. Verapamil inhibited the ischemia-reperfusion-induced increase in 6-keto-PGF(1α) but did not alter the effect of ischemia-reperfusion on TXB2. Our main results demonstrate the effectiveness of verapamil in preventing microvascular alterations leading to increased leakage of macromolecules.

Original languageEnglish (US)
Pages (from-to)1636-1642
Number of pages7
JournalCirculation Research
Volume66
Issue number6
DOIs
StatePublished - 1990

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology

Keywords

  • calcium entry blockade
  • ischemia-reperfusion injury
  • microvascular permeability
  • prostacyclin
  • skeletal muscle
  • thromboxane A
  • verapamil

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