Vascular rarefaction in peripheral skeletal muscle after experimental heart failure

David J. Nusz, David C. White, Qunsheng Dai, Anne M. Pippen, Michael A. Thompson, G. Brant Walton, Cyrus J. Parsa, Walter J. Koch, Brian H. Annex

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

A decrease in vascular density in peripheral skeletal muscle has been associated with exercise intolerance in humans with congestive heart failure (CHF). The purpose of this study was to determine whether CHF results in a reduction in vascular density in peripheral skeletal muscle. In this established model, CHF was induced by coronary artery ligation in New Zealand White rabbits and sham rabbits that underwent an identical surgical procedure without ligation of the coronary artery. At study termination, rabbits underwent hemodynamic testing and skeletal muscle analysis. The first series of rabbits was divided into sham (n = 6) and CHF (n = 6) 21 days postoperatively. Ten CHF rabbits were then examined 3 (n = 3), 7 (n = 3), and 14 days (n = 4) postoperatively. Vascular density in sham tibialis anterior muscle was 347 ± 41 capillaries/mm2 or 1.20 ± 0.11 capillaries/muscle fiber. In 21-day CHF rabbits, the capillary density was significantly lower, 236 ± 14 capillaries/mm2 or 0.84 ± 0.04 capillaries/muscle fiber (both P < 0.00001 vs. sham); PECAM protein was 2-fold lower (P < 0.0001) in muscle protein lysates; the fraction of apoptotic cells was greater, 3.8 ± 2.2 vs. 0.69 ± 0.56 (P < 0.02 vs. sham) with many TdT-mediated dUTP-biotin nick-end labeling-positive endothelial cells; and Bax protein was 2.8-fold greater (P < 0.0001). By regression analysis, vascular density tended to decrease over time (r 2 = 0.572, P < 0.0001). Vascular rarefaction and endothelial apoptosis develop after experimental CHF and may contribute to the skeletal muscle abnormalities in this disease. Modulating vascular density may provide new approaches to treat exercise intolerance in CHF.

Original languageEnglish (US)
Pages (from-to)H1554-H1562
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
DOIs
StatePublished - Oct 1 2003

Keywords

  • Angiogenesis
  • Apoptosis
  • Congestive heart failure
  • Endothelial cells
  • Growth factors
  • Oxidative metabolism

ASJC Scopus subject areas

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

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