Novel method to assess arterial insufficiency in rodent hind limb

Matthew A. Ziegler, Matthew R. Distasi, Steven Miller, Michael Dalsing, Joseph L. Unthank

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hind limb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. Materials and methods VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young, healthy rats (Wistar Kyoto, WKY; lean Zucker rats, LZR) and rats with cardiovascular risk factors (spontaneously hypertensive [SHR]; obese Zucker rats [OZR]) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. Results VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. Conclusions The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in preclinical rodent models.

Original languageEnglish (US)
Pages (from-to)170-180
Number of pages11
JournalJournal of Surgical Research
Volume201
Issue number1
DOIs
StatePublished - Mar 1 2016

Fingerprint

Rodentia
Extremities
Zucker Rats
Muscle Contraction
Perfusion
Ramipril
Losartan
Ischemia
Veins
Therapeutics
Animal Disease Models
Intermittent Claudication
Femoral Vein
Inbred WKY Rats
Femoral Artery
Thigh
Muscles

Keywords

  • Arterial insufficiency
  • Arterial occlusion
  • Arterial reserve capacity
  • Preclinical models
  • Venous flow

ASJC Scopus subject areas

  • Surgery

Cite this

Novel method to assess arterial insufficiency in rodent hind limb. / Ziegler, Matthew A.; Distasi, Matthew R.; Miller, Steven; Dalsing, Michael; Unthank, Joseph L.

In: Journal of Surgical Research, Vol. 201, No. 1, 01.03.2016, p. 170-180.

Research output: Contribution to journalArticle

Ziegler, Matthew A. ; Distasi, Matthew R. ; Miller, Steven ; Dalsing, Michael ; Unthank, Joseph L. / Novel method to assess arterial insufficiency in rodent hind limb. In: Journal of Surgical Research. 2016 ; Vol. 201, No. 1. pp. 170-180.
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N2 - Background Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hind limb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. Materials and methods VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young, healthy rats (Wistar Kyoto, WKY; lean Zucker rats, LZR) and rats with cardiovascular risk factors (spontaneously hypertensive [SHR]; obese Zucker rats [OZR]) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. Results VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. Conclusions The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in preclinical rodent models.

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