# CIRCULATORY AND METABOLIC ADAPTATIONS IN ISCHEMIC LIMBS

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1989 · $163,878

## Abstract

This project will probe for and document the adaptive response of
limb muscle to a limited blood supply.  The overall goal of this
project is to test for the existence and document the
characteristics of the dynamic and adaptive interrelationships
among (1) total limb blood flow and blood flow to a specific
skeletal muscle (gastrocnemiusplantaris), (2) the capacity of calf
muscle to perform work, and (3) the metabolic co of this work
during graded intensities of steady-state exercise of the normal
rat.  We will focus on the ischemic lower limb of the rat as an
animal model and study it at intervals after ligation of the
superficial femoral artery and in response to graded exercise
training.  We will assess the high-energy phosphate metabolic
state, intracellular pH, and muscle mechanical performance
during the phases of acute and chronic ischemia, both at rest and
in response to stimulation.  The mechanical work will be assessed
by measuring the muscle force during nerve stimulation.  The
metabolic cost of this contractile activity will be assessed from
the changes in muscle content of high-energy phosphate
compounds measured by nuclear magnetic resonance 31P
spectroscopy.  Content of key metabolic enzymes and isoforms of
myosin and other proteins will be measured.  We will document by
angiography the time course and extent of collateral circulation
development, and assess its functional capacity by direct blood
flow measurements.  We will test the hypotheses that the normal
and ischemic limb is both hemodynamically and biochemically
adaptable, and that the adaptive responses to femoral artery
ligation and stenosis are similar to those occurring in normal
exercise training.  Our working hypothesis is that, with a
reduction in flow that disturbs the balance between energy supply
and demand, there is an adaptation not only of the vasculature but
also the mechanical, myosin and other protein isoenzymes and
metabolic characteristics of the limb musculature.  The
postulated adaptations are expected to be those that decrease the
metabolic cost per unit work, i.e., adaptation towards a more
aerobic and slow-twitch muscle.  Our long range objective is to
work out these same parameters with respect to patients with
peripheral vascular disease.

## Key facts

- **NIH application ID:** 3158791
- **Project number:** 5R01AR038782-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** Martin J Kushmerick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $163,878
- **Award type:** 5
- **Project period:** 1988-10-01 → 1992-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158791

## Citation

> US National Institutes of Health, RePORTER application 3158791, CIRCULATORY AND METABOLIC ADAPTATIONS IN ISCHEMIC LIMBS (5R01AR038782-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158791. Licensed CC0.

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