# PROLONGED ANOXIA AND RESPONSIVENESS OF BONE VASCULAR BED

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1992 · $115,893

## Abstract

The long term objective of this proposal is to characterize the
autoregulatory humoral control mechanisms of bone blood flow, with
particular emphasis on how these mechanisms may contribute to impaired
bone flow with post-ischemic reperfusion.  Prior work related to this
project has indicated that both alpha1 and alpha2 adrenergic receptors are
important for control of bone vascular smooth muscle tone.  In adequate
dosage, alpha1 receptor blockade may produce nearly complete vascular
muscle relaxation and thus maximal vasodilation.  The specific interests
for this funding period will concern the role of endothelium, anorexia and
bone storage techniques and circulating blood on vasodilation and bone
blood flow with and without alpha adrenergic antagonism.  The major
portion of the study will utilize the cannulated canine tibia placed in an
ex vivo perfusion apparatus using an asanguine oxygenated perfusate.  This
model permits precise control of flow rate, vascular resistance perfusate
composition, pH and temperature and avoids intravascular thrombosis
problems.  The final year of this proposal will employ an in vivo model of
microvascular canine tibia transfer for validation of data derived from
the ex vivo studies.  The investigation will be divided into four phases
of one year each.  The first will evaluate the role of endothelial-derived
chemical mediators on vascular smooth muscle adrenergic receptors
following varying periods of anoxia.  The second phase will determine the
role of optimal storage techniques on preservation of bone vascular
endothelial integrity and smooth muscle receptor responsiveness.  The
third phase will identify the site of action within the bone vascular bed
of vasoconstrictor responses and the relation of vasoconstriction to
arteriovenous shunting and bone tissue bed capillary diffusion.  The final
phase will evaluate in vivo the influence of intraosseous vasodilation on
blood flow, bone cell survival or repopulation and vascular anastomosis
patency with and without prolonged anoxic storage.  The data derived from
this study is expected to be of particular relevance for understanding the
important factors of blood flow regulation in free vascularized autografts
and possibly future applications of vascularized bone allografts.  This
information may be useful for maximizing bone blood flow, intraosseous
cell survival and bone healing.  Many of the mechanisms ellucidated would
be anticipated to be of relevance in understanding bone blood flow
autoregulatory control under physiologic conditions as well.

## Key facts

- **NIH application ID:** 3158718
- **Project number:** 5R01AR038671-06
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** MICHAEL B WOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $115,893
- **Award type:** 5
- **Project period:** 1987-06-01 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158718

## Citation

> US National Institutes of Health, RePORTER application 3158718, PROLONGED ANOXIA AND RESPONSIVENESS OF BONE VASCULAR BED (5R01AR038671-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158718. Licensed CC0.

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