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Relationship of microvascular flow distribution to skeletal muscle metabolism

Newman, John M. B.(John Malcolm B.) 2002 , 'Relationship of microvascular flow distribution to skeletal muscle metabolism', PhD thesis, University of Tasmania.

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Previous research by others led to the proposal that a non-nutritive route in muscle
existed in association with the tendon and connective tissue of muscle. This non
nutritive route could carry a large proportion of flow directed to it under certain
vasomodulatory stimuli including norepinephrine (NE). Research by this laboratory
using the perfused rat hindlimb indicated that there are two types of vasoconstrictors,
A and B. Type A, of which NE and angiotensin II (All) are typical, increase
metabolism, while type B, of which serotonin (5-HT) is representative, decrease
metabolism. The perfused rat hindlimb was used to investigate whether flow
redistribution plays a role in these vasoconstrictor-mediated changes in metabolism.
The infusion of NE at low doses, but not 5-HT caused the release ofred blood cells
from the erythrocyte-free perfused hindlimb. NE also recruited a vascular space in
the hindlimb and trapped FITC-labeled dextran in that space which was released on
subsequent exposure to NE. 5-HT closed off part of the vasculature, which was only
reopened when 5-HT was removed. Both these vascular spaces were slowly cleared.
In addition, NE significantly increased the extent of filling of the arterial vascular
tree, while 5-HT decreased filling as assessed by vascular casts. The redirection of
flow caused by 5-HT was not through arterio-venous thoroughfares since the passage
15µm microspheres was not greatly enhanced compared to basal. All these effects
were in the absence of redistribution of total flow between individual muscle or
between muscle and non-muscle tissues.
In order to determine whether the tendon of muscle was involved in the
redistribution of flow in the perfused hindlimb, FITC labeled dextran was infused
during varying nutritive flow generated by NE and 5-HT. These experiments
showed that the fluorescence of the tendon of the biceps femoris was increased by 5
HT and decreased by NE. Photographs of the tendon vessels of the biceps femoris
highlighted with Indian Ink showed that there was constriction by NE, but
vasodilatation by 5-HT. These data were consistent with the notion that 5-HT
increased flow to the tendon region of muscle while NE denied flow to that region.
The possibility that 5-HT could be denying access to certain areas of the vasculature,
implied that it could deny access of other compounds, specifically type A vasoconstrictors. In a complementary fashion, type A vasoconstrictors may enhance
the delivery of type B vasoconstrictors. A ser!es of experiments were conducted to
test this idea whereby angiotensin II (All) was infused before or after 5-HT. Data
showed that infusion of All before 5-HT enhanced the effectiveness of 5-HT in
terms of both its vasoconstrictive and inhibitory metabolic potential. All was
significantly less effective when infused after 5-HT. The key to 5-HT denying
access to All, was due to its vasodilatory action into the tendon vessels since the
metabolic inhibitory effects of the specific 5-HT2 agonist a-methyl 5-HT (a-MT)
were not enhanced by prior infusion of AIL
Increasing the nutritive flow with NE was found to decrease the microdialysis outflow/inflow (0/1) ratio of 14C-ethanol and 3H20 over a range of perfusion flow
rates. Serotonin, however increased the ratio of both tracers. The addition of the
vasodilator nitroprusside (NP) restored the effects of the vasoconstrictors on the O/I
ratio as well as the constrictive and metabolic changes. These data are consistent
with the notion that as the nutritive flow past the microdialysis probe increased with NE, there was more blood to remove 14C-ethanol and 3H20 from the interstitial fluid
surrounding the probe and so decrease the 0/1 ratio. In the case of 5-HT, the
decrease in nutritive flow led to a decrease in the removal of the tracers by blood and
an increase in the O/I ratio.
A similar set of experiments were also done to investigate the changes in
microdialysis recovery of glucose and lactate in the perfused hindlimb while varying
nutritive flow. The recovery of glucose and lactate were both improved by NE and
All while the interstitial concentration of glucose and lactate were altered to be
closer to their respective arterial values. 5-HT, however, decreased the recovery of
glucose and lactate, while altering the interstitial concentration to be further from
their respective arterial values. The increased flow around the microdialysis probe
with NE and All would allow for greater exchange between the probe, interstitial
fluid and blood, whereas 5-HT would decrease exchange.
All of these data demonstrate that the blood flow distribution within skeletal muscle
has important implications for muscle metabolism with type A vasoconstrictors
improving muscle metabolism by increasing nutritive flow and type B
vasoconstrictors decreasing muscle metabolism by increasing non-nutritive flow.

Item Type: Thesis - PhD
Authors/Creators:Newman, John M. B.(John Malcolm B.)
Keywords: Musculoskeletal system, Cardiovascular system, Oxygen, Microcirculation
Copyright Holders: The Author
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Copyright 2002 the author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (Ph.D.)--University of Tasmania, 2002. Includes bibliographical references

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