Local Temperature Regulation of Microtissue Clearance from Rat Skeletal Muscle

Hyman, Chester; Paldino, Rita L.

doi:10.1161/01.res.10.1.89

Cited by 18 publications

(14 citation statements)

References 16 publications

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“…The fluorescent probe DAF‐FM cannot penetrate the cell membrane and is distributed only throughout the interstitial space of a muscle. The concentration of the low molecular weight dye in the interstitial space of a muscle decreases with time because of indicator washout (clearance), which in the spinotrapezius muscle is reported to be a simple mono‐exponential process (Hyman & Paldino, ; Hyman et al . ).…”

Section: Methodsmentioning

confidence: 99%

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Muscle contraction increases interstitial nitric oxide as predicted by a new model of local blood flow regulation

Golub

Song

Pittman

2014

The Journal of Physiology

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Key pointsr The metabolic theory of blood flow regulation suggests that, when tissue cells experience a reduction of oxygen supply, they produce metabolic vasodilators, which increase the lumen of arterioles and hence local blood flow.r A century of intensive research has not found a single metabolic vasodilator to account for observed flow changes, therefore current thought is that there are many vasodilators.r We have proposed an alternative hypothesis based on the interaction of two well-known molecular mechanisms for generation and removal of the intercellular signalling radicals nitric oxide (NO) and superoxide.r The proposed mechanism of regulation predicts a sharp increase in NO concentration in the intercellular space at the onset of muscle contraction.r Experiments with the NO-sensitive fluorescent indicator DAF-FM, loaded into the intercellular space, confirmed the rapid response of the NO-related signal at the beginning of contractions and rapid washout of the indicator after their termination. AbstractThe prevailing metabolic theory of local blood flow regulation suggests the dilatation of arterioles in response to tissue hypoxia via the emission of multiple metabolic vasodilators by parenchymal cells. We have proposed a mechanism of regulation, built from well-known components, which assumes that arterioles are normally dilated in metabolically active tissues, due to the emission of NO by the endothelium of microvessels. Regulation of local blood flow aims at preventing an excessive supply of oxygen (O 2 ) and glucose to the tissue and thus provides an adequate supply, in contrast to the metabolic regulation theory which requires permanent hypoxia to generate the metabolic vasodilators. The mediator of the restrictive signal is superoxide anion (O 2 − ) released by membrane NAD(P)H oxidases into the interstitial space, where it neutralizes NO at a diffusion-limited rate. This model predicts that the onset of muscle contraction will lead to the cessation of O 2 − production, which will cause an elevation of interstitial NO concentration and an increase in fluorescence of the NO probe DAF-FM after its conversion to DAF-T. The time course of DAF-T fluorescence in contracting muscle is predicted by also considering the washout from the muscle of the interstitially loaded NO indicator. Experiments using pulse fluorimetry confirmed an increase in the interstitial concentration of NO available for reaction with DAF-FM during bouts of muscle contraction. The sharp increase in interstitial [NO] is consistent with the hypothesis that the termination of the neutralizing superoxide flow into the interstitium is associated with the activation of mitochondria and a reduction of the interstitial oxygen tension. The advantage of the new model is its ability to explain the interaction of metabolic activity and local blood flow through the adequate delivery of glucose and oxygen.

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Section: Methodsmentioning

confidence: 99%

“…Stimulated muscle contraction is known as the cause of active hyperaemia, which changes the clearance rate for both forms of the indicator (Hyman & Paldino, ; Hyman et al . ).…”

Section: Methodsmentioning

confidence: 99%

Muscle contraction increases interstitial nitric oxide as predicted by a new model of local blood flow regulation

Golub

Song

Pittman

2014

The Journal of Physiology

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“…13 In "reactive hyperemia" clearance was measured by following disappearance of 4% Water Blue from a single micro-injection site before, during, and for 5 to 10 minutes after a period of occlusion. Blood flow to the muscle was stopped for periods of 30 seconds to 8 minutes by increasing the tension of a polyethylene loop around the viewing cylinder.…”

Section: Effective Blood Flow In Rat Skeletal Musclementioning

confidence: 99%

Local Regulation of Effective Blood Flow in Muscle

Hyman

Paldino

Zimmermann

1963

Circulation Research

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The techniques of macro- and micro-tissue clearance were used to study reactive hyperemia. Clearance of radioactive iodide from gross injection sites in muscles of rabbits and clearance of micro-injected diffusible dye from the exposed, directly observed spinotrapezius of rats gave evidence for an exact quantitative repayment of effective blood flow debt. In both types of preparation a subnormal clearance followed a thermally induced hyperemia as an apparent compensation. The exact quantitative repayment and compensation support the hypothesis that local effective blood flow is in a steady-state relation to the local concentration in tissue fluid of some agent with vasodilating properties. It is suggested that an extension of this method to studies of vasodilatation induced by drugs or other chemicals might offer an approach to identification of the normal vasodilator, and to physiological proof of its exact nature.

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“…On the other hand, the hyperemia induced by reflex heating does not change the capillary filtration coefficient (18). These stimuli differ in at least two ways: immersion in water for prolonged periods may modify the temperature and blood flow of the deeper tissues (21), while the effects of reflex heating are clearly restricted to the more superficial tissues (10); and second, increased tissue temperature raises local metabolism of all the tissues and thus acts directly on all vascular smooth muscle in the segment (22). Microcirculatory dynamics would be affected differently by the more restricted, directed ivasomotor nervous impulses.…”

Section: Hyman Wongmentioning

confidence: 99%

“…Theoretically, the capillary filtration coefficient might reflect three relatively independent changes: (1) an increase in capillary filtration area, (2) a shift in the ratio of preto postcapillary resistance, or (3) diversion of flow to distensible tissues where edema causes minimal tissue pressure increase. Local heating in other systems has been shown to increase the rate of removal of water-soluble crystalloids (22); if interpreted as an increase in the number of patent capillaries, this might be expected to increase capillary filtration coefficient. That the second mechanism may operate in reflex heating is implied by work on animals (4), and by the direct capillary pressure measurements in human skin reported by Landis (23).…”

Section: Hyman Wongmentioning

confidence: 99%

Capillary Filtration Coefficient in the Extremities of Man in High Environmental Temperatures

Hyman

Wong

1968

Circulation Research

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The capillary filtration coefficient was measured in human extremities by a simplified technique using the capacitance plethysmograph. The method was validated in terms of consistency of values obtained on the same individual at various times, the correspondence between values obtained on a group of normal persons, and the agreement between values reported here and those of earlier workers made under corresponding environmental conditions and duration of measurement after venous occlusion. The technique was used to evaluate the change in capillary filtration coefficient in the calves of subjects when ambient temperature was increased from 20° to 35°C. Corresponding measurements of total blood flow in this segment and determinations of the clearance of iodide ion from pretibial intradermal depots were made in both environments. Cutaneous blood flow increased by almost 170% and the capillary filtration coefficient by about 40%, whereas the clearance did not change. It is concluded that neither the capillary filtration coefficient nor the clearance of isotopes from tissue depots has been established as a valid measure of capillary surface area. The possibility that during venous occlusion, fluid accumulated primarily in the subcutaneous tissues of the extremity is suggested and discussed.

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Local Temperature Regulation of Microtissue Clearance from Rat Skeletal Muscle

Cited by 18 publications

References 16 publications

Muscle contraction increases interstitial nitric oxide as predicted by a new model of local blood flow regulation

Muscle contraction increases interstitial nitric oxide as predicted by a new model of local blood flow regulation

Local Regulation of Effective Blood Flow in Muscle

Capillary Filtration Coefficient in the Extremities of Man in High Environmental Temperatures

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