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Blood Flow in Human Skeletal Muscle: The Effect of Adrenaline and the Influence of a Small Muscle Injury
Dept of Physiology and Pharmacology, Karolinska Institutet. Dept of Hand Surgery, Södersjukhuset .
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A variety of vasoregulatory systems are involved in the complex control of blood flow inhuman skeletal muscle. The interaction between these systems where one system canoverride or modify the other makes blood flow regulation complicated. Determinations ofmuscle blood flow can thus be challenging especially when considering the shortcomingsand limitations of the available measurement methods. This thesis focuses on two differenttopics of which both are dependent on sympathetic tone.

First, the common use of venous occlusion plethysmography (VOP) with only one straingauge attached per limb is a method with obvious pitfalls. The inherent problems with thissimplification of the original VOP method are highlighted in Study I-II where small variationsin sympathetic tone and venous pressure proved to have a considerable influence on theresults. The basic circumstance to this variability is the curvo-linear pressure/volumerelationship in the veins and the fact that redistribution of blood can occur betweenindividual limb segments. The results clearly demonstrate that events taking place underone strain gauge cannot be strictly duplicated in adjacent portions of the limb.

Secondly, recent reports have indicated that a minor muscle trauma might change the localblood flow response to adrenaline. Two studies were conducted to test if an acute smallmuscle injury (Study III) and chronic muscle damage (Study IV) influences the normal bloodflow effect of adrenaline. In support of the hypothesis we found that the microdialysiscatheter-induced muscle injury in Study III caused a significant vasoconstriction during an i.v.adrenaline infusion, as measured with 133Xenon clearance next to the catheter, whereas nosignificant change in blood flow was seen with adrenaline-infusion in the absence of thecatheter (conventional 133Xe administration). The adverse adrenaline effect is likely to berelated to the degree of invasiveness. Hence, it would be expected that any type of invasivemeasuring device causing a muscle injury could possibly provoke a similar reaction. Thisfinding has a general physiological implication, but has also implications for the use ofinvasive techniques to study blood flow regulation in skeletal muscle.Previous studies of tennis elbow (TE) have reported signs of diffuse muscle damage anddecreased blood flow in the affected extensor carpi radialis brevis (ECRB) muscle. Weconducted a case-control study (IV) to test the hypothesis that the muscle damage in the ECRBin TE alters the blood flow response to adrenaline in a vasoconstrictory direction. Muscleblood flow was determined with local clearance of 99mTechnetium during an i.v. infusion ofadrenaline. In support of the hypothesis, the blood flow reaction to adrenaline was markedlydifferent in the two study groups. Whereas the infusion did not significantly influence99mTechnetium-clearance in the ECRB of controls there was a significantly decreased clearancein the patients. The altered adrenaline effect indicates a vascular dysregulation in TE, which islikely to be of clinical significance by contributing to the development and maintenance of thechronic muscle pain in this large patient group. Whether the vasoregulatory alteration, whichwould be expected to involve recurring relative muscle ischemia, represents the primaryaetiology in TE or is a secondary effect of the muscle injury cannot be determined.In conclusion, a small muscle injury, acute or chronic, seems to alter the effect of adrenalineon skeletal muscle blood flow in a vasoconstrictory direction.

Place, publisher, year, edition, pages
Stockholm: Karolinska Institutet , 2010. , 68 p.
Keyword [en]
adrenaline, blood flow, blood redistribution, ischemia, muscle injury, skeletal muscle, strain-gauge plethysmography, sympathetic tone, transmural pressure, 99mTechnetium clearance, tennis elbow, venous compliance, venous occlusion plethysmography, 133Xenon clearance
National Category
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-169655ISBN: 978-91-7409-659-0 (print)OAI: oai:DiVA.org:uu-169655DiVA: diva2:507500
Public defence
2010-12-10, Aulan Södersjukhuset, Stockholm, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-03-06 Created: 2012-03-05 Last updated: 2012-03-08Bibliographically approved
List of papers
1. Influence of leg position and environmental temperature on segmental volume expansion during venous occlusion plethysmography.
Open this publication in new window or tab >>Influence of leg position and environmental temperature on segmental volume expansion during venous occlusion plethysmography.
2003 (English)In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 104, no 6, 599-605 p.Article in journal (Refereed) Published
Abstract [en]

Blood flow determinations by venous occlusion plethysmography applying the strain-gauge technique are frequently used. A problem with the strain-gauge technique is that the relationship between venous volume and transmural pressure is not linear and, furthermore, changes with the sympathetic tone. The present study tests the hypothesis that these factors lead to a redistribution of venous blood, which may impair the accuracy of the technique. The relative volume expansion rates of four leg segments were studied with the leg in different positions and at disparate temperatures, thereby inducing varying venous pressures and sympathetic tone ( n =6). With elevated leg and relaxed veins (at 50 degrees C), the distal thigh showed a relatively low expansion rate (25.8+/-4.5 ml.min(-1).l(-1)), whereas values in the calf segments were higher (34.5-39.0 ml.min(-1).l(-1)). With lower initial transmural pressure, calf segments can increase their volume much more during occlusion compared with the distal thigh. In a higher transmural pressure region (lowered leg), the difference in compliance between limb segments is less. In this case, compliance and volume expansion rate was higher in the distal thigh (14.2, 13.5 and 22.2 ml.min(-1).l(-1) at 10, 20 and 50 degrees C respectively) than in the calf segments (for the distal calf: 6.4, 7.7 and 16.2 ml.min(-1).l(-1) respectively). There was a significant interaction ( P <0.001) between temperature and leg position, indicating a higher degree of sympathetic vasoactivity in the calf. It is concluded that blood flow determination by strain-gauge plethysmography is less accurate, due to a potential redistribution of the venous blood. Therefore possible influences of variations in sympathetic tone and venous pressure must be considered even in intra-individual comparisons, especially in interventional studies.

National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:uu:diva-169651 (URN)10.1042/CS20020257 (DOI)12529168 (PubMedID)
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07
2. Alterations in forearm position and environmental temperature influences the segmental volume expansion during venous occlusion plethysmography--special attention on hand circulation.
Open this publication in new window or tab >>Alterations in forearm position and environmental temperature influences the segmental volume expansion during venous occlusion plethysmography--special attention on hand circulation.
2009 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 5, 376-81 p.Article in journal (Refereed) Published
Abstract [en]

AIM: To find evidence that small changes in the positioning of the strain gauge, the environmental temperature (sympathetic activation) and position of the arm (venous pressure) alters the outcome of the venous occlusion plethysmography (VOP) measurement of forearm blood flow and to investigate if the hand circulation influences the results.

METHODS: Forearm blood flow was measured with VOP (n = 6) on three occasions with air temperatures of 13, 20 and 38 degrees C, respectively. At each occasion the arm position was varied; raised by 10 degrees , horizontal or lowered by 15 degrees . Strain gauges were placed on the forearm at the maximal circumference; 5 cm distal; and 5 cm proximal to this site, respectively. The hand circulation was excluded in half of the measurements.

RESULTS: The simple main effect of temperature was highly significant (P<0.001). With excluded hand circulation (but not when included), there was a two factor interaction between arm position - strain gauge position (P<0.05). The highest expansion rate was found in the proximal segment when the arm was elevated, but in the distal segment when the arm was lowered. With hand circulation (but not without) there was a two factor interaction between temperature and strain gauge position (P<0.01). The highest expansion rate was found in the distal segment at normal and high temperatures, but in the proximal segment at low temperature.

CONCLUSION: The volume expansion rate in a particular segment is dependent not only on arterial inflow. Segmental differences in capacity for venous expansion results in redistribution of blood to and from a segment, thus influencing the results obtained.

National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:uu:diva-169649 (URN)10.1111/j.1475-097X.2009.00883.x (DOI)19522855 (PubMedID)
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07
3. Intravenous adrenaline infusion causes vasoconstriction close to an intramuscular microdialysis catheter in humans.
Open this publication in new window or tab >>Intravenous adrenaline infusion causes vasoconstriction close to an intramuscular microdialysis catheter in humans.
2010 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 6, 399-405 p.Article in journal (Refereed) Published
Abstract [en]

AIM: To test if a small muscle injury influences the vascular reactivity to adrenaline in human skeletal muscle.

METHODS: Blood flow was measured by ¹³³Xenon clearance in the gastrocnemius muscle of eight male subjects at basal and during i.v. infusion of adrenaline (0.1 nmol kg⁻¹ min⁻¹) or placebo. Measurements were done with (expts 2 and 3) or without (expt 1) the influence of a small muscle injury induced by inserting a microdialysis catheter. ¹³³Xenon was administered either (expt 1) conventionally into the muscle via a fine needle, or (expts 2 and 3) through a fine tube close to the inserted microdialysis catheter. Expt 3 (control expt) was identical to expt 2 except that placebo was infused instead of adrenaline. Mean ± SEM, n= 8.

RESULTS:   The blood flow tended to increase during the adrenaline infusion in expt 1 (1.17 ± 0.10 to 1.39 ± 0.15, N.S.), whereas it decreased during the adrenaline infusion in expt 2, from 1.39 ± 0.14 to 1.03 ± 0.14 ml min⁻¹ 100 g tissue⁻¹ (P<0.001). The blood flow change in response to adrenaline infusion was significantly different in expt 1 and expt 2 (P<0.05). Blood flow also decreased during the placebo infusion in expt 3 (1.15 ± 0.10 to 1.00 ± 0.09, P<0.01), but this decrease was significantly smaller than in response to the adrenaline infusion in expt 2, P<0.01.

CONCLUSION: The present results are consistent with the hypothesis that the small muscle injury caused by the inserted microdialysis catheter influences the vascular reactivity to adrenaline in a vasoconstrictive direction.

National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:uu:diva-169652 (URN)10.1111/j.1475-097X.2010.00955.x (DOI)20618356 (PubMedID)
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07
4. Blood flow to the extensor carpi radialis brevis muscle following adrenaline infusion in patients with lateral epicondylitis.
Open this publication in new window or tab >>Blood flow to the extensor carpi radialis brevis muscle following adrenaline infusion in patients with lateral epicondylitis.
Show others...
2011 (English)In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 36, no 12, 1974-80 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Based on previous evidence of muscle fiber injury and decreased blood flow in the extensor carpi radialis brevis (ECRB) muscle in lateral epicondylitis (LE), we hypothesized that there would also be an abnormal (vasoconstrictive) vascular response to adrenaline in the ECRB muscle in LE.

METHODS: In a case-control study, we measured skeletal muscle blood flow in 8 patients with LE and in 8 healthy controls in response to a 30-minute intravenous infusion of adrenaline. We used local clearance of technetium-99m in the main portion of the ECRB muscle to calculate muscle blood flow.

RESULTS: In support of the hypothesis, the blood flow response to the adrenaline infusion was markedly different in the 2 study groups. Whereas the continuous decrease in technetium-99m clearance rate over time was interrupted by the adrenaline-induced vasodilatory effect in the control group, we detected no such effect in the patient group.

CONCLUSIONS: In the ECRB muscle in LE, there is a shift in the balance of vasodilatory and vasoconstrictory influences of adrenaline, leading to vasoconstriction during low-dose adrenaline infusion. The adverse adrenaline effect is similar to what was previously observed after minor muscle injury. Whether the vasoregulatory change, by causing relative muscle ischemia, represents the primary etiology in LE or results from muscle injury cannot be determined, but it is likely to contribute to the development and continuation of chronic muscle pain in LE. New ways of thinking about the condition may be required, and pharmacological treatment might be an option to improve the blood supply and avoid further damage to the affected ECRB muscle-tendon unit.

National Category
Physiology
Research subject
Physiology; Orthopaedics
Identifiers
urn:nbn:se:uu:diva-169653 (URN)10.1016/j.jhsa.2011.08.028 (DOI)22015074 (PubMedID)
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07

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