Effect of Intensive Walking Exercise on Skeletal Muscle Blood Flow in Intermittent Claudication

Th. Weiss, M.D. Y. Fujita, M.D. U. Kreimeier, M.D. and K. Messmer, M.D.

HEIDELBERG, GERMANY

Abstract valid therapeutic regimen in the treatment of peripheral arterial occlusive disease (PAOD) of Fontaine stage II. In order to quantify the effect of walking exercise and/or drug therapy on regional muscular blood flow, PAOD Fontaine stage II was induced by multiple ligations of the femoral artery and of all side branches in one hindlimb of mongrel

Walking

exercise is

generally accepted

as a

the contralateral extremity served as control. The animals underwent walking exercise with increasing intensities on a treadmill five days per week over one year; one group received 600 mg buflomedil (BF) per day orally in addition. At the end of the training period, the regional blood flow in all skeletal muscles of both hindlimbs was quantified by means of 15 μ m radioactively labeled microspheres at resting conditions, after treadmill exercise (ten minutes) with or without preinjection of BF (3 mg/kg body weight) into the abdominal aorta. At resting condition and at the end of treadmill exercise the regional muscular blood flow did not differ significantly between the diseased and control extremity. Supplementary oral treatment with BF over one year had no significant effect; the increase in muscular blood flow during treadmill exercise was not enhanced after intra-aortic injection of BF. Consequently walking exercise has the potential to increase the functional capacity of collaterals in intermittent claudication and to restore blood supply to skeletal muscle.

dogs;

From the

Department of Experimental Surgery, University of Heidelberg, Heidelberg, Germany

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64

Introduction

Walking exercise as a therapy for intermittent claudication was first suggested by Erb in 1898.’ Despite new approaches in interventional angiology, physical training is a wellestablished therapy for peripheral arterial occlusive disease (PAOD) according to Fontaine stage II. However, on which mechanism the improvement in painfree walking dis2 tance is predominantly based is still a matter of controversy . From clinical studies, increased functional capillary density, altered muscle metabolism, and improved blood flow have been postulated as possible factors.3-5 The measurement of skeletal muscle blood flow-the target for therapeutic interventions-is difficult in patients. For this reason, various animal models have been established.~’° Most of them, however, do not allow quantification of skeletal muscle blood flow during exercise . 6-1 With regard to the limited physical capacity of a subgroup of patients suffering from intermittent claudication, vasoactive substances have been advocated as adjunctive therapy. During recent years favorable results have been reported, particularly in claudicants treated with buflomedil (BF), 11,12 and bolus injection of BF has been demonstrated to significantly increase skeletal muscle blood flow in dogs.’3 The purpose of our experimental study was: (1) to quantify the effects of daily treadmill exercise for a period to one year on skeletal muscle blood flow in PAOD Fontaine stage II, (2) to evaluate the effect of supplementary oral administration of BF (600 mg/day), and (3) to investigate whether the effect of treadmill exercise can be enhanced by BF (3 mg/kg body weight [BW]) injected into the abdominal aorta. Materials and Methods

mongrel dogs an arterial occlusive disease Fontaine stage II was induced according to the method described by Sunder-Plassmann et al.l3,14 In the right hindlimb the following vessels were ligated: the external iliac, common femoral, deep femoral, cranial femoral, and superficial femoral arteries (Fig. 1). The left extremity served as control. After recovery from surgery the animals were daily trained on a treadmill except on Sunday. Three dogs received 600 mg BF/day orally in addition. Intensity and duration of exercise were set with respect to the baseline constitution of the dogs. After a training period of one year each dog was able to run with a velocity of 15 km/hr for ten minutes a day. For the final experiment the following catheters were inserted in pentobarbital anesthesia (0.4 mg/kg/hr): o Two silicone catheters were placed in the femoral veins of the lower extremities (blood analysis). . A Swan-Ganz catheter was inserted into the pulmonary artery via a jugular vein (central hemodynamics). · Two catheters were inserted via the right carotid artery and positioned in the abreference and the left atrium, respectively (injection of aorta dominal sample) (arterial microspheres). The arterial catheters were tunneled subcutaneously and exteriorized at In 5

the neck.

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65

FIG. 1. Localization of the ligathe arterial vessels of the dog hindlimb, from Messmer et al14 with

tures on

permission.

Two to four

days after recovery from surgery, hemodynamic measurements were made

under resting conditions and seven minutes after the onset of each exercise test on the treadmill (15 km/hr, ten minutes); the second exercise test was preceded by intra-aortal injection of BF (3 mg/kg BW). After each measurement the dogs were allowed to recover for forty-five minutes during which time the cardiac output normalized. Skeletal muscle blood flow was determined by injection of 3 million microspheres into the left atrium. The blood withdrawn for the reference sample from the abdominal aorta and the femoral veins was isovolemically replaced by 6% Dextran 60.5 After the third measurement the dogs were anesthetized and sacrificed by intracardiac injection of 30 mL saturated KCL. The following muscles were prepared in both hindlimbs: M. rectus femoris, M. vastus intermedius, M. vastus lat., M. vastus med., M. gracilis, M. semitendinosus, M. biceps femoris, M. abductor longus, M. sartorius, M. adductor magnus, M. gastrocnemius, M. soleus, and M. tibialis ant. Three samples (average 4 g each) of all muscles were analyzed. The radioactivity of the three different isotopes was measured in a gamma counter. The absolute values for skeletal muscle blood flow were calculated by means of a computer program. 15 For comparison between diseased (d) and control extremity (c) and between trained animals and animals undergoing daily exercise with supplementary BF, the Wilcoxon signed rank sum test was used (significance level p < 0.05) .

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66 -

Resting Conditions Under resting conditions

---------

difference in total blood flow or regional muscular blood flow was observed neither between the diseased and control extremity not between the two groups. The median values of total blood flow to the thigh and calf, respectively, are depicted in Table I. In addition the blood flow values of the gastrocnemius muscle are listed. a

Exercise

During exercise none of the animals showed symptoms of discomfort or pain and each dog completed the ten-minute run at a velocity of 15 km/hr. The regional blood flow significantly increased in both extremities without difference between diseased and control hindlimb. The distribution of blood flow to the thigh and calf muscles was not different, nor was total blood flow between the trained animals and those being trained during daily treatment with BF for

one

year. Data

on

all animals have been summarized in Table II

(Wilcoxon signed rank test). In Table III the values for P02 and the concentrations of lactate and pyruvate in blood samples from the femoral vein are listed for the individual animals. The data reflect the individual training status of the animals. No significant correla’

found between skeletal muscle blood flow and any of these parameters. Apparently the occlusion of the femoral artery was adequately compensated in all 5 dogs, so that blood supply could meet metabolic demand also under exercise conditions.

tion

was

TABLE I

Regional Muscular Blood Flow [mLlminl]00 gJ Under 5, median, Q1-/Q3-Quartile Resting Conditions, n =

Buflomedil Prior to Exercise After inj ection of 3 mg/kg BW BF into the abdominal aorta and subsequent exercise, regional blood flow to the diseased hindlimb increased above the exercise level in all animals, whereas in the control hindlimb BF did not increase skeletal muscle blood flow to values higher than already reached by exercise. The values for median, Ql-/Q3-quartiles are presented in Table IV. The distribution of blood flow within thigh and calf muscles of each extremity was not altered by injection of BF; this clearly indicates the absence of a steal phenomenon after intra-arterial injection of buflomedil.

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67 TABLE II

Regional Muscular Blood Flow [mLlminl]00 gJ of Diseased (d) and Control (c) Hindlimb Compared Under Resting Condition and During 10 Minute Treadmill Exercise, n 5, listed median, Q1-/-Q3-Quartile =

Wilcoxon signed rank test, *** : p

Effect of intensive walking exercise on skeletal muscle blood flow in intermittent claudication.

Walking exercise is generally accepted as a valid therapeutic regimen in the treatment of peripheral arterial occlusive disease (PAOD) of Fontaine sta...
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