Summary and ConclusionsThe present study is concerned with the skeletal muscle circulation in the hind limb of the dog anaesthetized with pentobarbital; the skin circulation was thoroughly excluded in all the experiments; only the bone circulation was not excluded.I. The vasodilator responses induced in the muscle circulation, when the corresponding arteries are left intact, are compared with the responses induced when the afferent artery is occluded in acute experiments. The occlusion was performed on the distal part of the aorta, more commonly on the femoral artery. The study was performed by using vasodilator stimuli, the effect of which is local enough. The vasodilators with extensive effect induce general responses such as cardiac output changes, hemometakinesia phenomenon, but also responses elicited by the mechanisms regulating blood pressure; the central regulating mechanisms called into action by way of the barorecep-tors are necessarily put in motion when it is needed to restore the blood pressure decreased by a generalized vasodilatation; however this depends on a vasoconstriction which may occasionally reduce a local vasodilator effect.The vasodilator stimuli used in these researches may be classified in two groups: the first one comprises the stimuli the effect of which originates upwards, relatively to the intrinsic muscle circulation; these were temporary arterial blood flow arrest inducing reactive hyperemia, ipsilateral lumbar sympathectomy, injections of vasodilator substances into the main afferent artery; in the second group, the vasodilatation was induced in the intrinsic muscle circulation itself by tetanic muscular contractions; it is possible to admit, on the basis of the collected data, that this vasodilatation spreads partly upwards.A. All the stimuli of the first group induce rather comparable effects: whether the blood is supplied through free arterial pathways or through collateral ones, these stimuli exert a powerful vasodilator effect of comparable importance; this effect is exceptionally maximal, even with reactive hyperemia; with equal experimental conditions, the response of the muscle circulation to lumbar sympathectomy can be of the same magnitude as reactive hyperemia. Thus the effect of sympathectomy is not a conclusive proof for the existence of a vascular basal myogenic tone in the skeletal muscle. When the arterial pathways are free, the vasodilatation does not induce important hemodynamic disturbances; it is accompanied by an increase of the capillary bed as long as the arterial head pressure remains above 50 to 60 mm Hg. On the contrary, when the afferent artery is occluded, whether the occlusion takes place on the distal part of the aorta or on the femoral artery, the hemodynamic disturbances are very important and induce quite different responses in the muscle circulation. In the case of femoral artery occlusion, it is shown that the changes occurring after sympathectomy or after intra-arterial injection of vasodilator substance, are a consequence of the fact that the collaterals are less capable of dilatation than the intrinsic muscle vascular bed. Indeed, nearly immediately after the arterial occlusion, the collaterals begin to dilate progressively, and it induces a progressive decrease of their dilatation capa-city. When the pre-existing collateral network is rich, its dilatation becomes promptly more important than the ischemic vasodilatation which is induced nearly immediately by the arterial occlusion in the distal muscle vascular bed and is necessarily moderate in such a case. On the contrary, when the pre-existing collateral network is poor, its dilatation takes more time to become greater than that of the corresponding muscle vascular bed where the ischemic vasodilatation is necessarily more important. Thus, at this early stage of arterial occlusion, there is a difference in the hemodynamic conditions between the two cases. These conditions become comparable in both cases, one or two hours later, when the ischemic vasodilatation in the muscle vascular bed has diminished because of collateral dilatation, whatever the importance of the collateral network. At this stage, the dilatation capacity of the collaterals which have dilated, has become lower than the dilatation capacity of the intrinsic muscle vascular bed which, on its own side, has increased progressively by reduction of the ischemic vasodilatation. The following events are then observed during the vasodilatation induced by the studied stimuli :a) The mean arterial pressure distal to the collaterals (distal pressure) decreases progressively and rises again only when the vasodilator effect has disappeared; the distal pressure gradient is parallel-ly reduced and it is shown that the collateral pressure gradient increases correspondently, because the collateral blood flow is necessarily more increased than the collateral resistance is reduced; at the same time the reverse occurs in the distal muscle vascular bed, the capacity of which has more greatly increased.b) The decrease of the mean distal arterial pressure induces a reduction of the muscle capillary bed, with blood diversion to more direct arterio-venous pathways, everytimc this pressure is reduced below a threshold of about 50 to 60 mm Hg; these changes of the capillary bed follow passively the changes of the local arterial blood pressure and occur in spite of the contemporary blood flow increase.As these hemodynamic changes occur with constancy only when the period of adaptation which follows the arterial occlusion has come to end, they were prone to escape an observation limited to a too early stage. The changes which occur after intra-arterial injections of vasodilator substances, are rather similar, whether the arterial occlusion is performed on the end part of the abdominal aorta or on the femoral artery; yet, the conditions are not the same on both sides :1) When the distal end of the abdominal aorta is occluded, the collaterals belong to a vascular network which docs not depend on the muscle circulation; thus, their responses arc not necessarily the same as those of the intrinsic muscle circulation; moreover, the intra-arterial injections arc performed at a downstream point relatively to the arterial obstruction.2) When the femoral artery is occluded, on the contrary, the collaterals belong, at least for a large part, to the intrinsic muscle circulation and supply, with quite different hemodynamic conditions, two intrinsic muscle vascular beds, a proximal one which depends on the proximal part of the collaterals, and a distal one which is supplied by the whole collateral network and where the hemodynamic conditions depend moreover on the proximal part of the collaterals. In this occurrence, during the vasodilatation induced by intra-arterial injection of one of the tested vasodilator substances, the dilatation of the distal intrinsic vascular bed is greater than that of the whole colla teral network; yet the injection is performed at an upstream point, relatively to the arterial occlusion; the case is probably the same for the vasodilatation of the proximal intrinsic vascular network; the collected data do not allow to decide whether the dilatation of the collaterals is less than that of the corresponding vascular beds at all levels or whether the collateral proximal part alone or the collateral distal part alone would dilate with the same magnitude as the corresponding dependent vascular bed; however this latter occurrence would not be easily understood and it has been possible to demonstrate that it is certainly not the case with the distal part of the collaterals.B. Induced tetanic muscle contractions give rise to a vasodilatation in the intrinsic muscle vascular beds, whether the muscles are supplied through free arterial pathways or through collateral pathways after femoral artery occlusion; in this latter case, the collaterals are also dilated, but certainly less than the intrinsic muscle vascular beds where the vasodilatation originates and is ascribed to metabolites or partly to physico-chemical changes which are induced by muscle contraction. At any rate, it may be thought that, as in the other group of experiments, the mechanism which operates nearly immediately after the arterial occlusion to reduce the collateral capacity of dilatation operates also in this case. However, the hemodynamic conditions generated by the peculiar behaviour of the collaterals are somewhat more complicated during the vasodilatation which accompanies and follows the tetanic muscle contraction induced one or two hours after artery occlusion : the mean distal arterial pressure is still once reduced distal to the femoral artery occlusion, with reduction of the distal pressure gradient, increase of the collateral pressure gradient and, whenever the mean distal arterial pressure becomes lower than 50 to 60 mm Hg, reduction of the muscle capillary bed with blood diversion to more direct arterio-venous pathways; however, the dilatation of the proximal muscle vascular bed supplied by the proximal part of the collaterals is much greater than the one of the distal vascular bed supplied by the whole collateral network, perhaps because the accumulation of vasodilator metabolites would be lesser in the distal vascular bed by reduction of its contractile energy due to a lesser blood supply to this bed.When the mean distal arterial pressure is not too much decreased in the resting level, it returns to the same level after each tetanus and the vascular responses maintain everytime comparable features in both the distal and proximal vascular beds.When the mean distal arterial pressure, on the contrary, is relatively low at the begin of the experiment, it does not rise again after the additional lowering induced by one or two further tetanic muscle contractions and either remains permanently reduced or rises less and less after each further tetanic contraction; each further tetanic contraction still induces a vasodilatation in the distal vascular bed, but the distal venous flow is but poorly increased and is finally reduced in the meantime.The sole possible explanation is that the proximal part of the collaterals would dilate less in such an occurrence than the proximal muscle vascular bed supplied by it. Indeed, as the vasodilatation brought about by the tetanic contraction affects the collaterals by ascending way, it may be assumed from the disparities of dilatation between the proximal and the distal vascular beds, that each part, respectively proximal and distal, of the collaterals dilates in connexion with the dilatation of the corresponding dependent vascular bed, but less than it does. The disparities observed in the responses of the distal blood flow are likely to depend, above all, on the magnitude of the pressure gradient increase in the proximal part of the collaterals, which induces a pressure gradient decrease downwards. According to the possibilities of the distal resistance decrease in comparison with the pressure gradient decrease in the vascular bed which is downstream relatively to the proximal part of the collaterals, the distal blood flow either will be insufficiently increased or will be reduced. These changes of the distal blood flow which are still maintained while the vasodilatation induced by the tetanic contraction is protracted in the distal vascular bed, can be kept on, at a time when the vasodilatation has left the proximal intrinsic vascular bed, by a vasoconstrictor effect which is maintained in the proximal part of the collaterals; this effect would interfere with the effect of the metabolic vasodilatation, in a proportion varying with the intensity of this one, in such a way that the increase of the proximal collateral pressure gradient is maintained at the same level.The vasodilatation tends thus to become permanent in the distal vascular bed because the distal blood flow becomes insufficient for completely removing or neutralizing the substances produced locally with each muscle contraction; it is not the case in the proximal vascular bed. This disturbance is necessarily more and more marked with each further tetanic contraction by increase of the distal blood flow insufficiency, for the distal permanent vasodilatation lowers more and more, by its own increase, the residual capacity of vasodilatation in the distal vascular bed, while neither the proximal part of the collaterals nor the proximal vascular bed are affected in such a way. The proportional difference between the reduction of the total collateral resistance and that of the distal resistance thus increases progressively and the distal pressure gradient is more and more reduced; as the vasodilatation in the distal vascular bed maintains the decrease of the distal pressure gradient which in its turn keeps up the vasodilatation by maintaining the blood flow insufficiency, a vicious circle is established and holds on; it could be only corrected by an increase of the dilatation of the collaterals themselves.Indeed, the intra-arterial injection of acetylcholine performed in these conditions induces still, in the distal vascular bed, an additional limited vasodilatation which affects also, but less, the collaterals, and which, nevertheless, allows a distinct increase of the distal blood flow, because the reduction of the distal pressure gradient is then lesser in comparison with the distal resistance decrease. This distal blood flow increase is proper to break off the vicious circle by allowing a better removal or conversion of the accumulated vasodilator metabolites and thus to reduce the permanent distal vasodilatation. However, this effect is strongly limited by the too great decrease of the perfusion pressure resulting from the insufficiency of the concomitant dilatation of the collaterals; this does not favour very much the exchanges in the capillaries of which the bed is reduced. Nevertheless, the consequence is that, during the decrease of the vasodilatation induced by the intra-arterial injection, the dilatation ratio between the collaterals and the distal vascular bed is changed on behalf of the collaterals, because of the persistence, to a certain degree, on cither side, of the pharmacological vasodilator effect which appears to be more marked on the collateral network than the metabolic ascending effect. Thus, at this later stage, the distal pressure gradient and parallclly, the distal perfusion pressure increase; the capillary perfusion should be improved. However, these effects are also limited because they occur at a late stage, when the proximal vasodilator effect is already exhausted and the distal blood flow already much less increased. An increase of the distal pressure requires indeed that its level be previously sufficiently freed from the influence of the pressure gradient increase in the proximal part of the collaterals induced by the disparity of the pharmacological effect between them and the proximal vascular bed. The vasodilating intra-arterial injection modifies thoroughly, in the same manner, but with the same limits, through the same mechanism, the response to a further tetanic contraction induced during the full effect of the injection. At any rate, the pharmacological effect is too temporary, so that, with a further tetanic contraction induced some minutes after the injection, its hemodynamic benefit is already thoroughly cancelled. These experiments show, at any rate, that the pharmacological effect is distinctly more important than the ascending metabolic effect of the muscle contraction on the degree of collateral dilatation.II. The intra-arterial injections of the vasodilator substances which have been tested, induce commonly during the vasodilatation of the muscle vascular bed, an increase of the oxygen con-sumption which occurs at all the levels of the mean arterial head pressure. However, the study ofthe circumstances in which vary the oxygen utilization by the muscle tissues leads to admit that, whatever the level of the mean arterial head pressure, there exists permanently, in a varying proportion, shunts which are proper to divert a part of the capillary bed supply.These deductions strengthen the likelyhood of the existence of a double circulation in skeletal muscle. Pre-existing shunts would be open in variable proportion and their number would increase in a reverse proportion during the vasodilatation; this would be a first blood flow diversion to which is added an additional mechanism of diversion by reduction of the capillary bed during the vasodilatation, everytime the mean arterial pressure is reduced under a threshold of about 60 to 50 mm Hg.III. The results of this study indicate that the vasodilator stimuli which were applied have but little power, in the experimental conditions used, to improve really the skeletal muscle nutritive supply, when the muscles are supplied through a collateral network which is insufficiently extensive. The complexity of the mechanisms put in motion by vasodilator stimuli in the musclecirculation must be taken into account whenever it is needed to test experimentally in animals the value of a substance or a procedure intended for use in man with the aim of improving the blood supply to the muscle tissues in a limb with arterial occlusion. Especially, in the pharmaco-logical research, it is necessary to foresee and avoid the various untoward circulatory effects which vasodilator substances would be able to exert or even solely the insufficiencies of efficacy of their use. Even when substances are capable, besides their vasodilator properties, of other favourable effects, these ones are exposed to be counteracted by hemodynamic disturbances or other ones induced on occasion by the vasodilator effect itself.