EFFECTS OF SELECTIVE BLOOD AND TISSUE HEATING ON BLOOD FLOW IN THE DOG HINDLIMB

Transcription

1 Experimental Physiology (1990), 75, Printed in Great Britain EFFECTS OF SELECTIVE BLOOD AND TISSUE HEATING ON BLOOD FLOW IN THE DOG HINDLIMB J. M. McMEEKEN* AND C. BELL Department of Physiology, University of Melbourne Medical Centre, Victoria, Australia (MANUSCRIPT RECEIVED 16 JUNE 1989, ACCEPTED 23 NOVEMBER 1989) SUMMARY This study investigated the effects of independent and combined heating of blood and tissue to 'C on femoral blood flow in the hindlimb of the anaesthetized dog. An increase in arterial blood temperature by means of an extracorporeal circuit increased femoral vascular resistance. An increase in limb tissue temperature, induced by external hot packs, decreased femoral vascular resistance. These responses occurred both before and after sympathetic blockade. Neither blood heating nor tissue heating affected the hyperaemic response to exercise. When blood and tissue heating were combined, femoral vascular resistance remained unaffected. We conclude that changes in blood temperature do not contribute to the hyperaemic effect of limb warming and that exercise combined with limb warming is no more effective as a therapeutic tool for promoting limb flow than exercise alone. INTRODUCTION The rate and quality of tissue repair after injury or disease is directly proportional to its blood and oxygen supply (Niinikoski, 1980). Healing relies on the transport of oxygen, nutrients, white cells and antibodies into the area of the damaged tissue, and on the removal of toxic waste and cellular debris. To promote tissue repair, a range of physical and electrophysical procedures are employed by physiotherapists. A number of these procedures involve tissue heating, which is considered to facilitate healing by increasing blood flow (Wadsworth & Chanmugam, 1980; Forster & Palastanga, 1981). Heating is usually applied in the resolution phase of injuries and in the chronic stage of injury or disease processes. Tissue heating to a temperature greater than 40 'C is generally recommended to achieve the optimal increase in blood flow required (de Lateur, Lehmann, Stonebridge, Warren & Guy, 1970; Lehmann & de Lateur, 1982): however, few objective data are available to document the actual extent of hyperaemia achieved, or the mechanisms by which local temperature increases might affect blood flow. In order to obtain more information on this situation, we have determined the effects on resting blood flow and exercise-induced hyperaemia in the hindlimb of the anaesthetized dog of heating the arterial blood without heating the surrounding tissue, heating the surrounding tissue while controlling the blood temperature, and simultaneously heating the arterial blood and the surrounding tissue. METHODS Adult mongrel dogs of either sex weighing 9-20 kg were anaesthetized with thiopentone followed by intravenous a-chloralose (70 mg kg-' initially, supplemented by mg as required). The criteria for maintenance of adequate anaesthesia were the persistence of miotic pupils and the absence of heart rate changes during the mild noxious stimulus of pinching the paw pad. Animals were * Present address: Department of Physiotherapy, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.

2 360 J. M. MCMEEKEN AND C. BELL artificially ventilated under positive pressure with a tidal volume of 20 ml kg-1, and a frequency of 15 breaths min-m. Blood pressure and heart rate were recorded from a catheter inserted into a splenic artery and an indwelling urinary catheter was inserted into the bladder. The abdominal aorta was ligated just distal to the renal arteries, and the arterial blood supply to the hindquarters was rerouted through a length of Silastic tubing placed in a temperature-controlled water bath which allowed the temperature of the blood to be changed by approximately 6 C min-'. The Silastic tubing re-entered the aorta just above the bifurcation. The tubing, 1 8 m long and containing 75 ml of fluid, was initially filled with heparinized saline. Heparin, 500 units kg-', was injected intravenously just prior to releasing the blood into the tubing. Blood flow through the left hindlimb was monitored with a cuff-type electromagnetic flow probe (Devices Instruments, UK) on the femoral artery in the thigh. Flows through the leg and paw were differentiated by temporary occlusion of the paw flow using a bandage tied just above the ankle (Bell & Lang, 1979). Body temperature was monitored with an oesophageal thermistor (YSI Probe 224, USA) and maintained at C by means of a heating pad. Hindlimb arterial blood and tissue temperatures were monitored with thermistors mounted on 24 gauge needles (YSI Probe 524, USA) inserted into the Silastic tubing as it entered the left femoral artery, and into the left gastrocnemius muscle at a depth of 20 mm. The left paw temperature was monitored with a disc-type skin thermometer (YSI Probe 344, USA) taped between the third and fourth toes. All parameters were continuously monitored through the experiments using a Grass model 7C polygraph (USA). Room temperature was held constant at 22 'C. When selective heating of the tissues was required, the limb was heated by a pack containing a heatretaining gel (Medical Products Division 3M, USA), pre-heated by 7 min immersion in water at 100 'C, wrapped in 6 mm of damp towelling and fastened securely around the part of the leg containing the gastrocnemius muscle. In most animals, the responses to heating were repeated following administration of the ganglionblocking agent hexamethonium in a dose of 10 mg kg-' intravenously. As hexamethonium caused a fall in systemic blood pressure and therefore in femoral perfusion pressure, data before and after hexamethonium treatment were compared in terms of femoral conductance as well as femoral blood flows. Femoral vascular conductance was calculated as mean femoral blood flow divided by mean arterial blood pressure. The effect of somatic activation of the gastrocnemius muscle was used as a measure of vascular reactivity. A standard test stimulus of I ms pulses at 5 Hz and V for I min, delivered transcutaneously with needle electrodes at either end of the muscle belly, elicited strong contractions of the gastrocnemius muscle without contractions of the muscles of the thigh. This stimulus produced a maximum increase in blood flow with a minimal effect on mean blood pressure and without postexercise hyperaemia. The significance of differences of means was tested using Student's two-tailed, paired t test, on the assumption that no difference existed. RESULTS For all sixteen dogs used, resting mean blood pressure was mmhg and heart rate beats min-1. Left femoral blood flow per kilogram of body weight was ml min-' kg-1 (range ) with ml min-1 kg-1 (range ) to the leg and ml min-1 kg-' (range ) to the paw. Femoral arterial blood temperature was 'C; core temperature, 'C; paw skin temperature, 'C and muscle temperature, IC. The effects of blood and tissue heating on tissue temperature and cardiovascular parameters are shown in Table 1. Increasing the blood temperature to 'C over 3-4 min increased paw skin temperature from to C. Hindlimb muscle and core body temperatures did not change. There was less than 3 % change in heart rate or blood pressure. Femoral blood flow decreased from to ml min-' kg-1, equivalent to a 33 % reduction. As blood temperature returned to resting values, blood flow increased to resting values. A representative example of the effects of blood heating is displayed in Fig. 1. The effects of blood heating persisted after sympathetic ganglion blockade with hexamethonium (Table 1).

3 TEMPERATURE AND BLOOD FLOW 361 Table 1. Increases in muscle, blood and paw temperatures ( C) and changes in femoral blood flow (ml min-' kg-') and conductance (ml min-' kg-' mmhg-') after blood heating, hot pack heating, and combined blood and hot pack heating, before and after administration of hexamethonium Blood and Blood Hot pack hot pack Muscle temperature Before hexamethonium ** ** (n = 8) (n = 6) (n = 4) After hexamethonium ** ** (n = 11) (n = 11) (n = 7) Aortic blood temperature Before hexamethonium ** ** (n = 8) (n = 6) (n = 4) After hexamethonium ** ** (n = 11) (n = 11) (n = 7) Paw skin temperature Before hexamethonium ** * (n = 8) (n = 6) (n = 4) After hexamethonium * * (n = 11) (n = 11) (n = 7) Femoral blood flow Before hexamethonium t * * (n = 8) (n = 6) (n = 4) After hexamethonium t * (n=l 1) (n = 11) (n = 7) Femoral conductance Before hexamethonium * * (n=8) (n=6) (n=4) After hexamethonium * (n = 11) (n = 11) (n = 7) Two-tailed paired t test comparing control and end-heating values: *P < 0 05, **P < Blood temperature (OC) 3 i Muscle temperature ( C) 411 j Cool muscle 36] 95 t Heat muscle Femoral blood flow (ml min-') 80- Blood pressure 140 (mmhg) 100-' Heart rate 1801 (beats min-') min II 1 min Fig. 1. A representative example of the effects of blood heating on muscle temperature, femoral blood flow, blood pressure and heart rate.

4 362 J. M. MCMEEKEN AND C. BELL 46 Cool blood Blood temperature ( C) Muscle temperature ( C) Femoral blood flow (ml min-') 35 55, ~~t Heat blood Blood pressure (mmhg) - 70-_ Heart rate 170 (beats min ) 150' 1 min Fig. 2. A representative example of the effects of heating by hot pack on muscle temperature, femoral blood flow, blood pressure and heart rate. Application of the hot pack increased muscle temperature from to 41b 'C. Blood and paw skin temperature did not change. In two dogs, skin temperature underneath the pack was determined. Skin temperature was 49 'C when the pack was applied and 43 'C at the peak of the muscle temperature increase, 10 min after commencement of application. Application of the hot pack did not affect heart rate or blood pressure. Femoral flow increased from to I0 ml min-' kg-', equivalent to a 26% increase in total femoral flow. There was also an increase in seven of eleven animals after hexamethonium, from 6& to ml min-' kg-', equivalent to a 15 % increase in total femoral flow. Blood flow did not change in the four remaining animals. The maximum increase in femoral flow was achieved within min and took an average of 5 min to return to control values. A representative example of the effects of heating by hot pack is displayed in Fig. 2. When blood heating and heating by hot pack were combined, blood temperature increased from to 'C; paw skin temperature increased from to 'C; and muscle temperature from to 'C. Core temperature increased by 0-2 'C. Once again there was no change in heart rate or blood pressure, and by contrast with the effects of heating either blood or tissue alone, there was no change in total femoral flow (mean increase from 7T to ml min- kg-' before sympathetic blockade and from i3 to ml min-' kg-' after sympathetic blockade). In three dogs pre-treated with hexamethonium, the effects of heating on the femoral

5 TEMPERATURE AND BLOOD FLOW 363 Table 2. Increase in femoral blood flow (ml min-1 kg-') after exercise under control conditions and when combined with blood heating, heating by means of a hot pack, and combined blood heating and hot pack heating, values obtained after administration of hexamethonium (n = 3) Blood and hot Exercise and... Blood heating Hot pack heating hot pack Before heating (116%) (65%) (102 %) After heating (152%) (33 %) 7-4± 2-9 (207%) Table 3. Changes in distribution offemoral blood flow (ml min-' kg-') as a result of blood heating, heating by means of a hot pack, and combined blood heating and hot pack heating, values obtained after administration of hexamethonium Blood and hot Blood heating Hot pack heating hot pack Femoral flow (-26%) (+40%) (+9%) Leg flow (+24%) (+ 135%) -1 1±2-0 (-6%) Paw flow (-88%) (-33%) (+28%) responses to somatic activity in gastrocnemius were studied. Somatic activation increased femoral blood flow by % under control conditions. There was a tendency towards a greater response during blood heating and during blood heating combined with hot pack heating (Table 2) but the response was not significantly different during either manoeuvre. The distribution between leg and paw of blood flow changes in response to heating was determined in several hexamethonium-pre-treated animals. These results are displayed in Table 3. Virtually all the flow reduction associated with blood heating occurred in the paw, while the flow increase associated with hot pack heating was predominantly in the leg. Combined blood and hot pack heating did not significantly change distribution of flow from resting. DISCUSSION It has been traditionally held that heating of blood vessel walls causes vasodilatation (Shepherd, 1963; Abramson, 1965). Therefore, the most striking finding of the present study was that intravascular warming of the arterial supply to the hindlimb provoked a large fall in vascular flow. This effect was not secondary to reflex effects, as it was unaltered by hexamethonium, but was likely to be due to a direct effect on the smooth muscle of the blood vessel wall. In isolated preparations of vessels from a number of species, heating from 37 to C increases vascular muscle tone and spontaneous contraction frequency (Vanhoutte & Lorenz, 1970; Vanhoutte & Shepherd, 1970; Millard & Reite, 1975; Vanhoutte, 1980; Cooke, Shepherd & Vanhoutte, 1984). Warming appears to increase the rate of tension development, increase adenosine triphosphatase activity and enhance metabolism in vascular smooth muscle (Vanhoutte, 1980). Heating from 37 to 48 C also causes an increase in passive wall tension in isolated preparations of rat aorta (McMeeken & Bell, 1984) and rat mesenteric bed (McMeeken, 1987). The experiments undertaken in this paper indicate that the same effects on smooth muscle that occur in isolated

6 364 J. M. MCMEEKEN AND C. BELL preparations also occur in vivo. This vasoconstrictive response may explain the observation of Snell (1954) who found that seven of twenty-one subjects did not respond to an intravenous infusion of saline at temperatures of C with vasodilatation in skin vessels of the hand. Differentiation of blood flow to the leg and paw by means of an occlusive bandage indicated that the vasoconstrictive effect of intraluminal heating was confined to the paw and did not occur in the vessels in the leg. This localization of response suggests the involvement predominantly of skin vessels and possibly of arteriovenous shunts, which are localized mainly in the skin of the toes (Bell, 1983). By contrast with the vasoconstrictive effect of blood heating, heating of the surrounding muscle tissue of the leg caused an increase in femoral flow which was also likely to be nonneural in origin as it persisted in the majority of animals after hexamethonium treatment. These results were closely similar to those obtained by Feucht, Richardson & Hines (1949), who also applied hot packs to the dog hindlimb. One mechanism by which tissue heating might increase local blood flow is by increasing local metabolism. The extent to which an increase in tissue temperature would increase the metabolic rate of the tissues can be assessed by calculation of Q10 values, using the following formula (Wilson, 1972). log Qio = 10 log (k2/k,) t2 - t where k1 = resting blood flow, k2 = post-heating blood flow, t1 = resting tissue temperature and t2 = post-heating tissue temperature. The data of Feucht et al. (1949) indicate Q1O values in their experiments of 15-18, while our present data gave a Q10 of 16. On the assumption that a temperature-dependent metabolic process would have a Qlo value of about 2 (Giese, 1973), the increased blood flow seen in response to tissue heating is therefore not directly contributable to increased metabolic rate, although this is likely to be a contributing factor. Textbooks of physiotherapy recommend combined application of heat and exercise for optimal enhancement of muscle blood flow, on the basis that both manoeuvres cause vasodilatation (Wadsworth & Chanmugam, 1980). In our experiments, an increase in temperature in the exercising muscle did not increase blood flow to any greater degree than that by exercise alone and further elevation of blood temperature, alone or in combination with increased muscle temperature, had no additive effect with exercise. It is of interest that Barcroft, Dornhorst, McClatchey & Turner (1952) showed in human subjects that the limb hyperaemia produced by whole-body warming was additive with the hyperaemic response to subsequent limb exercise. In view of the marked difference in experimental protocol between Barcroft's group and our studies, it is difficult to ascertain the basis for the different results obtained. However, one likely source of variation is the extent of the vasodilatation produced by exercise alone. We employed a frequency of 5 Hz to obtain a maximum muscle hyperaemia, whereas Barcroft et al. used a contraction frequency of 1 Hz which would have produced a submaximal exercise hyperaemia, thus permitting a further increase in blood flow with whole-body heating. There is therefore no reason to believe that combined treatment with heat and exercise has any therapeutic benefit over the use of exercise alone. In summary, we have shown that direct heating of arterial blood is an ineffective stimulus and direct heating of limb tissues is only a weak stimulus for enhancement of tissue blood flow. Our results contrast with previous reports of changes in limb blood flow following

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