Subsequently, Cunningham, Guttmann, Whitteridge & Wyndham (1953) remarked

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1 300 J. Physiol. (I957) I38, EFFECT OF BLADDER DISTENSION ON ARTERIAL BLOOD PRESSURE AND RENAL CIRCULATION IN ACUTE SPINAL CATS BY S. R. MUKHERJEE* From the Department of Physiology, University of Edinburgh (Received 1 June 1957) Guttmann & Whitteridge (1947) found that in paraplegics, when the urinary bladder is distended, the blood pressure rises. This is particularly marked when the lesion is in the lower cervical or in the higher thoracic region (C7-T5). Subsequently, Cunningham, Guttmann, Whitteridge & Wyndham (1953) remarked that splanchnic vasoconstriction is the likely mechanism for the rise in blood pressure. In another paper (Mukherjee, 1957), it has been shown that splanchnic vasoconstriction causes a rise in blood pressure when the urinary bladder is distended in cats (non-spinal preparations). Definite evidence of renal vasoconstriction was a!so obtained during bladder distension. Acute spinal preparations suitable for such investigations present experimental difficulties. When it was found that an acute spinal preparation can be made, in which vascular reflexes can be elicited satisfactorily, a study was made of the effects of bladder distension on blood pressure and renal circulation. The purpose of this paper is to report the technique used in preparing the experimental (acute) spinal cat and the investigations subsequently carried out. METHODS Female cats varying in body weight ( kg) have been used. Anaesthesia is induced with ethyl chloride followed by ether and maintained with chloralose (80 mg/kg body wt.). The trachea is cannulated and a T tube put in and nothing further is done for the next min. The animal is then placed in the prone position with a cotton bag under the clavicles, thus allowing the neck to be flexed slightly. Care is taken to see that the animal is breathing freely. An incision is made in the mid line from a point between the scapular spines to the occiput through skin, fasciae and muscles down to the vertebral spines. If the dissection is carried out meticulously in the middle line, the bleeding is insignificant. The muscles on the laminae are gently retracted on either side of the spines for a distance ofh in. This is done first by a few cuts with the scalpel on the margins * Present address: Department of Physiology, Science College, University of Calcutta.

2 VISCERO-VASCULAR REFLEXES IN SPINAL CAT 301 of spines and then by the use of its handle, or a rugine, and a piece of gauze. The piece of gauze is then tucked into the wound for a minute or two. The spine lying at the middle of the exposed area and whose root is at the level T1-T2 of the spinal cord, is removed. A very small hole is made between the vertebra whose spine has been removed and that below. This is usually made during the removal of the spine while either flexing the neck a little more or lifting up the spine with forceps. The laminae of the same vertebra are then removed by nibbling on each side of the central hole. The opening is also enlarged upwards for 1 in. The pulsating dura is now seen. It is incised in the mid line for 1 in. and a double loop of fine non-glazed linen thread is passed intradurally by a hook round the cord, just above the middle of the exposed intradural space. This usually corresponds to the C8-T1 level. The loops of the thread are then tied and the spinal cord is cut through. The tied ends are then lifted slightly and a small piece of oxidized cellulose gauze (Oxycel, Parke, Davis) is tucked in between to help in haemostasis. If the hook is passed gently round the cord, the bleeding is very slight. Artificial respiration, adjusted to 15-20/min, is always started just before the spinal cord is cut. The muscles are now sutured loosely, a piece of gauze wrung out of saline solution being used as a wick to drain from the area near the cut margins of the spinal cord, to indicate whether any active bleeding occurs during the period ofrecoveryfrom spinalshock. The skinandtheaponeurosis are sutured and the animal is then very gently turned on its back and covered with cotton blankets. The heating arrangements in the table are adjusted so that the rectal temperature of the animal remains at approximately C. At the end of the experiment the level of the transection is checked. Low blood pressure in the stage of spinal shock is due to extensive vasodilatation in which both small and large vessels participate. It appears therefore that increasing the intravascular fluid It has been the present volume is not the satisfactory and rational way to restore blood pressure. author's experience that the percentage fall of blood pressure following spinal transection has an important bearing on the degree of spinal shock. Usually cats have a high blood pressure for min following chloralose administration. If the spinal operation is performed during this period, the bleeding during dissection is more than 10 ml. and the blood pressure comes down to a very low level, mm Hg, immediately following transection. The recovery from this hypotensive state is very slow. Even after 4 hr the blood pressure has not risen to more than 60 mm Hg. If the spinal dissection is done min after chloralose administration the bleeding is much less. The smaller the percentage fall in blood pressure the quicker is the recovery. Usually within 2j-3 hr the blood pressure returns to mm Hg and by the end of 4 hr to mm Hg. In the period between chloralose administration and spinal dissection the ureters, urethra and the bladder were exposed in preparation for their connexion with the apparatus for irrigation. The latter operation was carried out when the animal's blood pressure had returned to the level of 90 mm Hg or more. A similar procedure was adopted for the exposure and preparation of the left kidney for plethysmography. The techniques used for these are the same as described previously (Mukherjee, 1957). The femoral artery blood pressure was recorded by mercury manometer. In some experiments, the vagi were cut at the middle of the neck to observe the effect of denervation on the size of the arterial pulse as recorded by mercury manometer during the rise of blood pressure while the bladder was being distended. Damage to the bladder, shown by the presence of blood in the fluid on bladder emptying, haematoma in the bladder wall and haemorrhage in the bladder mucosa were more frequently observed in the present series than in similar experiments on the non-spinal cats, when the bladder is distended to ml. of 0 9 % (w/v) saline. Once such damage occurred, it was not possible to elicit a viscero-vascular reflex.

3 302 32S. R. MUKHERJEE RESULTS Changes in blood pressure The findings obtained as the animals recover from hypotension can be grouped as follows: (a) When the blood pressure is below 40 mm Hg no response is obtained on distending the urinary bladder, whatever head of pressure and rate of distension are used. (b) When the blood pressure returns to mm Hg, 20-30% rise in blood pressure is obtained when the urinary bladder is distended at a pressure I E il: _ L bo I E E- co o L. Fig. 1. Effect of bladder distension on blood pressure. B.P., blood pressure; BL.P., bladder pressure; A before, B after bilateral vagotomy. Arrow below indicates when filling stopped; arrows above (in B) indicate drum was stopped for j min each time. Time, 5 sec. head of 65 mm Hg or more, and a high rate of distension ( ml./min) is used (Fig. 1). Such responses are quickly abolished on repetition of the experiments, however high the pressure head or rapid the rate of distension used. (c) When the blood pressure is between 60 and 90 mm Hg, 20-30% rise in blood pressure is obtained on distending the urinary bladder at a pressure of 65 mm Hg, using a rate of ml./min. Vasopressor responses can be

4 VISCERO-VASCULAR REFLEXES IN SPINAL CAT 303 obtained by repeating the experiment but rapidly become very poor. Then, by increasing the pressure head or the rate of distension, brisk vasopressor responses can be elicited, but only for a brief period. (d) When the blood pressure returns to a level of 90 mm Hg or above, bladder distension produces a rise in blood pressure, which may be even as high as % above the control level (Fig. 2). Vasopressor responses can now be elicited by distending the bladder at a pressure of 65 mm Hg, using a rate of 60 ml./min. When the filling is discontinued and the bladder is kept 130 E 110 r U ~o60k- E 40 F- 20 F- Time (sec) Fig. 2. Effect of bladder distension on blood pressure. B.P., blood pressure; BL.P., bladder pressure. 1st arrow indicates when filling stopped; 2nd arrow indicates when emptying starts. Note: as intravesical pressure remained the same during the stage of distension, blood pressure was rising. Fig. 3. Effect of bladder distension on renal volume; states of the bladder indicated at the top; T- indicates reduction in volume distended, the intravesical pressure may or may not remain the same as that in the filing stage. If it remains the same, the blood pressure continues to rise (Fig. 2). The rise in blood pressure is a continuous and progressive one (Fig. 2). In the vagotomized animal, the size of the arterial pulse as recorded by Hg manometer becomes smaller as the blood pressure rises. If the vagi are intact, the size of the pulse increases (Fig. 1).

5 304 S. R. MUKHERJEE Changes in renal circulation Definite evidence of renal vasoconstriction has been obtained in ten individual experiments, one of which is shown in Fig. 3. Both decrease in renal volume and diminution in the amplitude of renal pulse are obtained on distending the bladder, when the rise in blood pressure is also marked. When the vasopressor response is poor, renal vasoconstriction, though feeble, is distinctly seen. The renal vasoconstriction also becomes small when the experiments are repeated using the same head of pressure. As the rate of filling is increased renal vasoconstriction becomes more marked. DISCUSSION The present observations are interesting because in acute spinal preparations, when, after spinal shock, the blood pressure has returned to a level of 90 mm Hg or more, the vasomotor responses shown by the rise in blood pressure and increased renal vasoconstriction are similar to those observed in the non-spinal preparations following bilateral vagotomy and carotid sinus denervation (Mukherjee, 1957). When the blood pressure is between 60 and 90 mm Hg either a greater pressure or a quicker rate of distension of bladder has to be used to elicit satisfactorily these vasomotor responses. These findings suggest that in acute spinal preparations, in states of hypotension, the stimuli to be effective in producing viscero-vascular reflexes have to be more powerful than in non-spinal ones. Downman & McSwiney (1946-7) made similar observations in their experiments with acute spinal preparations. By his experiments on spinal animals Sherrington (1899) showed that the vascular tone can be altered by spinal reflexes and he also demonstrated, on the anaesthetized animal, that a rise of arterial blood pressure can result from stimulation of the viscera by distending the ureter or common bile duct. Downman & McSwiney (1946-7) have supplemented Sherrington's observations by showing similar vasomotor responses to intestinal stimulation in the spinal animal. The importance of such reflex viscero-vasomotor responses has only been realized lately. The insignificance of such reflexes was emphasized in the observations of Guttmann & Whitteridge (1947). 'These results suggested that, as a result of bladder distension, a large-scale redistribution of blood was going on, and we therefore recorded the effects of bladder distension on blood pressure and pulse rate, as well as skin and body temperature, in the next cases.' Cunningham et al. (1953), in reporting their observations on the effect of bladder distension on the skin and muscle beds of the limbs of paraplegics (C7-T5), noted that the vasoconstriction in these beds could not account for the extent of the rise in blood pressure and suggested splanchnic vasoconstriction as a possible mechanism.

6 VISCERO-VASCULAR REFLEXES IN SPINAL CAT 305 Evidence of renal vasoconstriction has been obtained in the present series. This is in agreement with the suggestion of the above authors. The additional evidence has been given here that the reflex vasomotor responses obtained are almost identical with those seen in non-spinal animals without buffer nerves. The level of the lesions in the present series varied from C7 to T1, higher than the highest level of splanchnic outflow from the spinal cord. Obviously, the baroreceptors in the arch of aorta and carotid sinus region and the buffer nerves connecting these with the suprasegmental vasomotor centre could not modify the spinal reflex vasopressor responses involving the splanchnic nerves (Fig. 3). This explains satisfactorily why Guttmann & Whitteridge (1947) found that the lower the spinal lesion the more restricted were the reflex vasomotor responses. When the vagi are intact the reflex cardiac slowing and increase in amplitude of the arterial pulse, due to increase in stroke volume, have been observed in the present investigations as in the series of Guttmann & Whitteridge (1947). Fig. 4. Effect of bladder distension on blood pressure. B.P., blood pressure; BL.P., bladder pressure. Note: Initially, as the bladder is filled, a slight fall in B.P. and pulse gets smaller; as the filling is continued, B.?. rises and pulse becomes bigger. Time: sec. In only one experiment where the vagi were intact was there a decrease in the size of the arterial pulse and a slight reduction in blood pressure during the early part of the filling of the bladder. As the filling continued, blood pressure rose above the control level (by 20 %), but the pulse became bigger in size than before filling. The pulse rate was increased during the period when blood pressure was low. It was reduced when the blood pressure rose (fig. 4). Though the present observations justify further investigation of the other components of the splanchnic vascular bed, it has not been found possible at the present because the difficulties encountered in studying circulation through the intra-abdominal organs are many. Any intra-abdominal manipulation causes deterioration of the animal and the blood pressure falls. Perhaps such difficulties can be overcome by using chronic spinal preparations.

7 306 S. R. MUKHERJEE SUMMARY 1. The use of the cat as an acute spinal preparation, suitable for studying reflex vasomotor responses on bladder distension, has been described. 2. Such reflex responses depend primarily on the state of recovery of the animal from spinal shock. 3. When the animal has recovered so that the blood pressure has returned to a level of 90 mm Hg or above, reflex vasopressor responses, similar to those obtained in non-spinal preparations without buffer nerves, can be elicited satisfactorily by distending the urinary bladder. 4. Definite evidence of renal vasoconstriction is present when the bladder is distended. I am indebted to Professor D. Whitteridge, F.R.S., for his stimulating interest throughout this work. REFERENCES CUNNINGHAM, D. J. C., GUTTMANN, L., WHITTERIDGE, D. & WYNDHAM, C. L. (1953). Cardiovascular response to bladder distension in paraplegic patients. J. Phy8iol. 121, DOWNNMAN, C. B. B. & MCSwINEY, B. A. (1946-7). Reflexes elicited by visceral stimulation in the acute spinal animal. J. Physiol. 105, GUTTMANN, L. & WHITTERIDGE, D. (1947). Effect of bladder distension on autonomic mechanism after spinal cord injuries. Brain, 70, MUKHERJEE, S. R. (1957). Effect of bladder distension on arterial blood pressure and renal circulation: role of splanchnic and buffer nerves. J. Phy8iol. 138, SHERRINGTON, C. S. (1899). On the spinal animal (Marshall Hall Prize address). Med.-chir. Trans. 82,