Captain John M. Howard, MC., USAR
Lieutenant Colonel Curtis P. Artz, MC, USA
Captain Robert R. Stahl, MC, USAFR

Purpose of Study

Observations

Table 1. Plasma Volume Deficiency in Patients With Hypertensive Response

Patient No. 1, who had a traumatic amputation of the lower leg, was admitted to the hospital with a blood pressure of 170/100. From the clinical appearance of the wounds, it was estimated that he had lost about 1,000cc. of blood. On this basis, he was given 1,000 cc. of blood rather rapidly but his blood pressure rose to 208/120, where it remained until after the administration of spinal anesthesia.

Effect of Changes in Posture

In five casualties (Patients No. 2, 3, 5, 7 and 10) the head was elevated30 degrees or the casualty was allowed to sit up, to determine the effect of such a change in posture on the hypertensive response. In three of these patients there was no change in the blood pressure associated with the change in posture; in Patient No. 10, the head was tilted up 30 degrees for 6 minutes on one occasion, and repeated later for a period of 10 minutes. Patient No. 2 was admitted with a blood pressure of 160/80; when he was moved to

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X-ray the pressure fell to 152/80 and finally stabilized at 142/72 (Fig.1). He was permitted to sit up for 2 minutes and his blood pressure fell to 135/60. He became pale but not dizzy. One minute after returning to a flat position his pressure was 152/70. Patient No. 3 had a slight fall in blood pressure when he sat up but he had previously received demerol(Fig. 2).

FIGURE1.
Graphic illustration of study of Patient No. 2. No change occurred in blood
pressure following demerol. There was a profound drop in blood pressure after
spinal anesthesia. Sitting up for 2 minutes caused pallor but only a slight fall in blood pressure.

Effect of Analgesia

Patients No. 2 and No. 3 received morphine prior to their admission to the hospital and were given demerol intravenously at the hospital in a dose large enough to put them to sleep. In neither instance was the hypertension affected. One other patient was observed, whose blood pressure increased after receiving morphine intravenously. Two patients had a very gradual subsidence of their blood pressure to normal 1 hour after the administration of a second dose of morphine (10 mg., intravenously).

In general, analgesia had little effect on the hypertensive response.

Effect of Anesthesia

Patient No. 2 had a drop from 150/80 to 80/30, with spinal anesthesia. His pressure responded readily to ephedrine. Patient No. 1 experienced a drop in blood pressure from 208/120 to 100/70, after the administration of spinal anesthesia.

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FIGURE2.
Graphic illustration of study of Patient No. 3. No change in blood pressure
occurred after demerol but a profound drop followed the induction of anesthesia.

Following the induction of pentothal anesthesia there was a drastic fall in blood pressure. The most precipitous drop was in Patient No. 4, whose systolic pressure fell from 200 to 100 mm. with induction. Patient No. 3 also experienced a sharp drop after pentothal (Fig. 2).

Patient No. 5 was somewhat resistant to pentothal. His systolic pressure gradually fell from 180 to 140, with no change in his diastolic pressure. He required a large dose of pentothal throughout the period of induction to keep him quiet. Postoperatively, he had a mild hypertension. His blood pressure became further elevated on re-entering the operating room for secondary closure of his wounds 5 days after the initial surgery. Again, an unusually large amount of pentothal was required. This was somewhat different from other patients.

With one exception pentothal and spinal anesthesia abolished the hypertensive response.

Effect of Anti-adrenergic and Sympathetic Ganglionic Blocking Agents

Regitine is reported to block the effect of circulating adrenalin and, to a lesser extent, noradrenalin. It may also depress the action of the sympathetic nervous system.^{2, 3, 4} Patients No. 6 and No. 7 were each given 5 mg. of Regitine intravenously. In Patient No. 6 it had a definite but minimal effect in causing a fall in blood pressure but

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the pulse rate increased. In Patient No. 7 the fall in blood pressure was profound.

An autonomic ganglionic blocking agent, hexamethonium (Bistrium)^7,8 25 mg., was given intravenously to Patients No. 5, 6 and 7. All three patients had a sharp drop in blood pressure. This fall was transient but the pressure did not rise as high as the pre-drug level. The duration of maximal effect, however, was shorter than might have been anticipated on the basis of its effect in other types of hypertension.

Hexamethonium abolished and Regitine depressed the hypertensive response in these patients.

Patient No. 1. This Korean soldier suffered a traumatic amputation of the lower leg on 6 August 1953 at 1100 hours, when he stepped on a land mine. He arrived at the hospital at 1800 hours with a blood pressure of 174/100, pulse 104. Although he was hypertensive, it was believed that he had lost a moderate amount of blood and that it would be advisable to replace the blood volume deficit. He was given 1,000 cc. of blood during the next hour. His blood pressure rose to 208/120. After spinal anesthesia at 1900 hours, his blood pressure slowly fell to 130/88. At operation, the leg was reamputated, a cast applied and additional blood (500 cc.)was given. Postoperatively the blood pressure was 120/90, pulse 114.

The replacement of blood volume deficiency did not cause the blood pressure to return to normal but produced further elevation. The hypertension persisted until spinal anesthesia was initiated.

Patient No. 2. This 19-year-old American soldier was wounded at 0700 hours, 19 April 1953, by mortar shell fragments. His injuries were fractures of the fibula, talus, and metatarsal on the right foot, fractures of several phalanges of the left foot, and multiple penetrating wounds of the feet and ankles.

At 0730 hours he was given 15 mg. of morphine and transferred to the collecting station where blood was started. He arrived at the hospital via helicopter at 0950 hours. His blood pressure was 160/80, pulse 80,respirations 19. His pulse volume was slightly decreased. He was quiet, slightly apprehensive, slightly pale, but had good capillary refilling. His blood loss was estimated to be 200 or 300 cc. His pupils were constricted and he complained of moderately severe pain.

When moved passively to x-ray (flat) his pressure fell from 160/80 to 152/80 and pulse rate rose from 108 to 128.

With his pressure stable at 142/72, pulse 96, he sat up for 2 minutes. His pressure fell to 135/60 and pulse rate rose to 150. He became pale but neither dizzy nor faint. One minute after reclining, his pressure was 152/70, pulse 108.

At 1100 hours, his pressure was 160/80, pulse 90, respirations18. He was given demerol (50 mg., intravenously). He became nauseated but did not vomit. His pressure rose slightly for a few minutes thereafter. He then fell asleep for 20 minutes but the hypertension persisted. Pain was present when he awoke.

He remained hypertensive for 3¹/2 hours after admission. Most of this time he lay quietly, unmolested on the stretcher. Pain was always present. He was given spinal anesthesia which rose to a level of T-4. Immediately, his pressure

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fell to 80/30 (Fig. 1) and he was nauseated. With ephedrine, his pressure rose to 120/70 and remained there throughout the short period of débridement. Postoperatively, the pressure remained normal. The only blood given was the 500 cc. which was started at the collecting station and which dripped in slowly until 1200 hours.

Patient No. 3. This 23-year-old American soldier was wounded at 1545 hours, 14 April 1953, by mortar shell fragments. His injuries included penetrating wounds of the left arm and shoulder, fracture of clavicle, penetrating wounds of both thighs, left leg and right buttock.

He was given penicillin (600,000 units) and tetanus toxoid at the battalion aid station at 1625 hours. A pressure dressing and a splint were applied to the forearm. At 1715 hours he was given morphine (30 mg., intramuscularly).

At 2126 hours at the clearing station his blood pressure was 70/60. He was given 1,000 cc. of blood and 500 cc. of dextran. On arrival at the hospital via ambulance at 2200 hours he was in good condition. His pulse was of a slightly diminished volume, rate 120 per minute. The blood pressure was 140/70. He was drowsy but complained of pain. In spite of the sedation, he appeared nervous. Because of the rapid pulse rate he was given another 1,500 cc. of blood preoperatively. The pulse rate did not decrease. In spite of mental depression from the morphine, he still maintained that pain was severe. Demerol (75 mg., intravenously) was given and he went to sleep. Hypertension was maintained (Fig. 2). He was encouraged to sit up for a few minutes and his blood pressure decreased slightly. Blood loss during operation approximated 1,000 to 1,500 cc. Muscle destruction was massive.

Postoperatively, his pressure was normal. He was evacuated on the second postoperative day in good condition.

Analgesia had no effect on this patient`s blood pressure but a rapid decline occurred with anesthesia.

Patient No. 4. This 39-year-old Korean was injured approximately 2 hours before admission, by fragments from a land mine. On admission, he was quite excited, tossing his hands and head, chattering and shivering. Pain was intense (he had received no treatment except one injection, presumably morphine). His blood pressure was 164/100, pulse 76, pupils dilated, skin of normal color and temperature. He was not sweating. His wounds consisted of a traumatic amputation of the left foot and minor wounds of the hand.

His pressure rose spontaneously to 210/138, pulse 72. With the onset of pentothal anesthesia his pressure fell to 100/70 (Fig.3). His pulse rate remained at 72.

He tolerated the operation well, received 500 cc. of blood and remained hypotensive throughout the operation. Postoperatively, his pressure rose to 140/80, pulse rate 68. His hematocrit postoperatively was 47 per cent.

This excited patient experienced a dramatic drop in blood pressure after induction with pentothal.

Patient No. 5. This 20-year-old American soldier had been in Korea 10 months and on the line 3 months when he was wounded by grenade fragments at 0630 hours, 25 April 1953.

At the battalion aid station, 0700 hours, his blood pressure was 130/75. He was given tetanus toxoid (1 cc.) and morphine (8 mg.) at 0710 hours.

He arrived at the hospital by ambulance at 0915 hours. He was in good condition. His blood pressure was 150/100, pulse 108 and of good volume. His skin color was normal and his capillary refilling was good. He was thirsty and in moderate pain. His pupils were not constricted. He was quiet but alert.

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FIGURE3.
Graphic illustration of study of Patient No. 4.
A dramatic drop in blood pressure followed induction with pentothal.

His wounds included penetrating injuries of the left calf and both thighs. Muscle destruction was about the size of one and one-half fists. Visible blood loss was only 100 to 300 cc. Preoperatively, his pressure remained 150/60 to 160/90. His pulse rate remained 60 to 70, respiratory rate 24. Sitting up for 3 minutes was associated with a sharp rise in pulse rate and in diastolic pressure.

At 1100 hours, 25 mg. of hexamethonium (Bistrium) was given intravenously. His systolic pressure dropped from 150 to 124 and the diastolic from 80 to 0 (Fig. 4). This was accompanied by a rise in the pulse rate from 68 to 126. There were no side effects. One and one-half hours later his pressure had returned to the pre-drug level but the pulse rate had fallen to only 96.

On admission to the operating room his pressure was 170/80, pulse rate 110. Pentothal induction was not associated with any marked change in the vital signs. Blood loss of approximately 75 cc. was accompanied by transfusion of 500 cc. of blood. The amount of anesthetic agents required to keep him from moving on the table seemed unduly large (weight of patient150 pounds, height 5 feet 10 inches, non-alcoholic). His pressure remained high throughout operation and slowly fell toward normal 24 hours later. There was a slight tendency toward hypertension noted during the ensuing week. On the seventh postoperative day his wounds were closed under general anesthesia. On entering the operating room his hypertension increased and persisted throughout operation. Again, large amounts of anesthesia were required to keep the patient from moving.

His entire course in the hospital was uneventful.

Patient No. 6. This 21-year-old 175-pound soldier was accidentally shot at close range by an M-1 rifle. The right patella was shattered and there was moderate destruction of the quadriceps muscle. The accident occurred at 2400 hours,

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FIGURE4.
Graphic illustration of study of Patient No. 5. A sharp fall in blood pressure
followed the administration of hexamethonium. This was the only patient in whom
pentothal did not cause a drop in blood pressure to normal levels.

FIGURE5.
Graphic illustration of study of Patient No. 6. Regitine caused a depression of the hypertension and
hexamethonium caused a profound drop in blood pressure but it again rose to a hypertensive level.
Demerol seemed to have no effect. The blood pressure fell after induction with pentothal.

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10 May 1953. At 0030 hours he was given 15 mg. of morphine and this was repeated at 0750 hours. Pain was evident in spite of heavy sedation.

On admission to the hospital his pressure was 160/90, pulse 92, respirations 24. He was quiet but somewhat nervous. His pulse was of fair quality. He appeared in excellent condition. His hematocrit was 48 per cent. His hypertension persisted.

He was found to be relatively insensitive to 5 mg. of Regitine intravenously, but very sensitive to 25 mg. of hexamethonium intravenously
(Fig. 5).

At the time of operation, he was sensitive to a small dose of pentothal. His operative course (débridement) was smooth except for the hypertension during induction. Postoperatively, his pressure was 140/90, thereafter his course was smooth.

Patient No. 7. This 24-year old soldier was wounded at 1350 hours, 20 March 1953, by the accidental discharge of his M-1 rifle. The bullet traversed the left arm, shattered the humerus, severed the radial and ulnar nerves, and left a pathway which would easily admit one`s fist. He was given albumin (100 cc.) and dextran (500 cc.) at the battalion aid station. He arrived at the hospital at 1530 hours. His blood pressure was 130/80, pulse 96. The radial pulsation was of low volume. His capillary refilling was good. He was nervous, shaking, and tossing his head. He complained of severe pain and moderate thirst. His skin color and temperature were approximately normal. He did not sweat.

At 1545 hours his blood pressure was 150/90, pulse 100.He was shifted to a sitting position for 1 minute. No change in his vital signs was discernible. He was then again placed in a supine position and his pressure rose to 170/120, pulse 92.

At 1552 hours, he was given morphine (15 mg., intravenously).His pupils constricted and he became quieter but his pressure remained elevated, 190/130 (at 1557 hours, 188/120, pulse 88). Catheterization at 1608 hours was followed by a rise of pressure to 210/130, pulse 88.

At 1630 hours, his pressure had subsided to 140/76, pulse 84. Regitine (5 mg.) was then given intravenously. Within 30 seconds his blood pressure dropped to 104/40, pulse 92. He became warmer and his pulse volume somewhat fuller. The hypotension persisted for only 2 minutes and his signs had returned to the pre-drug level after 8 minutes (Fig. 6).

At 1653 hours his blood pressure was 165/75, pulse 84. Hexamethonium (25 mg.) was given intravenously. Within 1 minute his pressure dropped to 130/60, pulse 108. Four minutes after the injection, his pressure reached its minimum of 90/40, pulse 112, and he was nauseated. The pressure had returned to 120/70, pulse 108, within 10 minutes. He remained pale. At 1730, his pressure was 140/90, pulse 96. The pressure was still steadily rising. His urine flow for the previous hour had been 8 cc.

With the pressure about 150/96, pentothal induction was begun. Immediately, the pressure fell to 90/60. It did not rise above 100/60, pulse 104, throughout the 1¹/2 hours of débridement. Muscle and bone injuries were extensive. Blood loss preoperatively was entirely into the swollen arm and approximated 500 to 1,000 cc. Blood (250cc.) was given during operation.

The following day his pressure ranged about 120 to 130 systolic, 90 diastolic. The pulse rate was 90/100. He was evacuated in good condition.

The hypertensive response in this patient was abolished by the sympathetic blocking agents and by anesthesia.

Patient No. 8. This 21-year-old American soldier was wounded at 1325 hours, 21 March 1953, by the accidental discharge of a .45 caliber pistol at

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FIGURE6.
Graphic illustration of study of Patient No. 7. Morphine had no effect on the hypertension. When Regitine
was given the blood pressure fell rapidly but returned rapidly to a hypertensive level. A sharp drop
occurred after hexamethonium. The blood pressure rose slowly but not as high as the pre-hexamethonium level.
A profound drop occurred after induction with pentothal.

close range. He was immediately given morphine (15 mg.).The wound included a severe fracture of the shaft of the right femur.

He was admitted to the hospital at 1630 hours via ambulance in excellent condition. There was no external evidence of blood loss. He lay perfectly quiet and seemed completely unemotional. In answer to questioning, he said he had rather severe pain. His blood pressure was 190/110, pulse96, respirations 18. The pulse was of good volume. Capillary refilling was good. The skin was warm and of normal color. There was no sweating and no thirst. The pupils were dilated.

The pressure rose spontaneously to 240/110 and then rapidly fell to a lower hypertensive level. Response to passive movement was minimal.

With the onset of pentothal anesthesia, his pressure fell rapidly from 170/100 to 130/80 (Fig. 7). Blood (500 cc.) was given during operation. The hematocrit postoperatively was 50 per cent. His subsequent course was smooth.

This patient`s hypertension disappeared after administration of pentothal.

Patient No. 9. This 19-year-old American soldier had been searching for an enemy sniper during the night. At 0645 hours, he was shot by the sniper. The wound penetrated the left deltoid area and shattered the neck of the humerus and perforated the scapula. Judging from the blood on his clothing and bandages, the external blood loss was minimal (150 to 250 cc.). Subsequent exploration, however, revealed moderately extensive soft tissue destruction.

At 0700 hours he was given morphine (15 mg.) subcutaneously. At 0815 hours his blood pressure was 135/80, pulse 76.

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FIGURE7.
Graphic illustration of study of Patient No. 8. The blood pressure fell spontaneously
to 160/70 before passive movement of the legs was started. The blood pressure dropped
following the administration of pentothal.

At 1015 hours after arrival at the hospital and without further therapy his blood pressure was 164/100, pulse 76, respirations 22 per minute. The radial pulse was of good quality; the respiratory movements regular and shallow. He complained of no pain but was moderately thirsty. His skin was normal in temperature and color. His pupils were not constricted. His peripheral veins were barely visible before the application of a tourniquet. He was reassured but stated that he was not unduly nervous.

During the ensuing 20 minutes, after having rested quietly on the litter for 1 hour, his pressure was 170/100, pulse 72, respirations 24.

Passive movement of the lower extremities was then begun and continued in bicycle-like fashion for 10 minutes. This was a painless procedure. Within 1 minute his pressure had risen to 185/100, pulse 78, respirations 21. At the end of 10 minutes of movement his blood pressure was 185/100, pulse 90, respirations 21. The depth of respiration was unchanged.

Two minutes after the movement was stopped the pulse rate had fallen to 76 but the pressure remained 184 systolic. Five minutes after the movement was stopped, the blood pressure and pulse had returned to the pre-movement levels. This was followed by a second spontaneous rise associated with pain, restlessness and movement. Forty-five minutes after the cessation of passive movement, the patient was quiet, blood pressure 160/105, pulse 76, respirations 20.

Morphine (10 mg.) was then given intravenously at 1130 hours. Immediately, he fell asleep. The only changes noted were a slight drop in pressure

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to 152/100, a slight slowing and deepening of the respirations, and the constriction of the pupils. He remained in this condition for 45 minutes.

At 1245 hours his pressure was down to 126/70, pulse 98. He was still asleep. With the induction of anesthesia, pentothal, ether, oxygen and nitrous oxide, his pressure dropped to 95/65. This then rose spontaneously to 120/80 and was maintained about this level for 2 hours of anesthesia (1 hour of surgical débridement). Modified fluid gelatin (250 cc.) was given during the latter part of the operation as his pulserate rose to 110 per minute.

On admission to the postoperative ward, 1500 hours, his pressure rose and stabilized at 130/100, pulse 120, respirations 20 per minute. His subsequent course was smooth.

Passive movement of the extremities was followed by a moderate rise in blood pressure.

Patient No. 10. This 26-year-old Korean soldier stepped on a land mine and suffered a compound fracture of the left tibia and fibula at the ankle, at 1520 hours, 13 May 1953. On admission to the battalion aid station 10 minutes later his hematocrit was 43 per cent. He arrived at the hospital at 1730 hours with blood pressure 145/90 and pulse 96. Soon thereafter his blood pressure was 170/110, pulse 80, and he complained of severe pain. His hands were warm, pulse was bounding and capillary refilling was fair. His blood pressure continued to be elevated to 175/110, pulse 78, for the next hour. His head was tilted up to 30 degrees for 6 minutes, but there was no appreciable change in the blood pressure. He was given morphine (10 mg.) intravenously at 1850 hours and there was no change in his blood pressure. At 1900 hours, his blood pressure was185/115, pulse 98. Again, he was tilted with the head up 30 degrees for a period of 10 minutes and there was no change in his blood pressure. He was observed for an additional hour and his blood pressure remained 164/112,pulse 110. He was taken to the operating room at 2040 hours and spinal anesthesia was induced. His blood pressure fell immediately to 140/90.The leg was amputated and the patient was evacuated the following day in good condition.

Neither morphine nor elevation of the head 30 degrees on two occasions affected the patient`s hypertension. The blood pressure, however, dropped sharply with spinal anesthesia.

The response to trauma is a response of every system and every organ in the body. This study reflects, in part, the response of the cardiovascular and sympathetic nervous system.

The hypertensive response to injury is not infrequent. This response does not necessarily occur within minutes after the injury. Some patients may have a normal pressure for a period and become hypertensive a few hours later. The response may persist for several hours. The pulse volume is usually good and the pulse rate is not markedly accelerated.

Changes in posture had little effect on the hypertension. It appears that this compensatory response was of such nature that it could not be abolished by elevating the head.

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The administration of large doses of morphine seldom affected the hypertensive response. Although some of the patients were moderately apprehensive and complained of pain, their hypertension persisted in spite of analgesia sufficient to cause them to fall asleep. Although pain was a rather common factor in all the casualties showing this response, it did not appear that pain was the sole factor causing the hypertension. Likewise, fear, excitement and other emotional stimuli cannot be called the sole etiologic agents although they may be contributing factors.

The systolic pressure varied from patient to patient between 140 and 240 mm. The diastolic pressure ranged between 80 and 100. The pulse pressure was invariably elevated, usually between 70 and 80 mm. and occasionally as high as 100 mm. Thus the pulse pressure and the mean pressure were elevated and there was suggestive evidence of both increased cardiac output and vasoconstriction. Burton¹ has suggested the possibility of aortic constriction as the cause of the hypertension.

In each instance the blood pressure fell after general or spinal anesthesia. Pentothal has previously been reported to be a sympathetic ganglionic depressant.⁶ Its administration was followed by a profound drop in pressure in several of the hypertensive patients. There was an immediate fall in blood pressure when Regitine or hexamethonium was given. These agents seemed to block the hypertensive response. Further study may indicate that the clinical picture presented by Patient No. 6, with a slow pulse, a marked hypertension, and a profound sensitivity to a ganglionic blocking agent, is mediated through the sympathetic nervous system by action of noradrenalin. On the other hand, an occasional patient with a labile blood pressure, rapid pulse, and a lesser sensitivity to sympathetic blocking agents may prove to have, in addition to the response of the nervous system, an adrenalin response through the adrenal medulla. In this latter group, fear and excitement may prove to be significant contributing factors to the production of the hypertension. Pain may be the foremost stimulus in some instances. It would appear that the hypertension seen immediately after injury was a response of the sympathetic nervous system due, perhaps, to efferent stimulation from the extremities. Although the exact mechanism is not clear, there is evidence that it is mediated through the sympathetic nervous system.

Grant and Reeves⁵ felt that hypertension was not an uncommon sequel to limb injuries and was usually associated with small or moderate wounds and blood volumes within 20 per cent of the predicted normal. They believed that the hypertension was the result of emo-

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tional and sensory stimuli associated with the injury. It was their impression that hypertension following injury in untransfused casualties was of good prognostic import. All of the patients in our series recovered, some of them after fairly severe injuries. Although this response most frequently followed injuries to the extremity it was occasionally seen associated with abdominal or thoracic wounds. It appears that the hypertensive response is an indication of the natural responsiveness of the patient. It is well recognized that responsiveness of the patient is one of the best indications of his future outcome. It appears that a hypertensive response to injury is an indication of a very favorable prognosis.

During the last 6 months of the Korean conflict, 52 casualties were observed who showed a hypertensive response (systolic blood pressure above 140 mm. of mercury) to their injury. This hypertension occurred within a few minutes to several hours after injury, and usually persisted until anesthesia was induced.

Most of the patients had moderate wounds of the extremities. In two patients in whom blood volume was measured, the deficiency was approximately 25 per cent.

Changes in posture (elevation of the head) and analgesic agents (morphine and demerol intravenously) did not affect the hypertension.

In every instance except one, the hypertension disappeared following the induction of general or spinal anesthesia.

Hexamethonium abolished and Regitine depressed the hypertensive response.

Although the exact mechanism of the hypertensive response to injury is not clear, the response appears to be mediated through the sympathetic nervous system. It is believed that hypertension, following injuries that do not involve the brain and spinal cord, is a good indication of the responsiveness of the battle casualty and is an indication of a favorable prognosis. 

The authors wish to acknowledge the stimulation and assistance of Dr. A. C. Corcoran of Cleveland, Ohio.

1. Burton, A. C.: Proceedings of the Josiah Macy, Jr., Foundation`s Third Conference on Shock and Circulatory Homeostasis. To be published.

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2. Emlet, J. R., Grimson, K. S., Bell, D. M., and Orgain, E. S.: Use of Piperoxan and Regitine as Routine Tests in Patients with Hypertension. J. A. M. A. 146: 1383, 1951.

3. Emlet, J. R., Grimson, K. S., and Metcalf, B. H.: Comparison of Adrenolytic Blocking Effects of Regitine and Benodaine. Am. J. Med.11:241, 1951.

4. Freis, E. D., Schnaper, H. W., Johnson, R. L., Rose, J. C., and Finnerty, F. A., Jr.: Clinical Evaluation of Hexamethonium, A New Ganglionic Blocking Agent. Preliminary Report. Am. J. Med. 11:242, 1951.

5. Grant, R. T., and Reeves, E. B.: Observations on the General Effect of Injury in Man, Medical Research Council, Special Report,  No. 217, His Majesty`s Stationery Office, London, 1951.

6. Larrabee, M. G., and Holaday, D. A.: Depression of Transmission through Sympathetic Ganglia during General Anesthesia. J. Pharmacol. and Exper. Therap. 105: 400, 1952.

7. Paton, W. D. M., and Zaimis, E. J.: The Pharmacological Actions of Polymethylene Bistrimethylammonium Salts. Brit. J. Pharmacol.4:381, 1949.

8. Schnaper, H. W., Johnson, R. L. Tuohy, E. B., and Freis, E. D.: The Effect of Hexamethonium as Compared to Procaine or Metycaine Lumbar Block on the Blood Flow to the Foot of Normal Subjects. J. Clin. Investigation 30: 786, 1951.