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Experimental Hypertension and Retinal Arterial Spasm
EXPERIMENTAL HYPERTENSION AND RETINAL ARTERIAL SPASM S. A. AGATSTON, M.D. NEW YORK CITY
The injection of fecal extract and blood serum from patients with essential hyper tension caused spasms of the retinal artery in rabbits. This effect was also noted in both rabbits and man after the injection of adrenalin. The author believes that if the cause of spasm can be found, the problem of essential hypertension will be solved. Read be fore the New York Academy of Medicine, Ophthalmological Section, May 16, 1932. From the ophthalmological service of Montefiore Hospital and Bellevue Hospital.
Most of the experimental work on hypertension in the past has been pur sued with the aim of producing lipoid degeneration and atheroma. Clinical observation shows that atheroma may exist without hypertension and that hypertension may exist without ather oma. Fishberg pointed out that ather oma and peripheral arteriosclerosis is frequently found in patients with myxoedema, and experimentally in duced atheromatous and renal changes in animals. Thyroid extract administra tion resulted in improvement. Newburgh and Clarkson report ex perimental work on rabbits in which atheroma, starting in the intima, was produced by a high protein diet. They denied the claim of Saltykow that cholesterin in the yolk of eggs and in milk caused atheroma in rabbits. Hans Liebig produced arteriosclerotic lesions in the aorta of rabbits by ad ministering cholesterin and linseed oil. Iodide prevented this effect. Hering claims that the function of the depressor nerves is to inhibit adre nalin secretion. C. Heymans and J. J. Bouckaert working on rabbits, showed that sec tion of the depressor nerves at the aorta and at the carotid sinus resulted not orily in tachycardia, but also in hyper tension. The heartbeat rose to 200-250 and the blood pressure to 250 mm. Hg. Depressants and digitalis had no effect on these animals. The same result was produced by Herring and others. Raab's animal experimentation brought out that lactic acid in a five percent solution caused a rise in blood pressure from 105 to 176. Carbon di oxide also caused an elevation of the
blood pressure. Sensitivity to it was materially augmented by the presence of lactic acid. Inhalation of carbon di oxide increased the hypertension in duced by lactic acid. This he claimed was produced by ischaemia of the med ullary center. Bell and Pedersen claimed that only a small percentage of advanced periph eral arteriosclerosis showed sclerotic changes in the arterioles; also that stimulation of the adrenals produced high blood pressure. This phenomenon is born out clinically. In Addison's dis ease, characterized by atrophy of the adrenals, the blood pressure is low. In neoplasm of the suprarenal gland, there occurs a paroxysmal elevation of the blood pressure. Cushing's experiment of introducing a canula into the subdural space dem onstrated that intracranial pressure and blood pressure could be made to rise to gether. Bell and Pedersen give a résumé of the various factors to be considered in hypertension. They are as follows: Psychic—worry, fear, excitement. Nephrosis causes very little hyperten sion. Glomerular nephritis is almost in variably associated with hypertension. Both kidneys may be removed without producing hypertension. Urinary ob struction below the kidney will cause hypertension. Blocking of the renal vein (experimental) will also cause hy pertension. They also claim that the original narrowing of the arterioles is spastic. Acute fulminating hyperten sion is probably of renal origin. Santenoise, Verdier and Vidacovitch isolated a hormone (which they called vagotonine) from insulin by means of neutral salts and alcohol. This vago-
327
S. A. AGATSTON
328
Table 1 INJECTIONS WITH FECAL ÌEXTRACT
Date
Rabbit no. 952 no. 950 1 ce.— }i c e — 1 ce.— Ϋ2 c e —
Date no. 953 2.5 c e . — 1/27/31 2.5 c e . — 1/28/31 5 ce* 1/29/31 S ce* 1/30/31 10 ce** 1/31/31 10 ce.** 2/1/31 10 ce* 2/3/31 10 ce* 2/5/31 10 ce* 2/6/31 10 ce* 2/7/31
Rabbit no. 938 no. 940 8 ce** 12 ce** ;l/2 to 2 hours 8 ce.** 12 ce*** after 8 ce** 12 ce*** injection 10 ce** 14 ce*** 10 ce** 14 ce*** 10 ce** 14 ce** 10 ce** 16 ce**
11/25/30 11/26/30 11/28/30 3 ce* 2 ce* 12/3/30 3 ce* 2 ce* 12/4/30 7.5 ce* 5 ce** 12/5/30 7.5 ce* 5 ce*** 12/6/30 7.5 ce* 5 ce*** 12/7/30 7.5 ce* 5 ce*** 10 ce** 16 ce** 12/11/30 7.5 ce* 5 ce*** 12 ce** 16 ce** 12/13/30 7.5 ce* 5 ce*** 12 ce** 16 ce.** 12/15/30 8 ce** 6 ce*** 12 ce* 12/16/30 8 ce* 6 ce*** 12 ce* 12/17/30 8 ce* 6 ce*** 12 C.C.*12/19/30 8 ce.*— 6 ce.*** 12 c.c*12/20/30 6 ce*** 12/21/30 7 ce*** 12/22/30 7 ce*** 12/24/30 7 ce*** 12/26/30 7 ce*** 12/27/30 Feces extract was made by allowing feces to stand in an equal amount of normal saline from 12 to 24 hours, then filtering through Berkefeld filter, filtrate being sterile. All in jections were intraperitoneal. Asterisks in this and succeeding tables indicate degree of intensity of reaction following injection of amount specified. Dash indicates no reaction. Spasms manifested themselves as irregular paling and alternating changes in color and caliber of retinal arteries. Smaller branches seemed to disappear entirely. Rabbit No. 952 showed the most marked spasm; No. 950 reacted next best; and No. 953 practically not at all. No. 938 showed moderate spasm; No. 940 marked spasm. Rabbits No. 950 and 953 began to show so little that they were discarded on Dec. 20, probably having become immune to toxin. Rabbit No. 952 Autopsy findings—autolysis— some peritonitis, which probably caused death. Eyes removed for microscopic study. No arteriosclerosis was found.
Table 2 INJECTIONS WITH BLOOD SERUM OF PATIENTS WITH HYPERTENSION
Date 3/3/31 3/4/31 3/5/31 3/6/31 3/7/31 3/8/31 3/9/31 3/10/31
no. 943 3 cc*** 3 cc*** 3 ce* 4 ce* 4 ce* 4 ce* 4 4 ce*
Rabbit
no. 949 3 ce* y2 to 2 hrs. after 3 3 ce* injection 4 ce* 4 ce* 4 ce* 4 ce*— 4 ce—
Date
Rabbit no. 946 ce.— ce. **
no. 944
3/24/31* 3/25/31 3/26/31 3/27/31
ce.— ce.*— ce—
reaction 20 to 30 min utes after injection
ce*
INJECTIONS WITH ADRENALIN
Rabbit 3/28/31 3 minutes 5 10
15 30
no. 944 6 ce
"
"
no spasm slight if any
no. 946 6 ce marked spasm it H spasm decreasing slight spasm
November 7th two rabbits were injected with yï c e adrenalin (1-20,000). One showed marked spasm 3 minutes after injection. The other showed no spasms.* * Since writing this paper, I have injected four rabbits with adrenalin and have obtained arterial spasms in three. This brings the total number of rabbits injected to six, with posi tive results in four.
EXPERIMENTAL HYPERTENSION
tonine has a stimulating effect on the vagus, or oculo-cardiac reflex, causing hypotension. They claim that insulin contains two hormones, one inducing hypoglycaemic action, the other having a hypotensive effect. They found that some samples of insulins do not con tain vagotonine which would modify the action on the vagus. With others
329
Passing through the kidney and other organs this compound splits up again, freeing the hormone, which can be identified in the urine. In the study of the etiology of arteri osclerosis many factors must be con sidered. In order to reach any definite conclusion we should get rid of the term "generalized arteriosclerosis," and
Table 3 INJECTION OF PATIENTS W I T H ADRENALIN
A. G. 25 yrs. Phys. condition—normal B.P. before injection 125/30 1 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 135/70 spasm not appreciable 10 m. " " B.P. 160/85 retinal arteries show spasm 15 m. " " B.P. 180/90 retinal spasm marked 20 m. " " B.P. 150/80 no spasm J. D. 38 yrs. B.P. 130/80 1 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 150/85 no spasm 10 m. " " B.P. 160/85 spasm slight 15 m. " " B.P. 160/85 spasm but not marked A. C. 26 yrs. B.P. 120/60 \Ϋ2 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection. B.P. 135/70 no spasm 10 m. " " BP. 170/80 vessels around disc show spasm 15 m. " " B.P. 185/85 marked spasm O. H. 26 yrs. B.P. 125/60 V/z c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 130/65 10 m. " " B.P. 135/65 slight spasm 15 m. " " B.P. 140/70 E. M. 26 yrs. B.P. 125/60 \y2 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 130/65 slight spasm 10 m. " " B.P. 145/70 slight spasm A. M. 46 yrs. τ B.P. 130/70 \ /ι c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 160/75 slight spasm 10 m. " " B.P. 180/80 definite spasm E. S. 37 yrs. τ B.P. 135/60 Ι /ί c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 170/80 spasm 10 m. " " B.P. 190/85 marked spasm 15 m. " " B.P. 170/70 slight spasm 20 m. " " B.P. 150/60 no spasm
they concluded that the depressing ef make an attempt to classify this disease fect on the vagus caused secretion of from the etiological standpoint. Myocardial and renal disease, as well adrenalin. Frey also found that the pancreas as senile arteriolar disease may produce contained a circulatory hormone, which hypertension. However the great group produced dilatation of small blood ves of hypertension cases should be classi sels causing hypotension. Intramuscu fied as a primary disease, caused by lar injection of this hormone produced arteriolar spasms followed by second a lasting effect in cases of hypertension. ary changes in the spastic arterioles. This substance forms some combina This group falls under the head of es tion in the blood, which is inactive. sential hypertension and arteriolar dis-
330
S. A. AGATSTON
ease. The work which has been done up to the present seems to point to the following hypotheses : 1. Spasms of the visceral and cere bral arterioles cause hypertension. 2. Spasms are caused by increased secretion of adrenalin. 3. Stimulation of the depressor nerve of the vagus causes a diminished adre nalin secretion and hypotension. 4. A paralyzing effect on the depres sor causes increased secretion of adre nalin and hypertension. 5. This paralyzing effect on the de pressor nerve may be caused by a dis turbance of the normal function of the thyroid, pancreatic, and pituitary glands. 6. Some change in the blood chem istry or the presence of certain toxins may cause the underlying endocrine disturbance producing hypertension. 7. "Vagotonine", a hormone ex tracted from insulin, has a hypotensive action. While subjective symptoms may suggest the occurrence of arteriolar spasm in the brain or elsewhere, objec tive signs are available only when the spasm occurs in the retinal artery. It seems self-evident that if the cause of spasms is found, the problem of es
sential hypertension and arteriolar dis ease will be solved. Starting with this premise, I thought it would further the progress of this study, if spasms could be produced ex perimentally and observed in the fundi. Normal rabbits were given intraperitoneal injection of the fecal extract from patients without hypertension. This was followed by the injection of blood serum from patients without hy pertension. W e then used fecal extract and blood serum taken from patients with essential hypertension in the ac tive stage. Finally adrenalin was injected into rabbits and normal human subjects. Spasms in the retinal arteries were induced in rabbits by the injection of fecal extract and of blood serum from patients with active hypertension, and in both rabbits and man also by the in jection of adrenalin. The controls were negative. 1 wish to express my thanks to Dr. M. Abeles of Montefiore Hospital for his able assistance in the experi mental work on rabbits; also to Drs. David Marine and E. J. Bauman of the pathological laboratories of Montefiore Hospital for their helpful cooperation. 2 West Eighty-seventh street.
References Agatston, S. A. Retinal angiospasm. Its relation to arteriolar disease. Amer. Jour. Ophth., 1930, April, v. 13, No. 4, pp. 309-313. Barker, Lewellys F. Paroxysmal angiospasm with gastric symptoms. Amer. Jour. Med. Sa, May, 1910. Bell, E. T. and Pederson, A. H. Ann. of Int. Med., 1930, Sept., v. 4, pp. 227-237. Cushing, H. Bull. Johns Hopkins Hospital, 1901, v. 12, p. 290. Fishberg, A. M. Thyroid deficiency. Jour. Amer. Med. Ass'n, 1924, Feb. 9, v. 82.1 Frey, E. K. Circulatory hormone of pancreas. Its therapeutic uses. Deutsche Ztschr. f. Chir., 1931, Oct. 21, pp. 233-481-544. Hering, H. E. Verhandl. d. deutsch Gesellsch. f. inn Med., 43. Kong., 1931, pp. 141-144. Heymans C. and Bouckaert, J. J. Chronic and experimental arterial hypertension. Compt. rend. Soc. de Biol., 1931, Feb. 20, v. 106, pp. 471-473. Knapp, Arnold. Cramp of the retinal vessels. Jour. Amer. Med. Ass'n, 1910, June 25, v. 54', p. 2118. Levin, I. and Larkin. Mechanical theory. Jour. Exp. Med., 1911, v. 29. Liebig, H. Riforma Med., 1931, Sept. 14, v. 47, pp. 1400-1401. Newburgh, L. H. and Clarkson, Sarah. Arch. Int. Med., 1923, May, v. 31, p. 653. Raab, W. Central vasomotor irritability. Contribution to the problem of essential hyper tension. Arch. Int. Med., 1931, May, v. 47, pp. 727-758. . Cerebro-médullary ischaemia as a cause of essential hypertension. Med. Klin., 1931, Feb. 13, v. 27, pp. 248-251. Saltykow. Beitr. z. path. Anat., 1913-1914, v. 57, p. 415. Santenoise, D., Verdier, H., and Vidacovitch, M. Isolation of new pancreatic hormone, which regulates vagai activity (vagotonine). Rev. franc. d'Endocrinol., 1930, June, pp. 204-260. Simmonds, M. Atrophie des Hypophysisvorderlappens and hypophysäre Kachexie. Deutsche med. Wchnschr., 1918, v. 44, p. 852. Sokolow, A. S. Relation of hypertension and allergy. Ztschr. f. Kinderheilkunde, 1930, v. 50, p. 661. Wagener, H. P. Retinal vascular changes in hypertension. Ann. Int. Med., Sept., 1930.
The injection of fecal extract and blood serum from patients with essential hyper tension caused spasms of the retinal artery in rabbits. This effect was also noted in both rabbits and man after the injection of adrenalin. The author believes that if the cause of spasm can be found, the problem of essential hypertension will be solved. Read be fore the New York Academy of Medicine, Ophthalmological Section, May 16, 1932. From the ophthalmological service of Montefiore Hospital and Bellevue Hospital.
Most of the experimental work on hypertension in the past has been pur sued with the aim of producing lipoid degeneration and atheroma. Clinical observation shows that atheroma may exist without hypertension and that hypertension may exist without ather oma. Fishberg pointed out that ather oma and peripheral arteriosclerosis is frequently found in patients with myxoedema, and experimentally in duced atheromatous and renal changes in animals. Thyroid extract administra tion resulted in improvement. Newburgh and Clarkson report ex perimental work on rabbits in which atheroma, starting in the intima, was produced by a high protein diet. They denied the claim of Saltykow that cholesterin in the yolk of eggs and in milk caused atheroma in rabbits. Hans Liebig produced arteriosclerotic lesions in the aorta of rabbits by ad ministering cholesterin and linseed oil. Iodide prevented this effect. Hering claims that the function of the depressor nerves is to inhibit adre nalin secretion. C. Heymans and J. J. Bouckaert working on rabbits, showed that sec tion of the depressor nerves at the aorta and at the carotid sinus resulted not orily in tachycardia, but also in hyper tension. The heartbeat rose to 200-250 and the blood pressure to 250 mm. Hg. Depressants and digitalis had no effect on these animals. The same result was produced by Herring and others. Raab's animal experimentation brought out that lactic acid in a five percent solution caused a rise in blood pressure from 105 to 176. Carbon di oxide also caused an elevation of the
blood pressure. Sensitivity to it was materially augmented by the presence of lactic acid. Inhalation of carbon di oxide increased the hypertension in duced by lactic acid. This he claimed was produced by ischaemia of the med ullary center. Bell and Pedersen claimed that only a small percentage of advanced periph eral arteriosclerosis showed sclerotic changes in the arterioles; also that stimulation of the adrenals produced high blood pressure. This phenomenon is born out clinically. In Addison's dis ease, characterized by atrophy of the adrenals, the blood pressure is low. In neoplasm of the suprarenal gland, there occurs a paroxysmal elevation of the blood pressure. Cushing's experiment of introducing a canula into the subdural space dem onstrated that intracranial pressure and blood pressure could be made to rise to gether. Bell and Pedersen give a résumé of the various factors to be considered in hypertension. They are as follows: Psychic—worry, fear, excitement. Nephrosis causes very little hyperten sion. Glomerular nephritis is almost in variably associated with hypertension. Both kidneys may be removed without producing hypertension. Urinary ob struction below the kidney will cause hypertension. Blocking of the renal vein (experimental) will also cause hy pertension. They also claim that the original narrowing of the arterioles is spastic. Acute fulminating hyperten sion is probably of renal origin. Santenoise, Verdier and Vidacovitch isolated a hormone (which they called vagotonine) from insulin by means of neutral salts and alcohol. This vago-
327
S. A. AGATSTON
328
Table 1 INJECTIONS WITH FECAL ÌEXTRACT
Date
Rabbit no. 952 no. 950 1 ce.— }i c e — 1 ce.— Ϋ2 c e —
Date no. 953 2.5 c e . — 1/27/31 2.5 c e . — 1/28/31 5 ce* 1/29/31 S ce* 1/30/31 10 ce** 1/31/31 10 ce.** 2/1/31 10 ce* 2/3/31 10 ce* 2/5/31 10 ce* 2/6/31 10 ce* 2/7/31
Rabbit no. 938 no. 940 8 ce** 12 ce** ;l/2 to 2 hours 8 ce.** 12 ce*** after 8 ce** 12 ce*** injection 10 ce** 14 ce*** 10 ce** 14 ce*** 10 ce** 14 ce** 10 ce** 16 ce**
11/25/30 11/26/30 11/28/30 3 ce* 2 ce* 12/3/30 3 ce* 2 ce* 12/4/30 7.5 ce* 5 ce** 12/5/30 7.5 ce* 5 ce*** 12/6/30 7.5 ce* 5 ce*** 12/7/30 7.5 ce* 5 ce*** 10 ce** 16 ce** 12/11/30 7.5 ce* 5 ce*** 12 ce** 16 ce** 12/13/30 7.5 ce* 5 ce*** 12 ce** 16 ce.** 12/15/30 8 ce** 6 ce*** 12 ce* 12/16/30 8 ce* 6 ce*** 12 ce* 12/17/30 8 ce* 6 ce*** 12 C.C.*12/19/30 8 ce.*— 6 ce.*** 12 c.c*12/20/30 6 ce*** 12/21/30 7 ce*** 12/22/30 7 ce*** 12/24/30 7 ce*** 12/26/30 7 ce*** 12/27/30 Feces extract was made by allowing feces to stand in an equal amount of normal saline from 12 to 24 hours, then filtering through Berkefeld filter, filtrate being sterile. All in jections were intraperitoneal. Asterisks in this and succeeding tables indicate degree of intensity of reaction following injection of amount specified. Dash indicates no reaction. Spasms manifested themselves as irregular paling and alternating changes in color and caliber of retinal arteries. Smaller branches seemed to disappear entirely. Rabbit No. 952 showed the most marked spasm; No. 950 reacted next best; and No. 953 practically not at all. No. 938 showed moderate spasm; No. 940 marked spasm. Rabbits No. 950 and 953 began to show so little that they were discarded on Dec. 20, probably having become immune to toxin. Rabbit No. 952 Autopsy findings—autolysis— some peritonitis, which probably caused death. Eyes removed for microscopic study. No arteriosclerosis was found.
Table 2 INJECTIONS WITH BLOOD SERUM OF PATIENTS WITH HYPERTENSION
Date 3/3/31 3/4/31 3/5/31 3/6/31 3/7/31 3/8/31 3/9/31 3/10/31
no. 943 3 cc*** 3 cc*** 3 ce* 4 ce* 4 ce* 4 ce* 4 4 ce*
Rabbit
no. 949 3 ce* y2 to 2 hrs. after 3 3 ce* injection 4 ce* 4 ce* 4 ce* 4 ce*— 4 ce—
Date
Rabbit no. 946 ce.— ce. **
no. 944
3/24/31* 3/25/31 3/26/31 3/27/31
ce.— ce.*— ce—
reaction 20 to 30 min utes after injection
ce*
INJECTIONS WITH ADRENALIN
Rabbit 3/28/31 3 minutes 5 10
15 30
no. 944 6 ce
"
"
no spasm slight if any
no. 946 6 ce marked spasm it H spasm decreasing slight spasm
November 7th two rabbits were injected with yï c e adrenalin (1-20,000). One showed marked spasm 3 minutes after injection. The other showed no spasms.* * Since writing this paper, I have injected four rabbits with adrenalin and have obtained arterial spasms in three. This brings the total number of rabbits injected to six, with posi tive results in four.
EXPERIMENTAL HYPERTENSION
tonine has a stimulating effect on the vagus, or oculo-cardiac reflex, causing hypotension. They claim that insulin contains two hormones, one inducing hypoglycaemic action, the other having a hypotensive effect. They found that some samples of insulins do not con tain vagotonine which would modify the action on the vagus. With others
329
Passing through the kidney and other organs this compound splits up again, freeing the hormone, which can be identified in the urine. In the study of the etiology of arteri osclerosis many factors must be con sidered. In order to reach any definite conclusion we should get rid of the term "generalized arteriosclerosis," and
Table 3 INJECTION OF PATIENTS W I T H ADRENALIN
A. G. 25 yrs. Phys. condition—normal B.P. before injection 125/30 1 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 135/70 spasm not appreciable 10 m. " " B.P. 160/85 retinal arteries show spasm 15 m. " " B.P. 180/90 retinal spasm marked 20 m. " " B.P. 150/80 no spasm J. D. 38 yrs. B.P. 130/80 1 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 150/85 no spasm 10 m. " " B.P. 160/85 spasm slight 15 m. " " B.P. 160/85 spasm but not marked A. C. 26 yrs. B.P. 120/60 \Ϋ2 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection. B.P. 135/70 no spasm 10 m. " " BP. 170/80 vessels around disc show spasm 15 m. " " B.P. 185/85 marked spasm O. H. 26 yrs. B.P. 125/60 V/z c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 130/65 10 m. " " B.P. 135/65 slight spasm 15 m. " " B.P. 140/70 E. M. 26 yrs. B.P. 125/60 \y2 c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 130/65 slight spasm 10 m. " " B.P. 145/70 slight spasm A. M. 46 yrs. τ B.P. 130/70 \ /ι c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 160/75 slight spasm 10 m. " " B.P. 180/80 definite spasm E. S. 37 yrs. τ B.P. 135/60 Ι /ί c.c. adrenalin (1-1000) injected hypodermically 5 m. after injection B.P. 170/80 spasm 10 m. " " B.P. 190/85 marked spasm 15 m. " " B.P. 170/70 slight spasm 20 m. " " B.P. 150/60 no spasm
they concluded that the depressing ef make an attempt to classify this disease fect on the vagus caused secretion of from the etiological standpoint. Myocardial and renal disease, as well adrenalin. Frey also found that the pancreas as senile arteriolar disease may produce contained a circulatory hormone, which hypertension. However the great group produced dilatation of small blood ves of hypertension cases should be classi sels causing hypotension. Intramuscu fied as a primary disease, caused by lar injection of this hormone produced arteriolar spasms followed by second a lasting effect in cases of hypertension. ary changes in the spastic arterioles. This substance forms some combina This group falls under the head of es tion in the blood, which is inactive. sential hypertension and arteriolar dis-
330
S. A. AGATSTON
ease. The work which has been done up to the present seems to point to the following hypotheses : 1. Spasms of the visceral and cere bral arterioles cause hypertension. 2. Spasms are caused by increased secretion of adrenalin. 3. Stimulation of the depressor nerve of the vagus causes a diminished adre nalin secretion and hypotension. 4. A paralyzing effect on the depres sor causes increased secretion of adre nalin and hypertension. 5. This paralyzing effect on the de pressor nerve may be caused by a dis turbance of the normal function of the thyroid, pancreatic, and pituitary glands. 6. Some change in the blood chem istry or the presence of certain toxins may cause the underlying endocrine disturbance producing hypertension. 7. "Vagotonine", a hormone ex tracted from insulin, has a hypotensive action. While subjective symptoms may suggest the occurrence of arteriolar spasm in the brain or elsewhere, objec tive signs are available only when the spasm occurs in the retinal artery. It seems self-evident that if the cause of spasms is found, the problem of es
sential hypertension and arteriolar dis ease will be solved. Starting with this premise, I thought it would further the progress of this study, if spasms could be produced ex perimentally and observed in the fundi. Normal rabbits were given intraperitoneal injection of the fecal extract from patients without hypertension. This was followed by the injection of blood serum from patients without hy pertension. W e then used fecal extract and blood serum taken from patients with essential hypertension in the ac tive stage. Finally adrenalin was injected into rabbits and normal human subjects. Spasms in the retinal arteries were induced in rabbits by the injection of fecal extract and of blood serum from patients with active hypertension, and in both rabbits and man also by the in jection of adrenalin. The controls were negative. 1 wish to express my thanks to Dr. M. Abeles of Montefiore Hospital for his able assistance in the experi mental work on rabbits; also to Drs. David Marine and E. J. Bauman of the pathological laboratories of Montefiore Hospital for their helpful cooperation. 2 West Eighty-seventh street.
References Agatston, S. A. Retinal angiospasm. Its relation to arteriolar disease. Amer. Jour. Ophth., 1930, April, v. 13, No. 4, pp. 309-313. Barker, Lewellys F. Paroxysmal angiospasm with gastric symptoms. Amer. Jour. Med. Sa, May, 1910. Bell, E. T. and Pederson, A. H. Ann. of Int. Med., 1930, Sept., v. 4, pp. 227-237. Cushing, H. Bull. Johns Hopkins Hospital, 1901, v. 12, p. 290. Fishberg, A. M. Thyroid deficiency. Jour. Amer. Med. Ass'n, 1924, Feb. 9, v. 82.1 Frey, E. K. Circulatory hormone of pancreas. Its therapeutic uses. Deutsche Ztschr. f. Chir., 1931, Oct. 21, pp. 233-481-544. Hering, H. E. Verhandl. d. deutsch Gesellsch. f. inn Med., 43. Kong., 1931, pp. 141-144. Heymans C. and Bouckaert, J. J. Chronic and experimental arterial hypertension. Compt. rend. Soc. de Biol., 1931, Feb. 20, v. 106, pp. 471-473. Knapp, Arnold. Cramp of the retinal vessels. Jour. Amer. Med. Ass'n, 1910, June 25, v. 54', p. 2118. Levin, I. and Larkin. Mechanical theory. Jour. Exp. Med., 1911, v. 29. Liebig, H. Riforma Med., 1931, Sept. 14, v. 47, pp. 1400-1401. Newburgh, L. H. and Clarkson, Sarah. Arch. Int. Med., 1923, May, v. 31, p. 653. Raab, W. Central vasomotor irritability. Contribution to the problem of essential hyper tension. Arch. Int. Med., 1931, May, v. 47, pp. 727-758. . Cerebro-médullary ischaemia as a cause of essential hypertension. Med. Klin., 1931, Feb. 13, v. 27, pp. 248-251. Saltykow. Beitr. z. path. Anat., 1913-1914, v. 57, p. 415. Santenoise, D., Verdier, H., and Vidacovitch, M. Isolation of new pancreatic hormone, which regulates vagai activity (vagotonine). Rev. franc. d'Endocrinol., 1930, June, pp. 204-260. Simmonds, M. Atrophie des Hypophysisvorderlappens and hypophysäre Kachexie. Deutsche med. Wchnschr., 1918, v. 44, p. 852. Sokolow, A. S. Relation of hypertension and allergy. Ztschr. f. Kinderheilkunde, 1930, v. 50, p. 661. Wagener, H. P. Retinal vascular changes in hypertension. Ann. Int. Med., Sept., 1930.