Catecholamines and myocardial damage in scorpion sting

creatinine clearance from urine and blood specimens obtained at the time of bilateral ureteral catheterization. It was apparent that, in those patients in whom the GFR in the contralateral kidney was normal or not reduced by more than 25 per cent of irormal, a cure could reasonably be expected. By demonstrating that the “normal” kidney was indeed functionally normal, the predictive accuracy of differential renal function studies was substantially improved. Vertes and associatesioair have stressed the desirability of establishing that the “normal” kidney is in fact normal, using as their criterion normal tissue architecture observed in biopsy specimens obtained from the contralateral kidney. However, there is insufficient evidence to support the thesis that function precisely parallels architecture or that the oathological changes which are observed are totally irreversible. Indeed, it has been reported that surgical cures have been obtained in patients with uni!ateral main renal artery stenosis in whom reduced renal function was present in the contralateral kidney.i2 This was true in one of our own patients.i3 However, in five of our patients, in whom contralateral renal function was significantly impaired, a cure was not obtained regardless of whether the differential renal function study was positive by other criterion for unilateral renal artery stenosis. Since differential renal function studies compare one kidney’s function with that of the other, they are less accurate in the presence of bilateral disease, whether the disease is small or large vessel in nature. In our experience, the accuracy of differential renal function studies is greatly enhanced when an estimation of the glomerular filtration rate or renal plasma flow of each kidney is made at the time of hiIatera1 ureteral catheterization. Stameyr” has pointed out the value of measuring the glomerular filtration rates or renal plasma flows of each kidney. We prefer the former, because of its relative simplicity and because we feel it more accurately reflects the intrarenal functional capacity. Richard A. Sckacht, M.D. Chief of Internal Medicine Research Associate United States Public Health Service Hospital New Orleam, La. James Conway, Ph.D., M.D. Associate Professor of Internal Medicine University of Michigan Medical Center Ann Arbor, Mich. ;Issistant

Catecholamines damage

and

in scorpion

REFERENCES 1.

2.

Goldblatt, H., Lynch, J., Hanzal, R. F., and Summerville, W. W. : Studies on experimental hypertension. 1. The production of persistent elevation of systolic blood pressure by means of renal ischemia, J. Exper. Med. 59:347, 1934. Butler, A. M.: Chronic pyeionephritis and arterial hypertension, J. Clin. Invest. 16:889, 1937.

3. 4.

5.

6.

7.

8.

9.

10.

11.

12.

Smith, H. W.: Hypertension and urologic disease, Am. J. Med. 4:724,1948. Howard, J. E., Berthrong, M., Gould, D. M., and Yendt, E. R. : Hypertension resulting from unilateral renal vascular disease and its relief by nephrectomy, Bull. Johns Hopkins Hosp. 94:51, 1954. Connor, T. B., Berthrong, M., Thomas, W. C., Jr., and Howard, J. E.: Hypertension due to unilateral renal disease: with a report on a functional test helpful in diagnosis, Bull. Johns Hopkins Hosp. 100:241, 1957. Rapoport, A.: Modification of the “Howard Test” for the detection of renal artery obstruction, New England J. Med. 263:1159, 1960. Stamey, T. A.: The diagnosis of curable unilateral renal hypertension by ureteral catheterization, Postgrad. Med. 29:496, 1961. Birchall, R., Batson, H. M., Jr., and Brannan, W.: Contribution of differential renal studies to the diagnosis of renal arterial hypertension, Am. J. Med. 32:164, 1962. Schacht, Ii. A., Conway, J., and Stewart, B. H.: Split renal function studies in hypertension, Arch. Int. Med. 119:588, 1967. Vertes, V., Grauel, J. A., and Goldblatt, H.: Renal arteriography, separate renal-function studies, and r-enal biopsy in human hypertension: selection of patients for surgical treatment, New England J. Med. 270:656, 1964. Vertes, V., Genuth, S., Leb, D. E., and Galvin, J. B.: TTnilateral renal plasma flow in the assessment of correctable renovascular hypertension, Kew England J. Med. 273:855, 1965. Strickler, W. L.: Surgical treatment of renovascular hypertension, Kew England J. Med. 274:52,

13.

14.

1966.

Schacht, R. A., Zweifler, Renal artery stenosis,

A. J., and Conway, J.: New England J. Med.

271:55,

1964.

Stanley, tensive

T. A.: In Gross, F., editor: Antihypertherapy, Berlin, 1966, Springer-S’erlag.

myocardial sting

Various species of scorpions have various kinds of poison that differ from one another in chemical structure and physiological effects. The effect of the sting depends upon the age of the scorpion, the season, and the size of the victim.1 Myocardial damage and heart failure are not a frequent complication in scorpion sting and have not been thoroughly investigated.*z3 Although the

manifestations of scorpion venom are attributed to a neurotoxic effect, the basic mechanism of cardiac damage and congestive heart failure remains obscure. Furthermore, pathological observations of the cardiovascular system in fatal scorpion sting are scarce.4 Electrocardiographic abnormalities have been reported in some patients and attributed to a toxic

716

Am. Heart J. May, 1968

Annotations

2.able I. An increase

of catecholamine

I -----------------‘_-_

metabolites

excretion

1st day

2nd say

~

Patient Total free

A. s.* *A. M.t

Wormai values for lamines, 1 y per iNorma values for catecholamines,

catecholamine (y/24 hr.)

Vanilmandelic acid (rlmg. 1

32 100

16 17

this patient (aged 2 years old)‘“-“: kilogram per 24 hours. this patient (aged 27 years old)‘:-‘7 20 to 60 y per 24 hours at rest.

Vanilmandelic vanilmande!ic

effect of scorpion venom on the heart,z,” although pathological documentation of myocardial damage was not available. In a recent communication,4 we reported a specific electrocardiographic pattern in patients with scorpion sting accompanied by heart failure or puhnonary edema; these cardiovascular manifestations of the venom we attributed to an increased level of circulating pressor amines-the result of a direct effect of scorpion venom on the adrenals and the sympathetic nervous system. The electrocardiographic changes were consistent with an “early myocardial infarction-like pattern,” believed to be the result of catecholamine-induced hypoxia through direct chemical interference accompanied by elevated serum transaminases.’ This was substantiated by the lack of morphological changes of the myocardium in fatal cases, despite heart fail~u-c or pulmonary edema.“,* In 1954, in a review of the clinical manifestations of scorpion sting, Barsoum and associates9 suggested that the majority of the clinical features of the venom are due to the presence of large amounts of circulating epinephrine. They reported increased plasma epinephrine content in six patients, who were examined 12 hours after the sting; the plasma epinephrine content was twice the normal level. Other author+ll expressed similar views on the basis of experimental data, but biochemical confirmation of increased circulating catecholamines in scorpion sting was not available. Two patients, who after a sting by the yellow scorpion,’ B&us pinguestriutus (commonly found in southern Israel), had heart failure and electrocardiographic changes similar to those reported in a prel,ious communication,~ were recently observed. Excretion of catecholamine metabolites was investigated in both patients during the iirst 48 hours after the sting. Except for mild sedation, medication was initially omitted. As clearly seen in Table I, a prominent increase of catecholamine metabolite excretion was present during the first 24 hours in both patients, substantiating our assumption of an increase in circulating pressor amines4; these results establish that the cardiovascular manifestations of scorpion sting are the clinical

Total free catecholanzine

Vanilmandelic (r/w)

acid

6 2

acid,

6 y per milligram

of creatinine

acid,

0.5 to 3.5 y per milligram

in urine; of creatinine

total

free c&echo

in urine;

total

iree

counterpart of the venom effect on the adrenals and sympathetic nervous system. Furthermore, a synergistic effect of scorpion venom and epinephI-ine has recently been reported.12 A11 these communications point out that the cause of death in scorpion sting is biochemical myocardial failure~~5~‘“~‘” and the neurotoxic effects of the venom are probably !ess important. Mosche Gueuon, X./I. Shimon Wbbman, M.D. Cuudiac Laboratory, The Negev Central

Hospital Beeusheva, Isvael 1. Shulov, A.: On some Israeli scorpions, Dapim Refouim 21:657, 1962. I. Sturman, N.: Scorpion sting poisoning in the Negev, Dapim Refouim 21:661, 1962. 3. Stanhke, H. I,.: The Arizona scorpion probleni, Arizona Med. 7:23, 1950. 4. Gueron, M., Stern, J., and Cohen, Iv.: Severe myocardial damage and heart failure in scorpion sting, Am. J. Cardiol. 19:719, 1967. 5. Poon King, T.: Myocarditis from scorpion sting. Brit. M. J. 1:374, 1963. 6. Brand Auraban, A., and Ro;ler, A.: The Heglin syndrome in myocarditis due to scorpion sting, Harefuah 73:14, 1967. 7. Raab, W.: Key position of cltecholamines in functional and degenerative cardiovascular pathology, Am. J. Cardiol. 5:571, 1960. 8. Gueron, M. : The pathology of the myocardium in fatal scorpion sting. Unpublished observations. 9. Barsoum, G. S., Nabavy,.M., and Salama, S.: Scorpion poisoning-its signs, symptoms, and treatment, J. Egyptian M. A. 37:857, 1954. 0. Patterson, R. A.: Physiological action of scorpion venom, Am. J. Trop. Med. 9:410, 1960. 1. Rohayem, H.: Scorpion toxin and autonomic drugs, J. Trop. Med. 56:150, 1953. 2. Stanhke, H. L.: Stress and toxicity of venom, Science 150:1436, 1965. 3. Cutting, 1%‘. A. M.: Letter to editor, Brit. M. J. 1:374, 1963.

Annottrtions

14. 15.

16.

Poon King, T.: Letter to editor, Brit. M. J. 1:1016, 1963. Herman, G. A.: The determination of urinary 3-Methoxy 4-Hydroxymandelic (Vanilmandelic) acid by means of electrophoresis with cellulose acetate membrane, Am. J. Clin. Path. 41:373, 1964. Donough, O., and Ibbot, F. A.: Estimation

Extracellular disease

treated

volume for

17.

of pressor amines metabolites in urine. Laboratory manual of pediatric micro and ultramicro biochemical technics, Hoeber Medical Books, 1962, Harper & Row, p. 169. Von Euler, U. S., and Floding, I.: Diagnosis of pheochromocytoma by Auorometric estimation of adrenalin and nonadrenalin in urine, Scandinav. J. Clin. & Lab. Invest. 8:288, 1956.

in patients hypertension

It has been demonstrated in a majority of patients undergoing maintenance hemodialysis that hypertension can be controlled successfully by reducing body weight using ultrafiltration.’ Patients with chronic renal failure who are being managed conservatively often require adequate control of total body sodium for the treatment of their hypertension, which tends to be resistant to drug treatment in the presence of sodium excess.2 It was of particular interest to determine whether extracellular volume (ECV) and exchangeable sodium (Na,) had been lowered below normal in patients with chronic uremia in whom reasonably good control of blood pressure had been achieved by restriction and/or removal of sodium. ECV and Ka, were measured with radioactive bromine-82 and sodium-24, respectively. In ten healthy controls both ECV and Na, were very closely related to lean body mass determined by a method which incorporates the measurements of body weight, height, and skin-fold thickness.3 Of eight patients with chronic renal insufficiency, seven had a decrease in blood pressure concomitant with the use of sodium restriction as the principal form of treatment. Measurements of EVC and Na, were with but one exception within or above the normal range. Four patients on longterm hemodialysis had an elevated ECV and Na, before a routine dialysis. Dialysis decreased the two parameters to normal but not below in all as well as in two more patients investigated only after dialysis. With one exception, blood pressure, which had been moderately elevated predialysis, was reduced to normal levels concomitantly. Two of these patients had been severely hypertensive at the time when regular dialysis treatment was started.4 When interpreting data of body spaces, one should question if measurements related to body weight or even lean body mass as a reference point in patients with chronic disease can be validly compared to values obtained in healthy controls. Malnourishment and wasting of the body’s cellular mass can result in a relative increase of the extracellular compartment.5s6 However, in the study mentioned above, patients were selected only if they were physically active and had maintained a stable body weight. Therefore, it seems valid to state that in the two groups of patients satisfactory blood pressure control was achieved when ECV and Sa, were reduced to normal levels. It should

717

with

chronic

by sodium

renal restriction

be pointed out that in many patients a time lag e&s between reduction of ;h&e parameters ani adequate control of blood pressure, which may require several weeks. These experiments demonstrate the importance of water and electrolyte balance for the management of hypertension in chronic renal disease. However, it is quite evident that other important factors must be operative in the pathogenesis of this form of hypertension: it has been shown that in a small minority of patients on maintenance dialysis efficient removal of fluid over a prolonged period of time will not result in correction of hypertension.?-9 In these patients, bilateral nephrectomy will usually normalize blood pressure, which then will become dependent only on the state of hydration and sodium balance.8~‘0 These findings support the hypothesis of a renal pressor system contributing to the hypertension. The nature of this pressor system is still a matter of conjecture. Increased concentrations of renin (in peripheral blood as well as in kidney tissue) have been found in some patients but not in all.“~‘* In occasional patients, hypertension persisted even after bilateral nephrectomy but was corrected by successful renal transp1antation.8,13 It is not entirely clear whether adequate removal of fluid and sodium had taken place in these cases before transplantation. Nevertheless, they may represent an argument in favor of a renoprival component of the hypertension. Alfred Blumberg, M.D. Medizinische Poliklinik University of Bern Switzerland REFERENCES I.

Scribner, B. H., Fergus, E. B., Boen, S. T., and Thomas, E. D.: Some therapeutic approaches to chronic renal insufficiency, Ann. Rev. Med. 16:285, 1965. 2. Scribner, B. H.: In Black, D. A. K., editor: Renal disease, Oxford, 1967, (in press). 3. Edwards, K. 0. G., and Whyte, H. M.: Creatinine excretion and body composition, Clin. SC. 18:361, 1959. 4. Blumberg, A., Nelp, W. R., Hegstrom, R. M., and Scribner, B. H.: Extra cellular volume in patients with chronic renal disease treated