WJCD  Vol.4 No.4 , April 2014
Hypertension, Autonomic Storm, Increased Counter Regulatory Hormones and Suppressed Insulin in Acute Myocarditis in Scorpion Envenoming Syndrome
ABSTRACT
Death due to scorpion envenoming syndrome is a common event in many of the tropical and non-tropical counties. Initial transient hypertension is commonly observed in scorpion sting victims. Scorpion envenoming causes autonomic storm resulting in initial transient hypertension followed by hypotension, cold clammy skin, hypothermia, cardiovascular disturbances, acute myocarditis, sarcolemmal defects, pulmonary oedema, acute pancreatitis, disseminated intravascular coagulation (DIC), Adult respiratory distress syndrome (ARDS), and many other clinical manifestations. All these manifestations could be due to sudden increase in catecholamines, angiotensin II, glucagon, Cortisol and either due to suppressed insulin secretion or insulin resistance and death. The sudden increase of metabolic A in counter-regulatory hormones along with either suppressed insulin secretion/or insulin resistance results in glycogenolysis in liver, cardiac and skeletal muscles causing hyperglycemia and a sudden increase in free fatty acid levels. Free Fatty Acids increase the susceptibility of the ventricles to the disorganized electrical behavior, inhibit cardiac sarcolemmal Na+-K+ ATPase activity, increase the tendency to intravascular thrombus, increase myocardial oxygen consumption, interfere with tropomyosin-troponin activation of Actin-Myosin coupling, show detergent effects on cell membranes and they could alter the stabilization of lysosomal membranes and probably become toxic to the myocardium. Based on our animal experiments in which insulin administration reversed the metabolic and ECG changes induced by scorpion envenoming and treating the poisonous scorpion sting victims with insulin, we consider that insulin has a primary metabolic role in preventing, counter-acting and reversing all the deleterious effects of FFA by inhibiting the catecholamine induced by lipolysis, and increasing intra-cellular K+, facilitating glucose transport to the myocardium and glucose metabolism through different pathways. Administration of insulin-glucose infusion to scorpion sting victims appears to be the physiological basis for the control of the metabolic response when that has become a determinant to survival. Treatment using continuous infusion of regular crystalline insulin should be given at the rate of 0.3 U/g glucose and glucose at the rate of 0.1 g/kg body weight/hour, for 48 - 72 hours, with supplementation of potassium as needed and maintenance of fluid, electrolytes and acid-base balance.

Cite this paper
Murthy, K. (2014) Hypertension, Autonomic Storm, Increased Counter Regulatory Hormones and Suppressed Insulin in Acute Myocarditis in Scorpion Envenoming Syndrome. World Journal of Cardiovascular Diseases, 4, 189-210. doi: 10.4236/wjcd.2014.44027.
References
[1]   Gueron, M., Margulis, G., Ilia, R. and Sofer, S. (1993) The Management of Scorpion Envenomation 1993. Toxicon, 31, 1071-1076.
http://dx.doi.org/10.1016/0041-0101(93)90122-Y

[2]   Gueron, M., Adolph, R., Gruff, L., Grup, O., Gabel, M., Grup, G. and Fowler, N.O. (1980) Hemodymamics and Myocardial Consequences of Scorpion Venom. The American Journal of Cardiology, 45, 979-986.
http://dx.doi.org/10.1016/0002-9149(80)90166-6

[3]   Gueron, M. and Ovsyshcher, I. (1987) What Is the Treatment for the Cardiovascular Manifestations of Scorpion Envenomation? Toxicon, 25, 121-124.
http://dx.doi.org/10.1016/0041-0101(87)90170-X

[4]   Gueron, M., Marqulis, G. and Sofer, S. (1990) Echocardiographic and Radionuclide Angiographic Observations Following Scorpion Envenomation by Leiurus quinquestriatus. Toxicon, 28, 1005-1009.
http://dx.doi.org/10.1016/0041-0101(90)90138-W

[5]   Gueron, M., Ilia, R., Shahak, E. and Sofer, S. (1992) Renin and Aldosterone Levels Following Envenomation by the Yellow Scorpion Leiurus quinquestriatus. Toxicon, 30, 765-767.
http://dx.doi.org/10.1016/0041-0101(92)90010-3

[6]   Ismail, M., Fatani, A.J.Y. and Dabeas, T.T. (1992) Experimental Treatment Protocols for Scorpion Envenomation: A Review of Common Therapies and on Effect of Kallikrein-Kinin Inhibitors. Toxicon, 30, 1257-1279.
http://dx.doi.org/10.1016/0041-0101(92)90442-8

[7]   Ismail, M. (1993) Serotherapy of the Scorpion Envenoming Syndrome Is Irrationally Convicted without Trial. Toxicon, 31, 1077-1083.
http://dx.doi.org/10.1016/0041-0101(93)90123-Z

[8]   Ismail, M. (1995) The Scorpion Envenoming Syndrome. Toxicon, 33, 825-858.
http://dx.doi.org/10.1016/0041-0101(95)00005-7

[9]   La Grange, R.G. (1977) Elevation of Blood Pressure and Plasma Renin Levels by Venom from Scorpions, Centruroides sculpturatus and Leiurus quinquestriatus. Toxicon, 15, 429-433.
http://dx.doi.org/10.1016/0041-0101(77)90121-0

[10]   Moss, J., Kazie, T., Henry, D.P. and Kopin, I.J. (1973) Scorpion Venom-Induced Discharge of Catecholamines Accompanied by Hypertension. Brain Research, 54, 381-385.
http://dx.doi.org/10.1016/0006-8993(73)90065-6

[11]   Natu, V.S., Murthy, R.K.K. and Deodhar, K.P. (2006) Efficacy of Species Specific Anti-Scorpion Venom Serum (AScVS) against Severe, Serious Scorpion Sings (Mesobuthus tamulus concanesis, Pocock)—An Experience from Rural Hospital in Western Maharashtra. Journal of the Association of Physicians of India, 54, 283-287.

[12]   Amaral, C.F.S., Lopes, J.A., Magalhaes, R.A. and Rezende, N.A. (1991) Electrocardiographic, Enzymatic and Echocardiographic Evidence of Myocardial Damage after Titus Serrulatus Poisoning. The American Journal of Cardiology, 67, 655-657.
http://dx.doi.org/10.1016/0002-9149(91)90912-5

[13]   Amaral, C.F.S., de Rezende, N.A. and Freire-Maia, L. (1993) Acute Pulmonary Oedema after Tityus serrulatus Scorpion Sting in Children. The American Journal of Cardiology, 71, 242-245.
http://dx.doi.org/10.1016/0002-9149(93)90746-Y

[14]   Amaral, C.F.S., Barbosa, A.J., Leite, V.H.R., Tafuri, W.L. and de Rezende, N.A. (1994) Scorpion Sting-Induced Pulmonary Oedema: Evidence of Increased Alveolocapillary Membrane Permeability. Toxicon, 32, 999-1003.
http://dx.doi.org/10.1016/0041-0101(94)90378-6

[15]   Bahloul, M., Rekik, N., Chabchoub, I., Chaari, A., Ksibi, H., et al. (2005) Neurological Complications Secondary to Severe Scorpion Envenomation. Medical Science Monitor, 11, CR196-CR202.

[16]   Balasubramaniam, P. and Murthy K.R.K. (1984) Liver Glycogen Depletion in Acute Myocarditis Produced by Scorpion Venom (Buthus tamulus). Indian Heart Journal, 36, 101-103.

[17]   Murthy, K.R.K. and Haghnazari, L. (1999) The Blood Levels of Glucagon, Cortisol and Insulin Following Scorpion (Mesobuthus tamulus concanesis, Pocock) in Dogs. Journal of Venomous Animals and Toxins, 5, 47-55.

[18]   Murthy, K.R.K. and Medh, J.D. (1986) Increase in Serum Free Fatty Acids, Phospholipids and Reduction in Total Cholesterol in Acute Myocarditis Produced by Scorpion (Buthus tamulus) Venom Injection in Dogs. Indian Heart Journal, 38, 369-372.

[19]   Murthy, K.R.K. and Vakil, A.E. (1988) Elevation of Plasma Angiotensin Levels in Dogs by Indian Red-Scorpion (Buthus tamulus) Venom and Its Reversal by Administration of Insulin and Tolazoline. Indian Journal of Medical Research, 88, 376-379.

[20]   Murthy, K.R.K. and Yeolekar, M.E. (1986) ECG Changes in Acute Myocarditis Produced by Scorpion (Buthus tamulus) Venom. Indian Heart Journal, 38, 206-210.

[21]   Murthy, K.R.K., Billimoria, F.R., Khopkar, M. and Dave, K.N. (1986) Acute Hyperglycemia and Hyperkalemia in Acute Myocarditis Produced by Scorpion (Buthus tamulus) Venom Injection in Dogs. Indian Heart Journal, 38, 71-74.

[22]   Murthy, K.R.K. (1982) Investigations of Cardiac Sarcolemmal ATPase Activity in Rabbits with Acute Myocarditis Produced by Scorpion Venom (Buthus tamulus). Japanese Heart Journal, 23, 835-842.
http://dx.doi.org/10.1536/ihj.23.835

[23]   Murthy, K.R.K., Hossein, Z., Medh, J.D., Kudalkar, J.A., Yeolekar, M.E., Pandit, S.P. and Billimoria, F.R. (1988) Disseminated Intravascular Coagulation & Disturbances in Carbohydrate and Fat Metabolism in Acute Myocarditis Produced by Indian Red Scorpion (Buthus tamulus) Venom. Indian Journal of Medical Research, 87, 318-325.

[24]   Murthy, K.R.K., Vakil, A.E., Yeolekar, M.E. and Vakil, Y.E. (1988) Reversal of Metabolic and Electrocardiographic Changes Induced by Indian Red Scorpion (Buthus tamulus) Venom by Administration of Insulin, Alpha Blocker and Sodium Bicarbonate. Indian Journal of Medical Research, 88, 450-457.

[25]   Murthy, K.R.K., Medh, J.D., Dave, B.N., Vakil, Y.E. and Billimoria, F.R. (1989) Acute Pancreatitis and Reduction of H+ Ion Concentration in Gastric Secretions in Experimental Acute Myocarditis Produced by Indian Red Scorpion (Buthus tamulus) Venom. Indian Journal of Experimental Biology, 27, 242-244.

[26]   Murthy, K.R.K., Vakil, A.E. and Yeolekar, M.E. (1990) Insulin Administration Reverses the Metabolic and Electrocardiographic Changes Induced by Indian Red Scorpion (Buthus tamulus) Venom in the Experimental Dogs. Indian Heart Journal, 42, 35-42.

[27]   Murthy, K.R.K., Shenoi, R., Vaidyanathan, P., Kelkar, K., Sharma, N., Mehta, M., et al. (1991) Insulin Reverses Haemodynamic Changes and Pulmonary Oedema in Children Stung by Indian Red Scorpion Mesobuthus tamulus concanesis, Pocock. Annals of Tropical Medicine and Parasitology, 85, 651-657.

[28]   D’Suze, G., Comellas, A., Pesca, L., Sevci, K.C. and Sanchez-De-León, R. (1999) Tityus discrepans Venom Produces a Respiratory Distress Syndrome in Rabbits through an Indirect Mechanism. Toxicon, 37, 173-180.
http://dx.doi.org/10.1016/S0041-0101(98)00180-9

[29]   Murthy, K.R.K. (2000) The Scorpion Envenoming Syndrome: A Different Perspective. The Physiological Basis of the Role Insulin in Scorpion Envenoming. Journal of Venomous Animals and Toxins, 6, 4-51.

[30]   Yugandhar, B., Murthy, K.R.K. and Sattar, S.A. (1999) Insulin Administration in Severe Scorpion Envenoming. Journal of Venomous Animals and Toxins, 5, 200-219.

[31]   Bucaretchi, F., Baracat, E.C., Nogueira, R.J., Chaves, A., Zambrone, F.A., et al. (1995) A Comparative Study of Severe Scorpion Envenomation in Children Caused by Tityus bahiensis and Tityus serrulatus. Revista do Instituto de Medicina Tropical de São Paulo, 37, 331-336.
http://dx.doi.org/10.1590/S0036-46651995000400008

[32]   de Dàvila, C.A.M., Dàvila, D.F., Donis, J.H., de Bellabarba, G.A., Villarreal, V. and Barboza, J.S. (2002) Sympathetic Nervous System Activation, Antivenin Administration and Cardiovascular Manifestations of Scorpion Envenomation. Toxicon, 40, 1339-1346.
http://dx.doi.org/10.1016/S0041-0101(02)00145-9

[33]   Hering, S.E., Jurca, M., Vichi, F.L., Azevedo-Marques, M.M. and Cupo, P. (1993) “Reversible Cardiomyopathy” in Patients with Severe Scorpion Envenoming by Tityus serrulatus: Evolution of Enzymatic, Electrocardiographic and Echocardiographic Alterations. Annals of Tropical Paediatrics, 13, 173-182.

[34]   Sofer, S. and Gueron, M. (1988) Respiratory Failure in Children Following Envenomation by the Scorpion Leiurus quinquestriatus: Hemodynamic and Neurological Aspects. Toxicon, 26, 931-939.
http://dx.doi.org/10.1016/0041-0101(88)90258-9

[35]   Sofer, S. and Gueron, M. (1992) Cardiovas-cular Aspects of Scorpion Envenomation. In: Gopalakrishnakone, P. and Tan, C.K., Eds., Recent Advances in Toxinology Research, Venom & Toxin Research Group, National University of Singapore, Singapore City, 40-49.

[36]   Sofer, S., Gueron, M., White, R.M., Lifshitz, M. and Apte, R.N. (1996) Interleukin-6 Release Following Scorpion Sting in Children. Toxicon, 34, 389-392.
http://dx.doi.org/10.1016/0041-0101(95)00136-0

[37]   Sofer, S. and Gueron, M. (1988) Respiratory Failure in Children Following Envenomation by the Scorpion Leiurus quinquestriatus: Hemodynamic and Neurological Aspects. Toxicon, 26, 931-939.
http://dx.doi.org/10.1016/0041-0101(88)90258-9

[38]   Duddin, A.A., Rambaud-Cousson, A., Thalji, A., Juabeh, I.I. and Abu-Libdeh, B. (1991) Scorpion Sting in Children in the Jerusalem Area: A Review of 54 Cases. Annals of Tropical Paediatrics, 11, 217-223.

[39]   Gueron, M., Marqulis, G. and Sofer, S. (1990) Echocardiographic and Radionuclide Angiographic Observations Following Scorpion Envenomation by Leiurus quinquestriatus. Toxicon, 28, 1005-1009.
http://dx.doi.org/10.1016/0041-0101(90)90138-w

[40]   Sofer, S., Shahak, E., Slonim, S. and Gueron, M. (1991) Myocardial Injury without Heart Failure Following Envenomation by the Scorpion Leiurus quinquestriatus in Children. Toxicon, 29, 382-385.
http://dx.doi.org/10.1016/0041-0101(91)90293-Z

[41]   de Dàvila, C.A.M., Dàvila, D.F., Donis, J.H., de Bellabarba, G.A., Villarreal, V. and Barboza, J.S. (2002) Sympathetic Nervous System Activation, Antivenin Administration and Cardiovascular Manifestations of Scorpion Envenomation. Toxicon, 40, 1339-1346.
http://dx.doi.org/10.1016/S0041-0101(02)00145-9

[42]   Bahloul, M., Kallel, H., Rekik, N., Ben, H.C., Chelly, H. and Bouaziz, M. (2005) Cardiovascular Dysfunction Following Severe Scorpion Envenomation. Mechanisms and Physiopathology. La Presse Médicale, 34, 115-120.

[43]   Tarasiuk, A., Janco, J. and Sofer, S. (1997) Effects of Scorpion Venom on Central and Peripheral Circulatory Response in an Open-Chest Dog Model. Acta Physiologica Scandinavica, 161, 141-149.
http://dx.doi.org/10.1046/j.1365-201X.1997.00202.x

[44]   Deshpande, S.B. (1988) Indian Red Scorpion (Buthus tamulus) Venom Prolongs Repolarization Time and Refractoriness of the Compound Action Potential of Frog Sciatic Nerve in Vitro. Indian Journal of Experimental Biology, 36, 1108-1113.

[45]   Balasubramaniam, P. and Murthy, K.R.K. (1981) Abnormal Cardiovascular and Electrocardiographic Profiles and Cardiac Glycogen Content in Rabbits Injected with Scorpion Venom. Indian Journal of Physiology and Pharmacology, 25, 351-355.

[46]   Venkateswaralu, D.Z. and Banu, K.S. (1987) Physiological Effects of Scorpion Venom on Frog’s Gastrocnemius Muscle. Indian Journal of Experimental Biology, 13, 429-431.

[47]   Achyuthan, K.E., Agarwal, O.P. and Ramachandran, L.K. (1982) Enzymes in the Venoms of Two Species of Indian Scorpions—Heterometrus bengalensis & Buthus tamulus. Indian Journal of Biochemistry and Biophysics, 19, 356-358.

[48]   Martin, C. (2004) Scorpion Venom: A Deadly Brew of Toxic Proteins. Biochemistry 4521: Protein Biochemistry.

[49]   Chatwal, G.S. and Habermann, E. (1981) Neurotoxins, Protease Inhibitors and Histamine Releasers in the Venom of the Indian Red Scorpion (Buthus tamulus): Isolation and Partial Characterization. Toxicon, 19, 807-823.
http://dx.doi.org/10.1016/0041-0101(81)90077-5

[50]   Tiwari, A.K. (1992) Isolation, Purification and Functional Characterization of Scorpion Buthus tamulus Venom. M.D. Thesis, Banaras Hindu University, Varanasi.

[51]   Hayet, S., Abrough, F. and Djeridane, Y. (2008) Effect and Mechanisms Underlying Scorpion Toxin Action from Androctonus australis garzonii on Atrial Natriuretic Peptide in Rat Atria: An in Vitro Study. Peptides, 29, 364-368.
http://dx.doi.org/10.1016/j.peptides.2007.11.019

[52]   Harvey, A.L., Anderson, A.J., Brage, M.E.M., Bragal, M.F.M., Marshall, D.L., Rowan, E.G., Vatapour, H., Castneda, O. and Karlson, E. (1992) Toxins Affecting Neuronal Ion Channels. In: Gopalakrishnakone, P. and Tan, C.K., Eds., Recent Advances in Toxinology Research, Venom & Toxin Research Group, National University of Singapore, Singapore City, 59-70.

[53]   Goudet, C., Chi, C.W. and Tytgat, J. (2002) An Overview of Toxins and Genes from the Venom of the Asian Scorpion Buthus martensi Karsch. Toxicon, 40, 1239-1258.
http://dx.doi.org/10.1016/S0041-0101(02)00142-3

[54]   Borges, A., Alfonzo, M.J., García, C.C., Winand, N.J., Leipold, E. and Heinmann, S.H. (2004) Isolation, Molecular Cloning and Functional Characterization of a Novel Beta-Toxin from the Venezuelan Scorpion, Tityus zulianus. Toxicon, 43, 671-684.
http://dx.doi.org/10.1016/j.toxicon.2004.02.022

[55]   Shivraj, A., Namoshi, A. and Gao, M.S. (1981) LV Function in Scorpion Sting. Indian Heart Journal, 33, 150-154.

[56]   Posani, L.D., Valdivia, H.H., Ramirez, A.N., Gurrola, G.B. and Martin, B.M. (1992) K+ Channel Blocking Peptides from the Venom of Scorpions. In: Gopalakrishnakone, P. and Tan, C.K., Eds., Recent Advances in Toxinology Research, Venom & Toxin Research Group, National University of Singapore, Singapore City, 39-58.

[57]   Jouirou, B., Mouhat, S., Andreotti, N., De Waard, M. and Sabatier, J.M. (2004) Toxin Determinants Required for Interaction with Voltage-Gated K+ Channels. Toxicon, 43, 909-914.
http://dx.doi.org/10.1016/j.toxicon.2004.03.024

[58]   D’Suze, G., Comellas, A., Pesca, L., Sevci, K.C. and Sanchez-De-León, R. (1999) Tityus discrepans Venom Produces a Respiratory Distress Syndrome in Rabbits through an Indirect Mechanism. Toxicon, 37, 173-180.
http://dx.doi.org/10.1016/S0041-0101(98)00180-9

[59]   Tiwari, A.K. and Deshpande, S.B. (1993) Toxicity of Scorpion (Buthus tamulus) Venom in Mammals Is Influenced by the Age and Species. Toxicon, 31, 1619-1622.
http://dx.doi.org/10.1016/0041-0101(93)90346-K

[60]   Edwin, K.J., Renin and Angiotensin (2006) Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th Edition, McGraw Hill Medical Publishing Division, New York, 795.

[61]   Johnson, D.G., Henry, D.P., Moss, J. and Williams, H.H. (1976) Inhibition of Insulin Secretion Released by Scorpion Toxin on Rat Pancreatic Islets. Diabetes, 25, 198-201.
http://dx.doi.org/10.1016/S0041-0101(98)00180-9

[62]   Johnson, D.G. and Ensinck, J.W. (1976) Stimulation of Glucagon Secretion by Scorpion Toxin in the Perfused Rat Pancreas. Diabetes, 25, 645-649.
http://dx.doi.org/10.2337/diab.25.8.645

[63]   Keele, C.A., Neil, E. and Joel, S.N. (2004) Samson Wright’s Applied Physiology. 13th Edition, Oxford University Press, Oxford, 405-512.

[64]   Harald, V.M. and Ole, D.M. (1981) Influence of Free Fatty Acids on Myocardial Oxygen Consumption and Ischemic Injury. The American Journal of Cardiology, 48, 361-365.
http://dx.doi.org/10.1016/0002-9149(81)90621-4

[65]   Devi, S., Reddy, C.N., Devi, S.L., Subramaniam, Y.R., Bhatt, H.V., Suvarnakumari, G., Murthy, D.P. and Reddy, C.R. (1970) Defibrination Syndrome Due to Scorpion Venom Poisoning. British Medical Journal, 1, 345-347.
http://dx.doi.org/10.1136/bmj.1.5692.345

[66]   Bondy, P.K. and Rosenberg, L.E. (1980) Metabolic Control and Disease. 8th Edition, WB Saunders Co., Phildelphia, 1621.

[67]   Fyge, T., Cochran, K.M., Baxter, R.H. and Booth, E.M. (1971) Plasma-Lipid Changes after Myocardial Infarction. Lancet, 298, 997-1001.

[68]   Goldstein, R.E., Abumrad, N.N., Lacy, D.B., Wasserman, D.H. and Cherrington, A.D. (1995) Effects of an Acute Increase in Epinephrine and Cortisol on Carbohydrate Metabolism during Insulin Deficiency. Diabetes, 44, 672-681.
http://dx.doi.org/10.2337/diab.44.6.672

[69]   Oliver, M.F. (1975) The Vulnerable Ischemic Myocardium and Its Metabolism. In: Oliver, M.F., Ed., Modern Trends in Cardiology, 3rd Edition, Butterworths, London, 280-291.

[70]   Murthy, K.R.K., Dubey, A.S., Abbas, Z. and Haghnazari, L. (2003) Investigations on the Role of Insulin and Scorpion Antivenom in Scorpion Envenoming Syndrome. Journal of Venomous Animals and Toxins Including Tropical Diseases, 9, 202-238.

[71]   Murthy, K.R.K. (2013) Treatment of Scorpion Envenoming Syndrome—Need for Scientific Magnanimity. Indian Medical Association, 111, 254-259.

[72]   Scheuer, J. and Stezoski, S.W. (1969) A Protective Effect of Increased Glycogen Stires in Cardiac Anoxia. Journal of Laboratory and Clinical Medicine, 74, 1007-1010.

 
 
Top