Acute myocardiopathy in alloxan treated experimental dogs and rabbits was induced by subcutaneous (SQ) injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Envenoming resulted in an initial transient hypertension (180-320 mm Hg.) followed by hypotension. Simultaneous administration of venom and species-specific scorpion antivenom (SAV) prevented hypertension and hypotension. Hypotension did not occur when SAV was given 60 min after envenoming. Blood glucose, triglycerides, cholesterol, amylase, insulin, glucagon, cortisol, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, red blood cell (RBC) count, hemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), and glutathione levels were increased 60 and 90 min after envenoming. Total white blood cell (WBC) count was reduced 60 min and increased 90 min after envenoming. Simultaneous administration of venom and SAV did not alter Hb, MCHC, and packed cell volume (PCV) levels, or ECG, and cardiovascular, biochemical, metabolic, and hormonal changes. Hematological parameters were reversed when SAV was given 30 and 60 min after envenoming. PCV, Hb, and MCHC values returned to normal 120 min after SAV. Alloxan-treated dogs showed increased blood glucose, cholesterol, glucagon, cortisol levels; reduced glycogen content of liver, cardiac and skeletal muscles; and reduced insulin levels and insulin/ glucagon ratio (I/G ratio). Envenoming in the alloxan pre-treated dogs further increased these levels and reduced tissue glycogen content, insulin levels, and I/G ratio. Administration of 4 U of insulin to alloxan pre-treated envenomed rabbits caused a biochemical and clinical improvement and increased glycogen content of all tissues in comparison with the values from those administered with SAV to alloxan pre-treated envenomed animals. SAV administration to envenomed alloxan pre-treated rabbits did not cause clinical or biochemical improvement. Severe scorpion envenoming causes an autonomic storm with a massive release of catecholamines and other counter-regulatory hormones; changes in insulin secretion resulting in fuel energy deficits producing multi-system-organ-failure (MSOF); and death. Administration of either insulin or SAV (through the release of insulin) appears to be the physiological basis for the control of the metabolic support to control the adverse effects triggered by counter-regulatory hormones.

Electrocardiographic (ECG) changes were induced in dogs by injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Venom (3 mg/kg body weight) was given subcutaneously (SQ) while 10 ml of scorpion antivenom (SAV) was administered intravenously (IV) to experimental dogs. Group 1 received only the venom; Groups 2, 3, and 4 received SAV at 0, 30, and 60 min, respectively, following envenoming. Thick, ropy and profuse salivation; muscle fasciculation; clonus and tetany-like contractions; frequent urination; and bowel emptying sometimes stained with bile and occasionally blood and bile were observed 20-25 minutes after envenoming. Following envenoming, hyperglycemia, increase in free fatty acid (FFA) levels, and reduction in triglyceride levels were observed in Groups 1, 3, and 4. There was an initial rise in insulin levels at 30 min followed by a reduction at 60 min. SAV caused a subsequent rise in insulin levels but there was a reduction in blood sugar to euglycemia levels and lipogenesis (reduction in FFA and increase in triglycerides levels) in Groups 3 and 4. Abnormal ECG changes and arrhythmias were not observed after SAV. Normal sinus rhythm was restored in Group 4. Scorpion envenoming with multi-system-organ failure (MSOF), characterized by a massive release of counter-regulatory hormones (catecholamines, glucagon, cortisol), angiotensin-II, and changes in insulin secretion, is a condition of fuel-energy deficits and an inability to utilize the existing metabolic substrates. These disturbances are reversed by SAV possibly through insulin release. It is concluded that SAV, under the laboratory conditions, effectively neutralizes, prevents, and reverses scorpion venom toxicity.

Acute myocarditis was induced in experimental dogs by subcutaneous (SC) injection of 3mg/kg of scorpion venom from Mesobuthus tamulus concanesis POCOCK (earlier called Buthus tamulus). An increase in hemoglobin (Hb), mean corpuscular hemoglobin concentration (MCHC), packed cell volume (PCV), plasma hemoglobin (Plasma Hb) levels, and increased osmotic fragility of erythrocytes in vivo was observed after envenoming. An increase in osmotic fragility of red blood cells (RBC) was also observed when the blood in vitro was incubated with different concentrations of scorpion venom. Species- specific scorpion antivenom (SAV) was administered to different groups of animals at different time intervals following scorpion envenoming. This resulted in a decrease in Hb, MCHC, PCV, and plasma Hb levels in the envenomed animals and reversal of osmotic fragility changes of erythrocytes. It has been suggested that scorpion venom causes an autonomic storm releasing massive amounts of counter-regulatory hormones, such as catecholamines, angiotensin-II, glucagon, cortisol, and changes in insulin secretion resulting in hematological and osmotic fragility changes of erythrocytes. Administration of SAV effectively neutralized, prevented, and reversed scorpion venom toxicity and related osmotic fragility changes of erythrocytes.

Labelling of scorpion (Mesobuthus tamulus concanesis Pocock) venom was successfully achieved with Tc 99m using direct tin reduction procedure. Biodistribution studies were carried out in Wistar rats at different time intervals after i.v. administration of the labelled venom. Scintiimages were obtained after scorpion envenoming using a large field of view gamma camera to ascertain the pharmacological action of venom in the body. Within 5 min of administration, labelled venom was found in the blood (27.7%), muscle (30.11%), bone (13.3%), kidneys (11.5%), liver (10.4%), and other organs. The level of venom in the kidneys was higher than in the liver. The labelled venom was excreted through renal and hepatobiliary pathways. An immunoreactivity study was carried out in rabbits after i.v. injection of labelled scorpion venom followed by the injection of the species specific antivenom. A threefold increase in uptake by the kidneys was observed compared with that seen with scorpion venom alone. The neutralisation of the venom in the kidneys was higher than in the liver.

Severe envenoming was induced in two groups of experimental dogs after subcutaneous (SQ) injection of venom of the scorpion (Mesobuthus tamulus concanesis, Pocock) (3.0 and 3.5 mg/kg body weight). The circulating levels of blood sugar, insulin, glucagon, and cortisol were assayed at 0, and 30, 60, 90 and 120 min after venom injection. There was an increase in the circulating levels of blood sugar, insulin, glucagon, and cortisol following envenoming. Scorpion envenoming causes an autonomic storm resulting in a massive release of catecholamines, angiotensin II, glucagon, and cortisol accompanied by changes in insulin secretion. The rise in the counter-regulatory hormones (glucagon, cortisol, and catecholamines) oppose the anabolic actions of insulin resulting in a variety of clinical manifestations. These changes may lead to a syndrome of fuel-energy deficits and to an inability of the vital organs to utilise the existing metabolic substrates, ultimately resulting in multisystem organ failure (MSOF) and death.

The efficacy of insulin-glucose infusion in reversing myocardial damage, haemodynamic changes, peripheral circulatory failure, and pulmonary oedema was evaluated in 25 victims of venomous scorpion stings from the Rayalaseema region in the south of India. Myocardial damage with peripheral circulatory failure was seen in all scorpion sting victims. Ten of these victims also had pulmonary oedema. All the patients received continuous infusion of regular crystalline insulin at the rate of 0.3 U/g of glucose and glucose at the rate of 0.1 g/kg/h with supplementary potassium as needed, inotropic agents, oxygen, as well as maintenance of fluid, electrolytes and acid-base balance. Insulin-glucose infusion was associated with reversal of cardiovascular and haemodynamic changes, and pulmonary oedema in 24 of the 25 victims. One severely envenomed victim admitted 72 hours after the sting died. The scorpion envenoming syndrome with myocardial damage, cardiovascular disturbances, peripheral circulatory failure, pulmonary oedema, and many other clinical manifestations may cause multi-system organ failure (MSOF). It is characterised by a massive release of catecholamines, angiotensin II, glucagon, cortisol, and inhibition of insulin secretion. Under these altered conditions in the hormonal milieu, scorpion envenoming essentially results in a syndrome of fuel-energy deficits and an inability to use the existing metabolic substrates by vital organs, causing MSOF and death. 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.

Acute myocardiopathy in experimental dogs and rabbits was induced by subcutaneous (SQ) injection of 3.5 mg/kg of scorpion venom from Mesobuthus tamulus concanesis, Pocock. An increase in circulating lactic dehydrogenase (LDH), serum glutamic oxalacetic transaminase (SGOT), creatine kinase-MB isoenzyme (CK-MB), serum glutamine pyrovate transaminase (SGPT) and alpha hydroxy butyrate dehydrogenase (HBDH) enzyme levels was observed in dogs 60 min after venom injection, and a further rise was observed 120 min after venom injection. The administration of the species-specific scorpion antivenom (SAV) at different time intervals after venom injection resulted in reversal of electrocardiographic changes and a reduction in cardiac enzyme levels. The administration of SAV to scorpion envenomed alloxan-pretreated animals did not cause clinical or biochemical improvement. On the other hand, administering insulin to envenomed only animals or envenomed alloxan-pretreated animals resulted in a biochemical and clinical improvement, as well as in a reduction of the cardiac enzyme levels. Insulin administration in scorpion envenoming syndrome is essentially a metabolic support to control the adverse effects triggered by catecholamines and other counter-regulatory hormones.