James A. Vick

Effects of whole bee venom and its fractions (apamin and melittin) on plasma cortisol levels in the dog

Abstract Crude bee venom was separated into 8 fractions using a G75-40 Sephadex column. Each fraction was analyzed for effect on arterial blood pressure, heart rate, EKG, EEG, respiration and plasma levels of cortisol. Fraction 3 (phospholipase A) produced a precipitous fall in arterial pressure, bradycardia and respiratory paralysis which terminated in death. Fraction 4 produced only modest physiological changes with no death. Fraction 5 (melittin) and Fraction 7 (apamin) also produced only minor physiological changes; however, sharp elevations in plasma cortisol were noted. The increases in cortisol usually occurred within 1 hr and persisted for from 24 to 48 hr. No other significant changes were noted in any of the animals. The observation that Fractions 5 and 7 produced significant and sustained elevations in plasma cortisol may indicate a specific stimulation of the adrenal cortex to release large quantities of corticosteroids.

Early Histamine Release and Death Due to Endotoxin

Summary The intravenous injection of a lethal dose of E. coli endotoxin into anesthetized dogs produces a precipitous fall in arterial blood pressure, a sharp increase in plasma histamine and an abrupt decrease in circulating platelets. The increase in histamine, like the fall in arterial pressure, occurs within 30-60 sec following the administration of a lethal dose of endotoxin. In contrast, sublethal doses of endotoxin produce only modest decreases in arterial blood pressure, no significant elevation in plasma histamine levels, and a slight fall in circulating platelets. In this study an increase in plasma histamine was always associated with a lethal outcome. In no instance was there death with no prior elevation in histamine. Results indicate that an early and marked increase in histamine seems to follow the injection of a lethal dose of endotoxin, and it is highly probable that this early release of histamine is in some way involved in both the cardiovascular changes and the ultimate lethality of this form of shock in the dog. The possible involvement of bradykinin, serotonin, and the catecholamines is indicated.

Beta adrenergic and anti-arrhythmic effects of cardiopep, a newly isolated substance from whole bee venom

Abstract Cardiopep is an acronym for cardioactive polypeptide. It is a newly isolated fraction of bee venom with an estimated molecular weight of 1940. The cardiovascular effects of cardiopep have been studied in a series of 30 isolated perfused Langendorff heart preparations, and in 12 intact animals. When injected into the coronary circulation of the perfused heart, cardiopep produces a 50 ± 10 per cent increase in rate, a 150 ± 50 per cent increase in force of contraction and no change in coronary vascular resistance. These effects lasted for the duration of the experiment. In those hearts in which intrinsic arrhythmias are present, a dose of 0·2 mg of cardiopep produced an immediate restoration of normal cardiac rhythm in addition to the effects on rate and force. In the intact monkey preparation, this same dose of cardiopep produces an increase in heart rate, aortic blood flow and right ventricular force. There are no significant changes in arterial blood pressure, central venous pressure or cortical activity. In addition cardiopep appears to be relatively nontoxic ( LD 50 = 15 mg/kg ) when compared to whole bee venom ( LD 50 = 3·5 mg/kg ). It would appear from these studies that cardiopep is a potent, nontoxic beta-adrenergic-like stimulant not entirely blocked by propranolol and possessing definite anti-arrhythmic properties.

Effect of bee venom and melittin on plasma cortisol in the unanesthetized monkey

Abstract Twenty-three adult Rhesus monkeys were injected subcutaneously with varying doses of bee venom or melittin which produced within 1–3 hr significant elevations in circulating plasma cortisol levels. These increases persisted for 72–96 hr, after which the cortisol levels returned to control values. The higher dose of venom or melittin usually produced the most pronounced elevations in cortisol. Reinjection at 72 hr resulted in a second increase in cortisol levels which persisted for 17–21 days followed by a gradual decline reaching near control levels at 30 days. The amount of melittin required to produce significant elevations in plasma cortisol was 1 10 that of whole bee venom. Four of the monkeys which received the higher doses of venom or melittin were autopsied and showed no significant gross or microscopic tissue changes. Surgical removal of the pituitary gland in four additional monkeys prevented the increase in cortisol previously noted in monkeys receiving either venom or melittin. Results indicate that bee venom or one of its components, melittin, appears to stimulate the production of cortisol from the adrenal gland through some action on the anterior pituitary gland. These observations may explain the reported beneficial effects of bee venom administration in a variety of disease conditions which also respond to adrenal steroid therapy.

Symptomatology of Experimental and Clinical Crotalid Envenomation

Rattlesnakes, indigenous to the North American continent, are all members of the family of poisonous snakes called Crotalidae (see Fig. 1). This family, Crotalidae, is one of the four families of poisonous snakes. The other three are: Elapidae, Viperidae, and Hydrophiidae. A fifth group of rear-fanged poisonous snakes has been described and is usually classified as Boiginae, a subfamily of Colubridae (Conant, 1958; Klauber, 1956; Stebbeirs, 1954).

Medical Studies of Poisonous Land and Sea Snakes

The comparative toxicity and pathophysiology of thirteen (13) of poisonous snakes indigenous to the area in and around Saudi Arabia were determined. Four snakes from the Viperidae family, six from the Elapidae family, and three representative sea snakes from the family Hydrophiodae were included. Anesthetized adult Beagle dogs and anesthetized monkeys were used in the study. Vital physiologic functions were recorded continuously as were changes in the blood coagulation system and any tissue damage produced by the venom at the site of envenomation. Venom was administered intravenously or by an actual bite. Venom from the snakes of the family Viperidae produced death in an average of 3 hours. The average lethal dose was 1.13 mg/kg. Depression of 1st and 2nd stage clotting factors and a decrease in fibrinogen levels and in platelet counts were observed with these venoms. Findings suggestive of intravascular coagulation also were observed with moderate hemolysis of the formed elements. Some local hemorrhage was seen at the site of envenomation. Venom from the Elapidae family of snakes produced death at an average of 1.7 hours. The average lethal dose was 0.70 mg/kg. Death appeared to be primarily due to respiratory paralysis after blockade at the neuromuscular junction. Only moderate hemolysis was seen with these venoms. No intravascular coagulation or tissue damage was seen. The venom of the family Hydrophiodae consistently produced death in less than 30 minutes at an average dose of 0.06 mg/kg. Tissue damage was not observed, and changes were not observed in the hematologic parameters monitored. Death in these studies was due primarily to respiratory paralysis; however, the breakdown of muscle tissue was observed. The area in and around Saudi Arabia has a number of snakes that are dangerous to humans.

The effect of treatment with whole bee venom on cage activity and plasma cortisol levels in the arthritic dog.

A series of 24 mixed-breed dogs were used to study the physiological effects of whole bee venom on canine arthritic-like conditions. 16 were randomly selected normal dogs and 8 were suspect arthritic animals confirmed by X-ray examination and special physical examination. The control dogs were divided into groups I and II and the arthritic groups III and IV. Groups I and III received injections of sterile saline while groups II and IV were given 1 mg whole bee venom subcutaneously on days 30, 37, 50, and 60. Plasma cortisol levels were measured weekly and cage activity recorded daily using a K and R Pedometer. Following bee venom injection plasma cortisol levels increased in both groups II and IV from a control of 5Μg/100 ml to 15Μg/100 ml 15 days after therapy. During this period of time the 4 arthritic dogs in group IV increased daily cage activity from 4 mile/day to 10 mile/day. Groups I, II, and III showed no increase or decrease in cage activity. No injections were given between day 60 and day 90. At 90, 97, 110 and 120 days, groups I and III were given bee venom and groups II and IV sterile saline. As before, bee venom increased plasma cortisol levels in both venom-treated groups and the daily cage activity in group III. At 120 days all injections were discontinued. Plasma cortisol levels returned to normal within 30 days, yet daily cage activity in both groups III and IV remained significantly above control (8 to 11 mile/day). Results indicate that whole bee venom stimulates the production of cortisol and the daily cage activity in dogs exhibiting arthritic-like conditions. No significant side effects were noted in any of the dogs treated with bee venom.

Effect of cobra and rattlesnake venoms on the central nervous system of the primate.

Abstract Monkeys with chronically implanted cortical and subcortical electrodes were given venom of Crotalus adamanteus or Crotalus atrox or Naja naja. Effects of the venoms upon the electrical activity of various structures of the central nervous system were studied. The electroencephalographic pattern was quite similar following administration of the three venoms. There was an initial dyssynchronization followed by the appearance of high voltage slow waves and eventual flattening of the record prior to death. There was a decrease in the level of consciousness of the monkeys with cardiac arrhythmias and progressive respiratory depression, which appeared simultaneously with the high voltage slow wave pattern. The possibility that respiratory depression is the cause of the electroencephalographic changes is indicated.