The Gaboon viper (Bitis gabonica): its biology, venom components and toxinology.

The Gaboon viper has acquired an impressive reputation which is at least partly unfounded. This handsome animal with such striking features is undoubtedly docile which accounts for the very low incidence of bite amongst humans. There are only six detailed clinical reports on the effect of bite and these are summarized in the review. The viper does indeed produce prodigious amounts of venom, but the toxicity, weight for weight, is rather low compared to other poisonous snakes. Venom extractions have been carried out on four snakes over a 13-year-period and the effects of this venom have been studied in a variety of experimental animals. Systemic envenomation is characterized by immediate abrupt hypotension, subsequent cardiac damage and dyspnoea. The individual venom components responsible for these effects have not been isolated but it seems likely that the two enzymes which have been studied extensively (phospholipase A2 and the thrombin-like enzyme, gabonase) do not contribute significantly to lethality. We propose three principal activities which give rise to the major signs of systemic envenomation. Haemorrhagin; causing widespread damage to microvasculature which leads to the pulmonary oedema and hence dyspnoea, and locally causes blistering. Cardiotoxin; a long-acting material causing cardiac muscle damage, arrhythmia and ultimately cardiac failure. Peripheral vasodilator; a short acting effect, operating either locally via bradykinin formation and/or unknown peptides or centrally on the vasomotor centre.

The effects of Gaboon viper (Bitis gabonica) venom on the electrical and mechanical activity of the guinea-pig myocardium.

The effects of Bitis gabonica venom were tested on guinea-pig heart, using both Langendorff preparations and isolated atrial strips or papillary muscles. In the self-paced whole heart, a single passage of 50 micrograms of venom per ml produced in sequence: irregularities of the A-V conduction and decrease of the contractile strength, progressive failure to relax and systolic arrest of the heart. Pretreatment with atropine reduced but did not abolish these effects. Venom recycled through the heart was effective at a much lower dose. The relationship between resting membrane potential and [K+]o was unaffected by envenomation, suggesting that the action of the venom cannot be ascribed to a loss of ionic selectivity of the cell membrane. The peak amplitude of action potentials declined in papillary muscle exposed to venom at physiological [K+]o, while in atrial cells it was affected only at higher [K+]o. Maximum upstroke rate of the action potential vs. resting potential at different [K+]o gave a sigmoid relationship, characterized by a higher upper asymptote as compared to controls, and by a shift of the curve towards more negative voltage values. A marked shortening of the action potential duration, paralleled by a decrease in time to peak tension, was recorded as well. 'Slow' action potentials, elicited in 20 mM K+ solution, were completely abolished within 10 min of perfusion with venom. These results are consistent with the hypothesis that the venom interacts with both transmembrane Ca2+ inflow and Ca2+ binding at the external side of the cell membrane. A transient positive inotropic effect induced by the venom was observed in papillary muscle and in atropinized atrium. This effect was abolished by previous administration of reserpine to the animal or by addition of propranolol to the perfusing solution, suggesting a venom-induced release of both adrenergic and cholinergic transmitters from nerve endings within the cardiac tissue.

The effect of Bitis gabonica (Gaboon viper) snake venom on external iliac and mesenteric arterial circulation in the dog.

The effects of Gaboon viper (Bitis gabonica) venom on external iliac and mesenteric arterial blood flow and resistance were investigated in eight anaesthetized, close-chest dogs. Venom doses in the range 0.125-0.5 mg/kg produced a profound fall in external iliac and mesenteric arterial resistance, which recovered to control values after 30 min. After a third dose of venom, the mean arterial blood pressure failed to recover and the animals died after a period of severe hypotension. External iliac arterial blood flow rose concomitantly with the fall in external iliac resistance and decreased to a value significantly below control after 30 min. Paradoxically, mesenteric blood flow fell during the period of vasodilation. The results suggest that widespread vasodilation of muscle vascular beds (of which the external iliac circulation is representative) leads to shunting of blood away from the less-dilated mesenteric circulation. Venom-induced peritoneal haemorrhage caused a fall in blood volume and increase in viscosity. These undoubtedly contributed to the severe haemodynamic deterioration of the preparations after the third injection of the venom.

The effect of gaboon viper (Bitis gabonica) venom on cardiac stroke work in the anaesthetized rabbit.

The effect of Bitis gabonica venom administered intravenously in the rabbit at the dose of 0.125 mg/kg (approximately 10% of LD50) has been studied. Venom caused marked changes in cardiovascular parameters principally a precipitous but transient fall in total peripheral resistance and arterial blood pressure. Furthermore in the period occurring between 5 and 30 min after the injection of venom, a transient increase in stroke work was observed as a result of the ejection of an increased stroke volume against a blood pressure which had already returned to normal. Such a transient inotropic effect has also been observed in other small mammals and could be attributed to an adrenergic mechanism.

The toxicity of thallium(I) to cardiac and skeletal muscle.

The effects of (a) partial or complete replacement of K+ by Tl+ in saline perfusing isolated rat heart and diaphragm preparations and (b) pulse injections of high concentrations of Tl+ or K+, have been studied. The immediate effect of Tl+ resembles that of higher concentrations of K+ and may reflect its more rapid penetration into the tissue. Tl+ appears to replace K+ on a 1:1 basis to an extent dependent upon the relative abundance of the two cations in the perfusion solution. However, analysis of diaphragm preparations after perfusion with salines containing increasing Tl+ but constant [K+ + Tl+] showed a related and progressive increase in total cation content. This effect, which was not seen in the presence of constant high (normal) K+ concentrations, may reflect an increase of the intracellular space brought about by the thallium. Functional effects of Tl+ were (a) preferential block of the phrenic nerve or neuromuscular junction over the muscle fibre and (b) transient but marked acceleration of cardiac frequency following pulse injections, which may be of value in analysing the pacemaker mechanism of the heart. In both tissues Tl+ is eventually toxic and probably irreversibly so.

Cardiac performance in the rabbit as affected by the venom of bitis gabonica. (A preliminary report).

The effect of the venom of Bitis gabonica administered intravenously in the rabbit at the dose of 0.125 mg/kg has been compared with that produced by the same dose of the compound in the dog. In the rabbit the effect on total peripheral resistance, aortic blood pressure and stroke volume is less marked and shorter than in the dog. Furthermore in a period included between 5 and 30 min after the injection, in the rabbit a transient increase of stroke work is observed as a result of the ejection of an increased stroke volume against a blood pressure which has already returned to normal. Such a transient inotropic effect of the venom was also observed in other small mammalians and might be attributed to an adrenergic mechanism.

Haemodynamic effect of the venom of Bitis Gabonica in the dog.

Intravenous injection of 0.125 mg/kg of venom of Bitis Gabonica in the anaesthetized dog produces an immediate but reversible decrease in total peripheral and coronary vascular resistance. Stroke volume show a transient increase followed by an irreversible reduction. A second dose of 0.25 mg/kg produces the same effect on total peripheral and coronary vascular resistance, but furtherly reduces the stroke volume. A third dose of 0.50 mg/kg kills the animal after an extreme reduction of the stroke volume. The progressive decrease of the stroke volume might be due to a failure of the ventricle to relax, whereas its transient increase immediately after the injection depends on the abrupt fall of the total peripheral resistance.