Sites of action of Mojave toxin isolated from the venom of the Mojave rattlesnake.

1 Mojave toxin isolated from the venom of the Mojave rattlesnake (Crotalus scutulatus scutulatus) produced an irreversible blockade of the contractile response of the mouse hemidiaphragm to stimulation of the phrenic nerve in vitro, at concentrations of 0.16 to 20 mug/ml; the response to direct stimulation was not affected over a testing period of several hours.2 Mojave toxin (1 to 4 mug/g) was injected into the tail vein of mice and the intoxicated hemidiaphragm preparation was removed either for testing the contractile response or for intracellular recording.3 In fully intoxicated hemidiaphragms the contractile response to indirect stimulation was either small and transient or absent, whilst the response to direct stimulation was well maintained.4 Intracellular recording showed that resting membrane potentials of the muscle fibres were within the normal range. Endplates were difficult to locate but miniature endplate potentials (m.e.p.ps) were recorded at sites at which neurally evoked responses either could not be detected or did not exceed 2 mV which corresponds to transmitter release of a few quanta only.5 The mean frequency of m.e.p.ps at fully intoxicated endplates was not significantly different from controls but potassium depolarization produced only a small increase in m.e.p.p. frequency relative to the control response. A 50 Hz tetanus had no effect on m.e.p.p. frequency.6 When a sub-lethal dose (3 mug) of Mojave toxin was injected into one hindlimb of mice and the tissues examined at 72 h, there was histological evidence of myonecrosis.7 The isolated perfused heart of the rat was exposed to recycled Mojave toxin (50 and 100 mug/ml) but showed no change in rate or force of ventricular contraction.8 Post-mortem examination of intoxicated mice showed a frequent incidence of localized areas of interstitial and intra-alveolar haemorrhage in the lungs. Other organs including skin and muscle were not affected.9 Mojave toxin showed antigenic similarities to crotoxin, the lethal neurotoxin in the venom of the South American rattlesnake, as determined by the ability of antiserum raised against crotoxin to neutralize Mojave toxin.10 With systemic Mojave intoxication of rapid onset, the cause of death was respiratory paralysis. However, the toxin acts at multiple sites at differing rates of action. With a slower rate of intoxication, impaired respiration may act synergistically with cardiovascular changes to produce circulatory failure. The desirability of using an antivenin with a high titre against Mojave toxin is indicated.

The sites in the duodenum of receptor areas which affect abomasal emptying in the calf.

Calves were prepared with abomasal and duodenal cannulae to assess the effects on abomasal emptying of duodenal infusates at different rates and different sites. In two calves infusions of isotonic NaHCO3 or 60 mM HCl 30 cm distal to the pylorus were as effective in controlling abomasal emptying as infusions of the duodenum from 5 cm distal to the pylorus, and in three other calves they were as effective as perfusing the whole duodenum including the most proximal 5 cm. Reducing the rate of duodenal infusion of 60 mM HCl from 10 to 2.5 ml/min diminished its effect from total inhibition of gastric emptying to slight or negligible inhibition. The stimulation of gastric emptying by duodenal infusion of isotonic NaHCO3 solution was undiminished by reduced rates of infusion. It is proposed that in the calf receptors which activate and inhibit gastric emptying are present throughout the duodenum.

A radiological study of gastric (abomasal) emptying in calves before and after vagotomy.

1. Gastric emptying has been studied in the conscious, standing calf by lateral radiography and fluoroscopy of radiopaque meals instilled into the abomasum before and after vagotomy. 2. Bilateral cervical vagotomy proved to be the only certain way of achieving total vagal transection. By instillation of milk into the abomasum through a cannula calves were maintained in normal, healthy condition for up to 36 days after vagotomy. 3. Motility of the antrum was not impaired by vagotomy so that some movement of gastric chyme to the duodenum occurred within minutes of instillation into the abomasum. Complete transference of the test meal was, however, delayed after vagotomy. 4. The greatest effect of vagotomy appeared to be on the abomasal body so that inadequate amounts of chyme were transferred to the antrum for pumping to the duodenum. 5. Delay in passage of contrast material through the intestine was related to delay in gastric emptying although vagotomy may have affected the intestine directly. 6. Following vagotomy the abomasum showed a resumption of normal motility and emptying after 7-29 days. This effect of vagotomy is similar to that seen in the simple stomach and is probably due to the establishment of intrinsic gastric control.