Rattling the border wall: Pathophysiological implications of functional and proteomic venom variation between Mexican and US subspecies of the desert rattlesnake Crotalus scutulatus.

While some US populations of the Mohave rattlesnake (Crotalus scutulatus scutulatus) are infamous for being potently neurotoxic, the Mexican subspecies C. s. salvini (Huamantlan rattlesnake) has been largely unstudied beyond crude lethality testing upon mice. In this study we show that at least some populations of this snake are as potently neurotoxic as its northern cousin. Testing of the Mexican antivenom Antivipmyn showed a complete lack of neutralisation for the neurotoxic effects of C. s. salvini venom, while the neurotoxic effects of the US subspecies C. s. scutulatus were time-delayed but ultimately not eliminated. These results document unrecognised potent neurological effects of a Mexican snake and highlight the medical importance of this subspecies, a finding augmented by the ineffectiveness of the Antivipmyn antivenom. These results also influence our understanding of the venom evolution of Crotalus scutulatus, suggesting that neurotoxicity is the ancestral feature of this species, with the US populations which lack neurotoxicity being derived states.

Neuromuscular action of venom from the South American colubrid snake Philodryas patagoniensis.

Snakes of the opisthoglyphous genus Philodryas are widespread in South America and cause most bites by colubrids in this region. In this study, we examined the neurotoxic and myotoxic effects of venom from Philodryas patagoniensis in biventer cervicis and phrenic nerve-diaphragm preparations and we compared the biochemical activities of venoms from P. patagoniensis and Philodryas olfersii. Philodryas patagoniensis venom (40 microg/mL) had no effect on mouse phrenic nerve-diaphragm preparations but caused time-dependent neuromuscular blockade of chick biventer cervicis preparations. This blockade was not reversed by washing. The highest concentration of venom tested (40 microg/mL) significantly reduced (p<0.05) the contractures to exogenous acetylcholine (55 microM and 110 microM) and K(+) (13.4 mM) after 120 min; lower concentrations of venom had no consistent or significant effect on these responses. Venom caused a concentration- and time-dependent release of creatine kinase (CK) from biventer cervicis preparations. Histological analysis showed contracted muscle fibers at low venom concentrations and myonecrosis at high concentrations. Philodryas venoms had low esterase and phospholipase A(2) but high proteolytic activities compared to the pitviper Bothrops jararaca. SDS-PAGE showed that the Philodryas venoms had similar electrophoretic profiles, with most proteins having a molecular mass of 25-80 kDa. Both of the Philodryas venoms cross-reacted with bothropic antivenom in ELISA, indicating the presence of proteins immunologically related to Bothrops venoms. RP-HPLC of P. patagoniensis venom yielded four major peaks, each of which contained several proteins, as shown by SDS-PAGE. These results indicate that P. patagoniensis venom has neurotoxic and myotoxic components that may contribute to the effects of envenoming by this species.

Chronotropic and inotropic effects of hyperosmotic solutions on right and left atria isolated from the rat heart.

The chronotropic and inotropic effects of hyperosmotic solutions (HS) on isolated rat atria were studied to determine the influences of solute, time and blockade of autonomic receptors. NaCl and sucrose HS (450 mOsm/1) exerted a time-dependent negative chronotropic effect on right atria. NaCl decreased whereas sucrose increased peak tension of the left atria. Phenoxybenzamine and propranolol did not change the chronotropic effects of hyperosmolality, but increased the peak tension of left atria exposed to HS. We conclude that chronotropic effects of HS seem to be non-specific while inotropic effects depend on the solute and may involve neurotransmitter release, probably acetylcholine.

Pharmacology and use of muscle relaxants in infants and children.

Succinylcholine is a short-acting depolarizing neuromuscular blocker used to facilitate intubation; pancuronium is a longer-acting, nondepolarizing agent commonly employed to control ventilation in pediatric patients. The neuromuscular block produced by both drugs may be modified by patient age, acid-base and electrolyte status, body temperature, and drugs such as aminoglycoside antibiotics; adjustment in dose or in technique of administration may be required. Cardiovascular side-effects, primarily arrhythmias, are occasionally associated with the use of either agent. In contrast to that of succinylcholine, the paralysis from pancuronium is pharmacologically reversible with the combination of atropine and neostigmine.