Echocardiography for in vivo assessment of hemodynamic effects of nanobodies therapy for neutralizing cardiac toxins in rats

Background: Many people and particularly children die every year from venom toxins of the scorpion Androctonus australis hector (Aah), secondary to hemodynamic and neurologic effects. The current immunotherapy for scorpion envenoming uses purified polyclonal fractions, but their therapeutic effects are still controversial and they may still exert adverse effects. Nanobodies (Nb), single-domain antigen-binding fragments derived from dromedary heavy-chain antibodies, due to their small size and high affinity for the antigen, might be developed into potent immunotherapeutics to treat scorpion envenoming. Therefore, we sought to investigate the hemodynamic effects of Nb therapy for neutralizing scorpion toxin effect in rats.
Methods: All rats (Male Wistar, n=24) underwent baseline echocardiograms under anaesthesia with a continuous recording of the ECG and blood pressure measurements during 60 minutes. Animals were divided into two groups, one receiving a lethal dose of the Aah venom (I) and a second one as control group receiving physiologic serum or Nb alone (II). The first group was divided into Nb treated (IA) and non-treated animals (IB).
Results: In group IB, all rats died within 25-30 minutes after envenomation, compared to none in group IA and II. Compared to baseline, heart rate (337 ± 34 vs. 92 ± 12 bpm, pConclusions:
1) Immunotherapy with Nb is a new treatment that prevents hemodynamic lethal effects of Aah toxin.
2) Echocardiography is a useful tool for monitoring cardiac function in a small animal model of toxin effects.
3) This model may open opportunities for new toxic models of cardiac dysfunction in small animals and for potential immunotherapeutics with Nb.