ABSTRACT
OBJECTIVE: To determine the feasibility of atrial septal pacing via a delivery catheter-guided small non-retracting helix pacing lead. ANIMALS: Six healthy beagles (8.3-12.9 kg). METHODS: Using single plane fluoroscopic guidance, Medtronic(®) 3830 SelectSecure leads were connected to the atrial septum via Medtronic® Attain Select® II standard 90 Left Heart delivery catheter. Pacing threshold and lead impedance were measured at implantation. The Wenckebach point was tested via atrial pacing up to 220 paced pulses per minute (ppm). Thoracic radiographs were performed following implantation to identify the lead position, and repeated at 24 h, 1 month, and 3 months post-operatively. RESULTS: Macro-lead dislodgement occurred in two dogs at 24 h and in three dogs at one-month post-implantation. Lead impedance, measured at the time of implantation, ranged from 583 to 1421 Ω. The Wenckebach point was >220 ppm in four of the six dogs. The remaining two dogs had Wenckebach points of 120 and 190 ppm. CONCLUSIONS: This pilot study suggests the selected implantation technique and lead system were inadequate for secure placement in the atrial septum of these dogs. The possible reasons for inadequate stability include unsuitable lead design for this location, inadequate lead slack at the time of implantation and inadequate seating of the lead as evidenced by low impedance at the time of implantation. Other implantation techniques and/or pacing leads should be investigated to determine the optimal way of pacing the atria in small breed dogs that are prone to sinus node dysfunction.
Subject(s)
Atrial Septum , Cardiac Pacing, Artificial/veterinary , Dog Diseases/therapy , Sick Sinus Syndrome/veterinary , Animals , Breeding , Cardiac Pacing, Artificial/methods , Dogs , Female , Male , Pilot Projects , Sick Sinus Syndrome/therapy , Treatment OutcomeABSTRACT
We characterized the pharmacokinetics and dynamics of dichloroacetate (DCA), an investigational drug for mitochondrial diseases, pulmonary arterial hypertension, and cancer. Adult Beagle dogs were orally administered 6.25 mg/kg q12h DCA for 4 weeks. Plasma kinetics was determined after 1, 14, and 28 days. The activity and expression of glutathione transferase zeta 1 (GSTZ1), which biotransforms DCA to glyoxylate, were determined from liver biopsies at baseline and after 27 days. Dogs demonstrate much slower clearance and greater inhibition of DCA metabolism and GSTZ1 activity and expression than rodents and most humans. Indeed, the plasma kinetics of DCA in dogs is similar to humans with GSTZ1 polymorphisms that confer exceptionally slow plasma clearance. Dogs may be a useful model to further investigate the toxicokinetics and therapeutic potential of DCA.
