Midazolam enhances the analgesic properties of dexmedetomidine in the rat.

OBJECTIVE: To investigate the analgesic properties of different dose combinations of midazolam and dexmedetomidine administered intraperitoneally (IP) in the rat. STUDY DESIGN: Prospective experimental trial. ANIMALS: Seventy adult male Sprague Dawley rats weighing 250-300 g. METHODS: Dexmedetomidine (D) 0.03, 0.06, 0.09, 0.12, 0.15, 0.18, 0.21 mg kg(-1) and midazolam (M) 5, 10, 25, 50 mg kg(-1) were administered IP, alone then in combinations ranging from 0.03 D:5 M to 0.18 D:30 M mg kg(-1). Analgesia was evaluated using the tail-flick test at time 0 (before injection), 15, 30, 45, 60 and 75 minutes. RESULTS: Midazolam at all doses administered (5-50 mg kg(-1)) did not significantly change tail-flick latencies from baseline values whereas D showed clear dose-dependent increases in tail-flick latency for doses administered in the range of 0.03-0.18 mg kg(-1). Tail-flick latencies in rats administered D+M combinations were significantly greater than D alone (p<0.05). CONCLUSIONS: A dose-related analgesic effect was demonstrated for D in the rat, which was enhanced by co-administration of M. CLINICAL RELEVANCE: The combination of D+M administered IP to rats at doses of 0.12:20 and 0.09:15 mg kg(-1) was shown to be a good combination to provide sedation/analgesia with a duration of action greater than 60 minutes. The onset of sedation was rapid (1-3 minutes), and onset of profound analgesia was reached within 5-10 minutes.

Animal model development for the Penn State pediatric ventricular assist device.

In March 2004, the National Heart, Lung, and Blood Institute awarded five contracts to develop devices providing circulatory support for infants and small children with congenital and acquired cardiac disease. Since 2004, the team at Penn State College of Medicine has developed a pneumatically actuated ventricular assist device (VAD) with mechanical tilting disk valves. To date, hemodynamic performance, thrombogenesis, and hemolysis have been chronically evaluated in 16 animals, including 4 pygmy goats and 12 sheep. Major complications, mainly respiratory failure, have been encountered and resolved by a multi-disciplinary team. Multi-modal analgesia, appropriate antibiotic therapy, and attentive animal care have contributed to successful outcomes. Time after implant has ranged from 0 to 40 days. Most recently, a sheep implanted with Version 3 Infant VAD was electively terminated at 35 days postimplant, with no major adverse events. This report describes a successful in vivo model for evaluating a pediatric VAD.

Complications of elastase-induced arterial saccular aneurysm in rabbits: case reports and literature review.

Endoluminal infusion and incubation of elastase with or without collagenase into the rabbit common carotid artery is an established model of arterial saccular aneurysm. The model mimics naturally occurring human cerebral aneurysms in many ways, including histologic and morphologic characteristics, hemodynamic pressures, and shear stresses. However, complications have been associated with the model. Here, we report 2 complications: 1) the first known case of iatrogenic laryngeal hemiplegia in a rabbit; and 2) histopathologically confirmed iatrogenic hippocampal and cerebellar infarcts (stroke). Finally, we present and review data from current literature on the morbidity and mortality associated with this model.

Chronic in vivo testing of the Penn State infant ventricular assist device.

The Penn State Infant Ventricular Assist Device (VAD) is a 12-14 ml stroke volume pneumatically actuated pump, with custom Björk-Shiley monostrut valves, developed under the National Heart, Lung, and Blood Institute Pediatric Circulatory Support program. In this report, we describe the seven most recent chronic animal studies of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 ± 4.1 kg. The goal of 4-6 weeks survival was achieved in five of seven studies, with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation was accomplished using unfractionated heparin, and study animals were divided into two protocol groups: the first based on a target activated partial thromboplastin time of 1.5-2 times normal, and a second group using a target thromboelastography R-time of two times normal. The second group required significantly less heparin, which was verified by barely detectable heparin activity (anti-Xa). In both groups, there was no evidence of thromboembolism except in one animal with a chronic infection and fever. Device thrombi were minimal and were further reduced by introduction of the custom valve. These results are consistent with results of adult VAD testing in animals and are encouraging given the extremely low levels of anticoagulation in the second group.