Luca Zilberstein

Animal studies with the Carmat bioprosthetic total artificial heart

OBJECTIVES The Carmat bioprosthetic total artificial heart (TAH) contains bioprosthetic blood-contacting surfaces, and is designed for orthotopic cardiac replacement. In preparation for clinical studies, we evaluated the TAH performance and its effects on end-organ function in an animal model. METHODS Twelve female Charolais calves, 2-3 months of age and weighing 102-122 kg, were implanted with the TAH through a mid-sternotomy to ensure an adequate anatomic fit. The intended support duration was 4-10 days. Haematological values, creatinine, bilirubin and lactate levels were measured and mean arterial and central venous pressure, central venous oxygen saturation and TAH parameters were monitored. RESULTS The calves were placed in a cage immediately postoperatively, and extubated on postoperative day 1 in most cases. Average support duration was 3 days, with 4 of 12 calves supported for 4, 4, 8 and 10 days. The initial procedures were used to refine surgical techniques and postoperative care. Pump output ranged from 7.3 to 10 l/min. Haemodynamic parameters and blood analysis were within acceptable ranges. No device failures occurred. No anticoagulation was used in the postoperative phase. The calves were euthanized in case of discomfort compromising the animal well-being, such as respiratory dysfunction, severe blood loss and cerebral dysfunction. Device explant analysis showed no thrombus formation inside the blood cavities. Histological examination of kidneys showed isolated micro-infarction in 2/12 animals; brain histology revealed no thromboembolic depositions. CONCLUSION The Carmat bioprosthetic TAH implanted in calves up to 10 days provided adequate blood flow to organs and tissues. Low levels of haemolysis and no visible evidence of thromboembolic depositions in major organs and device cavities, without the use of anticoagulation, may indicate early-phase haemocompatibility of the TAH.

Intramuscular administration of alfaxalone for sedation in rabbits

Alfaxalone is a neuroactive steroid derivative of pregnanedione that was recently reintroduced to the market for use as an induction agent in small animal anaesthesia. The aim of this study was to determine an intramuscular alfaxalone dose for safe immobilisation. Ten healthy New Zealand white rabbits were used to evaluate a single intramuscular injection of alfaxalone. The design of the study was a three-way, complete block, cross-over trial to compare the effect of alfaxalone at three doses (4, 6 and 8 mg). The mean duration of the effect for the 4, 6 and 8 mg/kg doses was, respectively, 36.9 (95% CI (31.6 to 42.3)), 51.8 (46.4 to 57.2) and 58.4 (52.8 to 63.9) minutes. The loss of the righting reflex was achieved after 3.1 (2.5 to 3.8), 2.4 (1.7 to 3.1) and 2.3 (1.6 to 2.9) minutes, respectively. The mean duration of the effect for the 6 and 8 mg doses was significantly higher than for the 4 mg dose (with estimated differences of 14.8 95% CI (8.8 to 20.8) minutes and 21.4 (15.3 to 27.6) minutes, respectively). No significant dose effect was observed before the loss of the righting reflex (P=0.14). Ear pinching and limb withdrawal were elicited in all groups at every dose. Doses of 4 or 6 mg/kg could be recommended; higher doses do not provide clinical benefits and can be associated with anaesthetic complication.

The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves

OBJECTIVES To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). DESIGN Preclinical study SETTING: Single-center biosurgical research laboratory. PARTICIPANTS Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. INTERVENTIONS Surgical implantation of TAH through a mid-sternotomy approach. MEASUREMENTS AND MAIN RESULTS Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. CONCLUSIONS Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies.

Antinociceptive activity of pre- versus post-operative intra-articular bupivacaine in goats undergoing stifle arthrotomy

OBJECTIVE To evaluate the peri-operative analgesic efficacy of intra-articular bupivacaine administered before or after stifle arthrotomy. STUDY DESIGN Prospective, randomized, blind, placebo-controlled experimental trial. ANIMALS Thirty-nine healthy goats. METHODS The goats were allocated randomly to one of three intra-articular treatment groups: group PRE (bupivacaine before and saline after surgery), group POST (saline before and bupivacaine after surgery) and group CON (saline before and after surgery). Anaesthesia was maintained with a constant end-tidal sevoflurane of 2.5%. Intra-operatively heart rate (HR), respiratory rate and mean arterial blood pressure (MAP) after critical surgical events (CSE) were recorded and compared with pre-incision values. Propofol requirements to maintain surgical anaesthesia were recorded. Flunixin was administered for 5 days. Post-operative pain assessment at 20 minutes, 2 hours, 4 hours after recovery and on day 2 and 3 included a multidimensional pain score (MPS), a lameness score and mechanical nociceptive threshold (MNT) testing. Rescue analgesia consisted of systemic opioids. Data were analysed using Kruskal-Wallis, Mann-Whitney, Friedman or chi-square tests as appropriate. RESULTS Intra-operatively, group PRE had lower HR and MAP at several CSEs than groups POST/CON and required less propofol [0 mg kg(-1) (0-0 mg kg(-1))] than group POST/CON [0.3 mg kg(-1) (0-0.6 mg kg(-1))]. Post-operatively, group POST had significantly higher peri-articular MNTs than groups PRE and CON up to 4 hours after recovery. No treatment effect was detected for MPS, lameness scores and rescue analgesic consumption at any time point. CONCLUSIONS AND CLINICAL RELEVANCE Pre-operative intra-articular bupivacaine provided notable intra-operative analgesia in goats undergoing stifle arthrotomy but did not reduce post-operative pain. Post-operative intra-articular bupivacaine provided a short lasting reduction of peri-articular hyperalgesia without affecting the requirements for systemic analgesia. Multimodal perioperative pain therapy is recommended to provide adequate analgesia for stifle arthrotomy in goats.

Luxation of the shoulder joint in a horse recovering from general anaesthesia

IT is well known and accepted that, in the horse, general anaesthesia, and especially its duration, is accompanied by a relatively higher risk of morbidity and mortality than in other species (Johnston and others 2002). There are a large number of contributory factors involved in this increased risk. It has been suggested that the size and temperament of horses are determinants for an increased rate of injury during the induction of and recovery from general anaesthesia. Fractures were the second highest cause of euthanasia after cardiac arrest in non-colic cases and amounted to 25·6 per cent of the total. However, in the survey of Johnston and others (2002) it would appear that no specific reference was made to the occurrence of luxations, which would suggest that the incidence is extremely low. A single case of subluxation of the elbow joint has been described in a pony; this probably occurred during the induction of anaesthesia and resulted in euthanasia of the animal (Senior and others 2002). It would also appear that no similar cases have been described in the