Canine Model of Ischemia-Induced Ventricular Tachycardia.

INTRODUCTION: Despite advances in antiarrhythmia therapies, ventricular tachycardia (VT) is a leading cause of sudden cardiac death. Investigation into the characteristics and new treatments for this arrhythmia is required to improve outcomes and a reproducible model of VT would be useful in these endeavors. We therefore created a canine model of ischemia-induced VT. MATERIALS AND METHODS: A pacing lead was implanted in the right ventricle in canines (n = 13) and the left anterior descending artery was occluded in two locations for 2 h and subsequently released to create an ischemia-reperfusion injury. In the 10 dogs that survived the first 48 h following the initial study, a terminal study was conducted 4-7 d later and VT was induced using premature stimulation or burst pacing through the right ventricle lead. The arrhythmia was terminated using either antitachycardia pacing or a defibrillatory shock. Multiple inductions into sustained VT were attempted. RESULTS: Sustained VT was induced in eight of 10 dogs with an average cycle length of 335 ± 70 bpm. Multiple episodes of VT were induced. Episodes of VT exhibited different electrocardiogram morphologies and cycle lengths in individual animals. CONCLUSIONS: This canine model provides a consistent technique for inducing multiple episodes of sustained VT. It may be useful for investigating VT mechanisms and testing novel therapeutics and treatments for patients with VT.

A canine model of chronic ischemic heart failure.

Preclinical large animal models of chronic heart failure (HF) are crucial to both understanding pathological remodeling and translating fundamental discoveries into novel therapeutics for HF. Canine models of ischemic cardiomyopathy are historically limited by either high early mortality or failure to develop chronic heart failure. Twenty-nine healthy adult dogs (30 ± 4 kg, 15/29 male) underwent thoracotomy followed by one of three types of left anterior descending (LAD) coronary artery ligation procedures: group 1 (n = 4) (simple LAD: proximal and distal LAD ligation); group 2 (n = 14) (simple LAD plus lateral wall including ligation of the distal first diagonal and proximal first obtuse marginal); and group 3 (n = 11) (total LAD devascularization or TLD: simple LAD plus ligation of proximal LAD branches to both the right and left ventricles). Dogs were followed until chronic severe HF developed defined as left ventricular ejection fraction (LVEF) < 40% and NH2-terminal-prohormone B-type natriuretic peptide (NT-proBNP) > 900 pmol/L. Overall early survival (48-h postligation) in 29 dogs was 83% and the survival rate at postligation 5 wk was 69%. Groups 1 and 2 had 100% and 71% early survival, respectively, yet only a 50% success rate of developing chronic HF. Group 3 had excellent survival at postligation 48 h (91%) and a 100% success in the development of chronic ischemic HF. The TLD approach, which limits full LAD and collateral flow to its perfusion bed, provides excellent early survival and reliable development of chronic ischemic HF in canine hearts.NEW & NOTEWORTHY The novel total left anterior descending devascularization (TLD) approach in a canine ischemic heart failure model limits collateral flow in the ischemic zone and provides excellent early survival and repeatable development of chronic ischemic heart failure in the canine heart. This work provides a consistent large animal model for investigating heart failure mechanisms and testing novel therapeutics.

Investigating individual differences in opioid-taking and opioid-seeking behavior in male rats.

RATIONALE: Understanding the behavioral and neurobiological factors that render some individuals more susceptible than others to opioid addiction will be critical in combatting the opioid crisis. OBJECTIVE: The purpose of the current study was to determine if behavioral traits associated with an increased likelihood to take and seek cocaine are the same traits that render one more susceptible to opioid-taking and opioid-seeking behavior. Individual differences in the acquisition of remifentanil self-administration and subsequent cue-induced reinstatement of remifentanil-seeking behavior were investigated using two animal models: the high-responder (HR)/low-responder (LR) and sign-tracker (ST)/goal-tracker (GT) models. Relative to LR rats, HR rats show increased novelty-induced locomotion or "sensation-seeking" behavior, and are more likely to acquire cocaine-taking behavior and do so at a faster rate. Relative to GT rats, ST rats attribute greater incentive motivational value to reward cues and are more likely to exhibit reinstatement of cocaine-seeking behavior. RESULTS: In contrast to previous work using cocaine, we did not observe individual differences with respect to the acquisition of remifentanil self-administration- or cue-induced reinstatement of remifentanil-seeking behavior within the context of either the HR/LR or ST/GT model. Thus, neither the sensation-seeking trait nor the propensity to attribute incentive motivational value to reward cues predicts remifentanil-taking or remifentanil-seeking behavior. CONCLUSIONS: These findings suggest that different traits may confer the initiation of opioid- vs. cocaine-taking behavior, and the propensity to relapse to opioid- vs. cocaine-seeking. Additional studies are needed to identify which neurobehavioral constructs confer liability to opioid use and relapse.

Effects of Pair Housing on Patency of Jugular Catheters in Rats (Rattus norvegicus).

Chronic vascular access devices are widely used in a variety of species for repeated blood sampling or substance administration. Jugular catheters are commonly used for studying addiction-related behaviors in rats. Rats with catheters have historically been individually housed for the duration of the study to prevent cage mates from damaging the catheter. The 2 goals of this study were to determine 1) the effects of pair housing on catheter patency and 2) the effects of pair housing on catheter patency of rats in a study of opioid self-administration and cue-induced reinstatement of opioid-seeking behavior. The latter study also represented an opportunity for experimental refinement as it evaluated the temporary use of a barrier that allowed for pair-housed rats to be physically separated. Male Heterogeneous Stock (HS; n = 24) and Sprague-Dawley (SD; n = 121) rats were allocated to either single- or pair-housed condition. To assess the effect of social housing on catheter patency, rats (HS, n = 24; SD, n = 36) were monitored in their assigned housing condition for one month, with scheduled evaluation of catheter patency and structural damage. To examine the effect of social housing on catheter patency during a study of opioid self-administration and cue-induced reinstatement of opioid-seeking behavior, rats (SD, n = 85) were monitored in their assigned housing condition with similar routine patency evaluations. Catheter patency rates between single- and pairhoused rats were not statistically different in the first experiment, and pair-housed animals were successfully maintained on an infusion study in the second experiment. The use of a barrier between pair-housed rats after surgery allowed continued social contact with no observed adverse effects. These results suggest that, pair housing is a viable option for rats with chronic vascular implants, and may improve their wellbeing by allowing them to display species-typical social behaviors.

Enrichment Preferences of Singly Housed Zebrafish (Danio rerio).

Despite the increasing popularity of zebrafish (Danio rerio) as an animal model, the environmental enrichment preferences of this species have been largely unexplored. We sought to determine the preferences of mature female zebrafish that were singly housed with or without access to one of 10 inanimate forms of enrichment. As a marker of preference, in-tank fish location was observed by video recording. All subjects showed a preference for the front of the tank when caretakers entered the room, demonstrating an effect of human presence on tank location. Among the 10 enrichment items tested, subjects showed the strongest preference for mirrored paper on the side of the tank when compared with the barren half of the tank. Fish also were observed interacting with PVC pipe, marbles, and tulle. Given the preference for enrichment imitating social interaction, we conducted a second study to assess the value of visual exposure of conspecifics in adjacent tanks. The experimental zebrafish were then provided one of 3 conditions-a singly housed neighbor fish, group-housed neighbor fish, or no neighbor fish. All zebrafish housed next to neighboring fish showed a preference to be on the side of the tank nearer to the other fish. Overall, our data indicate that singly housed zebrafish prefer enrichment items that resemble or promote social behaviors. Therefore items such as mirrored paper or housing next to conspecifics should be strongly considered as enrichment strategies for singly housed zebrafish.