Culture of care in animal research - Expanding the 3Rs to include people.

Research on animals is essential for science and medical progress. While it is still necessary to conduct this research, it is essential to apply the highest standards in animal welfare, including animal husbandry and care. Furthermore, it is important to recognize the special relationship between research animals and the people who care for them. Caring for research animals can be extremely fulfilling and meaningful, but it also comes with challenges, particularly when caring for animals experiencing pain or distress. These challenges can lead to work-related mental stress. To get more insight into the challenges of working in animal research, we organized a panel discussion at the GV-SOLAS (German Society for Laboratory Animal Science) and IGTP (Interest Group Animal Caretakers) conference 2021 about work wellbeing. This discussion was the first of its kind in Germany. The active panel contributions included the view of an ethical philosopher, a scientist, a lecturer for laboratory animal science, an animal facility manager and an animal caretaker. They gave insights from their perspective into key factors that can affect human wellbeing in animal research. Keys ideas included stigmatization of work, tension between research aims and animal wellbeing, and the importance of supportive culture to overcome work-related strains, as well as lack of education and supportive environments to cope with emotional stress in the workplace. Overall, the discussion has shown that we must also promote human wellbeing when promoting culture of care in animal research, because there is strong relationship between culture of care and individual performance.

Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo.

INTRODUCTION: Amiodarone is the gold standard in the prevention of recurrence of atrial fibrillation (AF), but the causes for its superior clinical efficacy are not understood. We hypothesized that atrial electrical remodeling increases the atrial efficacy of amiodarone. METHODS AND RESULTS: We investigated the effect of an acute intravenous dose of amiodarone on atrial refractory periods (AERP) in sinus rhythm (SR) and after 5, 24, and 72 hours of atrial tachypacing in comparison with the I(Kr) blocker dofetilide and the I(to)/IKur blockers AVE1231 and AVE0118 in five instrumented goats. Electrical remodeling progressively increased the AERP-prolonging effect of 3 mg/kg of AVE1231 and AVE0118 (2-fold increase in AERP at 72 hours vs SR, P < 0.01), but strongly decreased that of 10 mug/kg dofetilide (<0.5-fold, P < 0.05, at 300 and 400 ms basic cycle length). After 5 and 24 hours of tachypacing, the effect of 3 mg/kg amiodarone strongly increased (2-fold, P < 0.01 after 24 hours vs SR). This early gain in AERP prolongation was confirmed in anesthetized pigs with 3.5 hours of atrial tachypacing (2.4-fold increase, P < 0.01). At 72 hours of atrial tachypacing in the goat, however, the early gain was lost and the effect of amiodarone was similar again to that in SR. CONCLUSION: Atrial electrical remodeling changed the efficacy of the antiarrhythmic agents in a different way. The favorable efficacy profile of amiodarone during electrical remodeling, particularly the marked increase in AERP prolongation in early electrical remodeling, may explain its superior clinical efficacy over existing antiarrhythmic drugs.

Vasopeptidase inhibition prevents target organ damage and improves survival in spontaneously hypertensive rats.

BACKGROUND: Vasopeptidase inhibition has been shown to be an effective antihypertensive principle but its long-term effects on hypertensive target organ damage are not known. We investigated the myocardial, vascular and renal effects of chronic vasopeptidase inhibition in arterial hypertension. METHODS AND RESULTS: One hundred and thirty-nine male spontaneously hypertensive rats aged 15 months were treated chronically with either the pure angiotensin-converting enzyme (ACE) inhibitor, ramipril (1 mg/kg/d in drinking water, n=46), or the vasopeptidase inhibitor AVE7688 (30 mg/kg/d in chow, n=46), or placebo (n=47) and followed up until they died. After six months, both ramipril and AVE7688 had markedly reduced plasma ACE activity, normalised blood pressure (BP), reduced left ventricular mass and improved systolic function to similar extents. Acetylcholine mediated relaxation of aortic rings was improved by both ramipril and AVE7688. There was substantial albuminuria in the placebo group (albumin-to-creatinine ratio 107+/-54 microg/mg), which was significantly reduced by ramipril to 57+/-34 microg/mg, and practically abolished in the AVE7688 group (22+/-12 microg/mg, p<0.05 vs. placebo and ramipril). Tubulo-interstitial damage (semi-quantitative score) was significantly reduced by AVE7688 and ramipril. Overall mortality was markedly reduced in the ramipril and AVE7688 groups (13% and 16% at six months, respectively), both p<0.05 vs. placebo (71%). CONCLUSIONS: Vasopeptidase inhibition effectively controls BP and reduces myocardial, vascular and renal target organ damage, resulting in a markedly prolonged survival. At similar degrees of plasma ACE inhibition, AVE7688 compared to ramipril offers superior protection against hypertensive kidney damage.