Impact of sternotomy and pericardiotomy on cardiopulmonary haemodynamics in a large animal model.

NEW FINDINGS: What is the central question of this study? Invasive cardiovascular instrumentation can occur through closed- or open-chest approaches. To what extent will sternotomy and pericardiotomy affect cardiopulmonary variables? What is the main finding and its importance? Opening of the thorax decreased mean systemic and pulmonary pressures. Left ventricular function improved, but no changes were observed in right ventricular systolic measures. No consensus or recommendation exists regarding instrumentation. Methodological differences risk compromising rigour and reproducibility in preclinical research. ABSTRACT: Animal models of cardiovascular disease are often evaluated by invasive instrumentation for phenotyping. As no consensus exists, both open- and closed-chest approaches are used, which might compromise rigour and reproducibility in preclinical research. We aimed to quantify the cardiopulmonary changes induced by sternotomy and pericardiotomy in a large animal model. Seven pigs were anaesthetized, mechanically ventilated and evaluated by right heart catheterization and bi-ventricular pressure-volume loop recordings at baseline and after sternotomy and pericardiotomy. Data were compared by ANOVA or the Friedmann test where appropriate, with post-hoc analyses to control for multiple comparisons. Sternotomy and pericardiotomy caused reductions in mean systemic (-12 ± 11 mmHg, P = 0.027) and pulmonary pressures (-4 ± 3 mmHg, P = 0.006) and airway pressures. Cardiac output decreased non-significantly (-1329 ± 1762 ml/min, P = 0.052). Left ventricular afterload decreased, with an increase in ejection fraction (+9 ± 7%, P = 0.027) and coupling. No changes were observed in right ventricular systolic function or arterial blood gases. In conclusion, open- versus closed-chest approaches to invasive cardiovascular phenotyping cause a systematic difference in key haemodynamic variables. Researchers should adopt the most appropriate approach to ensure rigour and reproducibility in preclinical cardiovascular research.

Relevance of the Viborg Population Based Screening Programme (VISP) for Cardiovascular Conditions Among 67 Year Olds: Attendance Rate, Prevalence, and Proportion of Initiated Cardiovascular Medicines Stratified By Sex.

OBJECTIVE: To report sex specific overall attendance rate, prevalence of screen detected cardiovascular conditions, proportion of unknown conditions before screening, and proportion initiating prophylactic medicine among 67 year olds in Denmark. DESIGN: Cross sectional cohort study. METHODS: Since 2014, all 67 year olds in Viborg, Denmark, have been invited to screening for abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), carotid plaque (CP), hypertension, cardiac disease, and type 2 diabetes. Individuals with AAA, PAD, and or CP are recommended cardiovascular prophylaxis. Combining data with registries has facilitated estimation of unknown screen detected conditions. Up to August 2019, 5 505 had been invited; registry data were available for the first 4 826 who were invited. RESULTS: The attendance rate was 83.7%, without sex difference. Screen detected prevalence was significantly lower among women than men: AAA, 5 (0.3%) vs. 38 (1.9%) (p < .001); PAD, 90 (4.5%) vs. 134 (6.6%) (p = .011); CP, 641 (31.8%) vs. 907 (44.8%) (p < .001); arrhythmia, 26 (1.4%) vs. 77 (4.2%) (p < .001); blood pressure ≥ 160/100 mmHg, 277 (13.8%) vs. 346 (17.1%) (p = .004); and HbA1c ≥ 48 mmol/mol, 155 (7.7%) vs. 198 (9.8%) (p = .019), respectively. Pre-screening proportions of unknown conditions were particularly high for AAA (95.4%) and PAD (87.5%). AAA, PAD, and or CP were found in 1 623 (40.2%), of whom 470 (29.0%) received pre-screening antiplatelets and 743 (45.8%) lipid lowering therapy. Furthermore, 413 (25.5%) started antiplatelet therapy and 347 (21.4%) started lipid lowering therapy. Only smoking was significantly associated with all vascular conditions in multivariable analysis: odds ratios (ORs) for current smoking were AAA 8.11 (95% CI 2.27 - 28.97), PAD 5.60 (95% CI 3.61 - 8.67) and CP 3.64 (95% CI 2.95 - 4.47). CONCLUSION: The attendance rate signals public acceptability for attending cardiovascular screening. Men had more screen detected conditions than women, but prophylactic medicine was started equally frequently in both sexes. Sex specific cost effectiveness follow up is warranted.

Establishing an economical and widely accessible donation after circulatory death animal abattoir model for lung research using ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP), is a platform that allows simultaneous testing and treatment of the lungs. However, use of EVLP is costly and requires access to lab animals and accompanying facilities. To increase the use of EVLP for research, we developed a method to perform EVLP using abattoir procured lungs. Furthermore, we were also able to significantly decrease costs. METHODS: Six pair of lungs were procured from abattoir sheep. The lungs were then flushed and stored in ice for 3 h. A low-flow (20% of cardiac output) approach, a tidal volume of 6 ml/kg bodyweight and total perfusion time of 3 h were chosen. Perfusion fluids and circuits were self-made. Lung biopsies, perfusate collection, respiratory values, circulatory pressures were recorded and hourly blood gas analyses were performed. RESULTS: Mean pO2 remained stable from 60 min (49.3 ± 7.1 kPa) to 180 min (51.5 kPa ± 8.0), p = 0.66. Pulmonary artery pressure remained ≤15 mm Hg and the left atrial pressure remained between 3 and 5 mm Hg and peak respiratory pressures ≤20 cmH2 O. Lactate dehydrogenase increased from start (96.3 ± 56.4 U/L) to the end of perfusion (315.8 ± 85.0 U/L), p < 0.05. No difference was observed in ATP between procurement and post-EVLP, 129.7 ± 37.4 µmol/g protein to 132.0 ± 23.4 µmol/g, p = 0.92. CONCLUSIONS: Sheep lungs, acquired from an abattoir, can be ex vivo perfused under similar conditions as lab animal lungs with similar results regarding e.g., oxygenation and ATP restoration. Furthermore, costs can be significantly reduced by making use of this abattoir model. By increasing accessibility and lowering costs for experiments using lung perfusion, more results may be achieved in the field of lung diseases.