Right ventricular diastolic adaptation to pressure overload in different rat strains.

Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been made to test differences in RV response to pressure overload between rat strains. We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar (W), Sprague Dawley (SD), and Fischer344 (F) rats by hemodynamic profiling focusing on diastolic function. Age-matched male rat weanlings were randomized to sham surgery (W-sham, n = 5; SD-sham, n = 4; F-sham, n = 4) or PTB (W-PTB, n = 8; SD-PTB, n = 8; F-PTB, n = 8). RV function was evaluated after 5 weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure and increased RV systolic pressures four-fold in all three PTB groups compared with sham. W- and SD-PTB had a 2.4-fold increase in RV end-systolic volume index compared with sham, while F-PTB rats were less affected. Diastolic and right atrial impairment were evident by increased RV end-diastolic elastance, filling pressure, and E/e' in PTB rats compared with sham, again F-PTB the least affected. In conclusions, PTB caused RV failure with signs of diastolic dysfunction. Despite a similar increase in RV systolic pressure, F-PTB rats showed less RV dilatation and a more preserved diastolic function compared with W- and SD-PTB.

A Murine Model of Pressure Overload-Induced Right Ventricular Hypertrophy and Failure by Pulmonary Trunk Banding.

Right ventricular (RV) failure caused by pressure overload is strongly associated with morbidity and mortality in a number of cardiovascular and pulmonary diseases. The pathogenesis of RV failure is complex and remains inadequately understood. To identify new therapeutic strategies for the treatment of RV failure, robust and reproducible animal models are essential. Models of pulmonary trunk banding (PTB) have gained popularity, as RV function can be assessed independently of changes in the pulmonary vasculature. In this paper, we present a murine model of RV pressure overload induced by PTB in 5-week-old mice. The model can be used to induce different degrees of RV pathology, ranging from mild RV hypertrophy to decompensated RV failure. Detailed protocols for intubation, PTB surgery, and phenotyping by echocardiography are included in the paper. Furthermore, instructions for customizing instruments for intubation and PTB surgery are given, enabling fast and inexpensive reproduction of the PTB model. Titanium ligating clips were used to constrict the pulmonary trunk, ensuring a highly reproducible and operator-independent degree of pulmonary trunk constriction. The severity of PTB was graded by using different inner ligating clip diameters (mild: 450 µm and severe: 250 µm). This resulted in RV pathology ranging from hypertrophy with preserved RV function to decompensated RV failure with reduced cardiac output and extracardiac manifestations. RV function was assessed by echocardiography at 1 week and 3 weeks after surgery. Examples of echocardiographic images and results are presented here. Furthermore, results from right heart catheterization and histological analyses of cardiac tissue are shown.

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study.

BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

Pneumonectomy combined with SU5416 or monocrotaline pyrrole does not cause severe pulmonary hypertension in mice.

In the field of pulmonary hypertension (PH), a well-established protocol to induce severe angioproliferation in rats (SuHx) involves combining the VEGF-R inhibitor Sugen 5416 (SU5416) with 3 wk of hypoxia (Hx). In addition, injecting monocrotaline (MCT) into rats can induce inflammation and shear stress in the pulmonary vasculature, leading to neointima-like remodeling. However, the SuHx protocol in mice is still controversial, with some studies suggesting it yields higher and reversible PH than Hx alone, possibly due to species-dependent hypoxic responses. To establish an alternative rodent model of PH, we hypothesized mice would be more sensitive to hemodynamic changes secondary to shear stress compared with Hx. We attempted to induce severe and irreversible PH in mice by combining SU5416 or monocrotaline pyrrole (MCTP) injection with pneumonectomy (PNx). However, our experiments showed SU5416 administered to mice at various time points after PNx did not result in severe PH. Similarly, mice injected with MCTP after PNx (MPNx) showed no difference in right ventricular systolic pressure or exacerbated pulmonary vascular remodeling compared with PNx alone. These findings collectively demonstrate that C57/B6 mice do not develop severe and persistent PH when PNx is combined with either SU5416 or MCTP.NEW & NOTEWORTHY We attempted to establish a mouse model of severe and irreversible pulmonary hypertension by substituting hypoxia with pulmonary overcirculation. To do so, we treated mice with either SU5416 or monocrotaline pyrrole after pneumonectomy and performed hemodynamic evaluations for PH. Despite this "two-hit" protocol, mice did not exhibit signs of severe pulmonary hypertension or exacerbated pulmonary vascular remodeling compared with PNx alone.

Substantial transmission of SARS-CoV-2 through casual contact in retail stores: Evidence from matched administrative microdata on card payments and testing.

This paper presents quasiexperimental evidence of Covid-19 transmission through casual contact between customers in retail stores. For a large sample of individuals in Denmark, we match card payment data, indicating exactly where and when each individual made purchases, with Covid-19 test data, indicating when each individual was tested and whether the test was positive. The resulting dataset identifies more than 100,000 instances where an infected individual made a purchase in a store and, in each instance, allows us to track the infection dynamics of other individuals who made purchases in the same store around the same time. We estimate transmissions by comparing the infection rate of exposed customers, who made a purchase within 5 min of an infected individual, and nonexposed customers, who made a purchase in the same store 16 to 30 min before. We find that exposure to an infected individual in a store increases the infection rate by around 0.12 percentage points (P < 0.001) between day 3 and day 7 after exposure. The estimates imply that transmissions in stores contributed around 0.04 to the reproduction number for the average infected individual and significantly more in the period where Omicron was the dominant variant.

First-in-human left atrial appendage closure using the WATCHMAN FLX Pro device: a case report.

Background: Device-related thrombosis (DRT) is a known complication to left atrial appendage closure (LAAC). The surface of a LAAC device should ideally have antithrombotic properties. The novel WATCHMAN FLX Pro (WFP) incorporates a fluoropolymer-coated fabric membrane designed to increase thromboresistance and facilitate endothelialization. Such features could potentially allow for a minimal post-procedural antithrombotic regimen. Radiopaque platinum markers at the device shoulders and a large 40 mm device are other novel features of the WFP. Case summary: A 75-year-old man with atrial fibrillation was referred for LAAC due to prior subdural haemorrhage during direct-acting anticoagulation treatment. He underwent the first-in-human WFP implantation as part of the WATCHMAN FLX Pro CT study (NCT05567172). Computed tomography (CT) was used for pre-planning, and the procedure was performed under local analgesia guided by intracardiac echocardiography from the left atrium (LA) without any complications. Post-procedural antithrombotic treatment consisted of acetylsalicylic acid 75 mg/day only, and 45-day CT, transoesophageal echocardiography (TEE), and magnetic resonance imaging demonstrated optimal device position with complete LAAC. Hypoattenuated thickening (6 mm) appeared on the device as a smooth surface in continuity with the left atrial wall on CT and TEE. A specific magnetic resonance T1-weighted scan, used for visualization of fresh thrombus, suggested this to represent tissue ingrowth rather than thrombus. Discussion: The advanced follow-up imaging protocol suggested a good WFP implantation result with signs of tissue ingrowth at 45 days. The added radiopaque markers facilitated optimal deployment, evaluation of device stability during tug test, and assessment of device protrusion into the LA.

Changes in Pulmonary Vascular Resistance and Obstruction Score Following Acute Pulmonary Embolism in Pigs.

OBJECTIVES: To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN: Controlled, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (-284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (-8 ± 27 dynes; p = 0.4827) or day 2 (-18 ± 32 dynes; p = 0.0923). CONCLUSIONS: Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.

Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. METHODS: We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO2max <80%) at 18 months were analyzed. RESULTS: A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. CONCLUSIONS: Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function.

Long-Term Effects of Pulmonary Endarterectomy on Right Ventricular Stiffness and Fibrosis in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to the improvement of right ventricular (RV) function in the majority of patients with chronic thromboembolic pulmonary hypertension. However, RV mass does not always normalize. It is unknown whether incomplete reversal of RV remodeling results from extracellular matrix expansion (diffuse interstitial fibrosis) or cellular hypertrophy, and whether residual RV remodeling relates to altered diastolic function. METHODS: We prospectively included 25 patients with chronic thromboembolic pulmonary hypertension treated with PEA. Structured follow-up measurements were performed before, and 6 and 18 months after PEA. With single beat pressure-volume loop analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV-arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed). The extracellular volume fraction of the RV free wall was measured by cardiac magnetic resonance imaging and used to separate the myocardium into cellular and matrix volume. Circulating collagen biomarkers were analyzed to determine the contribution of collagen metabolism. RESULTS: RV mass significantly decreased from 43±15 to 27±11g/m2 (-15.9 g/m2 [95% CI, -21.4 to -10.5]; P<0.0001) 6 months after PEA but did not normalize (28±9 versus 22±6 g/m2 in healthy controls [95% CI, 2.1 to 9.8]; P<0.01). On the contrary, Eed normalized after PEA. Extracellular volume fraction in the right ventricular free wall increased after PEA from 31.0±3.8 to 33.6±3.5% (3.6% [95% CI, 1.2-6.1]; P=0.013) as a result of a larger reduction in cellular volume than in matrix volume (Pinteraction=0.0013). Levels of MMP-1 (matrix metalloproteinase-1), TIMP-1 (tissue inhibitor of metalloproteinase-1), and TGF-ß (transforming growth factor-ß) were elevated at baseline and remained elevated post-PEA. CONCLUSIONS: Although cellular hypertrophy regresses and diastolic stiffness normalizes after PEA, a relative increase in extracellular volume remains. Incomplete regression of diffuse RV interstitial fibrosis after PEA is accompanied by elevated levels of circulating collagen biomarkers, suggestive of active collagen turnover.

Catheter-directed mechanical thrombectomy in a patient with high-risk pulmonary embolism complicated by out-of-hospital cardiac arrest: a case report.

Background: Pulmonary embolism (PE) is common, and it is the third leading cause of cardiovascular death. The management of patients with high-risk PE generally consists of systemic thrombolysis; however, surgical or catheter-directed treatment (CDT) can be considered in selected cases. Case summary: A 78-year-old female patient presenting with acute severe dyspnoea develops out-of-hospital cardiac arrest (OHCA). She was admitted with return of spontaneous circulation and a critical haemodynamic state upon arrival to the catheterization laboratory with an estimated no-flow time of 1 min and low-flow time of 52 min. An acute pulmonary angiogram reveals massive PE. After a PE response team conference, the patient was not found eligible for extracorporeal membrane oxygenation, surgery, or thrombolysis. The patient was treated with catheter-directed mechanical thrombectomy 129 min after first medical contact. The patient recovered and was discharged without any neurological deficits. Discussion: Catheter-directed mechanical thrombectomy was a successful treatment in a patient with OHCA secondary to high-risk PE, where thrombolysis and surgical interventions were considered contraindicated. This case underlines the future perspectives of CDT and also that a multidisciplinary team approach may benefit patients with high-risk PE.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: a clinical consensus statement of the ESC working group on pulmonary circulation and right ventricular function.

The current treatment algorithm for chronic thromboembolic pulmonary hypertension (CTEPH) as depicted in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines on the diagnosis and treatment of pulmonary hypertension (PH) includes a multimodal approach of combinations of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapies to target major vessel pulmonary vascular lesions, and microvasculopathy. Today, BPA of >1700 patients has been reported in the literature from centers in Asia, the US, and also Europe; many more patients have been treated outside literature reports. As BPA becomes part of routine care of patients with CTEPH, benchmarks for safe and effective care delivery become increasingly important. In light of this development, the ESC Working Group on Pulmonary Circulation and Right Ventricular Function has decided to publish a document that helps standardize BPA to meet the need of uniformity in patient selection, procedural planning, technical approach, materials and devices, treatment goals, complications including their management, and patient follow-up, thus complementing the guidelines. Delphi methodology was utilized for statements that were not evidence based. First, an anatomical nomenclature and a description of vascular lesions are provided. Second, treatment goals and definitions of complete BPA are outlined. Third, definitions of complications are presented which may be the basis for a standardized reporting in studies involving BPA. The document is intended to serve as a companion to the official ESC/ERS guidelines.

Right-to-left ventricular ratio is higher in systole than diastole in patients with acute pulmonary embolism.

OBJECTIVES: In acute pulmonary embolism (PE), the right ventricle (RV) may dilate compromising left ventricular (LV) size, thereby increasing RV/LV ratio. End-diastolic RV/LV ratio is often used in PE risk stratification, though the cause of death is RV systolic failure. We aimed to confirm our pre-clinical observations of higher RV/LV ratio in systole compared to diastole in human patients with PE. METHODS: We blinded and independently analyzed echocardiograms from 606 patients with PE, evaluated by a Pulmonary Embolism Response Team. We measured RV/LV ratios in end-systole and end-diastole and fractional area change (FAC). Our primary outcome was a composite of 7-day clinical deterioration, treatment escalation or death. Secondary outcomes were 7-day and 30-day all-cause mortality. RESULTS: RV/LV ratio was higher in systole compared to diastole (median 1.010 [.812-1.256] vs. .975 [.843-1.149], p < .0001). RV/LV in systole and diastole were correlated (slope = 1.30 [95% CI 1.25-1.35], p < .0001 vs. slope = 1). RV/LV ratios in both systole and diastole were associated with the primary composite outcome but not with all-cause mortality. CONCLUSION: The RV/LV ratio is higher when measured in systole versus in diastole in patients with acute PE. The two approaches had similar associations with clinical outcomes, that is, it appears reasonable to measure RV/LV ratio in diastole.

Long-Term Prognostic Impact of Pulmonary Hypertension After Venous Thromboembolism.

Pulmonary embolism is a risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), but the prognostic impact of CTEPH on venous thromboembolism (VTE) mortality remains unclear. We examined the impact of CTEPH and other pulmonary hypertension (PH) subtypes on long-term mortality after VTE. We conducted a nationwide, population-based cohort study of all adult Danish patients alive 2 years after incident VTE without previous PH from 1995 to 2020 (n = 129,040). We used inverse probability of treatment weights in a Cox model to calculate standardized mortality rate ratios (SMRs) of the association between receiving a first-time PH diagnosis ≤2 years after incident VTE and mortality (all-cause, cardiovascular, and cancer). We grouped PH as PH associated with left-sided cardiac disease (group II), PH associated with lung diseases and/or hypoxia (group III), CTEPH (group IV), and unclassified (remaining patients). Total follow-up was 858,954 years. The SMR associated with PH overall was 1.99 (95% confidence interval 1.75 to 2.27) for all-cause, 2.48 (1.90 to 3.23) for cardiovascular, and 0.84 (0.60 to 1.17) for cancer mortality. The SMR for all-cause mortality was 2.62 (1.77 to 3.88) for group II, 3.98 (2.85 to 5.56) for group III, 1.88 (1.11 to 3.20) for group IV, and 1.73 (1.47 to 2.04) for unclassified PH. The cardiovascular mortality rate was increased approximately threefold for groups II and III but was not increased for group IV. Only group III was associated with increased cancer mortality. In conclusion, PH diagnosed ≤2 years after incident VTE was associated with an overall twofold increased long-term mortality driven by cardiovascular causes.

Biomarkers of collagen turnover and wound healing in chronic thromboembolic pulmonary hypertension patients before and after pulmonary endarterectomy.

BACKGROUND: In chronic thromboembolic pulmonary hypertension (CTEPH), fibrotic remodeling of tissue and thrombi contributes to disease progression. Removal of the thromboembolic mass by pulmonary endarterectomy (PEA) improves hemodynamics and right ventricular function, but the roles of different collagens before as well as after PEA are not well understood. METHODS: In this study, hemodynamics and 15 different biomarkers of collagen turnover and wound healing were evaluated in 40 CTEPH patients at diagnosis (baseline) and 6 and 18 months after PEA. Baseline biomarker levels were compared with a historical cohort of 40 healthy subjects. RESULTS: Biomarkers of collagen turnover and wound healing were increased in CTEPH patients compared with healthy controls, including a 35-fold increase in the PRO-C4 marker of type IV collagen formation and a 55-fold increase in the C3M marker of type III collagen degradation. PEA reduced pulmonary pressures to almost normal levels 6 months after the procedure, with no further improvement at 18 months. There were no changes in any of the measured biomarkers after PEA. CONCLUSIONS: Biomarkers of collagen formation and degradation are increased in CTEPH suggesting a high collagen turnover. While PEA effectively reduces pulmonary pressures, collagen turnover is not significantly modified by surgical PEA.

How to incorporate tricuspid regurgitation in right ventricular-pulmonary arterial coupling.

Adaptation of the right ventricle (RV) to a progressively increasing afterload is one of the hallmarks of pulmonary arterial hypertension (PAH). Pressure-volume loop analysis provides measures of load-independent RV contractility, i.e., end-systolic elastance, and pulmonary vascular properties, i.e., effective arterial elastance (Ea). However, PAH-induced RV overload potentially results in tricuspid regurgitation (TR). TR makes RV eject to both PA and right atrium; thereby, a ratio of RV end-systolic pressure (Pes) to RV stroke volume (SV) could not correctly define Ea. To overcome this limitation, we introduced a two-parallel compliance model, i.e., Ea = 1/(1/Epa + 1/ETR), while effective pulmonary arterial elastance (Epa = Pes/PASV) represents pulmonary vascular properties and effective tricuspid regurgitant elastance (ETR) represents TR. We conducted animal experiments to validate this framework. First, we performed SV analysis with a pressure-volume catheter in the RV and a flow probe at the aorta in rats with and without pressure-overloaded RV to determine the effect of inferior vena cava (IVC) occlusion on TR. A discordance between the two techniques was found in rats with pressure-overloaded RV, not in sham. This discordance diminished after IVC occlusion, suggesting that TR in pressure-overloaded RV was diminished by IVC occlusion. Next, we performed pressure-volume loop analysis in rats with pressure-overloaded RVs, calibrating RV volume by cardiac magnetic resonance. We found that IVC occlusion increased Ea, suggesting that a reduction of TR increased Ea. Using the proposed framework, Epa was indistinguishable to Ea post-IVC occlusion. We conclude that the proposed framework helps better understanding of the pathophysiology of PAH and associated right heart failure.NEW & NOTEWORTHY This study reveals the impact of tricuspid regurgitation on pressure-volume loop analysis in right ventricle pressure overload. By introducing a novel concept of parallel compliances in the pressure-volume loop analysis, a better description is provided for the right ventricular forward afterload in the presence of tricuspid regurgitation.

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.