Acute pulmonary embolism (PE) is the third most common cardiovascular cause of death after acute myocardial infarction and stroke. Patients are, however, often under‐treated due to the risks associated with systemic thrombolysis and surgical embolectomy. Novel pharmacological and catheter‐based treatment strategies show promise, but the data supporting their use in patients are sparse. We therefore aimed to develop an in vivo model of acute PE enabling controlled evaluations of efficacy and safety of novel therapies. Danish Landrace pigs (n = 8) were anaesthetized and mechanically ventilated. Two pre‐formed autologous PEs (PE1, PE2, 20 × 1 cm) were administered consecutively via the right external jugular vein. The intact nature and central location were visualized in situ by magnetic resonance imaging (MRI). The hemodynamic and biochemical responses were evaluated at baseline (BL) and after each PE by invasive pressure measurements, MRI, plus arterial and venous blood analysis. Pulmonary arterial pressure increased after administration of the PEs (BL: 16.3 ± 1.2, PE1: 27.6 ± 2.9, PE2: 31.6 ± 3.1 mmHg, BL vs. PE1: P = 0.0027, PE1 vs. PE2: P = 0.22). Animals showed signs of right ventricular strain evident by increased end systolic volume (BL: 60.9 ± 5.1, PE1: 83.3 ± 5.0, PE2: 99.4 ± 6.5 mL, BL vs. PE1: P = 0.0005, PE1 vs. PE2: P = 0.0045) and increased plasma levels of Troponin T. Ejection fraction decreased (BL: 58.9 ± 2.4, PE1: 46.4 ± 2.9, PE2: 37.3 ± 3.5%, BL vs. PE1: p = 0.0008, PE1 vs. PE2: P = 0.009) with a compensatory increase in heart rate preserving cardiac output and systemic blood pressure. The hemodynamic and biochemical responses were comparable to that of patients suffering from intermediate‐high‐risk PE. This porcine model mirrors the anatomical and physiologic changes seen in human patients with intermediate‐high‐risk PE, and may enable testing of future therapies for this disease.
30 November 2020 in Research and Practice in Thrombosis and Haemostasis
Background Venous thromboembolism (VTE) causes morbidity and mortality in the general population. Several events occur after lower limb orthopedic surgery, but the contribution from various types of lower limb surgery is not well known. Objective To investigate the postoperative incidence of VTE for all types of lower extremity orthopedic surgery compared with the background population. Methods Individual‐level linkage of Danish nationwide register data for all Danish residents with first‐time orthopedic surgery of the lower limb (1996‐2017) and, for each of these, four controls from the general population matched on age, sex, and history of VTE. Adjusted hazard ratios (HR) compared the postoperative risk of VTE to the matched controls. Results In total 7203 of the 1 012 823 patients with a first orthopedic procedure had a VTE within 180 days after surgery, corresponding to a postoperative cumulative incidence of 0.71% (95% confidence interval [CI], 0.70‐0.73). The cumulative incidence of VTE among controls was 0.11% (95% CI, 0.11‐0.12). The HR of VTE within the first 30 days after surgery below knee level was 20.5 (95% CI, 17.9‐23.5) compared with matched controls. The HRs of VTE after minor distal procedures (eg, meniscectomy and arthroscopies) were 2.9 (95% CI, 1.9‐4.4) to 7.1 (95% CI, 6.4‐8.0). Conclusion All types of lower limb orthopedic surgery including minor distal procedures were associated with higher rates of VTE compared with matched controls, in particular within the first 30 days after surgery.