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A porcine in-vivo model of acute pulmonary embolism.

ABSTRACT: 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.

SUBMITTER: Schultz J

PROVIDER: S-EPMC5798692 | biostudies-other | 2018 Jan-Mar

REPOSITORIES: biostudies-other

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A porcine in-vivo model of acute pulmonary embolism.

Schultz Jacob J Andersen Asger A Gade Inger Lise IL Ringgaard Steffen S Kjaergaard Benedict B Nielsen-Kudsk Jens Erik JE

Pulmonary circulation 20171003 1

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 safe ...[more]

PMID: 28971735

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Project description:BackgroundPrognostic assessment is important for the management of patients with acute pulmonary embolism (APE). Pulmonary Embolism Severity Index (PESI) and simple PESI (sPESI) are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events) in APE patients, and compare between these two PESIs.MethodsMEDLINE and EMBASE database were searched up to June 2012 using the terms "Pulmonary Embolism Severity Index" and "pulmonary embolism". Summary odds ratio (OR) with 95% confidence intervals (CIs) for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC) used to estimate overall predicting accuracies of prognostic outcomes.ResultsTwenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15), PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17) and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41), with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14), 0.09 (95% CI 0.03 to 0.26) and 0.40 (95% CI 0.31 to 0.51), respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16), 0.09 (95% CI 0.04 to 0.21), and 0.30 (95% CI 0.23 to 0.38), respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916), 0.411 (95% CI: 0.407 to 0.415), and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978), 0.374 (95% CI: 0.360 to 0.388), and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0.845), 0.389 (95% CI: 0.384 to 0.394), and 0.6809±0.0208, respectively. In sPESI subgroup, the AUC for predicting all-cause mortality, PE-related mortality, and serious adverse events was 0.7920±0.0117, 0.8317±0.0547, and 0.6454±0.0197, respectively. In PESI subgroup, the AUC was 0.7856±0.0075, 0.8158±0.0451, and 0.6609±0.0252, respectively.ConclusionsPESI has discriminative power to predict the short-term death and adverse outcome events in patients with acute pulmonary embolism, the PESI and the sPESI have similar accuracy, while sPESI is easier to use. However, the calibration for predicting prognosis can't be calculated from this meta-analysis, some prospective studies for accessing PESI predicting calibration can be recommended.

Dataset Information

A porcine in-vivo model of acute pulmonary embolism.

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A porcine in-vivo model of acute pulmonary embolism.

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