Evaluation of autologous blood clot subsegmental pulmonary thromboembolism in minimally invasive experimental canine model

Abstract

The incidence and significance of subsegmental pulmonary (SSP) thromboembolism is currently under investigation. We aimed to evaluate the clinical and diagnostic features of SSP thromboembolism in an experimental canine model. Obstruction of pulmonary arterial branches was induced in three beagle dogs by intravenous injection of a barium-coated autologous blood clot (size, approximately 1.7 × 5 mm). The clinical signs, haemodynamic changes (blood pressure, electrocardiogram, echocardiography), coagulation (aPTT, PT, FDPs and D-dimer test) and cytokine variations (TNF-a, IL-4, IL-6, and IL-10) were evaluated over a 24-hour period. Multidetector computed tomography (MDCT) with contrast was conducted to evaluate the pulmonary obstruction, and histopathological confirmation was performed. Pulmonary artery pressure gradient (PAPG) was increased 12 h after the autologous blood clot injection (14.2 ± 2.8 mmHg to 23.6 ± 1.7 mmHg, P = 0.003) and normalized 24 h later (P < 0.01). Infused radiopaque clots were confirmed with MDCT and histopathological examination. Pulmonary parenchymal changes such as arterial dilation and inflammatory reactions were also confirmed in histopathological examinations and were barely observable in MDCT. Usually small emboli are not easily detected through CT imaging, and the clinical relevance of these emboli is controversial. In this experimental study, we made radiopaque small emboli and induced SSP thromboembolism. Thus, we infer that obstruction of the small segmental and subsegmental pulmonary arteries does result in a pulmonary thromboembolism (PTE) and PTE-related pulmonary parenchymal changes which could be clinically significant.

The prevalence of intra‐tumoral and distant thrombi, as well as tumour‐cell emboli in canine neoplasia

“…Studies on experimentally induced pulmonary microthrombi in dogs have reported a significant drop in circulating platelet concentration with increased neutrophils and platelets within the pulmonary capillaries, increased mean pulmonary artery pressure and embolirelated arterial dilation, increased microvascular permeability to protein and severe lung injury. [22][23][24] In addition, microthrombi and tumour-cell emboli have been reported to result in localized ischemia and tissue hypoxia, both of which are directly linked to cancer metastasis through hypoxia-inducible factor target gene expression, inhibition of the transmembrane molecule E-cadherin, enhanced proteolytic activity at the tumour invasive front and increased cell motility towards the blood or lymphatic microcirculation. 40,42,49 No prevalence studies of microthrombi in canine solid tumours have previously been reported, making results of this study difficult to compare, but the true prevalence is likely higher than the 2.6% reported here.…”

“…[19][20][21] Experimentally induced pulmonary microthrombi have been reported to result in significant vascular injury and vessel permeability changes resulting in severe lung injury. [22][23][24] Microthrombi cannot be substantiated clinically as no single coagulation test is predicative for the detection of microthrombi.…”

“…Microthrombi have been documented in tumour tissue of dogs with gliomas (63%), meningiomas (66%) and mammary gland tumours (57%) 19–21 . Experimentally induced pulmonary microthrombi have been reported to result in significant vascular injury and vessel permeability changes resulting in severe lung injury 22–24 . Microthrombi cannot be substantiated clinically as no single coagulation test is predicative for the detection of microthrombi.…”

Research progress on biomarkers of pulmonary embolism

“…IL-1β, IL-4, IL-6 and hs-CRP can be used to monitor the occurrence of PE, guide treatment and monitor efficacy. 50,51 IL-10 can reduce lung injury and play a role in assisting tissue repair. 52 Moreover, plasma copeptin appears to be particularly useful for the prognostic assessment of acute cardiovascular diseases due to its rapid release kinetics, the level of which can reflect PE severity.…”

Texture analysis of pulmonary parenchymateous changes related to pulmonary thromboembolism in dogs – a novel approach using quantitative methods

“…This issue of resolution limits the use of CTPA for identification of minor clots in the pulmonary circulation [ 8 ]. Such small clots may however still be clinically important since they can alter the pulmonary parenchymal perfusion [ 9 ]. Based on the limitations of CTPA, it is obvious that tools for better identification of both large and small pulmonary thrombi as well as parenchymateous changes related to these would increase the applicability of CTPA for correct identification of PTE in dogs.…”