Pulmonary haemodynamics in awake rats following treatment with endotracheal pancreatic elastase

Sato, Shinobu; Kato, Shingo; Arisaka, Yasusi; Takahashi, Hakuo; Tomoike, Hitonobu

doi:10.1183/09031936.94.07071294

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…Animal studies of emphysema generally demonstrated mild to moderate pulmonary hypertension (16), but reached different conclusions as to its cause, and have raised some interesting alternate possibilities. Some studies (17,18) have emphasized the role of vascular reactivity, whereas others (19,20) have emphasized the impact of vascular obliteration by parenchymal destruction. The finding of inflammatory markers in the lungs and pulmonary vessels of patients with COPD (21,22) and smokers also suggests that inflammation plays a role in vascular remodeling or obstruction.…”

Section: Figurementioning

confidence: 99%

Hemodynamic Characterization of Patients with Severe Emphysema

Scharf

Iqbal

Keller

et al. 2002

Am J Respir Crit Care Med

378

302

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In 120 patients with severe emphysema evaluated for participation in the National Emphysema Treatment Trial, pulmonary hemodynamics and ventricular function were assessed. Pulmonary function tests were (%predicted): FEV(1) = 27%; residual volume = 224.6%; diffusion capacity = 26.7%. In 90.8% of patients, end-expiratory pulmonary artery mean pressure was > 20 mm Hg; in 61.4%, end-expiratory wedge pressure was > 12 mm Hg. Cardiac index was normal. Mean pulmonary artery pressure correlated inversely with arterial PO(2), and severity of emphysema, and directly with wedge pressure. Multiple stepwise regression revealed that arterial PO(2) was not an independent predictor of mean pulmonary artery pressure. No correlation was found between indices of emphysema severity and PA pressures. Diastolic ventricular pressures were increased without evidence of systolic dysfunction. We conclude that (1) elevations of pulmonary vascular pressures are common, (2) pulmonary hypertension may be related to factors other than hypoxia, (3) pulmonary hypertension does not impair resting systemic O(2) delivery, and (4) elevated cardiac diastolic pressures do not represent systolic dysfunction.

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Section: Figurementioning

confidence: 99%

Hemodynamic Characterization of Patients with Severe Emphysema

Scharf

Iqbal

Keller

et al. 2002

Am J Respir Crit Care Med

378

302

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“…The blood-gas analysis also confirmed that oxygen levels in PPE-challenged animals were normal. Although hypoxemia was reported previously in rats administered a similar dose of PPE per BW [ 30 ], the degree of emphysema in our model was not sufficient to cause global oxygenation changes. This result may be attributed to the presence of compensatory mechanisms preventing against hypoxemia [ 31 ].…”

Section: Discussionmentioning

confidence: 54%

Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema

et al. 2016

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PurposeA magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function.MethodNine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.Principal FindingsPPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.ConclusionsThe proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction–before global changes occur.

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“…Among these, some studies have explored cardiac alterations, especially on the right side and pulmonary artery. Indeed, right heart dilatation and hypertrophy correlated to emphysema 17 , pulmonary artery remodeling and hypoxic hyperactivity 18 , and echocardiographic documented alterations of pulmonary artery function (PAT/PET) 19 have been described in elastaseinduced emphysema rat models. Lately these experimental models have been combined with lipopolysaccharide (LPS) treatment to mimic acute pulmonary infection/exacerbation.…”

Section: Animal Modelmentioning

confidence: 99%

“…According to their classification, an increase of 54% of the mean linear intercept of ELA-LPS animals suggests that our animals exhibited moderate to severe emphysema. Emphysema has been shown to be accompanied by lung hyperinflation that could induce "mechanical" diastolic dysfunction, mimicking a gaseous tamponade 6,12 , either caused by reduced LV filling and, thus, reduced myocardial preload 34 , or caused by elevation of pulmonary arterial pressure/resistance 18 or right ventricle pressure 35 . De Oliviera et al 21 , employing a similar rat model of emphysema, showed pulmonary hyperinflation induced by emphysema as assessed by micro-computed tomography.…”

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confidence: 99%

Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema

Grillet

Desplanche

Wynands

et al. 2023

Am J Respir Cell Mol Biol

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Chronic Obstructive Pulmonary Disease (COPD) is a clinical entity of increasing significance. COPD involves abnormalities of the airways and in emphysema, parenchymal pulmonary destruction. Cardiovascular disease has emerged as a significant comorbidity to COPD. Heart Failure with preserved Ejection Fraction (HFpEF) appears to be particularly associated with COPD-Emphysema. Traditional treatments have shown limited efficacy in improving COPD associated HFpEF. This lack of therapeutic efficacy highlights the need to identify potential mechanisms that link COPD-Emphysema to HFpEF. Therefore, we aimed to study the delayed cardiac physiological impacts in a rat model with acute exacerbated emphysema. Emphysema was induced by 4 weekly 4UI elastase intra-tracheal pulmonary instillations and exacerbation by one final additional LPS instillation in male Wistar rats. At 5 weeks following the LPS/elastase exposure, in-vivo and ex-vivo pulmonary and cardiac measurements were performed. Experimental exacerbated emphysema resulted in decreased pulmonary function and exercise intolerance. Histological analysis revealed parenchymal pulmonary destruction without signs of inflammation or cardiac fibrosis. In-vivo cardiac functional analysis revealed diastolic dysfunction and tachycardia. Ex-vivo analysis revealed a cellular cardiomyopathy with decreased myofilament Ca 2+ sensitivity, cross-bridge cycling kinetics and increased adrenergic PKA-dependent phosphorylation of troponin-I. Experimental exacerbated emphysema was associated with exercise intolerance that appeared to be secondary increased β-adrenergic tone and subsequent cardiac myofilament dysfunction. A β1-receptor antagonist treatment (bisoprolol) started 24h post ELA-LPS instillation prevented in-vivo and ex-vivo diastolic dysfunction. These results suggest that novel treatment strategies targeted to the cardiac myofilament may be beneficial to combat exacerbated emphysema associated HFpEF.

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Pulmonary haemodynamics in awake rats following treatment with endotracheal pancreatic elastase

Cited by 5 publications

References 20 publications

Hemodynamic Characterization of Patients with Severe Emphysema

Hemodynamic Characterization of Patients with Severe Emphysema

Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema

Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema

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