Development of an ex vivo human-porcine respiratory model for preclinical studies.

Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures "pleural" depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with 81mKrypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies.

Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons.

To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region) of radioactive polydisperse aerosols ([d16-d84], equal to [0.15 µm-0.5 µm], [0.25 µm-1 µm], or [1 µm-9 µm]). Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm-9 µm] aerosol (72% ± 17%). The [0.15 µm-0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84% ± 4%). Airborne particles in the range of [0.25 µm-1 µm] showed an intermediate deposition pattern, with 49% ± 8% in the extrathoracic region and 51% ± 8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm-9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.

Leukoaraiosis and ambulatory blood pressure load in a healthy elderly cohort study: the PROOF study.

BACKGROUND: Old age and hypertension are consistently reported to be the main risk factors of leukoaraiosis. The association between white matter lesions (WMLs) and other cardiovascular risk factors (CVRF) remains controversial. We evaluated the association between CVRF and WMLs in a cohort study and determined the blood pressure variables that could predict WML severity. METHODS: 830 subjects (65+/-1 years of age, 60% women) from the PROOF study, with a reliable ABPM and brain MRI, were included. The exclusion criteria included prior myocardial infarction, stroke, heart failure, atrial fibrillation, type 1 diabetes mellitus, and pacing. White matter changes on MRI were defined as hyperintensities >5mm on FLAIR images. We used the total degree of WML (range: 0-30) by adding the region-specific scores of both hemispheres. RESULTS: Linear regression analyses demonstrated a significant relationship between total leukoaraiosis score and 24h systolic blood pressure (SBP), 24h diastolic BP, daytime SBP and DBP and nighttime SBP. No significant relationship was found between leukoaraiosis score and clinical SBP, clinical DBP, or nocturnal DIP. There was also no significant relationship between leukoaraiosis and other recognized cardiovascular risk factors. Based on a ROC curve analysis, we identified the optimal threshold separating high-risk WML patients for a mean 24h SBP above 123 mmHg (p<0.05). CONCLUSIONS: Even moderate increases in 24h SBP promote arteriolar fragility of the cerebral white matter in a population aged 65. The prognostic implications of such abnormalities in asymptomatic and moderate cardiovascular risk populations remain to be evaluated.