BACKGROUND: Organic chemicals have been known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis; however, the possibility that they do not cause irreversible pulmonary fibrosis has not been considered. Polyacrylic acid (PAA), an organic chemical, has caused irreversible progressive pulmonary fibrosis in exposed workers, indicating its potential to induce pulmonary inflammation and fibrosis. Although intratracheal instillation studies are commonly used for evaluating lung pathology, traditional methods face challenges with chemical substances, particularly nanoparticles, which tend to aggregate in suspension and prevent uniform pulmonary distribution. Such aggregation alters the qualitative and quantitative responses to lung injury, limiting accurate assessment of lung pathology. To overcome this limitation, we developed a 'molecular dispersion method' that uses pH modification to negative charges to PAA particles, maintaining their dispersion. Using this method, we investigated the effects of PAA on pulmonary inflammation and fibrosis in a rat model. METHODS: F344 rats were intratracheally instilled with PAA using molecular dispersion (0.1 mg/rat, 1.0 mg/rat), PAA without molecular dispersion (1.0 mg/rat), and normal saline (control group). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses. RESULTS: PAA caused persistent increases in neutrophil influx in the bronchoalveolar lavage fluid (BALF) from 3 days to 1 month following instillation. In histopathological findings, the group with molecular dispersion had almost no inflammatory masses in the lung tissue compared to the group without molecular dispersion, and exhibited relatively uniform dispersion. CONCLUSION Intratracheal instillation of dispersed PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA might have pulmonary inflammogenicity and fibrogenicity. Intrapulmonary dispersion of PAA particles following intratracheal instillation studies using the molecular dispersion method was similar to that following inhalation studies.
Animals ; Rats, Inbred F344 ; Acrylic Resins/adverse effects* ; Rats ; Inhalation Exposure/adverse effects* ; Male ; Pulmonary Fibrosis/pathology* ; Pneumonia/pathology* ; Lung/pathology* ; Bronchoalveolar Lavage Fluid/cytology*

There is disagreement regarding the indications of surgery for cases of severe aortic stenosis (AS) with a decrease in left ventricular ejection fraction (EF) and a low aortic pressure gradient (PG), since there is a high perioperative risk associated with this condition. Hence, we investigated the surgical outcome of AS cases with impaired left ventricular function. Our department performed 144 aortic valve replacements (AVRs) for cases of AS and AS-dominant mild regurgitation (ASr) between January 2000 and September 2005. Among these cases, 9 patients had an EF under 35%, and these patients were selected as subjects and compared with a control group with an EF of more than 35%. Patients with accompanying coronary artery diseases that required treatment were excluded to avoid confounding effects on cardiac function. The mean age of the 9 subjects (4 men and 5 women) was 67.8±10.8 years old, with a range from 53 to 80 years old, and the subjects had the following mean background data: EF, 34.4±0.5%; left ventricular end-diastolic dimension (LVDd), 57.3±5.8mm; left ventricular end-systolic dimension (LVDs), 49.3±5.7mm; interventricular septum thickness (IVSth), 11.9±1.9mm; and left ventricular posterior wall thickness (LVPWth), 11.1±2.6mm. Characteristics such as left ventricular dilatation and thinning of the left ventricle myocardium were noted in these data. The cases were classified as severe AS because the mean aortic valve area (AVA) was 0.58±0.2cm², but the peak aortic pressure gradient (peak PG) (65.2±32.7mmHg) in the 9 subjects was lower than that of the control group (97.0±65.2mmHg). All 9 subjects underwent aortic valve replacements (AVRs), with simultaneous mitral annuloplasty (MAP) in 3 cases, mitral valve replacement (MVR) in 1 case and performance of a Maze procedure in 1 case. No deaths occurred while the patients were in hospital. Postoperative complications included 2 cases of transient atrial fibrillation and 1 case of postoperative bleeding requiring rethoracotomy for hemostasis. The EF in the late postoperative period showed improvement in 8 cases and was unchanged in the remaining case; the mean postoperative EF was 56.9% for the 9 subjects. All cases were rated as improved based on the NYHA classification of cardiac performance, and the significant improvement in EF in 8 of the 9 cases suggests that surgery is safe and can improve prognosis for patients with advanced AS with myocardium thinning and decreased EF.