Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

Abstract

Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation (IT) and inhalation (INH) of residual oil fly ash (ROFA) in a rat model of pulmonary hypertension induced by monocrotaline (MCT). The present study was conducted to examine the effects of ROFA in this model on ventilatory function in unanesthetized, unrestrained animals. Sixty-day-old male CD rats were injected with MCT (60 mg/kg) or vehicle (VEH) intraperitoneally 10 days before IT of ROFA (8.3 mg/kg) or saline (SAL) (control) or nose-only INH of ROFA [15 mg/m3 for 6 hr on 3 consecutive days or air (control)]. At 24 and 72 hr after exposure, rats were studied individually in a simultaneous gas uptake/whole-body plethysmograph. Lungs were removed at 72 hr for histology. Pulmonary test results showed that tidal volume (VT) decreased 24 hr after IT of ROFA in MCT-treated rats. Breathing frequency, minute volume (VE), and the ventilatory equivalent for oxygen increased in MCT- and VEH-treated rats 24 hr after IT or INH of ROFA and remained elevated 72 hr post-IT. O2 uptake (VO2) decreased after IT of ROFA in MCT-treated rats. Carbon monoxide uptake decreased 24 hr after IT of ROFA, returning to control values in VEH-treated rats but remaining low in MCT-treated rats 72 hr post-IT. ROFA exposure induced histologic changes and abnormalities in several ventilatory parameters, many of which were enhanced by MCT treatment.

Therapeutic Approaches in Mitochondrial Dysfunction, Proteolysis, and Structural Alterations of Diaphragm and Gastrocnemius in Rats With Chronic Heart Failure

“…Rats were kept under pathogen‐free conditions in the animal house facility at PRBB, with a 12:12 h light: dark cycle. In all experimental groups of rats (except for control rodents), CHF was induced by an intraperitoneal injection of monocrotaline (50 mg/kg) on day 0, and all experimental groups were studied for a period of 30 days as previously shown (Reindel et al, ; Comini et al, ; Vescovo et al, ; Pichardo et al, ; Vescovo et al, ; Gardner et al, ; Dalla et al, ; Bertaglia et al, ). The following groups of rats were studied: 1) non‐CHF controls (N = 10), intraperitoneal administration of saline at day 0; 2) CHF‐cachexia group (N = 10), intraperitoneal administration of monocrotaline at day 0; 3) CHF‐cachexia + NAC group (N = 10), CHF induced cachectic rats treated with antioxidant NAC, intraperitoneal administration of monocrotaline at day 0 and oral administration (gavage) 3 mmol/Kg/24 h NAC during 30 days as previously described (Barreiro et al, ; Dominguez‐Alvarez et al, ); and 4) CHF‐cachexia + Bortezomib group (N = 10), CHF‐induced cachectic rats treated with proteasome inhibitor, intraperitoneal administration of monocrotaline on day 0, and intravenous (tail vein) administration of 0.15 mg/Kg Bortezomib on days 0, 6, 12, 18, 24, and 29 as previously reported (Lu et al, ) and without anesthesia.…”

Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

“…Particulate matter air pollution has been studied in a limited manner in more severe models of pulmonary hypertension, but with similar findings of exacerbated outcomes. Gardner and colleagues explored interactions between monocrotaline-induced pulmonary hypertension and bolus intratracheal exposures to a residual oil fly ash particulate and specifically noted an interaction in terms of vascular inflammation in histological analysis (Gardner et al , 2004). In a similar study, rats treated with monocrotaline exhibited greater bradycardic, arrhythmic, and hypothermic responses to residual oil fly ash instillation compared to healthy rats (Campen et al , 2000), along with exacerbated lung injury outcomes (Kodavanti et al , 1999).…”

Effects of Nanoparticles on the Pulmonary Vasculature

“…Inhalation exposure resulted in augmented markers of pulmonary infl ammation in MCT -treated rats but did not result in mortality (Kodavanti et al, 1999 ). Rats compromised by MCT treatment show exacerbated ventilatory responses with delayed recovery after fl y ash inhalation (Gardner et al, 2004 ). In addition to the cardiopulmonary effects of MCT treatment, it appears that the MCT rat model also interferes with particle clearance, leading to increased retention times and greater particle interactions with biological systems (Madl et al, 1998 ).…”