[show abstract][hide abstract] ABSTRACT: Remifentanil is a potent synthetic opioid with sedative effects. Intravenous remifentanil provides deep sedation and analgesia in laboratory animals during experimental procedures. We hypothesized that remifentanil would provide effective analgosedation during assisted mechanical ventilation without affecting respiratory mechanics in rats. Five male Sprague- Dawley rats (weight, 400 to 450 g) were assigned to receive assisted mechanical ventilation with continuous positive airway pressure for 5 h. Remifentanil (0.4 μg/kg/min IV) was delivered for the duration of ventilation. There were no differences between baseline, 1 h, and 5 h of ventilation in the mean arterial pressure, cardiac output, heart rate, and body temperature of all rats. Similarly, no differences were observed in the tidal volume, respiratory rate and minute ventilation, and gas exchange was equal in all rats at all time points. Frequent assessment of sedation by toe pinch documented loss of the pedal withdrawal reflex in all rats. We conclude that continuous remifentanil infusion provides sufficient analgosedation for mechanically ventilated rats without compromising hemodynamics, respiratory function, or gas exchange.
Journal of the American Association for Laboratory Animal Science: JAALAS 01/2012; 51(1):58-62. · 1.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.