Effects of almitrine on respiration in unanesthetized newborn rabbits.
We previously demonstrated that almitrine, a peripheral chemoreceptor stimulant, increased tidal volume (VT), expired minute ventilation (VE), and respiratory frequency (f) and decreased inspiratory (TI) and expiratory time (TE) in sleeping adult cats. We now hypothesized that almitrine would induce an increase in ventilation in a young animal model. Respiration was studied by the barometric method in 11 unanesthetized New Zealand White rabbit pups between 3 and 6 days of age. Recordings were made in 0.21 FIO2 at base line and after cumulative intraperitoneal infusions of almitrine (2.5, 5.0, and 7.5 mg/kg). The chamber pressure deflection (proportional to VT after appropriate calculation) was computer sampled at 200 Hz. At least 100 breaths for each dose in each animal were analyzed. We found that a 7.5-mg/kg intraperitoneal dose of almitrine increased f to 135 +/- 9% (SE) of base line and decreased TE and TI to 72 +/- 8% and 79 +/- 8% of base line, respectively. Changes in VE, VT/TI, and VT were not significant. Recognizing that apnea is associated with inadequate ventilation and a prolonged TE (failure of the "inspiratory on-switch"), these results, particularly the increase in f and decrease in TE, suggest that almitrine might be useful in treating apnea in preterm infants.
D015765:Almitrine; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008168:Lung / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*; D013990:Tidal Volume
D000697:Central Nervous System Stimulants; D010879:Piperazines; D015765:Almitrine