Measurement of respiratory function using whole-body plethysmography in unanesthetized and unrestrained nonhuman primates

Abstract

-Extended term, continuous measurement and observation of drug responses were performed to examine the feasibility of a custom-made whole-body plethysmograph for measuring respiratory function in unanesthetized, unrestrained monkeys. Using this apparatus, respiratory function (respiration rate, tidal volume, and minute volume) was observed for 23 hr in unanesthetized, unrestrained cynomolgus monkeys (Macaca fascicularis). The respiration rate, tidal volume, and minute volume in the light period (7:00 to 19:00) reached approximately 30% to 50% higher values than in the dark period (19:00 to 7:00), thus clearly exhibiting circadian variation in the cynomolgus monkey respiratory functions. Administration of morphine (10 mg/kg, s.c.) resulted in sustained reduction in tidal volume and minute volume, and ketamine (30 mg/kg [sub-anesthetic dose], i.m.) also produced sustained reduction in respiration rate, tidal volume, and minute volume. With dimorpholamine (1 mg/kg, i.v.) or caffeine (10 mg/kg, s.c.), respiration rate, tidal volume, and minute volume increased. Physiological saline (1 ml/kg, s.c. and 0.1 ml/ kg, i.v.) and chlorpromazine (10 mg/kg, s.c.) produced no clear-cut changes in respiration rate, tidal volume, or minute volume. From the above results, we conclude that our custom-made whole-body plethysmograph is useful for measuring respiratory function in unanesthetized and unrestrained monkeys.

Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates

“…(25,26) All tidal volume measurements were performed under anesthesia using ketamine and medetomidine, both agents known to potentially suppress respiration. (27,28) However, in our experience animals this sedation protocol results in reproducible and stable breathing. Interestingly, tidal volume and respiratory rate data obtained were close to those previously reported for conscious cynomolgus macaques (26 ml and 30 BPM, respectively).…”

Insights on animal models to investigate inhalation therapy: Relevance for biotherapeutics

“…Other limitations include the requirement of animal training prior to aerosol administration and the use of anesthetics that can affect breathing parameters (Iizuka et al, 2010). Despite the limited relevance of these methods to evaluate the relationship between the effectiveness/toxicity and the dose administered, and the difficulties to accurately predict lung deposition, these methods are used and validated for lung tolerance and regulatory toxicity studies.…”

Differences in aerosolization of Rift Valley fever virus resulting from choice of inhalation exposure chamber: implications for animal challenge studies

“…The minute volume of larger animals such as rabbits and NHPs is measured directly using a plethysmograph, typically either immediately before or during the exposure. NHPs are anesthetized during both the plethysmograph and the aerosol, which can suppress respiratory function including minute volume (Lopez et al ., ; Iizuka et al ., ). In agreement with this, cynomolgus macaques, rhesus macaques and African green monkeys had suppressed minute volumes compared with what was predicted by Guyton's formula (Fig.…”