期刊
ANESTHESIOLOGY
卷 119, 期 2, 页码 317-325出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0b013e3182910213
关键词
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资金
- National Science Foundation [CHE-1110911]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1110911] Funding Source: National Science Foundation
Introduction: To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n] uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular- blocking agent effects. Methods: A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/ kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a(1)H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure. Results: After the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 +/- 1.1 and 16.2 +/- 3.3 min with placebo to 4.6 +/- 1.8 min with neostigmine/glycopyrrolate to 15 +/- 8 and 84 +/- 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 +/- 2.8 and 9.9 +/- 1.7 min with placebo to 2.8 +/- 0.8 and 7.6 +/- 2.1 min with neostigmine/glycopyrrolate to 47 +/- 13 and 87 +/- 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h. Conclusion: Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.
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