Implications of ectothermy on sevoflurane kinetics: interactions between in silico and in vivo modeling in multicompartment anesthetic equilibrium.

• Grant number: 25/03047-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 25, 2025
• End date: July 19, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Adriano Bonfim Carregaro
• Grantee: André Augusto Justo
• Supervisor: Tobias Wang
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 23/01363-1 - Influence of pre-anesthetic acclimatization and seasonality on the Minimum Anesthetic Concentration (MAC) of Sevoflurane in Green Iguanas (Iguana iguana), BP.DR

Abstract

Inhalation anesthesia is widely used in human and veterinary medicine, with the minimum alveolar concentration (MAC) being the standard measure to guide anesthetic dosages. However, determining MAC values for reptiles has posed significant challenges due to their unique physiological characteristics, which often lead to inconsistent results. Traditional methods for determining MAC rely heavily on cardiorespiratory function, but reptiles possess the ability to divert blood from the pulmonary circuit and exhibit low minute volumes under anesthesia. These factors complicate the application of typical MAC determination methods. Additionally, variables such as intracardiac blood shunting and body temperature have been shown to influence anesthetic equilibration, but their precise contributions to this variable remain understudied. Recent developments in multi-compartmental modeling of anesthetic kinetics have opened new avenues for more accurate predictions of anesthetic behavior in reptiles. However, further validation of these models is needed to account for species-specific factors such as temperature fluctuations and variations in hemodynamics, which can significantly impact anesthetic uptake and distribution. This project is closely aligned with ongoing research in my lab, which seeks to better understand the relationship between reptilian physiology and anesthetic requirements. The aim of this study is to evaluate the applicability of an in silico multi-compartment model in predicting the time to sevoflurane equilibration in Squamates under different metabolic demand. We will also use the pythons (Python molurus) as experimental model for in vivo evaluation focusing on the impact of factors such as body temperature. This model, specifically developed for use in reptiles, will be compared with in vivo data to assess the model's accuracy and explore necessary adjustments. By integrating these findings with the ongoing doctoral research (FAPESP Project: 23/01363-1), which investigates the role of ectothermy in anesthetic requirements, this project represents an important step in refining anesthetic protocols for squamates and improving the predictability and safety of inhalation anesthesia across species. This is particularly relevant, as squamates represent the largest group of living reptiles, with many species commonly used in laboratory research.