Cardiorespiratory and Cardiac Biomarker Responses to Five Anesthetic Regimens in Rats
Abstract
Abstract General anesthetics enable invasive experimentation but can affect cardiovascular and respiratory physiology, biasing preclinical outcomes. We compared five anesthetic regimens in adult male Wistar rats, tribromoethanol (TBE, 250 mg/kg i.p.), chloral hydrate (CH, 400 mg/kg i.p.), ketamine–xylazine (KX, 80/10 mg/kg i.p.), thiopental (TP, 80 mg/kg i.p.), and isoflurane (ISO, 4% induction, 2% maintenance), to investigate integrated cardiorespiratory and biochemical markers. Femoral arterial catheterization allowed continuous blood pressure (BP) and derived heart rate (HR) recordings, while ventilation was assessed through pletysmography at baseline (awake), during induction, and recovery phases of anesthesia. Variability was evaluated in the time and frequency domains, including HR, systolic blood pressure (SBP), and spontaneous baroreflex sensitivity. In an independent cohort of rats, butyrylcholinesterase (BChE), CK-MB, cTnI, and LDH were measured. Baseline BP was unchanged by TBE and TP, whereas all anesthetics affected HR. Minute ventilation and breathing frequency were reduced with all agents, while tidal volume decreased with KX and TBE only. LDH and cTnI were unaffected, BChE was reduced by KX, TBE, and ISO, and CK-MB increased with CH and KX. Variability analysis showed that all anesthetics depressed pulse-interval and SBP variability and shifted spectral power toward higher frequencies, while baroreflex sensitivity and effectiveness were consistently reduced. During recovery, KX and TP restored most variability indices, whereas CH, TBE, and ISO showed persistent suppression. These findings highlight distinct profiles of cardiovascular depression and biomarker responses across anesthetics and underscore the importance of accounting for autonomic variability when selecting different anesthetics in experimental protocols. Highlights Five anesthetic regimens were tested in rats. All anesthetics reduced ventilation, and KX and TBE also reduced tidal volume. CH and KX increased CKMB, while KX, TBE and ISO reduced BChE. All anesthetics reduced blood pressure variability and baroreflex sensitivity. Variability recovered with TP and KX, whereas CH, TBE and ISO showed persistent suppression.
Fields of Study & Subjects
Heart Rate Variability and Autonomic Control
Vagus Nerve Stimulation Research
Veterinary Pharmacology and Anesthesia
Publication details
- Journal / source
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Publication date
- 8 April 2026
- Document type
- Preprint