Breathing and Blood Pressure in Conscious and 1% Isoflurane Anesthetized Mice

Abstract

Isoflurane is a commonly used inhaled anesthetic that can be adjusted for level of anesthetic depth and offers a rapid recovery for both clinical settings and laboratory animal research. Initial studies in our laboratory indicated no difference in PaCO2 (36.7±2.4 vs. 34.8±2.6 mmHg) or pH (7.43±0.02 vs. 7.43±0.02) between conscious (NO ISO) and 1% isoflurane (ISO) exposed CD‐1 mice. Our purpose was to investigate if arterial blood sampling with 1% ISO is a suitable alternative to conscious sampling for monitoring ventilation in a commonly studied mouse strain. This study aimed to test the hypothesis that breathing patterns and blood pressure in conscious and lightly isoflurane anesthetized B6/C57 mice are similar. At 3 months of age, 8 male B6/C57 mice (27.5±1.9 g body weight; MEAN±SD) underwent whole body unrestrained barometric plethysmography to quantify the pattern of breathing. Mice were tested during the light cycle with an isoflurane vaporizer preceding the animal chamber and a vacuum following the chamber (100 mL/min) to prevent accumulation of ISO. After a 30 min acclimation period with air (20.93% O2, balanced N2), mice were exposed to 5 minutes of the following: 2% ISO/air, 1% ISO/air, 1% ISO/10% O2 (hypoxia),1% ISO/air, 1% ISO/5% CO2 (hypercapnia); the last minute of each gas exposure was analyzed with Ponemah™ software. The same mice were administered these gas exposures without ISO (NO ISO) a week later; quiet baseline breathing was considered during this exposure as the 5 minutes when mice were not moving or sniffing in the cage. Breathing frequency (F; breaths/min), tidal volume (TV; mL/breath), and minute ventilation (MV; mL/min) were quantified; NO ISO vs. 1% ISO (MEAN±SD; *=p<0.05) shown in the following text. Quiet breathing compared to 1%ISO/air was not different for F: 185±30 vs. 168±31, TV: 0.29±0.04 vs. 0.31±0.16, or MV: 57.5±10.6 vs. 52.6±26.4. A blunted hypoxic response resulted with ISO; this was due to a lower F and MV (F: 265±31 vs. *176±22, TV: 0.41±0.07 vs. 0.39±0.14, MV: 123.8±27.1 vs. *72.3±29.9). Hypercapnia also resulted in a reduced response to ISO with F, TV and MV differences (F: 352±28 vs. *157±23, TV: 0.63±0.07 vs. *0.43±0.21, MV: 237.1±53.7 vs. *72.6±45.3). Conscious and 1% ISO arterial blood sampling in B6/C57 mice showed no difference in PaCO2 (38.8±1.9 vs. 35.2±2.3 mmHg), but differences did emerge with pH (7.43±0.02 vs. *7.38±0.03). Additional experiments were conducted to measure blood pressure with the volume‐pressure recording tail cuff method to determine other possible systemic changes with ISO, but no differences were uncovered (96±8 vs. 85±11 mmHg) although the data did approach significance. These experiments demonstrate the pattern of quiet breathing, ventilation and blood pressure are similar in conscious and 1% ISO exposed mice. However, the capacity to respond to respiratory stressors is attenuated with 1% ISO. Overall due to the near significant p‐values, along with clear differences from hypoxia/hypercapnia, we do not recommend blood sampling with 1% ISO as an alternative to monitoring conscious ventilation.Support or Funding InformationFunded by 1 R15 HD076379‐01A1, AML supported by McDevitt Fellowship, CNR supported by 1 R15 HD076379‐01A1S1.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.