Oxygen Consumption and Basal Metabolic Rate as Markers of Susceptibility to Malignant Hyperthermia and Heat Stroke
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. In Vivo Experiments
- -
- Basal indirect calorimetry. The basal metabolic rate of C57bl6, CASQ1-null, and Y522S mice was registered by indirect calorimetry. Briefly, each mouse was individually placed inside registration chamber of the calorimetry system (Pan Lab/Harvard Instruments, Cornellà, Spain) for 48 h. Measurement obtained during the first 24 h were discarded, because of the adaptation time needed for both mice and system. After adaptation, the volume of carbon dioxide production (VCO2) and the volume of oxygen consumption (VO2) were registered during the following 24 h using the Oxyletpro calorimeter system for mice (Pan Lab/Harvard Instruments, Cornellà, Spain). VCO2 production was then used to estimate O2 consumption and other parameters, as previously described [21]. The analysis of the respiratory quotient (RQ) and the energy expenditure (EE) were performed using Metabolism software (Pan Lab/Harvard Instruments, Spain). In detail, they were calculated as follows: RQ = VCO2/VO2; and EE = (3.815 + (1.32 × RQ)) × VO2 × 1.44. After collection, data were interpolated using Prism 9 software (GraphPad Software), to obtain 24 data (one per hour), and, finally, they were plotted as mean curve.
- -
- Heat-stress protocol and core temperature recording. To detect changes in metabolic rate and core temperature of mice during heat stress, animals were subjected to the heat-stress protocol during indirect calorimetry experiments. Briefly, mice were placed individually in the registration chambers intended for indirect calorimetry (Pan Lab/Harvard Instruments, Cornellà, Spain) and then they were placed inside an environmental chamber (custom made), where temperature and humidity can be controlled. Considering the different susceptibilities of CASQ1-null and Y522S mice to heat, we designed two different protocols of heat stress in order to avoid lethal crisis [18]. In detail, CASQ1-null mice were subjected to 41 °C for 20 min, while Y522S mice were exposed to 37 °C for 20 min. Two different WT mice groups were used as control, being exposed alternatively to 41 °C or 37 °C, for appropriated comparison with CASQ1-null mice and Y522S, respectively. During heat-stress protocol, indirect calorimetry parameters (see previous paragraph) were registered every 4 min and then plotted as VO2 consumption curve. In addition, immediately before and after the protocol, core temperature of each mouse was measured using a rectal thermometer (four channels thermometer TM-946, XS instruments, Milan, Italy). Finally, rise in core temperature during the test was plotted as delta variation.
2.3. Body Composition
2.4. Western Blot
2.5. Cytochrome-c Oxidase Activity
2.6. Ultrastructural Analyses
2.7. Statistical Analysis
3. Results
3.1. CASQ1-Null and Y522S Mice Display Increased Metabolic Rate at Rest
3.2. Increased Oxygen Consumption and Body Temperature during Heat Stress in CASQ1-Null and Y522Smice
- (a)
- in CASQ1-null mice, the final temperature reached at the end of the stress protocol at 41 °C (was only slightly higher than in control animals): CASQ1-null: 36.49 ± 0.07 °C to 38.93 ± 0.13 °C (vs. WT: 36.0 ± 0.10 °C to 38.49 ± 0.07 °C), with no difference in ΔT (ΔT = +2.44 °C in CASQ1-null vs. ΔT = +2.47 °C in WT). These results seem in disagreement with previous publications showing the susceptibility of CASQ1-null mice to heat stress. However, we should consider that in previous publications the challenge was applied for 1 h instead of only 20 min.
- (b)
- in Y522S mice, both final temperature and ΔT were significantly greater at the end of the stress protocol at 37 °C: Y522S: 36.50 ± 0.07 °C to 40.61 ± 0.15 °C (vs. WT: 36.00 ± 0.11 °C to 37.98 ± 0.07 °C), with ΔT in Y522S = +4.11 °C (vs. ΔT in WT = +1.98 °C).
3.3. Analysis of Mitochondria and SR Revealed Structural Alterations and Changes in Protein Expression in CASQ1-Null and Y522S Mice
4. Discussion
4.1. Main Findings of the Study
4.2. Hypermetabolism as a Marker of Mice Susceptibility to MH and HS
4.3. Discussing the Role of Mitochondria in the Hypermetabolism of Y522S and CASQ1-Null Mice
4.4. Discussing the Role of SR in the Hypermetabolism of Y522S and CASQ1-Null Mice
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Serano, M.; Pietrangelo, L.; Paolini, C.; Guarnier, F.A.; Protasi, F. Oxygen Consumption and Basal Metabolic Rate as Markers of Susceptibility to Malignant Hyperthermia and Heat Stroke. Cells 2022, 11, 2468. https://doi.org/10.3390/cells11162468
Serano M, Pietrangelo L, Paolini C, Guarnier FA, Protasi F. Oxygen Consumption and Basal Metabolic Rate as Markers of Susceptibility to Malignant Hyperthermia and Heat Stroke. Cells. 2022; 11(16):2468. https://doi.org/10.3390/cells11162468
Chicago/Turabian StyleSerano, Matteo, Laura Pietrangelo, Cecilia Paolini, Flavia A. Guarnier, and Feliciano Protasi. 2022. "Oxygen Consumption and Basal Metabolic Rate as Markers of Susceptibility to Malignant Hyperthermia and Heat Stroke" Cells 11, no. 16: 2468. https://doi.org/10.3390/cells11162468