Blood Cell Intracellular pH Dynamics and Metabolic Biomarkers Under Simulated Postmortem Interval Conditions: An Exploratory Pilot In Vitro Study
6 affiliations
- 1UCIBIO, Toxicologic Pathology Research Laboratory, CESPU University, 4585-116 Gandra, Portugal
- 2Associate Laboratory i4HB—Institute for Health and Bioeconomy, CESPU University, 4585-116 Gandra, Portugal
- 3Instituto Superior Politécnico de Benguela, Benguela, Angola
- 4Centre of Mathematics (CMAT), Department of Mathematics, School of Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
- 5UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- 6UCIBIO, Translational Toxicology Research Laboratory, CESPU University, Avenida Central de Gandra 1317, 4585-116 Gandra, Portugal
Abstract
Intracellular pH (pHi) may provide complementary information on postmortem cellular metabolism and homeostasis, but its temporal behavior remains poorly understood. This pilot in vitro study evaluated temporal changes in platelet pHi and pHi in a mixed non-platelet blood-cell population (predominantly erythrocytes and leukocytes), together with plasma glucose, lactate, and ammonia during a simulated postmortem interval (PMI). Venous blood from eight healthy volunteers was maintained at 24 ± 3 °C and analyzed at 0, 3, 6, and 24 h. Intracellular pH was assessed by BCECF-AM flow cytometry, and metabolites were quantified enzymatically. Platelet and non-platelet-cell pHi remained stable during the first 3 h, decreased significantly at 6 h, and increased toward baseline values at 24 h. Glucose concentrations decreased over time, lactate increased progressively, and ammonia increased significantly only at 24 h. Lactate was associated with pHi in both blood-cell populations. Intracellular pH exhibited a biphasic temporal pattern and distinct relationships with metabolic biomarkers during the simulated PMI. An exploratory mixed-effects model incorporating non-platelet-cell pHi, lactate, and glucose explained a substantial proportion of temporal variability (marginal R2 = 0.907) and yielded a leave-one-donor-out cross-validation RMSE of 0.4998 on the log-transformed time scale. These findings support further investigation of multi-marker approaches for PMI estimation.
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BibTeX
@article{ndunduma2026blood,
title = {{Blood Cell Intracellular pH Dynamics and Metabolic Biomarkers Under Simulated Postmortem Interval Conditions: An Exploratory Pilot In Vitro Study}},
author = {Paulino D. Ndunduma and Carolina Cordeiro and Susana Faria and M. Begoña Criado and Susana Coimbra and M. Céu Monteiro},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219931},
url = {https://www.mdpi.com/1422-0067/27/21/9931},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Blood Cell Intracellular pH Dynamics and Metabolic Biomarkers Under Simulated Postmortem Interval Conditions: An Exploratory Pilot In Vitro Study
AU - Paulino D. Ndunduma
AU - Carolina Cordeiro
AU - Susana Faria
AU - M. Begoña Criado
AU - Susana Coimbra
AU - M. Céu Monteiro
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219931
UR - https://www.mdpi.com/1422-0067/27/21/9931
AB - Intracellular pH (pHi) may provide complementary information on postmortem cellular metabolism and homeostasis, but its temporal behavior remains poorly understood. This pilot in vitro study evaluated temporal changes in platelet pHi and pHi in a mixed non-platelet blood-cell population (predominantly erythrocytes and leukocytes), together with plasma glucose, lactate, and ammonia during a simulated postmortem interval (PMI). Venous blood from eight healthy volunteers was maintained at 24 ± 3 °C and analyzed at 0, 3, 6, and 24 h. Intracellular pH was assessed by BCECF-AM flow cytometry, and metabolites were quantified enzymatically. Platelet and non-platelet-cell pHi remained stable during the first 3 h, decreased significantly at 6 h, and increased toward baseline values at 24 h. Glucose concentrations decreased over time, lactate increased progressively, and ammonia increased significantly only at 24 h. Lactate was associated with pHi in both blood-cell populations. Intracellular pH exhibited a biphasic temporal pattern and distinct relationships with metabolic biomarkers during the simulated PMI. An exploratory mixed-effects model incorporating non-platelet-cell pHi, lactate, and glucose explained a substantial proportion of temporal variability (marginal R2 = 0.907) and yielded a leave-one-donor-out cross-validation RMSE of 0.4998 on the log-transformed time scale. These findings support further investigation of multi-marker approaches for PMI estimation.
SN - 1422-0067
ER -