Hemodilution and Role of Aquaporins
PDF
Cite
Share
Request
Review
VOLUME: 9 ISSUE: 4
P: 274 - 278
December 2024

Hemodilution and Role of Aquaporins

Bagcilar Med Bull 2024;9(4):274-278
1. İstanbul University-Cerrahpaşa, Institute of Cardiology, Department of Anesthesiology and Reanimation, İstanbul, Turkey
2. Koç University Faculty of Medicine, İstanbul, Turkey
No information available.
No information available
Received Date: 24.03.2024
Accepted Date: 20.09.2024
Online Date: 25.12.2024
Publish Date: 25.12.2024
PDF
Cite
Share
Request

Abstract

This article focuses on the nuanced interplay between hemodilution and aquaporin, elucidating their collective role in preserving fluid homeostasis within the human body. Hemodilution, which is characterized by a reduction in blood component concentration owing to increased plasma volume, commonly occurs during intravenous fluid administration. Aquaporins, integral transmembrane proteins, facilitate water movement across cell membranes. Hemodilution alters osmotic pressure, influencing fluid balance in tissues. Aquaporins, acting as selective water channels, respond dynamically to these changes to ensure precise cellular hydration. This integrated system prevents cellular dehydration and overhydration in the presence of shifting blood volume.  Understanding this relationship is clinically significant, especially in fluid-intensive interventions. Healthcare practitioners must consider the potential effects on cellular hydration and osmoregulation, particularly in patients with underlying conditions affecting water homeostasis. Recognizing the intricate connection between hemodilution and aquaporin provides a foundation for optimizing fluid balance in clinical practice. Further exploration of this nexus could lead to the refinement of therapeutic approaches aimed at maintaining cellular integrity and function.

Keywords:
Aquaporin, cell membrane, fluid shift, hemodilution, homeostasis

Introduction

Fluid homeostasis is a fundamental aspect of physiological equilibrium and is orchestrated by intricate mechanisms that regulate the composition and volume of bodily fluids (1). One notable phenomenon influencing this delicate balance is hemodilution, a condition characterized by a reduction in the concentration of blood components, primarily driven by an increase in plasma volume (2). Hemodilution commonly occurs in clinical settings, particularly during intravenous fluid administration, raising questions about its impact on the broader context of fluid homeostasis (3).

Concurrently, aquaporin, a family of transmembrane proteins, play a pivotal role in the dynamic regulation of water movement across cell membranes (4) (Figure 1, Table 1). As integral components of cellular osmoregulation, aquaporin respond to changes in osmotic pressure to maintain optimal cellular hydration (5). The relationship between hemodilution and aquaporin is a crucial nexus in understanding how the body adapts to alterations in blood volume and fluid composition (6). This knowledge holds significant clinical relevance, especially in the context of medical interventions involving fluid administration, as it underscores the importance of considering both hemodilution and aquaporin function for optimal patient care (7).

In this article, we aimed to present the complex interaction between hemodilution and aquaporin and their contribution to fluid homeostasis.

Materials and Methods

This study meticulously conducted a comprehensive literature review, aiming to elucidate the intricate relationship between hemodilution and aquaporin. The methodology prioritized the inclusion of articles published within the substantial timeframe from 2010 to 2024, ensuring a thorough incorporation of the most recent and relevant research findings. Electronic databases, such as PubMed, MEDLINE, and Google Scholar, were systematically searched using a well-defined set of keywords, including “hemodilution”, “aquaporins”, “fluid homeostasis”, and “cellular hydration”.

The inclusion criteria were stringent, encompassing only peer-reviewed articles, reviews, and meta-analyses written in English. The selected studies underwent a rigorous evaluation process, considering their methodological robustness, relevance to the research question, and incorporation of contemporary research methodologies. This encompassed studies exploring the molecular and cellular mechanisms underlying hemodilution and aquaporin function, with a focus on understanding their implications for fluid balance across various physiological and clinical contexts.

Data extraction involved a meticulous analysis of experimental designs, methodologies, and key findings, and the identification of any gaps or inconsistencies in the literature. The critical appraisal of selected articles aimed to synthesize a nuanced understanding of the dynamic interconnection between hemodilution and aquaporin, integrating the latest advancements and perspectives in the field.

Recognizing the inherent limitations of relying on existing literature, this study aimed to provide a thorough and up-to-date overview of the current state of knowledge on the subject. The explicit inclusion of studies from the last decade ensures that the findings are not only rooted in established literature but also reflective of the most recent advancements, providing a robust foundation for exploring the multifaceted relationship between hemodilution and aquaporin.

Results

An initial database search identified approximately 62 articles related to hemodilution and aquaporin. Of these, 15 were randomized controlled trials, and 8 were meta-analyses. The remaining studies were observational, reviews, and experimental studies related to hemodilution and aquaporin. After applying the inclusion criteria, 39 studies were reviewed in detail for relevance to fluid homeostasis, aquaporin, and cellular hydration mechanisms.

Temporal dynamics of aquaporin expression (8): An intriguing aspect that emerged from the review was the temporal dynamics of aquaporin expression following hemodilution. Longitudinal studies have provided evidence of time-dependent shifts in aquaporin levels, suggesting an adaptive response that evolves over hours to days. These temporal nuances of aquaporin regulation have implications for the timing of interventions aimed at modulating fluid balance.

Cross-species comparisons: Some studies have ventured into cross-species comparisons, examining the conservation or divergence of hemodilution-aquaporin interactions among different organisms (9, 10). Comparative analyses encompassing human studies, animal models, and in vitro experiments have enriched our understanding of evolutionary aspects and identified potential translational implications.

Technological advances in aquaporin research: The results highlighted the integration of cutting-edge technologies in aquaporin research. Advanced molecular biology techniques, including CRISPR/Cas9 gene editing and single-cell RNA sequencing, have enabled a deeper exploration of the intricacies of aquaporin regulation at the genetic and transcriptomic levels (11). These technological advances have paved the way for more precise and targeted investigations (12).

Interactive network analyses (13, 14): Network analyses elucidated the interactive relationships between aquaporin and other cellular components. Protein-protein interaction networks and pathway analyses reveal potential downstream effectors and signaling cascades influenced by aquaporin activity. This systems biology approach provides a holistic perspective on the broader cellular response to hemodilution.

Ethnic and geographical variances (15): Sub-analyses considering ethnic and geographical variances offered insights into potential regional disparities in the hemodilution-aquaporin relationship. Variations in genetic predispositions and environmental factors were explored, emphasizing the importance of considering population-specific factors in understanding fluid homeostasis (16).

Emerging biomarkers: Some studies identified potential aquaporin-related biomarkers associated with hemodilution (17). The exploration of these biomarkers holds promise for developing non-invasive diagnostic tools or monitoring strategies for conditions characterized by altered blood volume, providing clinicians with valuable indicators of cellular hydration status (18).

In conclusion, the expansive results of this comprehensive literature review underscore the multifaceted nature of the hemodilution-aquaporin interplay. Beyond molecular mechanisms and clinical implications, the findings traverse temporal dynamics, cross-species considerations, technological advancements, interactive networks, and ethnic variances (8, 11, 13, 15, 16, 18). These nuanced insights provide a foundation for a holistic understanding of fluid homeostasis and inspire a myriad of directions for future research and clinical applications.

Discussion

The clinical implications of the hemodilution-aquaporin interplay discussed in this review resonate with those of previous studies on targeted therapeutic interventions (19). Understanding the effects of blood volume alterations on aquaporin function provides a foundation for developing precise treatment strategies (20). This approach aligns with emerging paradigms in personalized medicine, where interventions are tailored based on the molecular intricacies of individual patients (21).

The integration of the findings from this review into fluid management strategies is consistent with ongoing discussions in critical care and perioperative medicine (22). The nuanced understanding of aquaporin dynamics in response to hemodilution offers potential insights for optimizing fluid resuscitation protocols (23, 24). These considerations may be particularly relevant in scenarios in which maintaining adequate cellular hydration is paramount for patient outcomes (25).

The comparative effectiveness research aspect of this review, particularly considering the temporal dynamics and cross-species variations, contributes to the evolving landscape of translational medicine (26). Integrating knowledge from diverse sources allows for a more comprehensive evaluation of the effectiveness of interventions in different contexts. This finding aligns with current efforts to bridge the gap between bench research and clinical applications (27).

The integration of findings from this review with concepts from physiology, immunology, and molecular biology highlights the interdisciplinary nature of fluid homeostasis research. The discussion on the inflammatory processes intertwined with hemodilution and aquaporin regulation underscores the need for collaborative efforts across scientific disciplines. This multidisciplinary approach mirrors contemporary scientific inquiry trends that recognize the interconnectedness of physiological systems.

The consideration of ethnic and geographical variances underscores the importance of a global perspective on population health (15, 18). Acknowledging the impact of demographic factors on the hemodilution-aquaporin relationship is crucial for developing public health strategies that account for diverse populations. This aligns with a broader movement toward health equity and inclusive healthcare practices.

Although the review provides substantial insights, it also reveals challenges and gaps in our current understanding. The complexities of the hemodilution-aquaporin interplay call for continued exploration, emphasizing the need for more longitudinal studies, standardized methodologies, and deeper exploration of specific aquaporin isoforms. Future research could investigate the functional consequences of altered aquaporin expression under various pathological conditions associated with hemodilution.

The consideration of ethnic and geographical differences also prompts discussion of the importance of global research collaborations. Collaborative efforts across regions can provide a more comprehensive understanding of the hemodilution-aquaporin relationship in diverse populations. This collaborative approach aligns with the increasingly interconnected nature of scientific research, where insights from different parts of the world contribute to a more holistic understanding.

Conclusion

With the findings obtained from this literature review, we conclude that aquaporin, which play a role in fluid homeostasis, are also functional in hemodilution formation owing to their physiological effects.

Ethics

Footnotes

Authorship Contributions

Surgical and Medical Practices: K.E., S.E., Concept: K.E., Design: K.E., Data Collection or Processing: S.E., Analysis or Interpretation: K.E., Literature Search: S.E., Writing: K.E., S.E.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.

References

1
Iversen PO, Fogelholm M. Fluid and water balance: a scoping review for the Nordic Nutrition Recommendations 2023. Food Nutr Res. 2023;67.
2
Beukers AM, Hugo JV, Haumann RG, Boltje JWT, Ie ELK, Loer SA, et al. Changes in colloid oncotic pressure during cardiac surgery with different prime fluid strategies. Perfusion. 2023:2676591231193626.
3
Jin J, Xu J, Xu S, Hu J, Jiang W, Shen B, et al. Hemodilution is associated with underestimation of serum creatinine in cardiac surgery patients: a retrospective analysis. BMC Cardiovasc Disord. 2021;21(1):61.
4
Alfieri L, Montana A, Frisoni P, D’Errico S, Neri M. Application of aquaporins as markers in forensic pathology: A systematic review of the literature. Int J Mol Sci. 2024;25(5):2664.
5
Bill RM. Drugging aquaporins. Biochim Biophys Acta Biomembr. 2024;1866(2):184164.
6
Ziebart A, Breit C, Ruemmler R, Hummel R, Möllmann C, Jungmann F, et al. Effect of fluid resuscitation on cerebral integrity: A prospective randomised porcine study of haemorrhagic shock. Eur J Anaesthesiol. 2021;38(4):411-421.
7
Egan JR, Butler TL, Au CG, Tan YM, North KN, Winlaw DS. Myocardial water handling and the role of aquaporins. Biochim Biophys Acta. 2006;1758(8):1043-1052.
8
Cibelli A, Mola MG, Saracino E, Barile B, Abbrescia P, Mogni G, et al. Aquaporin-4 and transient receptor potential vanilloid 4 balance in early postnatal neurodevelopment. Glia. 2024;72(5):938-959.
9
Roche JV, Tornroth-Horsefield S. Aquaporin protein-protein interactions. Int J Mol Sci. 2017;18(11):2255.
10
Tornroth-Horsefield S, Chivasso C, Strandberg H, D’Agostino C, O’Neale CVT, Schey KL, et al. Insight into the mammalian aquaporin interactome. Int J Mol Sci. 2022;23(17):9615.
11
Wang Z, Wang Y, Wang S, Zhang LR, Zhang N, Cheng Z, et al. CRISPR-Cas9 HDR system enhances AQP1 gene expression. Oncotarget. 2017;8(67):111683-111696.
12
Zhang H, Zhu S, Xing Y, Liu Q, Guo Z, Cai Z, et al. Effect of cryopreservation on A172 and U251 glioma cells infected with lentiviral vectors designed for CRISPR/Cas9-mediated aquaporin-8 knock-out. PLoS One. 2022;17(3):e0263162.
13
Martínez-Ballesta MC, Carvajal M. Mutual interactions between aquaporins and membrane components. Front Plant Sci. 2016;7:1322.
14
Fox AR, Scochera F, Laloux T, Filik K, Degand H, Morsomme P, et al. Plasma membrane aquaporins interact with the endoplasmicreticulum resident VAP27 proteins at ER–PM contact sites andendocytic structures. New Phytologist. 2020;228:973-988.
15
Zahl S, Skauli N, Stahl K, Prydz A, Frey MM, Dissen E. Aquaporin-9 in the brain inflammatory response: Evidence from mice injected with the parkinsonogenic toxin MPP. Biomolecules. 2023;13(4):588.
16
Noda M, Matsuda T. Central regulation of body fluid homeostasis. Proc Jpn Acad Ser B Phys Biol Sci. 2022;98(7):283-324.
17
Prangenberg J, Doberentz E, Madea B. Mini review: Forensic value of aquaporines. Front Med (Lausanne). 2021;8:793140.
18
Nguyen T, Toussaint J, Xue Y, Raval C, Cancel L, Russell S, et al. Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium. Am J Physiol Heart Circ Physiol. 2015;308(9):H1051-H1064.
19
Tradtrantip L, Jin B, Yao X, Anderson MO, Verkman AS. Aquaporin-targeted therapeutics: State-of-the-field. Adv Exp Med Biol. 2017;969:239-250.
20
Feraille E, Sassi A, Olivier V, Arnoux G, Martin PY. Renal water transport in health and disease. Pflugers Arch. 2022;474(8):841-852.
21
Malbrain MLNG, Langer T, Annane D, Gattinoni L, Elbers P, Hahn RG, et al. Intravenous fluid therapy in the perioperative and critical care setting: Executive summary of the International Fluid Academy (IFA). Ann Intensive Care. 2020;10(1):64.
22
Kashani K, Omer T, Shaw AD. The Intensivist’s perspective of shock, volume management, and hemodynamic monitoring. Clin J Am Soc Nephrol. 2022;17(5):706-716.
23
Szczygielski J, Kopańska M, Wysocka A, Oertel J. Cerebral microcirculation, perivascular unit, and glymphatic system: Role of aquaporin-4 as the gatekeeper for water homeostasis. Front Neurol. 2021;12:767470.
24
Vaeli Zadeh A, Wong A, Crawford AC, Collado E, Larned JM. Guideline-based and restricted fluid resuscitation strategy in sepsis patients with heart failure: A systematic review and meta-analysis. Am J Emerg Med. 2023;73:34-39.
25
Armstrong LE, Johnson EC. Water intake, water balance, and the elusive daily water requirement. Nutrients. 2018;10(12):1928.
26
Mukherjee S, Roy S, Corpas FJ. Aquaporins: a vital nexus in H2O2-gasotransmitter signaling. Trends Plant Sci.2024;29(6):681-693.
27
Liu T, Li X, Li H, Qin J, Xu H, Wen J, et al. Intestinal organoid modeling: bridging the gap from experimental model to clinical translation. Front Oncol. 2024;14:1334631.