{
  "abstract": "Acute normovolemic hemodilution (ANH) maintains circulating volume with replacement fluids, but its harmful effects and whether crystalloid composition alters cardiovascular tissue stress remain unclear. This study compared normal saline (NS) and Ringer’s lactate (RL) during ANH to determine fluid-dependent molecular effects in the rat heart and aorta. In this study, twenty-four male rats were assigned to control (no procedure), sham (anesthesia only), normal saline (NS)–ANH, or Ringer lactate (RL)–ANH groups (n = 6/group). ANH was performed using a fixed 3:1 crystalloid-to-blood replacement ratio. Heart and aorta tissues were collected 24 h later. Apoptotic, inflammatory, oxidative, heat-shock, and aquaporin proteins were quantified by immunoblotting. Hematocrit decreased similarly in both ANH groups. Compared with NS-ANH, RL-ANH reduced apoptosis in both tissues and reduced cardiac TNF-α levels and aortic NF-κB p65 and TNF-α, but not cardiac NF-κB p65. Cardiac 4-HNE and MDA increased similarly with both fluids, whereas aortic lipid peroxidation markers were lower with RL. Hsp70 responses were comparable, but Hsp90 was consistently higher with RL. RL-ANH also induced distinct aquaporin remodeling, with higher cardiac AQP1 and aortic AQP1, AQP3, and AQP4 levels than NS-ANH, although aortic AQP3 remained significantly lower than in the sham group. Correlation analysis showed tissue-specific aquaporin–injury coupling: cardiac AQP1 was associated with reduced apoptosis and inflammation, cardiac AQP3 with increased oxidative injury, and aortic AQPs with predominantly inverse injury relationships. Consequently, crystalloid composition influenced cardiovascular adaptation to ANH. RL reduced apoptotic and vascular inflammatory activity, limited aortic oxidative stress, and produced distinct Hsp90 and aquaporin profiles. Tissue-specific aquaporin–stress associations further underscored mechanistic divergence between fluids. These molecular signatures reveal early shifts in stress-response pathways and highlight the biological importance of selecting the appropriate crystalloid during ANH.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology and Reanimation, Institute of Cardiology, Istanbul University-Cerrahpaşa, Istanbul 34098, Türkiye",
    "Department of Physiology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul 34098, Türkiye",
    "Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul 34010, Türkiye",
    "Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul 34134, Türkiye",
    "Clinic of Anesthesiology and Reanimation, University of Health Sciences, Bağcılar Training and Research Hospital, Istanbul 34200, Türkiye",
    "Center for Research and Practice in Biotechnology and Genetic Engineering, Istanbul University, Istanbul 34134, Türkiye",
    "Department of Physiology, Faculty of Medicine, Istanbul Aydın University, Istanbul 34295, Türkiye"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kerem Erkalp"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Aslıhan Şengelen",
      "orcid": "0000-0003-2512-319X"
    },
    {
      "affs": [
        4
      ],
      "name": "Serdar Demirgan",
      "orcid": "0000-0001-8129-5004"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Yunus Aksüt",
      "orcid": "0000-0001-9407-5019"
    },
    {
      "affs": [
        3
      ],
      "name": "Evren Önay-Uçar",
      "orcid": "0000-0003-1152-4881"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Nermin Yelmen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2yzr8pz3rr5kd.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219498",
  "fulltext_url": null,
  "id": "2yzr8pz3rr5kd",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9498",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2704|Blood transfusion and management"
    ]
  ],
  "openalex": "W7224021340",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/2yzr8pz3rr5kd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219498",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9498"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2704|Blood transfusion and management",
      "subfield": "general"
    }
  ],
  "title": "Crystalloid-Dependent Modulation of Aquaporins and Molecular Stress Pathways During Acute Normovolemic Hemodilution in Rat Heart and Aorta",
  "title_text": "Crystalloid-Dependent Modulation of Aquaporins and Molecular Stress Pathways During Acute Normovolemic Hemodilution in Rat Heart and Aorta",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/2yzr8pz3rr5kd",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}