GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Mediation of the Cardioprotective Effects of Mannitol Discovered, with Refutation of Common Protein Kinases
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 22 ( 2021-11-19), p. 12471-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 22 ( 2021-11-19), p. 12471-
    Abstract: The osmodiuretic agent Mannitol exerts cardioprotection against ischemia and reperfusion (I/R) injury when applied as a pre- and/or postconditioning stimulus. Previously, we demonstrated that these properties are mediated via the activation of mitochondrial ATP-sensitive potassium (mKATP) channels. However, considering Mannitol remains in the extracellular compartment, the question arises as to which receptor and intracellular signaling cascades are involved in myocardial protection by the osmodiuretic substance. Protein kinase B (Akt) and G (PKG), as part of the reperfusion injury salvage kinase (RISK) and/or endothelial nitric oxide (eNOS)/PKG pathway, are two well-investigated intracellular targets conferring myocardial protection upstream of mitochondrial potassium channels. Adenosine receptor subtypes have been shown to trigger different cardioprotective pathways, for example, the reperfusion injury. Further, Mannitol induces an increased activation of the adenosine 1 receptor (A1R) in renal cells conferring its nephroprotective properties. Therefore, we investigated whether (1) Akt and PKG are possible signaling targets involved in Mannitol-induced conditioning upstream of the mKATP channel and/or whether (2) cardioprotection by Mannitol is mediated via activation of the A1R. All experiments were performed on male Wistar rats in vitro employing the Langendorff isolated heart perfusion technique with infarct size determination as the primary endpoint. To unravel possible protein kinase activation, Mannitol was applied in combination with the Akt (MK2206) or PKG (KT5823) inhibitor. In further groups, an A1R blocker (DPCPX) was given with or without Mannitol. Preconditioning with Mannitol (Man) significantly reduced the infarct size compared to the control group. Co-administration of the A1R blocker DPXPC fully abolished myocardial protection of Mannitol. Interestingly and in contrast to the initial hypothesis, neither administration of the Akt nor the PKG blocker had any impact on the cardioprotective properties of Mannitol-induced preconditioning. These results are quite unexpected and show that the protein kinases Akt and PKG—as possible targets of known protective signaling cascades—are not involved in Mannitol-induced preconditioning. However, the cardioprotective effects of Mannitol are mediated via the A1R.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms222212471
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning—A Translational Approach
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 23 ( 2022-11-22), p. 14557-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 23 ( 2022-11-22), p. 14557-
    Abstract: The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p 〈 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p 〈 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p 〈 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p 〈 0.05 vs. HGl Con; HGl Con 59 ± 5%).
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232314557
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Bilirubin—A Possible Prognostic Mortality Marker for Patients with ECLS
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 6 ( 2020-06-03), p. 1727-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 6 ( 2020-06-03), p. 1727-
    Abstract: Extracorporeal life support (ECLS) is a promising therapeutic option for patients with refractory cardiogenic shock. However, as the mortality rate still remains high, there is a need for early outcome parameters reflecting therapy success or futility. Therefore, we investigated whether liver enzyme levels could serve as prognostic mortality markers for patients with ECLS. The present study is a retrospective single-center cohort study. Adult patients 〉 18 years of age who received ECLS therapy between 2011 and 2018 were included. Bilirubin, glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic-transaminase (GPT) serum levels were analyzed at day 5 after the start of the ECLS therapy. The primary endpoint of this study was all-cause in-hospital mortality. A total of 438 patients received ECLS during the observation period. Based on the inclusion criteria, 298 patients were selected for the statistical analysis. The overall mortality rate was 42.6% (n = 127). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) for bilirubin on day 5 was 0.72 (95% confidence interval (CI): 0.66–0.78). Cox regression with multivariable adjustment revealed a significant association between bilirubin on day 5 and mortality, with a hazard ratio (HR) of 2.24 (95% CI: 1.53–3.30). Based on the results of this study, an increase in serum bilirubin on day 5 of ECLS therapy correlates independently with mortality.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9061727
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    MiR-21-5p but not miR-1-3p expression is modulated by preconditioning in a rat model of myocardial infarction
    Springer Science and Business Media LLC ; 2020
    In:  Molecular Biology Reports Vol. 47, No. 9 ( 2020-09), p. 6669-6677
    Details
    In: Molecular Biology Reports, Springer Science and Business Media LLC, Vol. 47, No. 9 ( 2020-09), p. 6669-6677
    Abstract: Isoflurane (Iso) preconditioning (PC) is known to be cardioprotective against ischemia/reperfusion (I/R) injury. It was previously shown that microRNA-21-5p (miR-21-5p) is regulated by Iso-PC. It is unclear, if expression of cardiac enriched miR-1-3p is also affected by Iso-PC, and associated with activation of HIF1α (hypoxia-inducible factor 1-alpha).  Male Wistar rats (n = 6–8) were randomly assigned to treatment with or without 1 MAC Iso for 30 min, followed by 25 min of regional myocardial ischemia, with 120 min reperfusion. At the end of reperfusion, myocardial expression of miR-1-3p, miR-21-5p and mRNAs of two HIF-1α-dependent genes, VEGF (vascular endothelial growth factor) and HO-1 (heme oxygenase-1), were determined by quantitative PCR. Protein expression of a miR-21 target gene, PDCD4 (programmed cell death protein 4), was assessed by western blot analysis. Infarct sizes were analyzed with triphenyltetrazoliumchloride staining. MiR-21-5p expression was increased by Iso, whereas expression of miR-1-3p was not altered. The expression of VEGF but not HO-1 was induced by Iso. Iso-PC reduced infarct sizes compared to untreated controls. No regulation of miRNA and mRNA expression was detected after I/R. PDCD4 protein expression was not affected after Iso exposure. Expression of miR-21-5p, in contrast to miR-1-3p, is altered during this early time point of Iso-PC. HIF1α signaling seems to be involved in miR-21-5p regulation.
    Type of Medium: Online Resource
    ISSN: 0301-4851 , 1573-4978
    URL: Article
    DOI: 10.1007/s11033-020-05721-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1478217-0
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Chronic stable heart failure model in ovine species
    Wiley ; 2020
    In:  Artificial Organs Vol. 44, No. 9 ( 2020-09), p. 947-954
    Details
    In: Artificial Organs, Wiley, Vol. 44, No. 9 ( 2020-09), p. 947-954
    Abstract: Establishing a chronic heart failure (HF) model is challenging, particularly in the ovine model. The aim of this study was to establish a reproducible model of HF in an ovine model. Seventeen sheep were operated using the left thoracotomy approach. Chronic HF was induced through ligation of the diagonal and marginal branches only. Perioperative hemodynamic and echocardiographic parameters were compared. A total of (3 ± 1) coronary ligations were used. Thirteen animals survived the procedure and were followed up for (15 ± 5) days. The mean arterial pressure, heart rate (HR), mean pulmonary artery pressure (mPAP), central venous pressure, and cardiac output at baseline and prior to animal sacrifice was (75 ± 14 mmHg) and (68 ± 16 mmHg) P  = .261; (72 ± 9 bpm), (100 ± 28 bpm) P  = .01; (15 ± 4 mmHg) and (18 ± 5 mmHg) P  = .034; (10 ± 6 mmHg) and (8 ± 4 mmHg) P  = .326; (3.4 ± 1 L/min) and (3.9 ± 1 L/min) P  = .286, respectively. The LVEF at baseline and prior to animal sacrifice was (63 ± 13%) and (43 ± 6%) P  = .012. Twelve surviving animals were supported with LVAD in a follow‐up procedure. Chronic stable HF in sheep was successively established. Clinical symptoms and drastic increase in the mPAP and HR as well as echo findings were the most sensitive parameters of HF. This reproducible ovine model has proven to be highly promising for research regarding HF.
    Type of Medium: Online Resource
    ISSN: 0160-564X , 1525-1594
    URL: Issue
    URL: Article
    DOI: 10.1111/aor.v44.9
    DOI: 10.1111/aor.13772
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2003825-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Effluent from ischemic preconditioned hearts confers cardioprotection independent of the number of preconditioning cycles
    Public Library of Science (PLoS) ; 2020
    In:  PLOS ONE Vol. 15, No. 12 ( 2020-12-3), p. e0243220-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 12 ( 2020-12-3), p. e0243220-
    Abstract: Coronary effluent collected from ischemic preconditioning (IPC) treated hearts induces myocardial protection in non-ischemic-preconditioned hearts. So far, little is known about the number of IPC cycles required for the release of cardioprotective factors into the coronary effluent to successfully induce cardioprotection. This study investigated the cardioprotective potency of effluent obtained after various IPC cycles in the rat heart. Experiments were performed on isolated hearts of male Wistar rats, mounted onto a Langendorff system and perfused with Krebs-Henseleit buffer. In a first part, effluent was taken before (Con) and after each IPC cycle (Eff 1, Eff 2, Eff 3). IPC was induced by 3 cycles of 5 min of global myocardial ischemia followed by 5 minutes of reperfusion. In a second part, hearts of male Wistar rats were randomized to four groups (each group n = 4–5) and underwent 33 min of global ischemia followed by 60 min of reperfusion. The previously obtained coronary effluent was administered for 10 minutes before ischemia as a preconditioning stimulus. Infarct size was determined at the end of reperfusion by triphenyltetrazoliumchloride (TTC) staining. Infarct size with control effluent was 54±12%. Effluent obtained after IPC confers a strong infarct size reduction independent of the number of IPC cycles (Eff 1: 27±5%; Eff 2: 35±7%; Eff 3: 35±8%, each P 〈 0.05 vs. Con). Effluent extracted after one cycle IPC is comparably protective as after two or three cycles IPC.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0243220
    DOI: 10.1371/journal.pone.0243220.g001
    DOI: 10.1371/journal.pone.0243220.g002
    DOI: 10.1371/journal.pone.0243220.t001
    DOI: 10.1371/journal.pone.0243220.t002
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2020
    detail.hit.zdb_id: 2267670-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Perioperative cardioprotection — From bench to bedside : Current experimental evidence and possible reasons for the limited translation into the clinical setting
    Springer Science and Business Media LLC ; 2021
    In:  Der Anaesthesist Vol. 70, No. 5 ( 2021-05), p. 401-412
    Details
    In: Der Anaesthesist, Springer Science and Business Media LLC, Vol. 70, No. 5 ( 2021-05), p. 401-412
    Abstract: Perioperative cardioprotection aims to minimize the consequences of myocardial ischemia reperfusion injury. These strategies appear particularly relevant for anesthesia provision during on-pump cardiac surgery but they potentially affect any cause of perioperative myocardial ischemia. In recent years, several pharmacological and nonpharmacological strategies of cardioprotection have been explored. Results from studies in isolated tissue and animal experiments are promising; however, translation of myocardial conditioning strategies to the clinical setting has been disappointing: in large trials cardioprotective interventions failed to significantly improve outcome. Objective This review aims to provide an overview of the current experimental evidence regarding pharmacological and nonpharmacological cardioprotection. Moreover, it discusses reasons why translation from bench to bedside is hampered by potential confounders and suggests future approaches that might overcome these limitations. Material and methods Narrative review. Results and conclusion Results of experimental studies are convincing but translation into clinical practice remains challenging. Several confounders have been identified contributing to the mainly inconclusive results from clinical studies, such as comorbidities and comedications, choice of anesthetic regimen and also methodological issues. Carefully designed clinical trials in well-defined patient cohorts evaluating combinations of protective strategies targeting different pathways and cell types might support bench to bedside translation.
    Type of Medium: Online Resource
    ISSN: 0003-2417 , 1432-055X
    URL: Article
    DOI: 10.1007/s00101-020-00912-5
    RVK:
    XA 22100
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 3122926-8
    detail.hit.zdb_id: 1458421-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Cardioprotective Properties of Humoral Factors Released after Remote Ischemic Preconditioning in CABG Patients with Propofol-Free Anesthesia—A Translational Approach from Bedside to Bench
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 5 ( 2022-03-07), p. 1450-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 5 ( 2022-03-07), p. 1450-
    Abstract: The cardioprotective effect of remote ischemic preconditioning (RIPC) is well detectable in experimental studies but not in clinical trials. Propofol, a commonly used sedative, is discussed to negatively influence the release of humoral factors after RIPC. Further, results from experimental and clinical trials suggest various comorbidities interact with inducible cardioprotective properties of RIPC. In the present study, we went back from bedside to bench to investigate, in male patients undergoing CABG surgery, whether (1) humoral factors are released after RIPC during propofol-free anesthesia and/or (2) DM interacts with plasma factor release. Blood samples were taken from male patients with and without DM undergoing CABG surgery before (control) and after RIPC (RIPC). To investigate the release of cardioprotective humoral factors into the plasma, isolated perfused hearts of young rats (n = 5 per group) were used as a bioassay. The hearts were perfused with patients’ plasma without (Con) and with RIPC (RIPC) for 10 min (1% of coronary flow) before global ischemia and reperfusion. In additional groups, the plasma of patients with DM was administered (Con DM, RIPC DM). Infarct size was determined by TTC staining. Propofol-free RIPC plasma of male patients without DM showed an infarct size of 59 ± 5% compared to 61 ± 13% with Con plasma (p = 0.973). Infarct sizes from patients with DM showed similar results (RIPC DM: 55 ± 3% vs. Con DM: 56 ± 4%; p = 0.995). The release of humoral factors into the blood after RIPC in patients receiving propofol-free anesthesia undergoing CABG surgery did not show any cardioprotective properties independent of a pre-existing diabetes mellitus.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11051450
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 10 ( 2023-05-20), p. 1432-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 10 ( 2023-05-20), p. 1432-
    Abstract: Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆GATP, Na+, Ca2+, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH4, and NAD+). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca2+ overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12101432
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Perioperative Cardioprotection: Clinical Implications
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Anesthesia & Analgesia Vol. 131, No. 6 ( 2020-12), p. 1751-1764
    Details
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 131, No. 6 ( 2020-12), p. 1751-1764
    Abstract: Perioperative cardioprotection aims to minimize the consequences of myocardial ischemia–reperfusion injury. In isolated tissue and animal experiments, several treatments have been identified providing cardioprotection. Some of these strategies have been confirmed in clinical proof-of-concept studies. However, the final translation of cardioprotective strategies to really improve clinical outcome has been disappointing: large randomized controlled clinical trials mostly revealed inconclusive, neutral, or negative results. This review provides an overview of the currently available evidence regarding clinical implications of perioperative cardioprotective therapies from an anesthesiological perspective, highlighting nonpharmacological as well as pharmacological strategies. We discuss reasons why translation of promising experimental results into clinical practice and outcome improvement is hampered by potential confounders and suggest future perspectives to overcome these limitations.
    Type of Medium: Online Resource
    ISSN: 0003-2999
    URL: Article
    DOI: 10.1213/ANE.0000000000005234
    RVK:
    XA 22250
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2018275-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...