Kai Zacharowski

Goethe-Universität Frankfurt am Main · Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy
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Topics (19) View all

Publications (112) View all

  • Source
    Article: In reply.
    Anesthesiology 04/2013; 118(4):988-90. · 5.36 Impact Factor
  • Article: Point-of-care coagulation management in intensive care medicine.
    Critical care (London, England) 03/2013; 17(2):218. · 4.61 Impact Factor
  • Article: Determination of Organ-Specific Anemia Tolerance.
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    ABSTRACT: OBJECTIVE:: Utilization of anemia tolerance reduces the need for and risks of perioperative transfusion. Recent publications indicate that the critical limit for oxygen supply might not be the same for each organ system. Therefore, we investigated the effects of acute dilutional anemia on heart, brain, kidneys, liver, small intestine, and skeletal muscle to quantify organ-specific tolerance of different levels of acute anemic hypoxia. We hypothesized that, in some organs, tissue hypoxia occurs before the critical limits of systemic oxygen supply are reached. DESIGN:: Laboratory animal experiments. SETTING:: Animal research laboratory at university medical school. SUBJECTS:: A total of 18 domestic pigs of either sex (average weight: 19.6 kg). INTERVENTIONS:: Animals were anesthetized, ventilated, and randomized into three groups and then hemodiluted by exchange of 6% hydroxyethyl starch (130,000:0.4) for whole blood to the group-specific endpoint: Sham (no hemodilution), Hb4 (hemoglobin 4.3 g/dL), Hbcrit (2.7 g/dL). Subsequently, 10 mg/kg pimonidazole (which forms protein adducts in hypoxic cells) was injected. One hour after injection, tissue samples were collected and analyzed for pimonidazole-protein adduct quantification (dot blot) and as a surrogate for transcriptional activation during hypoxia the expression of vascular endothelial growth factor messenger RNA. Relevant hemodynamic and metabolic parameters were collected. MEASUREMENTS AND MAIN RESULTS:: Hemodynamics, metabolic parameters, or oxygen consumption did not indicate that tissue oxygenation was restricted before reaching Hbcrit. However, kidneys and skeletal muscle showed enhanced pimonidazole binding and vascular endothelial growth factor expression at Hb4. By contrast, liver oxygenation was actually improved at Hb4. Heart, brain, and liver showed no signs of tissue hypoxia at Hb4. CONCLUSIONS:: Heart, brain, kidneys, liver, small intestine, and skeletal muscle experience tissue hypoxia at different degrees of acute anemia, as assessed by the pimonidazole method and vascular endothelial growth factor expression. Further studies are needed to elucidate the mechanisms that determine organ-specific anemia tolerance.
    Critical care medicine 02/2013; · 6.37 Impact Factor
  • Article: Characterization of the LPS-induced inflammation of the adrenal gland in mice.
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    ABSTRACT: Systemic administration of endotoxin, which closely mimics the bacteria-induced systemic inflammatory response syndrome (SIRS) can ultimately lead to organ failure. Adrenal gland insufficiency is frequently diagnosed in critically ill patients; however, the underlying mechanisms are still unclear. In the present study, we studied comprehensively the characteristics of adrenal gland dysregulation, including inflammation, leukocyte infiltration and cell death in the adrenal glands in the course of LPS-induced systemic inflammation in mice. LPS enhanced expression of many proinflammatory cytokines, chemokines and adhesion molecules, which resulted in rapid recruitment of leukocytes into the adrenal gland. Furthermore, LPS-mediated inflammation was associated with increased apoptosis of adrenocortical and chromaffin cells. Our results performed in mice, suggest that LPS-induced adrenal gland inflammation and cell death might be mechanisms potentially involved in the adrenal gland dysfunction in patients with sepsis.
    Molecular and Cellular Endocrinology 01/2013; · 4.19 Impact Factor
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    Article: Remote ischemic preconditioning regulates HIF-1α levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study.
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    ABSTRACT: Transient episodes of ischemia in a remote organ (remote ischemic preconditioning, RIPC) bears the potential to attenuate myocardial injury, but the underlying mechanisms are only poorly understood. In the pilot experimental study presented we investigated cellular and molecular effects of RIPC in heart tissue of cardiosurgical patients with cardiopulmonary bypass (CPB) and focussed on apoptotic events, local and systemic inflammation as well as the regulation of the hypoxia induced factor-1α (HIF-1α). RIPC was induced by four 5-min cycles of transient upper limb ischemia/reperfusion using a blood-pressure cuff. Right atrial tissue and serum were obtained from patients receiving RIPC (N = 32) and control patients (N = 29) before and after CPB. RIPC patients showed reduced troponin T serum concentrations in the first 48 h after surgery (P < 0.05 vs. control) indicating cardioprotective effects of RIPC. Samples from RIPC patients that were collected before CPB contained significantly increased amounts of HIF-1α and procaspase-3 (HIF-1α: P < 0.05 vs. control, procaspase-3: P < 0.05 vs. control), whereas activities of caspases 3 and 7 were by trend reduced. Samples from RIPC patients that were taken after CPB showed an increased activity of myeloperoxidase (P < 0.05 vs. control; P < 0.05 vs. RIPC before CPB) as well as elevated tissue concentrations of the interleukin (IL)-1β (P < 0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1β and TNFα were significantly increased in RIPC patients before CPB (P < 0.05 vs. control before CPB). In summary, RIPC regulates HIF-1α levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.
    Archiv für Kreislaufforschung 01/2013; 108(1):314. · 7.35 Impact Factor

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