title: Hemolyzed Blood Elicits a Calcium Antagonist and High CO2Reversible Constriction via Elevation of [Ca2+]iin Isolated Cerebral Arteries.
abstract: During acute subarachnoid hemorrhage, blood is hemolyzed, which is followed by a significant cerebrovascular spasm resulting in a serious clinical condition. Interestingly, however, the direct vasomotor effect of perivascular hemolyzed blood (HB) has not yet been characterized, preventing the assessment of contribution of vasoconstrictor mechanisms deriving from brain tissue and/or blood and development of possible treatments. We hypothesized that perivascular HB reduces the diameter of the cerebral arteries (i.e., basilar artery [BA]; middle cerebral artery [MCA]) by elevating vascular tissue [Ca2+]ilevel. Vasomotor responses were measured by videomicroscopy and intracellular Ca2+by the Fura2-AM ratiometric method. Adding HB to the vessel chamber reduced the diameter significantly (BA: from 264 ± 7 to 164 ± 11 μm; MCA: from 185 ± 15 to 155 ± 14 μm), which was reversed to control level by wash-out of HB. Potassium chloride (KCl), HB, serum, hemolyzed red blood cell (RBC), plasma, and platelet suspension (PLTs) elicited significant constrictions of isolated basilar arteries. There was a significant increase in K+concentration in hemolyzed HB (7.02 ± 0.22 mmol/L) compared to Krebs' solution (6.20 ± 0.01 mmol/L). Before HB, acetylcholine (ACh), sodium-nitroprussid (SNP), nifedipin, and CO2elicited substantial dilations in cerebral arteries. In contrast, in the presence of HB dilations to ACh, SNP decreased, but not to nifedipine and CO2. After washout of HB, nitric oxide-mediated dilations remained significantly reduced compared to control. HB significantly increased the ratiometric Ca signal, which returned to control level after washout. In conclusion, perivascular hemolyzed blood elicits significant-nifedipine and high CO2reversible-constrictions of isolated BAs and MCAs, primarily by increasing intracellular Ca2+, findings that can contribute to the refinement of local treatment of subarachnoid hemorrhage.
authors.affiliation: 1 Institute of Translational Medicine, University of Pecs , Medical School, Pecs, Hungary .|2 Department of Central Anesthesiology and Intensive Therapy, Petz Aladar County Teaching Hospital , Gyor, Hungary .|6 Szentagothai Research Centre, University of Pecs , Pecs, Hungary .
authors.forename: Peter
authors.initials: P
authors.lastname: Cseplo
authors.affiliation: 3 Department of Anaesthesiology and Intensive Therapy, University of Pecs , Medical School, Pecs, Hungary .
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Vamos
authors.affiliation: 1 Institute of Translational Medicine, University of Pecs , Medical School, Pecs, Hungary .
authors.forename: Orsolya
authors.initials: O
authors.lastname: Torok
authors.affiliation: 1 Institute of Translational Medicine, University of Pecs , Medical School, Pecs, Hungary .
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivic
authors.affiliation: 4 Institute of Cardiology, Division of Clinical Physiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: Attila
authors.initials: A
authors.lastname: Toth
authors.affiliation: 5 Department of Neurosurgery, University of Pecs , Medical School, Pecs, Hungary .|6 Szentagothai Research Centre, University of Pecs , Pecs, Hungary .|7 MTA-PTE Clinical Neuroscience MR Research Group , Pecs, Hungary .
authors.forename: Andras
authors.initials: A
authors.lastname: Buki
authors.affiliation: 1 Institute of Translational Medicine, University of Pecs , Medical School, Pecs, Hungary .|5 Department of Neurosurgery, University of Pecs , Medical School, Pecs, Hungary .|6 Szentagothai Research Centre, University of Pecs , Pecs, Hungary .|8 Institute of Natural Sciences, University of Physical Education , Budapest, Hungary .|9 Department of Physiology, New York Medical College , Valhalla, New York.
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D002536:Cerebral Arteries / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006461:Hemolysis / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
chemical_list: D002245:Carbon Dioxide; D002118:Calcium
keywords: CBF autoregulation; in vitro studies; subarachnoid hemorrhage; traumatic brain injury; vascular injury