title: Cerebral vasoconstriction during sustained ventricular tachycardia induces an ischemic stress response of brain tissue in rats.
abstract: Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF) and induces an ischemic stress response of the brain. CBF-measurements and morphological studies were performed without and with blockade of alpha-adrenergic receptors in order to determine the impact of MHT-VF on brain perfusion and brain tissue. Using a model of MHT-VT, CBF was measured with colored microspheres in 71 rats during control conditions. after the onset of MHT-VT, after the onset of moderate hypotensive hypovolemia (MHH), and after additional non- selective (alpha-blockade with phentolamine and selective alpha1-blockade with prazosin, respectively (0.2-0.4 mg/kg body weight). Plasma catecholamine concentrations were measured in 18 additional rats during control conditions. during MHT-VT and during MHH. The occurrence of heat shock protein (hsp) 72 and activated microglia in the brain was analysed in 18 additional rats in controls, after MHT-VT and MHH. After 20 min of the respective induced hypotension, control conditions were restored for a period of 8 h, by stopping VT or by infusion of isotonic saline solution. CBF was 0.98+/-0.16 (mean+/-S.D.) ml/g/min during control conditions at an arterial pressure of 118+/-13 mmHg, 0.50+/-0.05 ml/g/min (P<0.05 v control) during MHT-VT (76+/-4 mm Hg) and 0.75+/-0.14 ml/g/min (P<0.05 v control and v MHT-VT ) during MHH (71 +/- 8 mm Hg). CBF was better preserved with non-selective alpha-blockade during MHT-VT (0.78+/-0.15 ml/g/min, P<0.05 v MHT-VT and control) as well as with selective alpha1-blockade (0.67+/-0.08 ml/g/min, P<0.05 v MHT-VT and control). Plasma catecholamines were elevated during MHT-VT (P<0.05 v control) but not during MHH (P = N.S. v control). hsp 72 and activated microglia were found in hippocampal regions only after MHT-VT (P<0.05 v control and MHH). These morphological changes were prevented by non-selective alpha-blockade. Stable sustained MHT-VT further reduce the already compromised CBF leading to morphological alterations in the brain which are characteristic of an early ischemic stress response. alpha-Blockade prevents alpha1-adrenergic vasoconstriction and attenuates cerebral hypoperfusion.
authors.affiliation: Department of Cardiology, University of Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hagendorff
authors.forename: C
authors.initials: C
authors.lastname: Dettmers
authors.forename: P
authors.initials: P
authors.lastname: Danos
authors.forename: M
authors.initials: M
authors.lastname: Hümmelgen
authors.forename: C
authors.initials: C
authors.lastname: Vahlhaus
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: G
authors.initials: G
authors.lastname: Heusch
authors.forename: B
authors.initials: B
authors.lastname: Lüderitz
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D006439:Hemodynamics; D006624:Hippocampus / Q000473:pathology; D007022:Hypotension / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*; D017180:Tachycardia, Ventricular / Q000503:physiopathology*; D014661:Vasoconstriction
chemical_list: D000317:Adrenergic alpha-Antagonists; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine