title: The effect of UK14,304-18 (an alpha-2 adrenergic agonist) on myocardial blood flow during cardiopulmonary resuscitation.
abstract: Several recent studies have suggested that adrenergic drugs with peripheral postsynaptic alpha-2 agonist properties increase aortic diastolic pressure (ADP), and thus in the setting of CPR, may improve myocardial blood flow (MBF). This preliminary study investigated the effect of UK14,304-18, a postsynaptic alpha-2 adrenergic agonist on ADP, MBF, myocardial oxygen delivery/utilization (MDO2/MVO2), endocardial/epicardial blood flow ratio (EN/EP), coronary sinus oxygen content (CcsO2) and extraction ratio (ER) during CPR. Five swine were instrumented for MBF measurements using tracer microspheres. Catheters were also placed to measure arterial oxygen content (CaO2) and CcsO2. ADP, MBF, MDO2/MVO2, EN/EP, ER, CaO2 and CcsO2 were measured during normal sinus rhythm (NSR), and during CPR following a 10-min cardiorespiratory arrest. Following this, each animal received 2.0 mg/kg of UK14,304-18 through a right atrial line. ADP, MBF, MDO2/MVO2, EN/EP, ER, CaO2 and CcsO2 were again determined. Defibrillation was then attempted. To determine whether UK14,304-18 improved ADP, MBF and MDO2 over MVO2, compared to CPR alone, results were compared using a paired Student t-test. Statistical significance was considered at the P less than or equal to 0.05 level. No significant improvement in ADP, MBF, MDO2 or ER was noted following the administration of UK14,304-18. The lack of improvement in ADP and MBF may be secondary to a centrally acting postsynaptic alpha-2 agonist effect because of disruption of the blood brain barrier following a prolonged cardiac arrest or because of pharmacologically or structurally distinct populations of peripheral postsynaptic alpha-2 adrenoreceptors that develop in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Preventive Medicine, Ohio State University, Columbus 43210.
authors.forename: C G
authors.initials: CG
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Jenkins
authors.forename: H A
authors.initials: HA
authors.lastname: Werman
authors.forename: P
authors.initials: P
authors.lastname: Van Ligten
authors.forename: J
authors.initials: J
authors.lastname: Ashton
authors.forename: R L
authors.initials: RL
authors.lastname: Hamlin
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D003326:Coronary Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D012151:Resuscitation; D013552:Swine
chemical_list: D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D000068438:Brimonidine Tartrate