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Medline ® Abstract for Reference 43

of 'Neurogenic pulmonary edema'

Different impacts ofα- andβ-blockers in neurogenic hypertension produced by brainstem lesions in rat.
Lu WH, Hsieh KS, Lu PJ, Wu YS, Ho WY, Cheng PW, Lai CC, Hsiao M, Tseng CJ
Anesthesiology. 2014 May;120(5):1192-204.
BACKGROUND: Bilateral lesions of nucleus tractus solitarii in rat result in acute hypertension, pulmonary edema, and death within hours. The hypertension results from excessive catecholamine release. Catecholamine can activate connexin43 to regulate cell death. There is no study investigating the cardiopulmonary impacts of different adrenergic blockers and apoptosis mechanism in rat model.
METHODS: The authors microinjected 6-hydroxydopamine into nucleus tractus solitarii of the rat (n = 8 per group) and evaluated the cardiopulmonary changes after treatment with different concentrations ofα1-blockers,α2-blockers,β-blockers, andα-agonists.
RESULTS: In the rat model, the authors found that prazosin (0.15 mg/kg) treatment could preserve cardiac output and reverse neutrophil infiltrations in lungs and lead to prevent pulmonary hemorrhagic edema. The time-dependent increases in connexin43 and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells induced by 6-hydroxydopamine lesions were decreased after prazosin treatment (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells at 6 h: 64.01±2.41% vs. 24.47±3.10%; mean±SD, P<0.001, in heart, and 80.83±2.52% vs. 2.60±1.03%, P<0.001, in lung). However, propranolol caused further compromise of the already impaired cardiac output with consequence of rapid death. Phenylephrine enhanced the phenotype in the link between connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells but not yohimbine. Connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were more decreased with prazosin (0.15 and 0.3 mg/kg) than that with prazosin (0.05 mg/kg) treatment.
CONCLUSIONS: α1-Receptors are the keystones of the phenotype. In some brainstem encephalitis and brain injury with nucleus tractus solitarii involvement, earlyα1-receptor blockade treatment may prevent acute death from tissue apoptosis.α-Blockers can also decrease cerebralperfusion pressure, and further studies are needed in translation to brain injury with increased intracranial pressure.
From the Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. (W.-H.L., C.-J.T.); Department of Pediatrics (W.-H.L., K.-S.H.), Department of Medical Education and Research (Y.-S.W., P.-W.C., C.-J.T.), and Department of Cardiovascular Center (C.-C.L.), Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.; Graduate Institute of Aerospace and Undersea Medicine (W.-H.L.), and Department of Pharmacology (C.-J.T.), National Defense Medical Center, Taipei, Taiwan, R.O.C.; Institute of Clinical Medicine, National Cheng-Kung University, Tainan, Taiwan, R.O.C. (P.-J.L.); Division of General Internal Medicine, Department of Internal Medicine, Kaoshiung Medical University Hospital, Kaoshiung Medical University, Kaohsiung, Taiwan, R.O.C. (W.-Y.H.); Genomics Research Center, Academia Sinica, Taipei, Taiwan, R.O.C. (M.H.); and Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, R.O.C. (C.-C.L., C.-J.T.).