Kinetics of antifibrillatory effects of bretylium: Correlation with myocardial drug concentrations
dc.contributor.author | Anderson, Jeffrey L. | en_US |
dc.contributor.author | Patterson, Eugene | en_US |
dc.contributor.author | Conlon, Marilyn E. | en_US |
dc.contributor.author | Pasyk, Stanislaw | en_US |
dc.contributor.author | Pitt, Bertram | en_US |
dc.contributor.author | Lucchesi, Benedict Robert | en_US |
dc.date.accessioned | 2006-04-07T17:30:09Z | |
dc.date.available | 2006-04-07T17:30:09Z | |
dc.date.issued | 1980-10 | en_US |
dc.identifier.citation | Anderson, Jeffrey L., Patterson, Eugene, Conlon, Marilyn, Pasyk, Stanislaw, Pitt, Bertram, Lucchesi, Benedict R. (1980/10)."Kinetics of antifibrillatory effects of bretylium: Correlation with myocardial drug concentrations." The American Journal of Cardiology 46(4): 583-592. <http://hdl.handle.net/2027.42/23417> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T10-4C7V3JS-10/2/8c9edc89acaf93c71f112e5bbe657ba4 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/23417 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=7416018&dopt=citation | en_US |
dc.description.abstract | To determine the kinetics of the antifibrillatory effects of bretylium tosylate and to assess the relative importance of myocardial versus serum drug concentrations, studies were performed in 32 dogs after they received bolus injections of bretylium tosylate (6 mg/kg or 2 mg/kg body weight) or saline solution. Parallel determinations were made of drug concentrations in serum and myocardium, together with antifibrillatory and electrophysiologic effects, both with and without 2 minutes of coronary ischemia produced by temporary coronary ligation. Serum bretylium concentration decreased rapidly after intravenous injection, whereas myocardial concentrations increased gradually, peaking at 1.5 to 6 hours in both open and closed chest dogs. The ratio of myocardial to serum drug concentration increased to 6.4 to 12.6 at 12 hours. Parallel elimination of the drug in serum and myocardium occurred thereafter, with elimination half-life of 10.5 hours (closed chest dogs).Electrophysiologic and antifibrillatory effects paralleled myocardial rather than serum drug kinetics with peak effects at 3 to 6 hours. The ventricular effective refractory period was 24 to 26 ms greater at 3 hours in dogs treated with the drug than in those receiving saline solution. The ventricular fibrillation threshold increased 6 to 10-fold after 2 mg/kg of the drug was given at 3 to 6 hours in dogs both with and without ischemia in comparison with that in control animals treated with saline solution. The average increase in threshold exceeded 12-fold after administration of 6 mg/kg of the drug (2 minutes to 12 hours). The repetitive ventricular response threshold 3 hours after drug administration increased 5-fold after 2 mg/kg and 18-fold after 6 mg/kg of the drug was administered in dogs with or without ischemia.These studies elucidate canine serum and myocardial drug kinetics of bretylium, quantify the prolonged antifibrillatory effect of this drug with its delayed maximal effect and emphasize the importance of tissue levels of bretylium in determining drug action. | en_US |
dc.format.extent | 1334885 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Kinetics of antifibrillatory effects of bretylium: Correlation with myocardial drug concentrations | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | From the Departments of Internal Medicine and Pharmacology, and the Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | From the Departments of Internal Medicine and Pharmacology, and the Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | From the Departments of Internal Medicine and Pharmacology, and the Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | From the Departments of Internal Medicine and Pharmacology, and the Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | From the Departments of Internal Medicine and Pharmacology, and the Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | From the Departments of Internal Medicine and Pharmacology, and the Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.identifier.pmid | 7416018 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/23417/1/0000365.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0002-9149(80)90507-X | en_US |
dc.identifier.source | The American Journal of Cardiology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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