title: A Rapid, Cost-Effective Pre-Clinical Method to Screen for Pro- or Antiarrhythmic Effects of Substances in an Isolated Heart Preparation.
abstract: This study describes a rapid, cost-effective pre-clinical method to screen for pro- or antiarrhythmic effects of substances in an isolated heart preparation in line with the regulatory requirements of ICHS7B. The computational method "MFC method" quantifies arrhythmic episodes from isolated perfused hearts based on measuring the variation in the maximum force of contraction. Experiments were performed on hearts isolated from male Wistar rats. Arrhythmias were induced by the addition of tefluthrin or by ligation of the left coronary artery. The "MFC method" accurately measures the maximum force of every myocardial contraction and correlates it with the magnitude of the preceding beat. Arrhythmias were quantified by determining the coefficient of variation in the maximum force of contraction. This method is a useful approach to quickly identify the pro- or antiarrhythmic effects of drugs prior to more detailed analysis; particularly where the effects are varied and not easily classified under the Lambeth Conventions. Therefore, the "MFC method" can be used as a rapid screen for the antiarrhythmic effects of novel compounds or for rapidly determining potential cardiac toxicity.
authors.affiliation: 8, No 40 Dingli Court, Howard Str, Sliema, SLM 1751, Malta; Department of Pharmacology, Medical School, University of Bristol, BS81TD, United Kingdom.
authors.forename: John Joseph
authors.initials: JJ
authors.lastname: Borg
keywords: Arrhythmia; Contractile variation; Coronary ligation; ICHS7B; Lambeth Conventions
references.citation: Br Heart J. 1969 May;31(3):273-80
references.pmid: 4100820
references.citation: J Pharm Pharm Sci. 1999 Jan-Apr;2(1):30-5
references.pmid: 10951660
references.citation: J Electrocardiol. 1998 Oct;31(4):317-25
references.pmid: 9817215
references.citation: IEEE Trans Biomed Eng. 1989 Oct;36(10):1050-5
references.pmid: 2793197
references.citation: Arch Surg. 1946 Jun;52:677-89
references.pmid: 20989265
references.citation: J Electrocardiol. 1982 Jan;15(1):55-60
references.pmid: 6175712
references.citation: IEEE Trans Biomed Eng. 1992 Apr;39(4):317-29
references.pmid: 1592397
references.citation: IEEE Trans Biomed Eng. 1991 Aug;38(8):785-94
references.pmid: 1937512
references.citation: J Physiol. 1887 Oct;8(5):296-310
references.pmid: 16991467
references.citation: IEEE Trans Biomed Eng. 1996 Apr;43(4):425-30
references.pmid: 8626192
references.citation: J Pharmacol Exp Ther. 2001 Sep;298(3):1067-82
references.pmid: 11504804
references.citation: J Electrocardiol. 1980;13(1):17-24
references.pmid: 7359059
references.citation: Cardiovasc Res. 1988 Jul;22(7):447-55
references.pmid: 3252968
references.citation: Cardiovasc Res. 1988 May;22(5):303-14
references.pmid: 3056616
references.citation: J Gen Physiol. 1988 Jan;91(1):133-55
references.pmid: 3343586