title: Reduction in QT dispersion and ventricular arrhythmias by ischaemic preconditioning in anaesthetized, normotensive and spontaneously hypertensive rats.
abstract: QT dispersion is a marker for dispersion of ventricular repolarization and electrical instability of the heart. However, QT dispersion remains undocumented in both normotensive rats (NTRs) and spontaneously hypertensive rats (SHRs), in particular in conditions of myocardial ischaemia/reperfusion (isch./rep.) and ischaemic preconditioning (IP). Therefore, we assessed the effects of IP on the dynamic change of QT and QTc dispersion during isch./rep., and on isch.- and rep.-induced ventricular arrhythmias in both NTRs and SHRs. Isch. and rep. were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of IP (three cycles of 3 min coronary artery occlusion and 5 min rep.) on myocardial repolarization and on development of isch.- and rep.-induced ventricular arrhythmias was studied in 12 NTRs and 12 SHRs. Another 12 NTRs or 12 SHRs were subjected to 10 min of isch. followed by 10 min rep. without IP. SHRs have significantly longer QT- and QTc-intervals as well as QT and QTc dispersion before isch. compared to NTRs. Myocardial isch. and early rep. largely increased QT and QTc dispersion in both NTRs and SHRs and resulted in a high incidence of isch.- and rep.-induced ventricular tachycardia (VT) and fibrillation (VF). IP significantly reduced QT and QTc dispersion in SHRs before isch., and remarkably reduced the elevation of QT and QTc dispersion during a prolonged period of isch. and rep. in all rats. This protective effect on electrophysiology of IP was associated with an antiarrhythmic effect against both isch.- and rep.-induced ventricular arrhythmias in NTRs and SHRs. Our data indicate that: 1) SHRs have a significantly higher baseline dispersion of ventricular repolarization than NTRs; 2) IP provides protection against ventricular arrhythmias in SHRs; 3) the increasing QT dispersion provoked by myocardial isch. and rep. is associated with a high incidence of isch.- and rep.-induced ventricular arrhythmias and; 4) the reduction of QT dispersion by IP may be involved in its protective effect against isch.- and rep.-induced arrhythmias in both NTRs and SHRs.
authors.affiliation: Department of Cardiovascular and Pulmonary Pharmacology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: H R
authors.initials: HR
authors.lastname: Lu
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.forename: D Z
authors.initials: DZ
authors.lastname: Dai
authors.forename: P
authors.initials: P
authors.lastname: Remeysen
authors.forename: F
authors.initials: F
authors.lastname: De Clerck
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000473:pathology; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology; D003327:Coronary Disease / Q000150:complications / Q000473:pathology; D004562:Electrocardiography; D006339:Heart Rate; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015425:Myocardial Reperfusion / Q000009:adverse effects; D051381:Rats; D011918:Rats, Inbred SHR; D013610:Tachycardia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D018879:Ventricular Premature Complexes / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*