title: Exacerbation of reperfusion arrhythmias by sudden oxidant stress.
abstract: A burst of free oxygen radical production has been demonstrated during the early moments of reperfusion, coincident with the onset of reperfusion arrhythmias, which can be attenuated by antioxidants. We have investigated whether a sudden burst of oxidant stress, superimposed on that occurring during reperfusion, can exacerbate reperfusion arrhythmias. Rat hearts (n = 12/group) were subjected to 12 minutes of aerobic perfusion; during the last 2 minutes, rose bengal (1 mumol/l) was added to the perfusion fluid. Then, regional ischemia was induced, and rose bengal-free perfusion was restored. After 5 minutes of ischemia, reperfusion was initiated for 5 minutes, and during the first 30 seconds of reperfusion, hearts were uniformly illuminated (8,500 lux) with green light (530-590 nm). The photoactivation of rose bengal trapped in the tissue, producing singlet oxygen and superoxide, resulted in an exacerbation of reperfusion arrhythmias. Thus, 92% of hearts developed ventricular premature beats, 83% ventricular tachycardia, and 33% ventricular fibrillation. In contrast, hearts with regional ischemia and reperfusion in the absence of rose bengal and/or illumination did not develop ventricular fibrillation; only one heart exhibited ventricular tachycardia, and the incidence of ventricular premature beats was lower (42-50%). Furthermore, the burst of oxidant stress shortened the time to onset of ventricular premature beats from 21.7 +/- 5.6 to 9.9 +/- 2.1 seconds. Additional studies revealed that rose bengal photoactivation without reperfusion was less arrhythmogenic compared with the combination of reperfusion plus photoactivation. These results demonstrate that a sudden burst of oxidant stress during the early moments of reperfusion can exacerbate the vulnerability to reperfusion arrhythmias.
authors.affiliation: Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Kusama
authors.forename: M
authors.initials: M
authors.lastname: Bernier
authors.forename: D J
authors.initials: DJ
authors.lastname: Hearse
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology; D005336:Fiber Optic Technology; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012395:Rose Bengal / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D012395:Rose Bengal