Photoactivation of porphyrins: studies of reactive oxygen intermediates and arrhythmogenesis in the aerobic rat heart.
OBJECTIVE
In situ production of reactive oxygen intermediates (singlet oxygen and superoxide) during the photoactivation of rose bengal can induce arrhythmias in the aerobically perfused rat heart. The present study was undertaken (1) to assess whether these effects occur with other photosensitizers; (2) to identify the injurious intermediates; (3) to probe the site of action of these phenomena. DESIGN - The study involved the use of meso-tetra-(4-sulphonatophenyl)-porphine (TPPS), a porphyrin which, in contrast to rose bengal, promotes the production of singlet oxygen alone when illuminated. After 10 min of TPPS free perfusion, rat hearts (n = 6 per group) were perfused aerobically with TPPS (1, 5, 10 or 50 mumol.litre-1) for 25 min; during the last 20 min, the hearts were illuminated (3600 lux). In additional studies, TPPS (50 mumol.litre-1) was washed out before illumination.


METHODS
Hearts from 30 male Wistar rats, weighing 220-280 g, were excised and perfused retrogradely.


RESULTS
Cardiac function was unaffected with TPPS alone. Upon illumination, electrocardiographic changes (increase in QT interval and/or T wave changes) and arrhythmias developed in a dose dependent manner. At the highest dose, electrocardiographic changes occurred within 7.0(SEM 0.4) s; all hearts exhibited ventricular premature beats and complete atrioventricular block; 67% developed ventricular tachycardia and 17% ventricular fibrillation. During illumination, hearts also exhibited a dose and time dependent decrease in coronary flow. In additional studies, despite the absence of TPPS in the perfusate, all hearts exhibited complete atrioventricular block, 67% developed ventricular premature beats and 33% ventricular tachycardia; none exhibited ventricular fibrillation.


CONCLUSIONS
The results suggest that singlet oxygen, as opposed to superoxide, is responsible for the injury which occurs at tissue surfaces to which photosensitizer is bound.
Kusama
Y
Y
Cardiovascular Research, Rayne Institute, St Thomas's Hospital, London.
Bernier
M
M
Hearse
D J
DJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008027:Light; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D010777:Photochemistry; D011166:Porphyrins / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D026082:Singlet Oxygen
D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D026082:Singlet Oxygen; C016136:tetraphenylporphine sulfonate; D010100:Oxygen