title: In vivo canine coronary artery laser irradiation: photodynamic therapy using dihematoporphyrin ether and 632 nm laser. A safety and dose-response relationship study.
abstract: This study examined the safety and dose-response relationships of 632-nm laser irradiation of photosensitized normal coronary arteries in 27 dogs. Fifteen received 2.5 mg/kg dihematoporphyrin ether (DHE), seven received no sensitizer, and five had coronary instrumentation but no laser (sham laser procedures) at nine coronary sites--four sensitized, five non-sensitized. Laser energy of 82 to 1,640 J/cm2 was delivered via a 584 microns diffusing-tip optical fiber, providing estimated tissue fluences of 20 to 410 J/cm2. Serial electrocardiograms and selective coronary arteriograms were performed up to 1 month post laser irradiation. Histologic examination was performed of all treated sites. Tissue fluences less than 200 J/cm2 produced no permanent electrocardiographic or angiographic changes; reversible spasm occurred in 2/8 photosensitized-lased, 0/2 non-photosensitized-lased. Minor medial damage occurred in 1/8 sensitized-lased, 1/2 non-sensitized-lased, and 0/9 sham-lased sites. At tissue fluences greater than 200 J/cm2 4/7 sensitized-lased animals died prematurely--one due to immediate and irreversible coronary spasm and Q wave infarction, one due to fibrillation during 48-hour follow-up coronary angiography (normal angiograms), two with normal electrocardiograms and angiograms within one day of undetermined death; 0/5 non-sensitized-lased animals expired or had coronary spasm; and 3/7 sensitized-lased and 0/5 non-sensitized/lased had significant medial to adventitial histologic damage. Coronary irradiation at less than 200 J/cm2 appears to be safe for photodynamic treatment of atherosclerotic lesions. Pretreatment for coronary spasm is appropriate.
authors.affiliation: Department of Medicine, LDS Hospital, Salt Lake City 84143.
authors.forename: R W
authors.initials: RW
authors.lastname: Mackie
authors.forename: G M
authors.initials: GM
authors.lastname: Vincent
authors.forename: J
authors.initials: J
authors.lastname: Fox
authors.forename: E C
authors.initials: EC
authors.lastname: Orme
authors.forename: E H
authors.initials: EH
authors.lastname: Hammond
authors.forename: C
authors.initials: C
authors.lastname: Chang-Zong
authors.forename: M D
authors.initials: MD
authors.lastname: Johnson
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D016342:Angioplasty, Laser; D000818:Animals; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects* / Q000601:surgery; D017323:Dihematoporphyrin Ether; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004547:Elastic Tissue / Q000473:pathology; D004562:Electrocardiography / Q000187:drug effects / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000473:pathology; D006415:Hematoporphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D053685:Laser Therapy; D010778:Photochemotherapy / Q000379:methods*; D011829:Radiation Dosage; D012449:Safety; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D006415:Hematoporphyrins; D017323:Dihematoporphyrin Ether