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.

Photoangioplasty

“…In experimental treatments of canine coronary arteries in vivo, light doses Ͼ200 J/cm 2 elicited angiographic spasm, histological necrosis, and even transmural injury. 18 In this study, the cases of premature death were ascribed to the effects of coronary artery spasm, because only minor medial damage was seen in some of these specimens. In fact, even at high light doses, no embolization, vessel perforation, or aneurysmal dilatation was seen.…”

“…The light is then delivered to the treatment site either directly or via hollow wave guides or fibers terminating in optical configurations to achieve either a circumferential, segmental, or conical beam profile. 16 Radially emitting fibers, with a variety of designs, have been used for endovascular PDT in animals, [17][18][19] and in one case, a 2-patient clinical study. 17 Another important advance in photoangioplasty is the development of compact, portable, and relatively inexpensive diode-based lasers to replace the older, large systems requiring special electrical and plumbing infrastructures; the latter are mostly dye lasers pumped by another laser (argon, 19 -21 KTP YAG) or pulse lasers (copper vapor).…”

A first trial in the clinical application of photodynamic therapy for the prevention of restenosis after coronary‐stent placement

“…In 1991, Mackie et al [20] reported that a light dose, greater than or equal to 200 J/cm 2 , elicited angiographic spasms, histological necrosis, and transmural injuries to canine coronary arteries. In this study, no adverse events concerning laser irradiation were detected in any patients.…”

Photodynamic Therapy of Atherosclerosis Using YAG-OPO Laser and Porfimer Sodium, and Comparison With Using Argon-Dye Laser

“…There have been few reports on the efficacy of PDT in the treatment of atheroma, [11][12][13][14][15][16][17][18][19][20][21][22][23] and we were unable to find any reports using the YAG-OPO laser. In this present study we conducted PDT using the YAG-OPO laser in an intravascular approach on atherosclerotic rabbit aortas, investigating the regression effect on hypertrophic intima.…”