Uptake of hematoporphyrin derivative by valvular vegetations in experimental infective endocarditis.
Drugs that localize in valvular vegetations may be useful in the diagnosis and treatment of infective endocarditis. We therefore tested the hypothesis that parenterally injected hematoporphyrin derivative (HPD), which is concentrated in tumors and atherosclerotic plaques, localizes in the vegetations of experimental infective endocarditis. In 14 rabbits, various bacteria were given intra-arterially immediately after injury to the aortic valve. In 12 additional rabbits, sterile vegetations on the aortic valve were produced by the trauma caused by an indwelling catheter that had been in place over a long period. HPD, 2.5 mg/kg, was injected intravenously 1 to 2 days before the animals were killed in six rabbits with sterile vegetations and in seven rabbits with infected vegetations. In all rabbits, multiple vegetations on the aortic valve leaflets were identified. On exposure to ultraviolet light, strong porphyrin fluorescence of all vegetations, whether sterile or infected, was observed only in rabbits given HPD. In two rabbits given HPD 10 weeks after catheter implantation across the aortic valve, however, only mild fluorescence could be detected in healing endocardial vegetations. In frozen sections of HPD-laden lesions, a patchy distribution of fluorescence was observed that was similar to the pattern of HPD localization in atheromatous plaques. Since vegetations in experimental infective endocarditis selectively concentrate HPD, porphyrins could be useful in the diagnosis and treatment of infective endocarditis.
Spokojny
A M
AM
Sinclair
I N
IN
Schnitt
S
S
Paulin
S
S
Spears
J R
JR
D000818:Animals; D004697:Endocarditis, Bacterial / Q000175:diagnosis* / Q000188:drug therapy; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000627:therapeutic use; D011817:Rabbits; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000188:drug therapy; D013290:Streptococcal Infections / Q000175:diagnosis* / Q000188:drug therapy
D006415:Hematoporphyrins; D017324:Hematoporphyrin Derivative