Effects of different antibiotics on the endothelium of the porcine aortic valve.
Homograft heart valves are usually sterilized by exposure to multiple-antibiotic solutions at 4 degrees C for 24 hours. Several combinations of antibiotics have been proposed and discussed in the literature, but their toxicity to cusp endothelium has not been investigated yet. We studied the endothelial cell viability of porcine aortic valves by measuring their in vitro prostacyclin (PGI2) production after being exposed to different antibiotics solutions. Porcine aortic valves were immersed for 24 hours at 4 degrees C in RPMI medium to which antibiotics (Gentamycin 80 micrograms/ml, Azlocillin 500 micrograms/ml, Cloxacillin 25 micrograms/ml, Metronidazole 100 micrograms/ml, Amphotericin B 50 micrograms/ml, GACMA) were added separately or in combination. The basal and bradykinin (10 microM) stimulated PGI2 release of these valves in the medium were measured during consecutive incubation lasting 15 minutes at 37 degrees C, using a radioimmunoassay for 6-oxo-PGF1 alpha. Valves treated with the combination of all five antibiotics produced significantly less PGI2 in basal and stimulated conditions (1.64 +/- 0.63--7.25 +/- 1.73 ng/ml x cm2, p < 0.05) than the controls (4.66 +/- 0.66--30.55 +/- 3.84 ng/ml x cm2, p < 0.001). Although all antibiotics, when studied separately at the above mentioned concentrations, tended to reduce the biosynthesis of PGI2, amphotericin B was responsible for the most pronounced decrease in its production. The toxic effect of amphotericin B was dose dependent; at a low concentration (5 micrograms/ml), which is usually enough for antifungal action, toxicity was undetectable. At 50 micrograms/ml PGI2 production was half of that found at 5 micrograms/ml, although concentrations as high as 100 micrograms/ml have been used clinically to disinfect homografts. Scanning electron microscopy (SEM) also confirmed the extensive loss of endothelium after exposure to high concentrations of amphotericin B. Our study suggests that the other four antibiotics used in the concentrations described above do not damage endothelial function; amphotericin B is also harmless if used at a concentration of 5 micrograms/ml.
Feng
X J
XJ
Department of Cardiac Surgery, Faculty of Medicine, University of Antwerp, Belgium.
van Hove
C E
CE
Mohan
R
R
Walter
P J
PJ
Herman
A G
AG
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001021:Aortic Valve / Q000187:drug effects* / Q000648:ultrastructure; D001390:Azlocillin / Q000008:administration & dosage / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003023:Cloxacillin / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004727:Endothelium / Q000187:drug effects / Q000648:ultrastructure; D011464:Epoprostenol / Q000096:biosynthesis; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology; D008795:Metronidazole / Q000008:administration & dosage / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D013242:Sterilization; D013552:Swine; D014184:Transplantation, Homologous
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D005839:Gentamicins; D008795:Metronidazole; D000666:Amphotericin B; D011464:Epoprostenol; D001390:Azlocillin; D003023:Cloxacillin; D001920:Bradykinin