Romain Clerc1,2, Sophia Doll1,2, Laurent M Riou3,4,5, Pascale Perret1,2, Alexis Broisat1,2, Audrey Soubies1,2, Marie-Dominique Desruet1,6, Daniel Fagret1,6, Carole Schwebel1,2,7, Catherine Ghezzi1,2. 1. INSERM U1039, Radiopharmaceutiques Biocliniques, Grenoble, France. 2. Université Grenoble Alpes, Grenoble, France. 3. INSERM U1039, Radiopharmaceutiques Biocliniques, Grenoble, France. Laurent.Riou@univ-grenoble-alpes.fr. 4. Université Grenoble Alpes, Grenoble, France. Laurent.Riou@univ-grenoble-alpes.fr. 5. INSERM U1039, Faculté de Médecine de Grenoble, 38700, La Tronche, France. Laurent.Riou@univ-grenoble-alpes.fr. 6. Nuclear Medicine Department, Grenoble University Hospital, Grenoble, France. 7. Intensive Care Unit, Grenoble University Hospital, Grenoble, France.
Abstract
BACKGROUND: Sympathetic system abnormalities have been reported in sepsis-related cardiac dysfunction. The present study aimed at evaluating the potential of the norepinephrine radiolabeled analogue [123I]-meta-iodobenzylguanidine (123I-MIBG) for the noninvasive assessment of modifications in cardiac sympathetic activity occurring in lipopolysaccharide (LPS)-induced experimental acute sepsis by single-photon emission computed tomographic imaging (SPECT). METHODS AND RESULTS: Sepsis was induced in male Wistar rats by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide (n = 16), whereas control animals (n = 7) were injected with vehicle (NaCl 0.9%). Echocardiography in LPS-injected animals (n = 8) demonstrated systolic and diastolic cardiac dysfunction. 123I-MIBG was injected 1 hour after LPS or vehicle administration (n = 8 and 7, respectively), and in vivo SPECT imaging was performed early and late (20 and 180 minutes) after tracer injection prior to animal euthanasia and ex vivo assessment of 123I-MIBG biodistribution. Global and 17-segment SPECT image analysis indicated that early 123I-MIBG activity was not affected by LPS treatment, whereas late cardiac tracer activity was significantly decreased in LPS-treated animals. Consequently, the cardiac washout of 123I-MIBG was significantly higher in LPS-treated (63.3% ± 4.0%) than that in control animals (56.7% ± 5.8%) (P < .05). CONCLUSION: Sepsis-induced modifications in cardiac sympathetic nervous system activity were evidenced by noninvasive in vivo 123I-MIBG SPECT imaging.
BACKGROUND:Sympathetic system abnormalities have been reported in sepsis-related cardiac dysfunction. The present study aimed at evaluating the potential of the norepinephrine radiolabeled analogue [123I]-meta-iodobenzylguanidine (123I-MIBG) for the noninvasive assessment of modifications in cardiac sympathetic activity occurring in lipopolysaccharide (LPS)-induced experimental acute sepsis by single-photon emission computed tomographic imaging (SPECT). METHODS AND RESULTS:Sepsis was induced in male Wistar rats by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide (n = 16), whereas control animals (n = 7) were injected with vehicle (NaCl 0.9%). Echocardiography in LPS-injected animals (n = 8) demonstrated systolic and diastolic cardiac dysfunction. 123I-MIBG was injected 1 hour after LPS or vehicle administration (n = 8 and 7, respectively), and in vivo SPECT imaging was performed early and late (20 and 180 minutes) after tracer injection prior to animal euthanasia and ex vivo assessment of 123I-MIBG biodistribution. Global and 17-segment SPECT image analysis indicated that early 123I-MIBG activity was not affected by LPS treatment, whereas late cardiac tracer activity was significantly decreased in LPS-treated animals. Consequently, the cardiac washout of 123I-MIBG was significantly higher in LPS-treated (63.3% ± 4.0%) than that in control animals (56.7% ± 5.8%) (P < .05). CONCLUSION:Sepsis-induced modifications in cardiac sympathetic nervous system activity were evidenced by noninvasive in vivo 123I-MIBG SPECT imaging.