Aimee Zhang1, Eric J Charles1, Jinyan Xing2, Robert G Sawyer3, Zequan Yang4. 1. Department of Surgery, University of Virginia Health System, Charlottesville, Virginia. 2. Department of Surgery, University of Virginia Health System, Charlottesville, Virginia; Department of Critical Care Medicine, the Affiliated Hospital of Qingdao University, Qingdao, China. 3. Department of Surgery, Western Michigan University, Kalamazoo, Michigan. 4. Department of Surgery, University of Virginia Health System, Charlottesville, Virginia. Electronic address: Zy6b@virginia.edu.
Abstract
BACKGROUND: The spleen is an important contributor to the uncontrolled, excessive release of proinflammatory signals during sepsis that leads to the development of tissue injury and diffuse end-organ dysfunction. Therapeutic pulsed ultrasound (pUS) has been shown to inhibit splenic leukocyte release and reduce cytokine production in other inflammatory disease processes. We hypothesized that pUS treatment inhibits spleen-derived inflammatory responses and increases survival duration in rats with severe intra-abdominal sepsis leading to septic shock. MATERIALS AND METHODS: Rats with intra-abdominal sepsis, induced by cecal ligation and incision, underwent abdominal washout, intra-peritoneal administration of cefazolin, and then either no further treatment (control), splenectomy, or pUS of the spleen. Animals were observed for the primary endpoint of survival duration. RESULTS: Survival curves were significantly different for all groups (P < 0.01). Median survival increased from 9.5 h in control rats to 19.8 h in pUS rats and 35.0 h in splenectomy rats (P < 0.01). At 4 h after cecal ligation and incision, the pUS group had decreased splenic contraction and leukocyte count (P = 0.03) compared with control, indicating reduced exodus of splenic leukocytes. In addition, elevation in plasma TNF-α and MCP-1 was significantly attenuated in the pUS group (P < 0.05 versus control). Splenic β2 adrenergic receptor levels and phosphorylated Akt were significantly more elevated in the pUS group (P < 0.01 versus control). CONCLUSIONS: pUS significantly prolonged the survival duration of rats with severe intra-abdominal sepsis. This treatment may be an effective, noninvasive therapy that dampens detrimental immune responses during septic shock by activating β2 adrenergic receptor-Akt phosphorylation in the cholinergic anti-inflammatory pathway.
BACKGROUND: The spleen is an important contributor to the uncontrolled, excessive release of proinflammatory signals during sepsis that leads to the development of tissue injury and diffuse end-organ dysfunction. Therapeutic pulsed ultrasound (pUS) has been shown to inhibit splenic leukocyte release and reduce cytokine production in other inflammatory disease processes. We hypothesized that pUS treatment inhibits spleen-derived inflammatory responses and increases survival duration in rats with severe intra-abdominal sepsis leading to septic shock. MATERIALS AND METHODS:Rats with intra-abdominal sepsis, induced by cecal ligation and incision, underwent abdominal washout, intra-peritoneal administration of cefazolin, and then either no further treatment (control), splenectomy, or pUS of the spleen. Animals were observed for the primary endpoint of survival duration. RESULTS: Survival curves were significantly different for all groups (P < 0.01). Median survival increased from 9.5 h in control rats to 19.8 h in pUS rats and 35.0 h in splenectomy rats (P < 0.01). At 4 h after cecal ligation and incision, the pUS group had decreased splenic contraction and leukocyte count (P = 0.03) compared with control, indicating reduced exodus of splenic leukocytes. In addition, elevation in plasma TNF-α and MCP-1 was significantly attenuated in the pUS group (P < 0.05 versus control). Splenic β2 adrenergic receptor levels and phosphorylated Akt were significantly more elevated in the pUS group (P < 0.01 versus control). CONCLUSIONS: pUS significantly prolonged the survival duration of rats with severe intra-abdominal sepsis. This treatment may be an effective, noninvasive therapy that dampens detrimental immune responses during septic shock by activating β2 adrenergic receptor-Akt phosphorylation in the cholinergic anti-inflammatory pathway.
Authors: Jonathan Cohen; Jean-Louis Vincent; Neill K J Adhikari; Flavia R Machado; Derek C Angus; Thierry Calandra; Katia Jaton; Stefano Giulieri; Julie Delaloye; Steven Opal; Kevin Tracey; Tom van der Poll; Eric Pelfrene Journal: Lancet Infect Dis Date: 2015-04-19 Impact factor: 25.071
Authors: Rhett N Willis; Eric J Charles; Christopher A Guidry; Mahendra D Chordia; Stephen W Davies; Zequan Yang; Robert G Sawyer Journal: J Surg Res Date: 2017-04-07 Impact factor: 2.192
Authors: Andrew Rhodes; Laura E Evans; Waleed Alhazzani; Mitchell M Levy; Massimo Antonelli; Ricard Ferrer; Anand Kumar; Jonathan E Sevransky; Charles L Sprung; Mark E Nunnally; Bram Rochwerg; Gordon D Rubenfeld; Derek C Angus; Djillali Annane; Richard J Beale; Geoffrey J Bellinghan; Gordon R Bernard; Jean-Daniel Chiche; Craig Coopersmith; Daniel P De Backer; Craig J French; Seitaro Fujishima; Herwig Gerlach; Jorge Luis Hidalgo; Steven M Hollenberg; Alan E Jones; Dilip R Karnad; Ruth M Kleinpell; Younsuk Koh; Thiago Costa Lisboa; Flavia R Machado; John J Marini; John C Marshall; John E Mazuski; Lauralyn A McIntyre; Anthony S McLean; Sangeeta Mehta; Rui P Moreno; John Myburgh; Paolo Navalesi; Osamu Nishida; Tiffany M Osborn; Anders Perner; Colleen M Plunkett; Marco Ranieri; Christa A Schorr; Maureen A Seckel; Christopher W Seymour; Lisa Shieh; Khalid A Shukri; Steven Q Simpson; Mervyn Singer; B Taylor Thompson; Sean R Townsend; Thomas Van der Poll; Jean-Louis Vincent; W Joost Wiersinga; Janice L Zimmerman; R Phillip Dellinger Journal: Intensive Care Med Date: 2017-01-18 Impact factor: 17.440
Authors: Jared M Huston; Mahendar Ochani; Mauricio Rosas-Ballina; Hong Liao; Kanta Ochani; Valentin A Pavlov; Margot Gallowitsch-Puerta; Mala Ashok; Christopher J Czura; Brian Foxwell; Kevin J Tracey; Luis Ulloa Journal: J Exp Med Date: 2006-06-19 Impact factor: 14.307