Investigating the role of ischemia vs. elevated hydrostatic pressure associated with acute obstructive uropathy.
Obstructive uropathy can cause irreversible renal damage. It has been hypothesized that elevated hydrostatic pressure within renal tubules and/or renal ischemia contributes to cellular injury following obstruction. However, these assaults are essentially impossible to isolate in vivo. Therefore, we developed a novel pressure system to evaluate the isolated and coordinated effects of elevated hydrostatic pressure and ischemic insults on renal cells in vitro. Cells were subjected to: (1) elevated hydrostatic pressure (80 cm H(2)O); (2) ischemic insults (hypoxia (0% O(2)), hypercapnia (20% CO(2)), and 0 mM glucose media); and (3) elevated pressure + ischemic insults. Cellular responses including cell density, lactate dehydrogenase (LDH) release, and intracellular LDH (LDH(i)), were recorded after 24 h of insult and following recovery. Data were analyzed to assess the primary effects of ischemic insults and elevated pressure. Unlike pressure, ischemic insults exerted a primary effect on nearly all response measurements. We also evaluated the data for insult interactions and identified significant interactions between ischemic insults and pressure. Altogether, findings indicate that pressure may sub-lethally effect cells and alter cellular metabolism (LDH(i)) and membrane properties. Results suggest that renal ischemia may be the primary, but not the sole, cause of cellular injury induced by obstructive uropathy.
Russ
Alissa L
AL
Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Dr., West Lafayette, IN 47907-1791, USA. alissa.russ@va.gov
Dadarlat
Iunia A
IA
Haberstroh
Karen M
KM
Rundell
Ann E
AE
D000208:Acute Disease; D000818:Animals; D019149:Bioreactors; D001783:Blood Flow Velocity; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002478:Cells, Cultured; D006801:Humans; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology*; D011312:Pressure; D013552:Swine; D014524:Urethral Obstruction / Q000150:complications / Q000503:physiopathology*