The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping.

BACKGROUND: Propofol has been reported to provide protection against ischemia-reperfusion injury. Nuclear transcription factor kappa B (NFkappaB) plays a key role in oxidative stress and the inflammatory response during ischemia-reperfusion. We compared the effect of propofol with sevoflurane on kidney NFkappaB expression and systemic inflammatory responses induced by aortic clamping. METHODS: Twenty piglets were divided into four groups: sham surgery group with propofol (group SP, n = 5); sham group with sevoflurane (group SS, n = 5); and suprarenal clamping for 30 min with aorta-aortic bypass under propofol (group CP, n = 5) or sevoflurane (group CS, n = 5) anesthesia. Propofol was administered at 4 mg x kg(-1) x h(-1) i.v. and sevoflurane given at 1.5% inspiratory concentration. Peripheral blood and kidney biopsies were taken before the start of surgery, 15 min after unclamping the aorta, 24, 48, 72 h, and 7 days after surgery. Plasma creatinine, myeloperoxidase, tumor necrosis factor-alpha, interleukin 1-beta; and kidney superoxide anion and superoxidase dismutase were measured. The expression of inducible nitric oxide synthase and renal tissue NFkappaB was measured using Western blotting. RESULTS: Compared with the CS group, animals in the CP group had lower concentrations of myeloperoxidase, tumor necrosis factor-alpha, interleukin 1beta, superoxide anion, superoxidase dismutase (P < 0.05) from 24 to 72 h after surgery and diminished NFkappaB expression and inducible nitric oxide synthase activity (P < 0.05) at 48 and 72 h after surgery, respectively. CONCLUSIONS: Compared with sevoflurane, propofol administration during suprarenal aortic clamping and unclamping led to modulation of markers of inflammation and decreased NFkappaB expression.

Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery.

PURPOSE: A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in an in vivo experimental model of aortic surgery in comparison with sevoflurane. METHODS: Twenty young male piglets were anesthetized with either propofol 4 mg.kg(-1).hr(-1) (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, and interferon-gamma; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed. RESULTS: In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, interferon-gamma, superoxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05). CONCLUSION: In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting.

Exogenous nitric oxide modulates the systemic inflammatory response and improves kidney function after risk-situation abdominal aortic surgery.

OBJECTIVE: Renal impairment is a very frequent complication of aortic surgery requiring prolonged suprarenal clamping, especially if it is associated with previous hemorrhage. The aim of this study was to assess the beneficial effect of the administration of a nitric oxide (NO) donor on renal function through a modulation of the systemic inflammatory response in a model of abdominal aortic surgery. METHODS: Twenty-five minipigs were divided into five groups. Under anesthesia, the animals were subjected to suprarenal aortic-iliac clamping (for 30 minutes) and bypass with a Dacron-collagen prosthetic graft impregnated in rifampicin, with or without associated hemorrhage (40% of total blood volume). Prophylaxis with cefazolin was implemented. The five groups were (1) the sham group (only aortic dissection), (2) the clamping and bypass (C) group, (3) hemorrhage preclamping and bypass (H+C) group, (4) the same as group C but with the administration of the NO donor molsidomine (4 mg/kg intravenously) (C+NO group), (5) the same as the H+C group but with the administration of the NO donor molsidomine (4 mg/kg intravenously) (H+C+NO group). The following were determined: (1) kidney function (serum creatinine), (2) serum cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-10 [IL-10]); (3) neutrophil infiltration (myeloperoxidase [MPO]) in the kidney, (4) oxygen free radicals (superoxide anion [SOA] and superoxide dismutase [SOD]) in the kidney, (5) serum nitrites, (6) soluble and kidney tissue cell adhesion molecule (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]), (7) inducible nitric oxide synthase (iNOS) in the kidney, and (8) nuclear factor-kappaB (NF-kappaB) in the kidney. Determinations were made during ischemia at 15 minutes post-reperfusion; at 24, 48, and 72 hours; and on day 7. RESULTS: The different insults used in the experimental model led to deterioration in kidney function and an increase in the systemic (and renal) inflammatory response at all levels investigated. Treatment with an NO donor, both with and without associated hemorrhage, reduced the inflammatory response at the systemic (TNF-alpha and IL-10) and kidney (MPO, SOA, and SOD) levels, normalizing kidney function. Likewise, exogenous administration of NO improved the excessive production of NO (nitrites) via iNOS. This was also reflected in a reduction in CAMs and of NF-kappaB expression. The hypotension induced by molsidomine was transitory and did not elicit hemodynamic repercussions. CONCLUSION: In our experimental model, prophylactic treatment with the NO donor molsidomine regulates the systemic inflammatory response and minimizes damage at the kidney level. Clinical Relevance The importance of this article resides in the fact that an experimental study that clarifies the effect of the donors of NO under circumstances as similar as possible to those of the human clinic, such as aortic surgery under hypovolemic shock (ruptured aortic aneurysm) have been little studied, most of these studies being performed in rodents without bypass. Using a model with one or two simultaneous insults (aortic clamping with/without previous hemorrhage) that is very similar to the human clinical situation (abdominal aortic rupture), we confirm the findings of previous work related to the beneficial effects of NO donors.