Biomedical subjects

Francisco J García-Criado

Publications and source records attributed to Francisco J García-Criado.

7 recordsLinked to original sources

PubMed2006

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.

Anesthetics, Inhalation↗

PubMed2006

Bacterial translocation as a source of Dacron-graft contamination in experimental aortic operation: the importance of controlling SIRS.

BACKGROUND: Several experimental studies have shown the beneficial effects of nitric oxide (NO) in the modulation of the systemic inflammatory response syndrome (SIRS). Nitric oxide is involved in and affects almost all stages in the development of inflammation. We have attempted to ascertain whether the nitric oxide donor molsidomine prevents aortic graft contamination through control of the SIRS and a decrease in bacterial translocation (BT). METHODS: Twenty-four mini-pigs were divided into 4 groups. The animals were subjected to suprarenal aortic/iliac cross-clamping (for 30 minutes) and by-pass with a Dacron-collagen prosthetic graft impregnated in rifampicin. Groups: 1) sham (aortic dissection alone); 2) cross-clamping and bypass; 3) hemorrhage of 40% of total blood volume before cross-clamping and by-pass; and 4) the same as in group 3 but also including the administration of the NO donor molsidomine (4 mg/kg) 5 minutes before cross-clamping. VARIABLES: 1) bacteriology of mesenteric lymph nodes (MLN), kidney, blood, and prosthesis; 2) serum TNF-alpha (ELISA); and 3) iNOS expression in kidney and liver (Western blot). RESULTS: Aortic cross-clamping with or without hemorrhage was associated with BT in 80% and 100% of the animals, respectively. About 86% of the bacteria isolated in the graft were also present in MLN. This contamination coincided with an increase in TNF-alpha and with a greater expression of iNOS. Molsidomine administration decreased TNF-alpha and iNOS, decreased BT (from 100% to 20% of the animals), and decreased graft contamination (from 83% to 20%). CONCLUSIONS: The present model induces high levels of BT and SIRS, both acted as sources of contamination for the implanted Dacron graft. Molsidomine administration decreased the presence of bacteria in the graft by controlling BT and modulating SIRS.

Animals↗

PubMed2005

Exogenous nitric oxide can control SIRS and downregulate NFkappaB.

BACKGROUND: Nitric oxide (NO) participates in inflammation and affects almost all steps of its development. Several experimental studies have unveiled the beneficial effects of NO through modulation of the Systemic Inflammatory Response Syndrome (SIRS). In this sense, in the present work we attempted to evaluate the beneficial effects of exogenous NO and its levels of action (biochemical and cellular) in a model of SIRS induced by two sequential insults. MATERIALS AND METHODS: Dacron graft implantation (first insult) and subsequent administration of Zymosan A (second insult) in Wistar rats. The animals were divided into four groups: 1) No manipulation (Basal); 2) Laparotomy (L) + mineral oil (Sham); 3) L + Graft-Zymosan (GZ) (Control); and 4) L + GZ + NO (Assay). Determinations: Survival, TNF-alpha, SOA, ICAM-1, and NFkappaB. RESULTS: The model established (Control) induced a mortality rate of 20%. Also, it significantly increased the levels of TNF-alpha (P <0.001) and SOA (P <0.01), ICAM-1 expression, and NFkappaB levels (P <0.05). Treatment with NO reduced mortality to 0%, significantly decreasing TNF-alpha (P <0.001) and SOA (P <0.01) levels, ICAM-1 expression, and NFkappaB levels (P <0.05). CONCLUSION: The exogenous administration of NO before the two sequential insults controlled SIRS at biochemical level (TNF-alpha, SOA) and at cellular level (transcription) in a lasting manner. The cascade-like interrelationship of both levels and the study design do not allow us the pinpoint the key to its modulation.

Animals↗

PubMed2005

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.

Animals↗

PubMed2003

Comparative study of the expression of proteins involved in the cell cycle in renal secondary hyperparathyroidism.

BACKGROUND: In renal hyperparathyroidism, parathyroid cell proliferation seems to play a key role in the progression of the disease. Therefore, G1/S transition, a main cell cycle regulatory step, could be deregulated in these patients. METHODS: One hundred and one parathyroid glands, taken from parathyroidectomies performed on 41 patients on hemodialysis (HD), and 15 glands, taken from 7 patients with post-transplantation persistent hyperparathyroidism (HPT), were studied. Twelve normal parathyroid (PT) glands were used as the control. Biochemical data, immunohistochemical (IHC) profiles of G1/S transition regulators belonging to the two main pathways (cyclin D1/p16INK4A/pRb and p14ARF/p53/MDM2), and proliferation rate (Ki67) were correlated. RESULTS: All of the other proteins differed from normal IHC profiles in both groups that showed significant higher proliferating rates, decreases in p27KIP1, pRb, and cyclin D1, as well as increases in p16INK4A, p53, MDM2, and p21WAF1 levels, in comparison with normal PT glands, with the exception of cyclin D3. Contrary to patients with HPT who were on hemodialysis, in post-transplantation HPT, consistent correlations between biochemical data and IHC profiles were obtained. CONCLUSION: In both groups IHC profiles of proteins involved in G1/S transition regulation significantly differed from normal PT glands. The results support partial reversion to normal IHC profile in post-transplantation HPT.

Adult↗

PubMed2002

Systemic inflammatory response induced by dacron graft and modulation by antimicrobial agents: experimental study.

BACKGROUND: The purpose of this work was to evaluate the effect that different antimicrobial agents and different forms of administering them would have over a systemic inflammatory response (SIR) induced by an intraperitoneally implanted collagen-coated Dacron graft. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly allocated into six groups of 6 animals each: (I) control, (II) "sham," (III) graft but no antibiotic, (IV) graft plus systemic cefazolin, (V) graft plus locally applied gentamicin, and (VI) graft soaked in rifampicin. After 72 h, mesenteric lymph nodes, liver, kidney, and the implanted graft were sent to the microbiology laboratory and cultured for aerobic and anaerobic organisms in order to evaluate bacterial translocation. Serum cytokines (IL-1beta and TNF-alpha), myeloperoxidase activity in liver and kidney, and superoxide anion and superoxide dismutase activities in liver were also determined to evaluate the level of SIR. RESULTS: Microbiologic and biochemical data indicated that intraperitoneal implantation of a collagen-coated Dacron graft induced a significant (P < 0.05) bacterial translocation and a high inflammatory response, both of which decreased significantly with antibiotic treatment regardless of the means of administration (P < 0.05). CONCLUSIONS: The present experimental model shows that the antibiotics used, in different means of administration, reduce bacterial translocation and behave as modulators of the SIR induced by an intraperitoneal collagen-coated Dacron graft.

Animals↗

PubMedDate not supplied

P- and E-selectin blockade can control bacterial translocation and modulate systemic inflammatory response.

Bacterial translocation is an important phenomenon in clinical medicine and leads to an increase in patient morbidity and mortality by multiple organ failure. The selectin family plays an important role in the pathogenesis of inflammation, causing an increase in leukocyte-endothelium interactions and inducing a greater leukocyte's migration. This study considered the effect of a sulfo derivative of Sialyl-Lewis(X), GM 1998-016, that will block the P- and E-selectins interaction with a ligand, the Sialyl-Lewis(X), valuing the modulation of the systemic inflammatory response and the induced translocation. Seventy-five Wistar male rats were injected intraperitoneally with Zymosan A and treated with different doses of GM 1998-016 according to study groups. Measurements of values of qualitative and quantitative microbiology, neutrophil infiltration (myeloperoxidase), oxygen free radicals (superoxide anion, superoxide dismutase, catalase, and gluthatione peroxidase), and cytokines (tumor necrosis factor-alpha and interleukin-1beta) were taken at different times after Zymosan administration. A significant decrease of bacterial translocation, both local (MLN) and systemic (p < .05), was observed, with a decrease in the neutrophil infiltration (p < .001), the oxygen free radicals production (p < .01) and the studied cytokines (p < .01). In conclusion, GM 1998-016 showed a protective effect in an in vivo experimental model of bacterial translocation, downregulating the inflammatory response and the leukocyte-endothelium interactions.

Animals↗