Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats

BACKGROUND: Our prior study showed that resveratrol could suppress infarct volume and exert neuroprotective effect on rats subjected to focal cerebral ischemia (FCI) injury. Recently, it has been reported in some literature that resveratrol protects the spinal cord, kidney, and heart from ischemia-reperfusion injury through upregulation of nitric oxide (NO). Therefore, this study was designed to investigate the role of nitric oxide on the neuroprotective mechanisms of resveratrol on rats after FCI injury. METHODS: The FCI injury was induced by the middle cerebral artery (MCA) occlusion for 1 hour and then a 24-hour reperfusion followed in the anesthetized Long-Evans rats. Resveratrol was intravenously injected after 1 hour MCA occlusion. RESULTS: Treatment of resveratrol (0.1 and 1 microg/kg) decreased the lactate dehydrogenase (LDH) in plasma and malondialdehyde (MDA) in FCI injury brain tissue, whereas the level of NO in plasma was increased. In addition, resveratrol downregulated protein and mRNA expression of inducible nitric oxide synthase (iNOS), and upregulated protein and mRNA expression of endothelial nitric oxide synthase (eNOS), while the expression of protein and mRNA of neuronal nitric oxide synthase (nNOS) was unchanged. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, the nonselective NOS inhibitor) or L-N(5)-(1-iminoethyl)-ornithine (L-NIO, the eNOS selective inhibitor) completely blocked the effect of resveratrol in decreasing infarction volumes. CONCLUSIONS: This study demonstrated the important role of NO in the neuroprotective effect of resveratrol in FCI injury.     

Beating heart aortic valve replacement after previous coronary artery bypass surgery with a patent internal mammary artery graft

Re-sternotomy for aortic valve replacement (AVR) in patients with a patent internal mammary artery (IMA) graft may present a challenging surgical problem. Thus, strategies to prevent IMA graft injury include avoiding its dissection and leaving the graft open. However, when aortic cross clamping and cardioplegia are required, this approach may be associated with cardioplegia washout, suboptimal myocardial protection, and anterior myocardial wall injury. We herein describe an alternative technique for AVR on the beating heart in 4 patients with patent IMA grafts. The IMA was left unclamped and continuous retrograde coronary sinus perfusion (RCSP) was administered. Additional simultaneous antegrade venous bypass graft perfusion was established according to the extent of native coronary artery disease as well as patency and level of aortic proximal anastomoses. Using additional coronary ostia backflow control, the aortic valve was successfully replaced on the beating heart in all four cases without perivalvular leak. Postoperatively, low creatine kinase-MB fraction levels and preserved or improved ventricular function suggested very good myocardial protection. No myocardial infarction occurred in any patient. In our experience, aortic valve replacement on the beating heart using simultaneous antegrade-retrograde blood perfusion is a safe and effective method in this challenging subset of patients to prevent myocardial injury and to minimize the risk of patent IMA injury.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

The superficial inferior epigastric artery fascia flap in the rabbit

In reconstructive surgery, fascial flaps provide thin, pliable tissue for mucosal closure or serve as a highly vascularized support for skin grafts. Their angiogenic potential is used for experimental neovascularization of avascular tissue grafts. However, most fascial flaps in animal surgery have random pattern design with short reach. As a pilot study for a femur revascularization project in rabbits, a new axial fascial flap is described based on the superficial inferior epigastric (SIE) vessels. They were used in this species previously only as ligated bundles or in fasciocutaneous flaps. The topographical anatomy of the SIE-vessels, lower abdominal fascia, and panniculus carnosus are outlined. The angiogenic capabilities are demonstrated microangiographically by abundant vessel formation in a femur allograft. Used in a pedicled fashion, this flap is an alternative to femoral and saphenous vessels for prefabrication or revascularization procedures in the lower abdomen, genital area, and thigh. Distant recipient sites seem possible with microsurgical transfer.     

Host-derived angiogenesis maintains bone blood flow after withdrawal of immunosuppression

A novel method of living bone allotransplantation combining microvascular repair of the nutrient circulation, implantation of host-derived arteriovenous (AV) bundles, and short-term immunosuppression is described. We hypothesized that neoangiogenesis from the implanted vessels would maintain graft viability and circulation after withdrawal of FK506 (Tacrolimus) immunosuppression. Vascularized femoral transplantation was performed between DA and PVG rats. In addition to microsurgical pedicle anastomoses, a saphenous AV bundle from the recipient animal was implanted in the medullary space. Ninety-seven rats were randomly allocated to groups differing in immunosuppression and AV bundle patency. Implanted vessels significantly improved capillary density and bone blood flow in nonimmunosuppressed and immmunosuppressed groups, respectively. A lower incidence of spontaneous AV bundle thrombosis was found with Tacrolimus treatment. More viable osteocytes were seen at 4 weeks when the AV bundle was patent. Further investigations may confirm host-derived neoangiogenesis as an alternative to tolerance induction or immunosuppression in bone allotransplantation.     

Effect of body mass index on the survival benefit of liver transplantation.

Obese patients are at higher risk for morbidity and mortality after liver transplantation (LT) than nonobese recipients. However, there are no reports assessing the survival benefit of LT according to recipient body mass index (BMI). A retrospective cohort of liver transplant candidates who were initially wait-listed between September 2001 and December 2004 was identified in the Scientific Registry of Transplant Recipients database. Adjusted Cox regression models were fitted to assess the association between BMI and liver transplant survival benefit (posttransplantation vs. waiting list mortality). During the study period, 25,647 patients were placed on the waiting list. Of these, 4,488 (17%) underwent LT by December 31, 2004. At wait-listing and transplantation, similar proportions were morbidly obese (BMI>or=40; 3.8% vs. 3.4%, respectively) and underweight (BMI<20; 4.5% vs. 4.0%, respectively). Underweight patients experienced a significantly higher covariate-adjusted risk of death on the waiting list (hazard ratio [HR]=1.61; P<0.0001) compared to normal weight candidates (BMI 20 to <25), but underweight recipients had a similar risk of posttransplantation death (HR=1.28; P=0.15) compared to recipients of normal weight. In conclusion, compared to patients on the waiting list with a similar BMI, all subgroups of liver transplant recipients demonstrated a significant (P<0.0001) survival benefit, including morbidly obese and underweight recipients. Our results suggest that high or low recipient BMI should not be a contraindication for LT.     

Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients

BACKGROUND: Elderly patients (ages 70 yr and older) are among the fastest-growing group starting renal-replacement therapy in the United States. The outcomes of elderly patients who receive a kidney transplant have not been well studied compared with those of their peers on the waiting list. METHODS: Using the Scientific Registry of Transplant Recipients, we analyzed data from 5667 elderly renal transplant candidates who initially were wait-listed from January 1, 1990 to December 31, 2004. Of these candidates, 2078 received a deceased donor transplant, and 360 received a living donor transplant by 31 December 2005. Time-to-death was studied using Cox regression models with transplant as a time-dependent covariate. Mortality hazard ratios (RRs) of transplant versus waiting list were adjusted for recipient age, sex, race, ethnicity, blood type, panel reactive antibody, year of placement on the waiting list, dialysis modality, comorbidities, donation service area, and time from first dialysis to first placement on the waiting list. RESULTS: Elderly transplant recipients had a 41% lower overall risk of death compared with wait-listed candidates (RR=0.59; P<0.0001). Recipients of nonstandard, that is, expanded criteria donor, kidneys also had a significantly lower mortality risk (RR=0.75; P<0.0001). Elderly patients with diabetes and those with hypertension as a cause of end-stage renal disease also experienced a large benefit. CONCLUSIONS: Transplantation offers a significant reduction in mortality compared with dialysis in the wait-listed elderly population with end-stage renal disease.     

Can a surgeon predict the risk of postoperative hypoparathyroidism during thyroid surgery? A prospective study on self-assessment by experts

Background

Thyroid surgery can cause postoperative hypocalcemia (POH) and permanent hypoparathyroidism (PEH). Surgeons implicitly assess the risk and adapt their surgical strategy accordingly.

Methods

The outcome of this intraoperative decision-making process (the surgeons' ability to predict the risk of POH and PEH on a numerical rating scale and their actual incidence) was studied prospectively in 2,558 consecutive thyroid operations.

Results

POH and PEH occurred in 723 and 64 patients, respectively. In multivariate analysis, the surgeons' risk assessment score was an independent predictive factor for both complications (P < .05). Surgeons' differed significantly (P = .015) in their rates of POH but not of PEH (P = .062). Six and 3 (of 9) surgeons correctly predicted an increased risk of PEH and POH (adjusted odds ratios 1.67 to 2.21 and 1.47 to 12.73), respectively.

Conclusion

The risk for hypoparathyroidism can be estimated, but surgeons differ substantially in this ability and in the extent to which this implicit knowledge is translated into lower complication rates.