Effects of glucocorticoids on lung glutamine and alanine metabolism

The role of the glucocorticoid hormones as possible mediators of the accelerated lung glutamine and alanine release that occurs during critical illness was investigated. Studies were done in adult rats receiving dexamethasone (0.6 mg intramuscularly/100 gm body weight/day for 2 consecutive days; n = 24) or saline solution (controls; n = 20). Measurements were made in the postabsorptive state and amino acid flux was calculated by multiplying pulmonary blood flow by the right ventricular-arterial concentration difference for glutamine and alanine. Lung glutamine release was 703 +/- 184 nmol/100 gm body weight/min in control rats. This release rate doubled in the dexamethasone-treated rats (1476 +/- 256; p less than 0.05). The activity of the glutamine synthetase enzyme increased by 33% in the dexamethasone-treated animals and there was a 50% decrease in lung glutamine content (p less than 0.01). Likewise, dexamethasone accelerated the release of alanine by the lungs twofold (559 +/- 173 nmol/100 gm body weight/min in controls vs 1113 +/- 184 nmol/100 gm body weight/min in dexamethasone-treated rats; p less than 0.05). The increased release of both amino acids was caused by a significant increase in the concentration difference across the lungs and not a change in pulmonary blood flow. Glucocorticoids appear to be key mediators of the accelerated lung amino acid release that characterizes catabolic diseases.     

The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced systemic inflammatory response.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations. METHODS: Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight: group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-alpha were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points. RESULTS: No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively reduced the increase in TNF-alpha and IL-6 secretion (P<0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10 mg/kg). CONCLUSIONS: The results indicate that a single low-dose of methylprednisolone (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp.     

Cyclosporine interactions with miconazole and other azole-antimycotics: a case report and review of the literature.

Several antimicrobial drugs have been shown to pharmacokinetically interact with cyclosporine. On two separate occasions, we observed increases in cyclosporine plasma concentrations during concomitant miconazole therapy in a heart transplant patient with an infection secondary to Pseudallescheria boydii. To our knowledge, no interaction between cyclosporine and miconazole has previously been reported. In addition, drug interactions were observed between cyclosporine and ketoconazole and possibly between cyclosporine and SCH 39304, an investigational azole-antifungal agent. No interaction was noted between cyclosporine and fluconazole. In general, clinicians should anticipate drug interactions between cyclosporine and azole-antimycotic agents.     

The CarboMedics Prosthetic Heart Valve in the Mitral Position: Results of the Multicenter International Trial

A bstract Isolated mitral valve replacement using the CarboMedics prosthetic mitral valve (CarboMedics, Inc., Austin, TX) was studied in 13 centers in the United States, Canada, and Scandinavia between 1987 and 1993 in 428 patients with a mean age of 57 ± 14 years. Actuarial survivals at 1, 2, and 5 years were 88.2% and 75.8%. Freedom from events at 5 years were 94.8% for major thromboembolism, 96.6% for thrombosis, and 96.7% for endocarditis. Linearized morbidity rates (events per 100 patient years) for events at > 30 days postoperatively were .51 thrombosis, 1.1 major thromboembolism, and .37 endocarditis. These results at early to mid-term compare favorably with the first generation bileaflet valve.