Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction

Objective: To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction. Design: Prospective, randomized, placebo-controlled, double-blind, clinical study. Setting: Cardiothoracic anesthesia department at a university hospital. Participants: Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass, with a preoperatively elevated serum creatinine level (n = 24). Interventions: Randomized infusions of diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7 pg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes before induction of anesthesia and continued for 24 hours. Measurements and Main Results: Median plasma concentrations of diltiazem (DTZ group) were 79 mug/L before cardiopulmonary bypass, 67 mug/L at the end of cardiopulmonary bypass, and 164 mug/L at 24 hours postoperatively. Serum creatinine levels; on postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between groups. lohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery (median, 51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-β-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively. Conclusion: Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the limits of this study, the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage resulting from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines