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Objective: During off-pump coronary artery bypass (OPCAB) surgery, the heart is subjected to ischemia and reperfusion. The authors hypothesized that the volatile anesthetics are as effective as ischemic preconditioning (IPC) in preserving myocardial function during off-pump cardiac surgery, and this effect is because of multiple mechanisms of action. Therefore, the effects of enflurane with its calcium inhibition and antioxidative properties were compared with mechanical IPC in preserving myocardial cellular markers. Design: A prospective, randomized, controlled, and partly blinded study. Setting: A tertiary care university hospital. Participants: Twenty-five patients undergoing elective single-graft OPCAB surgery. Interventions: Patients were randomized into 3 groups: (1) control (n = 8), (2) a single 5-minute ischemia/reperfusion interval of IPC before coronary occlusion (n = 9), and (3) 1.6% enflurane anesthesia 15 minutes before and during graft attachment (n = 8). Arterial and coronary sinus venous blood were analyzed for biochemical indices of ischemia and hydroxyl radical generation. Measurements and Main Results: Although the hemodynamic changes were small, myocardial lactate production in the control group increased by 120%, whereas in the enflurane group it decreased significantly (p < 0.01) compared with the control and IPC groups. Oxygen utilization in the control group was 44% higher (p < 0.03), and there was also a larger release of the hydroxyl radical-dependent adduct 2,3-dihydroxybenzoic acid (225% increase, p < 0.05) compared with both study groups. During reperfusion, initial anterior wall hypokinesis by TEE was observed, with slow recovery during reperfusion compared with early recovery in both study groups. Conclusions: Coronary occlusion during OPCAB surgery results in increased production of ischemia-related metabolic products. The application of methods such as IPC or volatile anesthesia appears to reduce the metabolic deficit, free-radical production, and physiologic changes. [Copyright &y& Elsevier]

: BackgroundThe purpose of this study was to determine whether the damaging effects of cardiopulmonary bypass, ischemia, and reperfusion would be more pronounced in patients with glucose-6-phosphate dehydrogenase deficiency undergoing cardiac surgery.: MethodsForty-two patients with glucose-6-phosphate dehydrogenase deficiency underwent open heart procedures using cardiopulmonary bypass. This group was matched with a control group of identical size for comparison of operative course and postoperative outcome. The perioperative variables were compared between the two groups using univariate and multivariate analysis.: ResultsThe duration of ventilation after the operation was significantly longer in the glucose-6-phosphate dehydrogenase–deficient group (13.7 ± 7.6 hours versus 7.7 ± 2.8 hours; p < 0.0001). Minimal value of arterial oxygen tension was lower in patients with glucose-6-phosphate dehydrogenase deficiency (66 ± 12 mm Hg versus 85 ± 14 mm Hg; p < 0.0001), and more cases of hypoxia (arterial oxygen tension < 60 mm Hg) were found in this group (11 versus 1; p = 0.001). Compared with the control group, patients with glucose-6-phosphate dehydrogenase deficiency had significantly elevated hemolytic indices expressed by bilirubin levels (26 ± 10 mmol/L versus 17 ± 6.7 mmol/L; p < 0.0001) and lactic dehydrogenase levels (970 ± 496 U/L versus 505 ± 195 U/L; p < 0.0001). They also required significantly more blood transfusion perioperatively (1.9 ± 1.4 packed cell units/patient versus 0.8 ± 1.0 packed cell units/patient; p = 0.0001).: ConclusionsPatients with glucose-6-phosphate dehydrogenase deficiency who are undergoing cardiac surgery may have a more complicated course with a longer ventilation time, more hypoxia, increased hemolysis, and a need for more blood transfusion. Because this difference may be caused by subnormal free radical deactivation, strategies that minimize bypass in general and free radicals specifically may be beneficial. [Copyright &y& Elsevier]

This is the first report of successful cryopreservation and transplantation of an intact ovary in a large animal (sheep). Three of eight transplanted sheep had resumed hormonal cyclicity. [Copyright &y& Elsevier]

Abstract: Background:: Cytocbrome P450 (CYP) 2C9 polymorphism affects the warfarin dosage requirement in stable outpatients. However, it is not known whether the CYP2C9 genotype contributes to the variability in warfarin dosage in the presence of drug-disease and drug-drug interactions. Objective:: The aim of this study was to examine the effects of CYP2C9 genetic polymorphism on warfarm dosage requirements in patients with severe comorbid conditions and those treated with medications that potentially interact with warfarin. Methods:: This prospective, observational study was conducted at Hadassah University Hospital, Jerusalem, Israel. Data from consecutive patients treated with warfarin for at least 3 months and admitted to the internal medicine ward were eligible for inclusion. Clinical data, international normalized ratio (INR), and warfarin dosage were recorded from medical records. The CYP2C9 genotype was determined using polymerase chain reaction restriction fragment length polymorphism, and plasma concentrations of (S)- and (R)-warfarin were determined by high-performance liquid chromatography using chiral methods. Results:: One hundred nineteen subjects (52% women) were studied. Mean age was 65.8 years (95% CI, 63.1–68.4), and weight was 74.9 kg (95% CI, 72.1–77.7). The mean warfarin dosage was 33% lower in patients with the CYP2C9-*1/*3 genotype (mean [SEM], 0.045 [0.006] mg/kg · d−1) compared with the CYP2C9-*1/*1 genotype (0.067 [0.004] mg/kg · d−1) (P = 0.008); an intermediate value was found for the CYP2C9-*1/*2 genotype (0.062 [0.008] mg/kg · d−1). However, despite the lower dosage, INR was significantly higher in patients with the *1/*3 genotype (mean [95% CI], 3.29 [2.44-4.14]) (n = 18) compared with the *1/*1 genotype (2.52 [2.34-2.71]) (n = 64) (P = 0.029). In addition to genotype, older age, congestive heart failure (CHF), and treatment with antibiotics were associated with lower warfarin dosages, whereas treatment with drug-metabolism inducers was associated with higher warfarin dosages. In addition, the ratios of (S)- to (R)-warfarin concentrations were significantly higher in patients with *1/*3 compared with those in patients with the *1/*1 genotype. Conclusions:: In this study population of patients with severe comorbid conditions and those treated with medications that potentially interact with warfarm, CYP2C9 *1/*3 genotype, older age, CHF, and the use of antibiotics were associated with lower warfarm dosage requirements. The CYP2C9*1/*3 genotype, compared with CYP2C9 *1/*1, was associated with 33% lower mean warfarin dosage requirements and higher INR values, which were higher than the upper therapeutic range of INR (ie, 3). Genetic CYP2C9 polymorphism contributed to the variability in warfarm dosage requirements in the presence of drug-disease and drug-drug interactions. [Copyright &y& Elsevier]