A perfluorocarbon emulsion prime additive improves the electroencephalogram and cerebral blood flow at the initiation of cardiopulmonary bypass

Depression in electroencephalogram (EEG) has been documented clinically and is reproducible in swine at the initiation of cardiopulmonary bypass (CPB) utilizing a crystalloid prime. The physiological cause of this transient alteration in electrical brain activity appears to be associated with the transient drop in arterial pressure. The etiology is unknown but may be attributable to the bolus of the crystalloid prime or micro emboli, either air or fibrin-platelet. Thirteen swine (17-26 kg) were anesthetized and received 4 mg/kg dexamethasone, and following a tracheotomy were ventilated with halothane in 100% O2. Surgical preparation included: sternotomy and preparation for right atrial-aortic CPB. The CPB circuit consisted of a hollow fiber membrane oxygenator, a hard-shell venous reservoir, a roller pump, and PVC tubing. The circuit was randomly primed with either 1200 ml Plasmalyte-A or 10 ml/kg perfluorocarbon emulsion (PFE) and Plasmalyte-A to total 1200 ml. The animals were monitored continuously for systemic hemodynamics and electrocardiogram, and cerebral monitoring included blood flow and bitemporal EEG. Arterial blood gases were measured and PaCO2 was kept between 30-45 mmHg both before and during CPB. Cerebral blood flow (CBF) was measured pre-CPB and at 10 minutes after initiation of CPB. Bitemporal computerized EEG was analyzed every 60 seconds. Total power of each hemisphere, power in frequency bands, and spectral edge were recorded. All animals demonstrated a relative decrease in EEG total power at the onset of CPB. Animals that received PFE demonstrated a more stable arterial blood pressure, an increased CBF, and a lesser decrease and an earlier recovery of the EEG power.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis

Naegleria fowleri is responsible for producing a rapidly fatal central nervous system infection known as primary amebic meningoencephalitis (PAM). To date, amphotericin B, an antifungal agent, is the only agent with established clinical efficacy in the treatment of PAM. However, amphotericin B is not always successful in treating PAM and is associated with severe adverse effects. We previously found azithromycin to be more effective than amphotericin B in a mouse model of PAM. We therefore investigated the combination of amphotericin B and azithromycin in vitro and in a mouse model of PAM. For the in vitro studies, 50% inhibitory concentrations were calculated for each drug alone and for the drugs in fixed combination ratios of 1:1, 3:1, and 1:3. We found amphotericin B and azithromycin to be synergistic at all three of the fixed combination ratios. In our mouse model of PAM, a combination of amphotericin B (2.5 mg/kg of body weight) and azithromycin (25 mg/kg) protected 100% of the mice, whereas amphotericin B alone (2.5 mg/kg) protected only 27% of mice and azithromycin alone (25 mg/kg) protected 40% of mice. This study indicates that amphotericin B and azithromycin are synergistic against the Lee strain of N. fowleri, suggesting that the combined use of these agents may be beneficial in treating PAM.     

Comparison of bioimpedance versus thermodilution cardiac output during cardiac surgery: evaluation of a second-generation bioimpedance device.

OBJECTIVE: To compare a second-generation thoracic electrical bioimpedance (TEB) hemodynamic monitoring system with the clinically used pulmonary artery catheter thermodilution (TD-PAC) system. DESIGN: Blinded, simultaneous measurements at specified key time points during surgery. SETTING: University teaching hospital cardiac surgical operating rooms. PARTICIPANTS: Forty-seven patients undergoing primary elective coronary artery bypass surgery. INTERVENTIONS: Timed cardiac output measurements by thermodilution and continuous monitoring of bioimpedance were performed. MEASUREMENTS AND MAIN RESULTS: Cardiac index (TEB and TD-PAC) and other hemodynamic parameters were measured at 4 time points: (1) after anesthesia induction, (2) with the mediastinum open, (3) immediately after cardiopulmonary bypass, and (4) at the end of the case. Pearson's correlation and Bland-Altman analysis were carried out. Cardiac index by TEB and TD-PAC had an overall correlation of r = 0.71 (p < 0.0001). The Bland-Altman statistics showed a mean difference of -0.28 L/min/m2 and precision of 0.67 L/min/m2. The best correlation was at time 1, and the lowest correlation was at time 4. Mediastinal opening and cardiopulmonary bypass had little or no effect on the correlation between technologies. CONCLUSION: TEB reporting of cardiac index during coronary artery surgery generally agreed with TD-PAC cardiac index except at the end of the case (time 4).     

Does the Type of Surgery Effect Systemic Response Following Cardiopulmonary Bypass?

BACKGROUND: Clinical studies conducted to elucidate the systemic response to cardiopulmonary bypass (CPB) did not differentiate possible effect of different types of cardiac surgical pathologies and operations on outcomes and have typically combined different procedures. We hypothesized that valve surgery induces more prominent systemic reaction compared to isolated on-pump CABG. METHODS: Twenty-seven patients undergoing primary on-pump CABG (Group 1, n = 14) or valve surgery with or without CABG (Group 2, n = 13) were prospectively enrolled. Heparin-bonded circuits were used in all patients. Cardiotomy suction was only used in Group 2. Clinical and laboratory markers were evaluated. RESULTS: Clinical measurements, including chest tube output, blood transfusion requirement, inotropic support requirement, and duration of ICU stay were not significantly different. Thrombin generation (PF-1.2) was significantly higher in Group 2 (p = 0.001). tPA was also significantly higher in Group 2 at 15 and 60 minutes on CPB (p < 0.01). Group 2 had significantly higher inflammatory response shown by elevation of IL6 (p = 0.005). Neuronal injury markers, S100beta and NSE, were significantly higher at the termination of CPB in Group 2 (p < 0.01). At no point of time course for any marker, Group 1 had significantly higher response compared to Group 2. CONCLUSIONS: Valve surgery induced more prominent systemic response than CABG. The possible explanations include the difference in baseline disease pathophysiology, and/or difference associated with the procedures such as open systems and use of cardiotomy suction. Future clinical studies assessing systemic response to CPB and therapies to blunt these need consider and account for these observed differences.     

Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production

The semi-essential amino acid, l-arginine (l-Arg), is the substrate for endogenous synthesis of nitric oxide, a molecule that is involved in myoblast proliferation and fusion. Since l-Arg supply may limit nitric oxide synthase (NOS) activity in endothelial cells, we examined l-Arg supplementation in differentiating mouse myoblasts and tested the hypothesis that l-Arg exerts direct effects on myoblast fusion via augmentation of endogenous nitric oxide production. C₂C₁₂ myoblasts in differentiation media received one of␣the␣following treatments for 120 h: 1 mM l-Arg, 0.1 mM N-nitro-l-arginine methyl ester (l-NAME), l-Arg + l-NAME, 10 mM l-Lysine, or no supplement (Control). Cultures were fixed and stained with hematoxylin and eosin for microphotometric image analysis of myotube density, nuclear density, and fusion index (% of total nuclei in myotubes). Endogenous production of nitric oxide during the treatment period peaked between 24 and 48 h. l-Arg amplified nitric oxide production between 0 and 24 h and increased myotube density, total nuclei number, and nuclear fusion index. These l-Arg effects were prevented by the NOS inhibitor, l-NAME. Further, l-Lysine, a competitive inhibitor of l-Arg uptake, repressed nitric oxide production and reduced myotube density and fusion index. In summary, l-Arg augments myotube formation and increases nitric oxide production in a process limited by cellular l-Arg uptake.     

Limitation of thrombin generation, platelet activation, and inflammation by elimination of cardiotomy suction in patients undergoing coronary artery bypass grafting treated with heparin-bonded circuits

OBJECTIVE: Reports evaluating the efficacy of heparin-bonded circuits to blunt inflammation, platelet dysfunction, and thrombin generation in response to cardiopulmonary bypass have varied. We hypothesized that this variability may in part be related to the use of cardiotomy suction, which has been demonstrated to reintroduce procoagulant and proinflammatory factors into the systemic circulation during cardiopulmonary bypass. A prospective, randomized study was undertaken to evaluate the specific effects of cardiotomy suction. METHODS: Thirty-six patients undergoing first-time, nonemergency coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to one of three treatment groups: group I, non-heparin-bonded circuits with the use of cardiotomy suction (n = 12); group II, Duraflo II (BCR-3500; Jostra Bentley Corp, Irvine, Calif) heparin-bonded circuits with cardiotomy suction (n = 12); and group III, Duraflo II heparin-bonded circuits without cardiotomy suction (n = 12). Thrombin generation, neutrophil activation (polymorphonuclear elastase), platelet activation (beta-thromboglobulin), and neuronal injury (neuron-specific enolase) were analyzed by enzyme-linked immunosorbent assays after cardiopulmonary bypass and compared with prebypass levels. Results are presented as mean +/- SEM. RESULTS: Prebypass levels of all markers were similar among treatment groups. However, postbypass levels were significantly and consistently highest in group I relative to groups II and III. Thrombin generation levels were 5.0 +/- 0.9 nmol/L in group I, 3.0 +/- 0.6 nmol/L in group II, and 1.5 +/- 0.1 nmol/L in group III (P <.05 vs group II and P <.001 vs group I). Polymorphonuclear elastase levels were 307 +/- 64 microg/L in group I, 128 +/- 24 microg/L in group II (P <.05 vs group I), and 75 +/- 14 microg/L in group III (P <.001 vs group I). beta-Thromboglobulin levels were 2692 +/- 401 IU/mL in group I, 912 +/- 99 IU/mL in group II (P =.001 vs group I), and 646 +/- 133 IU/mL in group III (P =.001 vs group I). Neuron-specific enolase levels were 9.8 +/- 0.9 ng/mL in group I, 10.5 +/- 1.6 ng/mL in group II, and 4.2 +/- 0.5 ng/mL in group III (P =.001 vs groups I and II). CONCLUSIONS: Use of cardiotomy suction resulted in significant increases in thrombin, neutrophil, and platelet activation, as well as the release of neuron-specific enolase, after cardiopulmonary bypass. Limiting increases in these markers would be best accomplished by eliminating cardiotomy suction and routinely using heparin-bonded circuits whenever possible.