Influence of anesthesia on the threshold of pacing-induced ischemia.

Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/- 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow.     

The Manual for Blood Conservation. D. Thomas and B. Ridler (editors). Published by Tfm Publishing Ltd, Shrewsbury. Pp. 285; illustrated. Price {pound}25.00. ISBN 1-903378-24-9

In this book the editors give a broad overview of today's knowledge,policies and organization of blood transfusion with the goalto provide the clinician with essential information and practicaltips on how to rationalize and organize transfusion practicein their hospital. In the foreword, Marcela Contreras emphasizesthe increasing complexity and costs     

Perflubron Emulsion in Prolonged Hemorrhagic Shock: Influence on Hepatocellular Energy Metabolism and Oxygen-dependent Gene Expression

Background: Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion.

Methods: Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation.

Results: Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone.     

Piracetam in alcoholic organic mental disorder: a placebo controlled study comparing two dosages

The following paper presents an investigation of the efficacy of piracetam in alcoholic organic mental disorder. A double-blind placebo-controlled study design was used to compare 2 dosages of the substance (2 X 3 g vs. 2 X 12 g). Cognitive function was assessed on days 0, 7, 14, 28, 42. Analysis of the results from 24 patients showed a clear-cut amelioration of cognitive functions in all 3 treatment groups. No difference could be demonstrated between the administration of placebo and the lower dose of piracetam. Patients on the higher dose showed an earlier improvement on one of the tests, but the final scores were similar in all three treatment groups.     

Is Post Cardiopulmonary Bypass Dysfunction a Special Form of Stunning?

Abstract It has been suggested that cardioplegic arrest during cardiopulmonary bypass (CPB) produces global myocardial ischemia with a risk of myocardial stunning. It has also been postulated that anesthetic technique may affect the course of post-CPB myocardial stunning via exaggerated myocardial depression. However, we have previously found that global ventricular and regional myocardial responses to halothane do not differ in post-CPB and pre-CPB dogs. Our examination of the effects of CPB on the beta-adrenergic function revealed that beta-adrenergic receptor function is only slightly decreased immediately following (i.e., 1 min) and 30 minutes post-CPB. A dose-response relationship was established for dobutamine, with decreased responsiveness noted at both times. Since other data show normal inotropic stimulation of stunned myocardium, decreases in dobutamine responsiveness cannot be explained by beta-receptor desensitization. Overall, these data indicate that CPB does not result in myocardial stunning. The differences between these data and others showing myocardial stunning following CPB may be due to several factors, such as anesthetic regimen, lack of coronary blood flow abnormalities, and a reduction in sarcoplasmic reticular damage due to the hypothermic conditions used.     

The percutaneous vena cava umbrella filter in the prevention of pulmonary embolism

The Kimray-Greenfield filter is the most commonly used of all filters. Percutaneous insertion technique has made this filter more attractive also for interventional radiology. Its drawbacks are, in particular, the large calibre of the insertion instruments and its low effectivity in case of eccentric placing. Good results have been obtained to date with the specially developed cava filters that can be introduced percutaneously. Clinical and experimental studies have shown that some filters are particularly effective, such as the "basket filter"; at the same time, these have also a higher thrombogenicity. However, independent of the choice of the cava filter, it seems that the operatively inserted filters are increasingly a thing of the past.     

Radioreceptor Assay of Metoprolol in Human Plasma: Comparison with an Enantiospecific High-Performance Liquid Chromatographic (HPLC) Procedure

Plasma concentrations of metoprolol after acute and repetitive administration of R/S-metoprolol to healthy volunteers were measured by a -adrenoceptor subtype-specific radioreceptor assay (RRA) and by an enantiospecific high-performance liquid chromatographic (HPLC) method. In the RRA, R/S-metoprolol showed a 20-fold ₁-subtype selectivity: the S-( – )-enantiomer was 35-fold more potent than the R-( + )-enantiomer. A comparison between S-( – )-metoprolol concentrations detected in the plasma samples by HPLC and those detected by RRA yielded a 1/1 relationship, indicating that active metabolites are not present to a significant extent. These results were independent of the widely scattering metabolic clearance of metoprolol (with the potential of differences in the rate and extent of formation of active metabolites) in the volunteers. In general, HPLC methods can be validated by comparison with RRA in order to clarify whether active metabolites are present and—on the basis of the K_i value from RRA—whether the detection limit of the physicochemical procedure is sufficient to cover the therapeutically relevant range.     

Procedures to Characterize In Vivo and In Vitro Enantioselective Glucuronidation Properly: Studies with Benoxaprofen Glucuronides

The diastereoisomeric glucuronic acid conjugates of R/S-benoxaprofen are the major benoxaprofen metabolites and are found in urine at high concentrations. The conjugates of R- and S-benoxaprofen can be separated directly on a C₁₈ reversed-phase column using a mixture of acetonitrile and tetrabutylammonium hydroxide buffer, pH 2.5 (28:72, v/v), as the mobile phase. The k values of S- and R-benoxaprofen glucuronides are 57.5 and 63.0, respectively. Diluted urine or deproteinized plasma samples were injected without further treatment. With fluorescence detection at 313/365 nm, quantifiable limits of 50 ng equiv./ml were found for the conjugates. The intra- and interday variability was below 12%. Utilizing this analytical procedure it is possible to characterize enantioselective glucuronidation both in vivo and in vitro. For in vitro procedures, apparent rates of formation and the R/S ratio may be substrate (benoxaprofen) and cosubstrate (UDPGA) dependent. Moreover, enantioselective cleavage of the formed benoxaprofen glucuronides by alkaline hydrolysis, hydrolytic enzymes, and acyl migration must be controlled for both in vitro and in vivo studies since R-benoxaprofen glucuronide is degraded faster than the S-diastereomer under certain conditions.     

Sequence analysis of L RNA of Lassa virus

The L RNA of three Lassa virus strains originating from Nigeria, Ghana/Ivory Coast, and Sierra Leone was sequenced and the data subjected to structure predictions and phylogenetic analyses. The L gene products had 2218-2221 residues, diverged by 18% at the amino acid level, and contained several conserved regions. Only one region of 504 residues (positions 1043-1546) could be assigned a function, namely that of an RNA polymerase. Secondary structure predictions suggest that this domain is very similar to RNA-dependent RNA polymerases of known structure encoded by plus-strand RNA viruses, permitting a model to be built. Outside the polymerase region, there is little structural data, except for regions of strong alpha-helical content and probably a coiled-coil domain at the N terminus. No evidence for reassortment or recombination during Lassa virus evolution was found. The secondary structure-assisted alignment of the RNA polymerase region permitted a reliable reconstruction of the phylogeny of all negative-strand RNA viruses, indicating that Arenaviridae are most closely related to Nairoviruses. In conclusion, the data provide a basis for structural and functional characterization of the Lassa virus L protein and reveal new insights into the phylogeny of negative-strand RNA viruses.     

Effect of depressive symptoms on survival after heart transplantation

OBJECTIVE: This study explored the value of preoperative self-reported assessment for depression and anxiety in patients who had undergone heart transplantation (HTx). The initial sample was divided into subgroups of patients with ischemic (ICMP) and dilated cardiomyopathy (DCMP). Patient depression and anxiety scores were measured in both subgroups and their impact on pre- and postoperative mortality investigated. METHOD: An initial sample of 152 patients with either ICMP (N = 57) or DCMP (N = 95) and end-stage heart disease awaiting heart transplantation were assessed in a multidimensional longitudinal study, including psychological and somatic variables. One hundred and three patients received a HTx and were followed up for a mean of 4.4 years. Proportional hazard models were computed to test for the influence of psychosocial and somatic factors on outcome. RESULTS: Preoperative depression and state anxiety scores were significantly higher in the ICMP group. In addition to donor and recipient age, ICMP patients in the preoperative high depression group also showed a significantly higher mortality after HTx. This result remained significant even after controlling for sociodemographic and somatic variables. CONCLUSIONS: Patient self-reported depression, but not anxiety, can contribute to the identification of subgroups of patients with an unfavorable outcome after HTx. It therefore may be helpful to screen for depression, particularly in patients with an ischemic cause of their end-stage heart disease. Specific intervention programs should be further developed and evaluated.