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Because biplane and multiplane transesophageal echocardiography (TEE) are more complex and expensive than single-plane TEE, we performed this study to determine whether the use of multiple single-plane (transverse) cross sections is as reliable for detection of left ventricular segmental wall-motion abnormalities (SWMA) as biplane TEE. We used biplane TEE to acquire nine standard cross sections of the left ventricle in 41 consecutive adults undergoing cardiac or vascular surgery. Six of these cross sections were in the transverse plane (i.e., achievable with single-plane TEE) and three in the longitudinal plane (i.e., achievable only with biplane or multiplane TEE). Each cross section was divided into myocardial segments for analysis. A total of 1810 segments were analyzed by independent investigators using a standardized evaluation system. Seventeen percent of all SWMA detected in this study were in the midpapillary transverse-plane cross section, an additional 48% in other transverse-plane cross sections, and 35% exclusively in the longitudinal-plane cross sections. Thus, most (65%), but not all, SWMA were in cross sections achievable with single-plane TEE. We conclude that the MP-T cross section should be the foundation for assessment of segmental function, but additional cross sections in the transverse and longitudinal planes are required for detection of the majority of segmental wall-motion abnormalities.

We studied monovalent permeability of Ca2+ release-activated Ca2+ channels (ICRAC) in Jurkat T lymphocytes following depletion of calcium stores. When external free Ca2+ ([Ca2+]o) was reduced to micromolar levels in the absence of Mg2+, the inward current transiently decreased and then increased approximately sixfold, accompanied by visibly enhanced current noise. The monovalent currents showed a characteristically slow deactivation (tau = 3.8 and 21.6 s). The extent of Na+ current deactivation correlated with the instantaneous Ca2+ current upon readdition of [Ca2+]o. No conductance increase was seen when [Ca2+]o was reduced before activation of ICRAC. With Na+ outside and Cs+ inside, the current rectified inwardly without apparent reversal below 40 mV. The sequence of conductance determined from the inward current at -80 mV was Na+ > Li+ = K+ > Rb+ >> Cs+. Unitary inward conductance of the Na+ current was 2.6 pS, estimated from the ratios delta sigma2/delta Imean at different voltages. External Ca2+ blocked the Na+ current reversibly with an IC50 value of 4 microM. Na+ currents were also blocked by 3 mM Mg2+ or 10 microM La3+. We conclude that ICRAC channels become permeable to monovalent cations at low levels of external divalent ions. In contrast to voltage-activated Ca2+ channels, the monovalent conductance is highly selective for Na+ over Cs+. Na+ currents through ICRAC channels provide a means to study channel characteristics in an amplified current model.

T cell activation requires contact with APCs. We used optical techniques to demonstrate T cell polarity on the basis of shape, motility, and localized sensitivity to antigen. An intracellular Ca2+ clamp showed that T cell shape and motility are extremely sensitive to changes in [Ca2+]i (Kd = 200 nM), with immobilization and rounding occurring via a calcineurin-independent pathway. Ca2+ dependent immobilization prolonged T cell contact with the antigen-presenting B cell; buffering the [Ca2+]i signal prevented the formation of stable cell pairs. Optical tweezers revealed spatial T cell sensitivity to antigen by controlling placement on the T cell surface of either B cells or alpha-CD3 MAb-coated beads. T cells were 4-fold more sensitive to contact made at the leading edge of the T cell compared with the tail. We conclude that motile T cells are polarized antigen sensors that respond physically to [Ca2+]i signals to stabilize their interaction with APCs.

An infant with pulmonary atresia and intact ventricular septum is presented who, after initial patch reconstruction of the right ventricular outflow tract and bidirectional cavopulmonary anastomosis through a fifth median sternotomy, underwent an echocardiographically guided closed atrial septotomy, which resulted in marked long-term clinical improvement. The technique of intraoperative transesophageal echocardiography as used in the presented case represents an expanded role for this diagnostic modality in congenital cardiac surgery.

This article evaluates the costs and outcomes associated with TEE during and after cardiac surgery. The costs include the direct and indirect costs--the complications of TEE. The outcomes include the positive consequences or the benefits: money and lives saved. The article uses liberal (high) estimates of the direct and indirect costs of TEE and conservative (low) estimates of the benefits. The exact cost or benefit depends on the number of cases performed. The analysis shows that patients having surgery for congenital heart disease derive the greatest overall benefit: around $600 per case studied. Patients having valvular repair surgery derive the next greatest benefit: around $450 per case studied. In contrast patients having valve replacement have an overall cost of around $150 per case studied. Patients having surgery for coronary artery disease also derive an overall benefit: around $100-$300 per case studied, depending upon assumptions regarding TEE's role in prevention of intraoperative strokes. This analysis indicates that the financial benefits of TEE are substantial and frequently outweigh costs in patients requiring cardiac surgery.

Video microscopy and whole-cell patch-clamp recording were used to monitor changes in relative cell volume (V/Vo), chloride conductance (gCl), and membrane capacitance (Cm) during osmotically induced swelling in Jurkat T lymphocytes. Cellular swelling was initiated with hyperosmotic pipette solutions. Simultaneous evaluation of V/Vo and gCl revealed a 59-s delay between the inception of swelling and the activation of outwardly rectifying, ATP-dependent Cl- channels. Following the delay, increases in V/Vo and gCl progressed in parallel. In contrast, Cm, a measure of cell surface area, fell gradually at a rate of approximately 150 fF/min after whole-cell access was achieved. The decline in Cm lasted 200 s and was followed by a rapid rise (approximately 750 fF/min). The rise in Cm coincided with a variable increase in "leak" current, gCl increased at a slower rate and reached lower peak values in experiments performed without ATP; ATP had no effect on the biphasic Cm time course. The temporal separation of conductance and capacitance during swelling suggests that gCl and Cm vary independently, supporting the hypothesis that a large portion, if not all, of the whole-cell Cl- conductance activated during swelling is provided by volume-sensitive Cl- channels preexisting in the plasma membrane.

Qualitative TEE assessment is used to guide administration of fluids and inotropic drugs and to monitor left ventricular function intraoperatively. Left ventricular hypovolemia or depression is easily recognized by directly noting a small end-diastolic area or low ejection fraction. Appropriate therapy can be instituted and continuously monitored. In contrast, pulmonary artery pressure monitoring does not accurately indicate loading conditions during major cardiovascular procedures or whenever left ventricular compliance is impaired, mitral valve dysfunction is present, or right ventricular distention occurs. New applications and technical improvements in TEE are being developed at a remarkable rate. Future versions of ABD technology are likely to address the problem of anisotropy, require less user intervention, and incorporate 3-D information from multiplane probes to produce real-time estimates of left ventricular volumes. The raw information in the returning signal will most likely be further analyzed to allow characterization of ischemic but still viable tissue. Coupled with the ability to assess regional myocardial perfusion by contrast echocardiography, the clinician will be able to institute more timely and appropriate medical and surgical therapy. TEE assessment of mitral valve function has become the standard of care after mitral valve repair, and in a similar fashion, assessment of myocardial perfusion by TEE may become the standard of care during cardiac and major noncardiac surgery.

Background: Although transesophageal echocardiography (TEE) produces real-time images depicting left ventricular (LV) filling and ejection, the quantitative analysis of these images has been too time consuming to be of practical value in the operating room. Therefore, the authors investigated whether a new automated border detection system (ABD) could track the endocardial border continuously and compute the cross-sectional area of the LV cavity., Methods: Using data from 25 patients who were monitored with TEE as part of their routine clinical care, the authors compared ABD estimates of LV end-diastolic area (EDA in square centimeters), end-systolic area (ESA in square centimeters), and fractional area change (FAC) with the laboratory measurements made independently by an expert., Results: ABD slightly underestimated EDA (10.7 +/- 1.0 vs. 11.2 +/- 1.0 cm2) and slightly overestimated ESA (5.6 +/- 0.7 vs. 4.8 +/- 0.6 cm2, mean +/- standard error). However, when ABD tracking of the endocardial border was judged as "good" or "excellent" (84% of the patients at end diastole and 72% at end systole), the limits of agreement between ABD and the expert's findings were within the limits expected for two experts. By contrast, ABD significantly underestimated FAC (0.44 +/- 0.03 vs. 0.56 +/- 0.03) and the limits of agreement between ABD and the expert were more than twice as great as expected for experts, even when ABD performance was judged as "excellent.", Conclusion: The authors conclude that, when ABD appears to be performing adequately, it underestimates LV FAC, but provides valid real-time estimates of LV EDA and ESA. Thus, it warrants further evaluation as a potentially powerful clinical and research tool.

Objectives: We hypothesized that the directional movement of the interatrial septum and its curvature may reflect the pressure relations between the left and right atria., Background: Interventricular septal shape is primarily dependent on the pressure gradient between the left and the right ventricle. No analogous study has carefully evaluated the determinants of interatrial septum shape and motion., Methods: Patients (n = 52) undergoing cardiac or vascular surgery were studied intraoperatively at multiple intervals with transesophageal echocardiography and simultaneous measurement of central venous pressure, pulmonary capillary wedge pressure and airway pressure., Results: Overall interatrial septum shape, which usually curved toward the right atrium, changed concordantly with the interatrial pressure gradient (pulmonary capillary wedge pressure-central venous pressure difference). The degree of interatrial septum curvature was also primarily dependent on the interatrial pressure gradient and, to a lesser extent, was affected by changes in left atrial size (F = 130.4 vs. F = 14.1). During passive mechanical expiration, the interatrial pressure gradient, usually positive, often reverses transiently and the interatrial septum momentarily bows toward the left atrium. Midsystolic reversal was seen in 64 of 72 episodes when the pulmonary capillary wedge pressure was < or = 15 mm Hg but in only 2 of 40 episodes when it was > 15 mm Hg (sensitivity = 0.89, specificity = 0.95, positive predictive value = 0.97)., Conclusions: These findings suggest that overall interatrial septum shape depends on the pressure gradient between the left and right atria. Midsystolic reversal of the interatrial septum, which probably reflects the increased venous return in the right relative to the left atrium during mechanical expiration, may be a useful indicator of the pulmonary capillary wedge pressure.

T lymphocytes exhibit three distinct types of voltage-gated K+ channels, n, n', and l, that are distributed in the T cell lineage according to subset, as well as the cells' activation and developmental status. Type l K+ channels are found sparingly in cytotoxic T cells from normal mice and abundantly in a specific T cell subset (CD4- CD8- Thy1+) from mice with autoimmune disease. Here, we show that the mouse Kv3.1 gene, when expressed in Xenopus oocytes, encodes a channel with properties remarkably similar to those of the l-type channel. Kv3.1 transcripts were found in T cells isolated from the lymph nodes of MRL-lpr mice with systemic lupus erythematosus and in a human lymphoma cell line that also expresses the l channel phenotype. By these criteria, we conclude that Kv3.1 encodes the voltage-gated type l K+ channel in lymphocytes. The Kv3.1 gene maps to human chromosome 11; the related Kv1.1 and Kv3.2 genes are localized on human chromosome 12, while the IsK gene maps to human chromosome 21.

There is no adequate explanation for the highly variable response of systemic blood pressure to nitroglycerin (glyceryl trinitrate [GTN]). Aging produces cardiovascular changes that should alter the effects of GTN, but elderly patients usually have been excluded from studies of GTN. Accordingly, the authors compared the effects of GTN on systemic blood pressure in elderly and younger patients. Fifty-three patients, aged 49-87 (with 30 patients older than 70), were studied. Before elective vascular surgery, 14 patients received an infusion of placebo; 26, a constant infusion of GTN; and 13, a stepwise increasing infusion of GTN. After a standardized anesthetic induction and the start of surgery, the identical infusion protocols were repeated in each group. Data on GTN infusion rate, arterial blood pressure, and GTN concentrations versus time, age, and other potentially influencing variables were pooled for analysis. Before anesthesia and surgery, GTN more commonly caused excessive hypotension in patients older than 70 yr than in younger patients, but none of the patients had complications. A repeated-measures model analysis indicated that age significantly influenced the effects of GTN on blood pressure. That is, patients who are in their 70s who receive 0.5 micrograms.kg-1.min-1 of GTN are predicted to experience a twofold greater decrease in systolic arterial pressure (approximately 33 mmHg) than patients in their 50s. However, no apparent effect of age on intraoperative GTN responsiveness was discernible nor was a predictable relationship found between the preoperative and intraoperative responsiveness or between arterial concentrations of GTN and blood pressure or age. Therefore, the authors conclude that, in the absence of the effects of anesthesia and surgery, elderly patients have a more pronounced blood pressure response to GTN than younger patients. Furthermore, the authors conclude that preoperative blood pressure responsiveness to GTN is not a reliable predictor of intraoperative responsiveness.

Rat basophilic leukaemia cells, like mast cells from which they are derived, have surface Fc epsilon receptors that trigger secretion of inflammatory mediators when crosslinked. Both GTP-binding proteins and a rise in cytosolic calcium concentration ([Ca2+]i) are implicated in the secretory mechanism. Here we use a video-imaging technique to report that transient rises in [Ca2+]i initiated in an individual cell can spread from cell to cell in a wave-like pattern by means of a secreted intermediate, in the absence of gap-junctional communication. We find that the leukaemia cells, peritoneal mast cells and mucosal mast cells have cell-surface P2-type purinergic receptors that can trigger similar [Ca2+]i transients. We provide evidence that ATP is rapidly released, and that it can amplify [Ca2+]i signals and initial secretory responses during antigen-stimulation of rat basophilic leukaemia cells.

We examined the potential toxicity of desflurane in 13 young 25.0 +/- 2.3 (mean +/- SD) yr-old men, given 7.35 +/- 0.81 MAC-hours of desflurane anesthesia. Hepatic and renal function tests, serum electrolytes, and standard urine and hematologic tests were performed before, during, and after anesthesia. No toxicity was found. There were no changes in tests of hepatocellular integrity (plasma alanine transferase activity), synthetic function (serum albumin, prothrombin time, partial thromboplastin time), or renal function (serum creatinine concentration, blood urea nitrogen concentration). Decreases in red blood cell count, hematocrit, and blood hemoglobin concentration during and immediately after anesthesia were attributed to blood sampling and infusion of intravenous electrolyte solution. These values returned by 4 days after anesthesia to values not different from those before anesthesia. Increased white blood cell counts and blood glucose concentrations noted during anesthesia with other inhaled anesthetics were also seen in these volunteers. Desflurane appears to have no greater toxicity than currently used inhaled anesthetics and, because of its lesser metabolism, may have lesser or not toxicity.

To determine the accuracy, utility, and limitations of intraoperative transesophageal echocardiography (TEE) in infants and children, we performed prebypass and postbypass TEE in 90 children undergoing surgical repair of congenital heart lesions, comparing the results to those obtained using intraoperative epicardial echocardiography and pre- and postoperative precordial echocardiography. Patients ranged in age from 4 days to 21 yr (mean 4.1 yr) and in weight from 3 to 68 kg (mean 15.4 kg). Prebypass, we obtained high-quality, two-dimensional TEE images in 86 patients, with correction of the preoperative precordial diagnosis in 3 and confirmation of the preoperative diagnosis in the rest. Adequate epicardial images were obtained in 78 patients, with confirmation of the preoperative diagnosis in all. Shunt lesions that were well delineated prebypass by both TEE and epicardial imaging included interatrial, interventricular, and atrioventricular septal defect lesions. TEE failed to detect the exact size and location of lesions involving the right ventricular outflow tract, i.e., doubly committed subarterial (supracristal) ventricular septal defects. Regurgitant lesions (n = 30) were identified and their severity evaluated in all patients by both TEE and epicardial imaging. Obstructive lesions (n = 33), excluding those involving the right ventricular outflow tract, were well defined by both echocardiographic approaches. Postbypass, we obtained high-quality, two-dimensional, color and Doppler TEE images in 86 patients and epicardial images in 78 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Little information is available about the incidence of severe adverse outcomes, and even less information is available about the identification and quantification of independent predictors of severe perioperative adverse outcomes. The purpose of this study was to identify and quantitate independent predictors of severe perioperative adverse outcomes in a prospective randomized clinical trial of general anesthesia in 17,201 patients. Twenty-nine prognostic variables for 15 severe outcomes in 847 patients were tested by multiple stepwise logistic regressions from which 20 significant (P less than 0.05) predictors were identified. A history of cardiac failure or myocardial infarction less than or equal to 1 yr; ASA physical status 3 or 4; age greater than 50 yr; cardiovascular, thoracic, abdominal or neurologic surgery; and the study anesthetics were significant predictors of "any severe outcome, including death." There were 17 significant predictors for 10 severe cardiovascular outcomes in 608 patients, including a history of ventricular arrhythmia, hypertension, cardiac failure, myocardial ischemia, myocardial infarction less than or equal to 1 yr or myocardial infarction greater than 1 yr, and smoking; ASA physical status; age; cardiovascular, thoracic, abdominal, eyes-ears-nose-throat/endocrine, neurologic, musculoskeletal, or gynecologic surgery; and the study anesthetics. There were 9 significant predictors for 4 severe respiratory outcomes in 163 patients, including a history of cardiac failure, myocardial ischemia, or chronic obstructive pulmonary disease; obesity; smoking; male gender; ASA physical status; abdominal surgery; and the study anesthetics. Colinearity between related prognostic variables (such as disease and ASA physical status) was assessed using progressively segregated groups of variables in eight stepwise logistic regressions. We conclude that the comprehensive stepwise logistic regression of 29 prognostic variables reported here provides a valid estimate of the risks of severe perioperative outcomes associated with general anesthesia.

We have previously shown that the systolic and diastolic pulmonary venous flow (PVF) distribution is predictive of left atrial pressure. This study was designed to define the confounding influences of left atrial expansion, descent of the mitral anulus, and left ventricular contractile function on that relationship; to define normal PVF patterns; and to document the interaction of PVF with mitral inflow. Therefore we studied 27 consecutive intraoperative patients with coronary artery disease (22 men and 5 women, ages 35 to 78 years) using transesophageal echocardiography. A group of 12 normal subjects served as a control. Doppler and two-dimensional echocardiographic parameters were obtained simultaneously with monitoring pulmonary capillary wedge pressure (PCWP). We found that neither left atrial expansion nor the descent of the mitral anulus influenced the relationship between PVF and PCWP, but that left ventricular fractional shortening confounded this relationship. In normal subjects PVF was dominant in systole, whereas PVF in patients with elevated PCWP was dominant in diastole (systolic fraction of 68 +/- 6% [SD] in normals versus 42 +/- 15% in patients with PCWP greater than or equal to 15 mm Hg). PVF velocities interacted with transmitral flow velocities. Peak early diastolic mitral inflow velocities increased linearly with peak early diastolic PVF velocities (r = 0.62). We conclude that systolic and diastolic PVF distribution is mainly determined by the level of PCWP and to a lesser extent by left ventricular contraction, but not by left atrial expansion or by mitral anulus descent. Transesophageal pulsed Doppler echocardiography of PVF provides useful clinical information about the level of PCWP in intraoperative patients with coronary artery disease.

The accuracy and limitations of intraoperative two-dimensional (2-D) and color Doppler flow mapping transesophageal echocardiography (TEE) of ventricular septal defect (VSD), before and after cardiopulmonary bypass, were analyzed in 62 children. Twenty-one patients had an isolated VSD, and 41 had a VSD plus additional cardiac anomalies. Two-dimensional and color Doppler flow mapping TEE were performed with a miniaturized 5-MHz single (transverse) plane transducer in the 51 of 62 patients weighing less than 20 kg. The remaining 11 were monitored using a single plane adult probe (n = 4) and a biplane (transverse plus longitudinal) probe (N = 7). Prebypass TEE provided a correct diagnosis in 57 of 62 cases (92%) and corrected an erroneous preoperative transthoracic echocardiographic diagnosis in three of 62 cases (5%). Single plane TEE diagnosis was erroneous in five patients: four with doubly-committed subarterial VSD and one with multiple small apical muscular defects and pulmonary hypertension. Biplane TEE (transverse longitudinal) provided clear and complete imaging of the right ventricular outflow tract in all seven cases in whom it was used. Postbypass TEE showed absence of a hemodynamically significant residual VSD in 30 of 40 patients (95%) who underwent VSD patch closure, prospectively identified two of 40 with significant residual VSD, and accurately measured the color Doppler jet width of all residual VSDs. We conclude that hemodynamically significant VSDs can be identified immediately after cardiopulmonary bypass based on the width of the residual VSD color Doppler flow map jet. Therefore, 2-D and color Doppler flow mapping TEE provide an accurate diagnosis in most cases of VSD but may miss doubly-committed subarterial and apical muscular VSD unless biplane TEE is used.

To determine the accuracy and utility of single-plane transesophageal echocardiography in analyzing atrioventricular (AV) septal defect, intraoperative transesophageal echocardiography was performed before and after institution of cardiopulmonary bypass in 16 patients (age 24 days to 14 years, weight 3 to 47 kg). Prebypass transesophageal echocardiography (including two-dimensional echocardiography, Doppler color flow mapping and pulsed wave Doppler ultrasound) correctly diagnosed divided AV valve, common AV valve and unbalanced AV valve, as well as atrial or ventricular septal defect, or both, in all cases. It correctly analyzed AV valve regurgitation in all 10 patients with right and all 14 with left AV valve regurgitation and correctly analyzed 30 of 33 additional cardiac anomalies. Transesophageal echocardiography was able to detect the absence of normal pulmonary venous connections but failed to demonstrate all of the complex anomalous pulmonary venous connections in three patients with atrial isomerism. Postbypass transesophageal echocardiography documented the absence of a significant residual shunt in 11 of 11 patients undergoing corrective surgery and verified residual AV valve regurgitation in 7 of 9 patients with tricuspid regurgitation and 11 of 13 with mitral regurgitation. Transesophageal echocardiographic information that altered or refined the surgical treatment was obtained in 5 (31%) of 16 patients. Epicardial and transesophageal echocardiography results were concordant in all 13 patients in whom both were performed. Transesophageal echocardiography provides useful and accurate imaging of the important two-dimensional, pulsed wave Doppler ultrasound and Doppler color flow mapping features in AV septal defect.

We investigated the cardiovascular actions of desflurane (formerly I-653) during spontaneous ventilation. We gave 0.8-0.9, 1.2-1.3, and 1.6-1.7 MAC desflurane in oxygen (n = 6) and in 60% nitrous oxide, balance oxygen (n = 6) to unmedicated healthy male volunteers. Both anesthetic regimens decreased ventilation, increased partial pressure of arterial carbon dioxide, and produced similar cardiovascular changes. In comparison with values obtained when the volunteers were conscious, desflurane anesthesia with spontaneous ventilation decreased systemic vascular resistance and mean arterial blood pressure. Cardiac index, heart rate, stroke volume index, and central venous blood pressure increased. Left ventricular ejection fraction increased at 0.83 MAC desflurane in oxygen, and otherwise did not differ from the conscious value. The velocity of ventricular circumferential fiber shortening, estimated by echocardiography, increased with desflurane in oxygen but did not change with desflurane in nitrous oxide. Oxygen consumption increased during desflurane and oxygen anesthesia, but not when nitrous oxide plus oxygen was the background gas. Desflurane increased oxygen transport, the ratio of oxygen transport to oxygen consumption, mixed venous partial pressure of oxygen, and oxyhemoglobin saturation. The cardiovascular changes with desflurane during spontaneous ventilation differ from those during controlled ventilation. With both background gases, spontaneous ventilation, in comparison with controlled ventilation, increased cardiac index, stroke volume, central venous pressure, left ventricular ejection fraction, velocity of circumferential fiber shortening, oxygen transport, and the ratio of oxygen transport to oxygen consumption but did not change mean arterial blood pressure except at 1.66 MAC desflurane in oxygen (when it was higher with spontaneous than with controlled ventilation).

The cardiovascular actions of three concentrations of desflurane (formerly I-653), a new inhalation anesthetic, were examined in 12 unmedicated normocapnic, normothermic male volunteers. We compared the effects of 0.83, 1.24, and 1.66 MAC desflurane with measurements obtained while the same men were conscious. Desflurane caused a dose-dependent increase in right-heart filling pressure and a decrease in systemic vascular resistance and mean systemic arterial blood pressure. As measured by echocardiography, left ventricular end-diastolic area did not change except for a small increase at 1.66 MAC desflurane, and systolic wall stress was less at all concentrations of desflurane than during the conscious state. Desflurane did not change cardiac index or left ventricular ejection fraction. Heart rate did not change at 0.83 MAC, but progressively increased with deeper desflurane anesthesia. Stroke volume index was less at all concentrations of desflurane than while the men were conscious, but desflurane did not alter the velocity of ventricular circumferential fiber shortening. Mixed venous blood PO2 and oxyhemoglobin saturation were higher during all concentrations of desflurane anesthesia than during the conscious state. No volunteer developed a metabolic acidosis. We conclude that desflurane with controlled ventilation and constant PaCO2 causes cardiovascular depression, as indicated by the increased cardiac filling pressure and decreased stroke volume index and by no change in the velocity of circumferential fiber shortening in the presence of decreased systolic wall stress. However, cardiac output is well maintained, and heart rate does not increase at light levels of anesthesia. The cardiovascular actions of 0.83 and 1.66 MAC desflurane were also reexamined in 6 of the 12 men during the seventh hour of anesthesia. Prolonged desflurane anesthesia resulted in lesser cardiovascular depression than was evidenced during the first 90 min. The measures of cardiac filling (central venous pressure and left ventricular end-diastolic cross-sectional area) did not differ between the early and late periods of anesthesia. Systemic vascular resistance decreased further during the late period, but systolic wall stress did not differ between the two time periods. During the seventh hour of desflurane anesthesia, heart rate and cardiac index were higher at both anesthetic concentrations than during the first 90 min of anesthesia. Left ventricular ejection fraction and velocity of fiber shortening did not change with duration of desflurane anesthesia. Oxygen consumption, oxygen transport, the ratio of the two, mixed venous PO2, and mixed venous oxyhemoglobin saturation (SO2) increased late in the anesthetic in comparison with the first 90 min.

We determined the cardiovascular effects of 0.91, 1.34, and 1.74 MAC of desflurane/nitrous oxide anesthesia (60% inspired nitrous oxide contributed 0.5 MAC at each level) in 12 healthy, normocapnic male volunteers. Desflurane/nitrous oxide anesthesia decreased systemic blood pressures, cardiac index, stroke volume index, systemic vascular resistance, and left ventricular stroke work index, and increased pulmonary arterial pressures and central venous pressure in a dose-dependent fashion, while heart rate was 10%-12% and mixed venous oxygen tension was 2-4 mm Hg higher at all MAC levels than at baseline (awake). Desflurane/nitrous oxide anesthesia modestly increased left ventricular end-diastolic cross-sectional area (preload) and decreased velocity of left ventricular circumferential fiber shortening, systolic wall stress (afterload), and area ejection fraction; this combination of changes indicates myocardial depression. At approximately comparable MAC levels, heart rate was lower and systemic blood pressures, central venous pressure, left ventricular stroke work index, and systemic vascular resistance usually were significantly higher during anesthesia with desflurane and nitrous oxide than during desflurane anesthesia alone (same volunteers, data collected in crossover design). After 7 h of anesthesia, regardless of the background gas, somewhat less cardiovascular depression and/or modest stimulation was apparent: cardiac index, area ejection fraction, and velocity of left ventricular circumferential fiber shortening recovered to or toward awake values, whereas heart rate was further increased. Evidence of circulatory insufficiency did not develop in any volunteers during the study. Segmental left ventricular function was normal at baseline, and no segmental wall-motion abnormalities, ST-segment change, or dysrhythmias developed.(ABSTRACT TRUNCATED AT 250 WORDS)

We asked if desflurane with or without nitrous oxide at 0.83, 1.24, and 1.66 MAC prevented cardiovascular responses to stimulation. We measured cardiac output, heart rate, systemic arterial blood pressure, central venous pressure, pulmonary arterial blood pressure, and systemic vascular resistance in six healthy male volunteers before (control) and at 0, 1, 2, 4, and 6 min after tetanic electrical stimulation (50, 100, and 200 Hz) of the ulnar nerve. At 0.83 and 1.24 MAC, cardiac output, mean systemic arterial blood pressure, heart rate, and pulmonary arterial blood pressure increased. Peak changes averaged 13%-20% and most frequently occurred 0-2 min after stimulation (P less than 0.05) with return to control values at 4-6 min (except for pulmonary arterial blood pressure). At 1.66 MAC, heart rate and systemic blood pressure responses were attenuated, but this level of anesthesia had equivocal effects on the cardiac output and pulmonary blood pressure responses. The addition of nitrous oxide attenuated the peak response of heart rate and cardiac output but not the peak response of mean systemic arterial blood pressure. In summary, 0.83 and 1.24 MAC desflurane did not abolish cardiovascular responses to stimulation, but 1.66 MAC attenuated the responses.

The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed.

The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.

To determine whether transesophageal echocardiography could be used to estimate intraoperative cardiac output, the authors studied 35 consecutive patients undergoing cardiovascular surgery (coronary artery disease [n = 22], aortic valve disease [n = 5], mitral valve stenosis [n = 5], peripheral vascular disease [n = 3]). Two-dimensional echocardiographic and pulsed-wave Doppler signals of the pulmonary artery and mitral valve flow velocity were obtained simultaneously with thermodilution measurements of cardiac output. Cardiac output derived from pulsed Doppler imaging of pulmonary artery systolic flow velocity modestly correlated with the thermodilution-derived cardiac output (r = 0.65), but output determined from the mitral valve diastolic flow velocity did not (r = 0.24). Transesophageal echocardiography of pulmonary artery systolic flow satisfactorily detected intraoperative increases in cardiac output greater than 15% (sensitivity, 71%; specificity, 82%) but not decreases (sensitivity, 54%; specificity, 90%). Although this technique identifies increases in cardiac output greater than 15%, it does not detect decreases as accurately as those detected by thermodilution measurements. At this time, therefore, transesophageal Doppler echocardiography has significant limitations as an off-line monitor of cardiac output.

To determine the echocardiographic and Doppler characteristics of mitral regurgitation associated with a flail mitral valve, precordial and transesophageal echocardiography with pulsed wave and Doppler color flow mapping was performed in 17 patients with a flail mitral valve leaflet due to ruptured chordae tendineae (Group I) and 22 patients with moderate or severe mitral regurgitation due to other causes (Group II). Echocardiograms were performed before or during cardiac surgery; cardiac catheterization was also performed in 28 patients (72%). Mitral valve disease was confirmed at cardiac surgery in all patients. By echocardiography, the presence of a flail mitral valve leaflet was defined by the presence of abnormal mitral leaflet coaptation or ruptured chordae. Using these criteria, transesophageal imaging showed a trend toward greater sensitivity and specificity than precordial imaging in the diagnosis of flail mitral valve leaflet. By Doppler color flow mapping, a flail mitral valve leaflet was also characterized by an eccentric, peripheral, circular mitral regurgitant jet that closely adhered to the walls of the left atrium. The direction of flow of the eccentric jet in the left atrium distinguished a flail anterior from a flail posterior leaflet. By transesophageal echocardiography with Doppler color flow mapping, the ratio of mitral regurgitant jet arc length to radius of curvature was significantly higher in Group I than Group II patients (5.0 +/- 2.3 versus 0.7 +/- 0.6, p less than 0.001); all of the Group I patients and none of the Group II patients had a ratio greater than 2.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrous oxide (N2O) has been implicated as a cause of myocardial ischemia. We investigated whether substitution of N2O for a portion of the anesthesia supplied by isoflurane increased myocardial ischemia in patients at risk for such ischemia. Seventy patients having carotid endarterectomies (63 patients) or other carotid surgery (seven patients) were prospectively, randomly assigned to an anesthetic regimen that included or excluded N2O. All other aspects of anesthetic management were similar, except for greater concentrations of oxygen and isoflurane in patients not given N2O. Perioperative monitoring for myocardial ischemia and infarction included 12- or 5-lead electrocardiography, transesophageal echocardiography, and creatine kinase isoenzyme levels. By transesophageal echocardiographic or electrocardiographic criteria, 44% of patients given oxygen but only 21% of those given N2O had myocardial ischemia intraoperatively (P = 0.065). Similarly, myocardial infarction, identified by changes in creatine kinase isoenzymes, occurred in only one patient given N2O but in three given oxygen (not significantly different). Thus we found no trend indicating a greater incidence of myocardial ischemia or infarction associated with the use of N2O.

We tested the hypothesis that the administration of nitrous oxide (N2O) causes major (e.g., myocardial infarction, neuronal injury, hypoxemia, infection, death) or minor (e.g., nausea, vomiting, headache, earache) untoward effects in patients requiring anesthesia for 1.5-4 h. Given the higher morbidity and mortality associated with aging, we also tested whether aging increased any untoward effect of N2O. Finally, we investigated whether the substitution of N2O for a fraction of the anesthesia supplied by isoflurane altered the latter's pharmacologic effects. We studied 270 patients scheduled for elective total hip arthroplasty (n = 100), carotid endarterectomy (n = 70), or transsphenoidal hypophysectomy (n = 100) who were randomly assigned within each surgical group to receive isoflurane with or without 60% N2O. Regardless of patient age, we found no difference in major or minor untoward outcomes between anesthetic groups, nor a trend to suggest that a larger data cohort would reveal a significant adverse effect of N2O. The addition of N2O administration decreased the isoflurane requirement for clinical anesthesia but did not alter most of the clinical variables measured in practice, including blood pressure, heart rate, rate of recovery from anesthesia, development of postoperative pain, patient satisfaction with anesthesia, or duration of anesthesia or of hospitalization. Patients given N2O were no more likely to dream during anesthesia, remember events during anesthesia, or be frightened by those events. Our results support the continued use of N2O to anesthetize patients for elective surgery.

To determine the utility and limitations of intraoperative transesophageal echocardiography in infants and children with congenital intracardiac shunts, intraoperative transesophageal (n = 50) and epicardial (n = 49) echocardiograms were performed before and after cardiopulmonary bypass in children from 4 days to 16 years old and 3 to 45 kg in body weight. A miniaturized transesophageal probe (6.9 mm maximal diameter) was used in 36 patients weighting less than or equal to 20 kg. Epicardial imaging was performed with a 5 MHz precordial probe. The intraoperative transesophageal echocardiographic findings before and after cardiopulmonary bypass were correct and complete in 94% of patients. Transesophageal echocardiography correctly identified atrial septal defects, most types of ventricular septal defects, anomalous pulmonary veins, atrioventricular septal defects, tetralogy of Fallot, truncus arteriosus and double inlet ventricles. It failed to provide a correct diagnosis in only three patients, all of whom had doubly committed subarterial ventricular septal defects. Epicardial echocardiography identified all cases that had a doubly committed subarterial ventricular septal defect. A correct and complete intraoperative diagnosis was obtained with the use of epicardial imaging in 92% before and after cardiopulmonary bypass, but this technique required interruption of surgery and could not be completed in three patients because of induced arrhythmias and hypotension. These results demonstrated that intraoperative transesophageal echocardiography consistently defined important morphologic, color and pulsed Doppler ultrasound features of most congenital shunt lesions. Lesions that involved the right ventricular outflow tract are sometimes difficult to image with uniplane transesophageal echocardiography. There were no complications in any of the 50 subjects.

Using the patch-clamp technique in combination with fluorescence microscopy we have found an abnormality in voltage-gated K+ channel expression in T cells that represents the first molecular marker linking three disparate autoimmune diseases in mice. CD4-CD8-Thy-1.2+ (double-negative or DN) lymphocytes from every known murine model for systemic lupus erythematosus, type-1 diabetes mellitus and experimental allergic encephalomyelitis exhibit abnormally high numbers of an unusual K+ channel, termed type l compared to their phenotypic counterparts in normal mice. Other T cell subsets from these diseased mice retain their normal pattern of K+ channel expression. The unique K+ channel phenotype of DN T cells arises in parallel with the onset of autoimmunity. Although mitogen-activated T cells and rapidly proliferating thymocytes exhibit large numbers of K+ channels, these channels are of an electrophysiologically distinct type called n. Thus, abundant expression of type l K+ channels appears to be a useful marker for DN T cells associated with autoimmunity and may provide a valuable tool for delineating the role of DN T cells in the pathogenesis of autoimmune diseases.

Transesophageal echocardiography (TEE) has become a commonly used monitor of left ventricular (LV) function and filling during cardiac surgery. Its use is based on the assumption that changes in LV short-axis ID reflect changes in LV volume. To study the ability of TEE to estimate LV volume and ejection immediately following CABG, 10 patients were studied using blood pool scintigraphy, TEE, and thermodilution cardiac output (CO). A single TEE short-axis cross-sectional image of the LV at the midpapillary muscle level was used for area analysis. Between 1 and 5 h postoperatively, simultaneous data sets (scintigraphy, TEE, and CO) were obtained three to five times in each patient. End-diastolic (EDa) and end-systolic (ESa) areas were measured by light pen. Ejection fraction area (EFa) was calculated (EFa = (EDa - ESa)/EDa). When EFa was compared with EF by scintigraphy, correlation was good (r = 0.82 SEE = 0.07). EDa was taken as an indicator of LV volume and compared with LVEDVI which was derived from EF by scintigraphy and CO. Correlation between EDa and LVEDVI was fair (r = 0.74 SEE = 3.75). The authors conclude that immediately following CABG, a single cross-sectional TEE image provides a reasonable estimate of EF but not LVEDVI.

The application of patch-clamp and video-imaging techniques has enabled responses of lymphocytes to be examined at the level of individual cells. Eight distinct types of ion channel activity have been revealed in T lymphocytes. A variety of external stimuli shifts the pattern of channel activity from the resting state, which is dominated by voltage-gated K+ channels. Channel regulation is achieved both by acute modulation and by altered expression in the membrane. During mitogen stimulation, Ca2+ channels and Ca(2+)-activated K+ channels become active and appear to underlie Ca2+ oscillations. These acute changes are followed by increased expression of voltage-gated K+ channels. In response to osmotic challenge in hypotonic media, cell swelling initiates activation of Cl- channels, which may, in turn, indirectly activate K+ channels and trigger a regulatory decrease in cell volume.

A prospective, stratified, randomized clinical trial of the safety and efficacy of four general anesthetic agents (enflurane, fentanyl, halothane, and isoflurane) was conducted in 17,201 patients (study population). Patients were studied before, during, and after anesthesia for up to 7 days. Nineteen patients died (0.11%), and in seven of these (0.04%) the anesthetic may have been a contributing factor. The rates of death, myocardial infarction, and stroke in the study population were so low (less than 0.15%) that no conclusions regarding the relative rates of these outcomes among the four anesthetic agents could be reached. The rates of 16 of 66 types of adverse outcomes in the study population were significantly different among the four study agents. Most of these outcomes were minor. However, severe ventricular arrhythmia (P less than 10(-6)) was more common with halothane, severe hypertension (P less than 10(-6)) and severe bronchospasm (P = 0.028) were more common with fentanyl, and severe tachycardia (P = 0.001) was more common with isoflurane. Recovery from anesthesia during the first 30 min was slowest in those patients who received halothane (P less than or equal to 0.001). In addition, patients who received fentanyl experienced less pain during the first hour in the recovery room (P less than 10(-6)). In conclusion, clinically important differences do exist for some outcomes among the four study agents.

Using the patch-clamp technique, we studied regulation of potassium channels by G protein activators in the histamine-secreting rat basophilic leukemia (RBL-2H3) cell line. These cells normally express inward rectifier K+ channels, with a macroscopic whole-cell conductance in normal Ringer ranging from 1 to 16 nS/cell. This conductance is stabilized by including ATP or GTP in the pipette solution. Intracellular dialysis with any of three different activators of G proteins (GTP gamma S, GppNHp, or AlF-4) completely inhibited the inward rectifier K+ conductance with a half-time for decline averaging approximately 300 s after "break-in" to achieve whole-cell recording. In addition, with a half-time averaging approximately 200 s, G protein activators induced the appearance of a novel time-independent outwardly rectifying K+ conductance, which reached a maximum of 1-14 nS. The induced K+ channels are distinct from inward rectifier channels, having a smaller single-channel conductance of approximately 8 pS in symmetrical 160 mM K+, and being more sensitive to block by quinidine, but less sensitive to block by Ba2+. The induced K+ channels were also highly permeable to Rb+ but not to Na+ or Cs+. The current was not activated by the second messengers Ca2+, inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, or by cyclic AMP-dependent phosphorylation. Pretreatment of cells with pertussis toxin (0.1 microgram/ml for 12-13 h) prevented this current's induction both by guanine nucleotides and aluminum fluoride, but had no effect on the decrease in inward rectifier conductance. Since GTP gamma S is known to stimulate secretion from patch-clamped rat peritoneal mast cells, it is conceivable that K+ channels become inserted into the plasma membrane from secretory granules. However, total membrane capacitance remained nearly constant during appearance of the K+ channels, suggesting that secretion induced by GTP gamma S was minimal. Furthermore, pertussis toxin had no effect on secretion triggered by antigen, and triggering of secretion before electrical recording failed to induce the outward K+ current. Finally, GTP gamma S activated the K+ channel in excised inside-out patches of membrane. We conclude that two different GTP-binding proteins differentially regulate two subsets of K+ channels, causing the inward rectifier to close and a novel K+ channel to open when activated.

A prospective randomized clinical trial of enflurane, fentanyl, halothane, and isoflurane is described. The 17,201 patients were stratified into two groups (preanesthetic medication and no preanesthetic medication) and were randomized to one of four study agents: enflurane, fentanyl, halothane, and isoflurane. Fifteen university-affiliated hospitals in the United States and Canada participated. All patients were first assessed preoperatively. Data were collected during anesthesia, in the immediate recovery period, and for up to 7 days after anesthesia/surgery. The mean age of the patients was 43 yr, the mean height 167 cm, and the mean weight 68 kg. Sixty-five percent of patients were female. In this study 90.7% of patients were classified as ASA Physical Status 1 or 2, and 34.7% of patients smoked. It is concluded that pooling of data across institutions was valid and does allow determination of the efficacy and relative safety of the four study agents.

We speculated that the inhibitory effect of isoflurane on the metabolism of halothane might reduce hepatic injury produced by halothane. To test this hypothesis we pretreated male rats with phenobarbital and 24 hr later exposed them to one of three types of anesthesia. One group of rats was anesthetized with 0.6 MAC isoflurane in 21-25% oxygen for 20 min, followed by exposure to 0.3 MAC isoflurane and 0.3 MAC halothane either in 9% oxygen for 46 min (n = 5) or in 12% oxygen for 60 min (n = 11). A second group of rats received 0.3 MAC halothane in 9% oxygen for either 46 min (n = 12) or in 12% oxygen for 60 min (n = 10). The third group received 0.3 MAC isoflurane in 9% oxygen for either 46 min (n = 12) or for 120 min (n = 8). The rats were killed 24 hr after the exposures and liver slides prepared. Histologic examination revealed that rats treated with isoflurane plus halothane, or with halothane alone showed a significant hepatic injury (P less than 0.005) when compared with those treated with isoflurane. Thus isoflurane failed to protect the liver from halothane-induced injury.

The recent development of the gigaohm seal voltage clamp technique has provided an approach to study individual cells of the immune system. Six distinct types of ion channels, most resembling channels found in nerve and muscle, have been identified in immune cells. Some of these channels appear to play important roles in various aspects of immune function. This article summarizes recent studies on ion channels in lymphocytes and macrophages.

A variety of scorpion venoms and purified toxins were tested for effects on ion channels in human T lymphocytes, a human T leukemia cell line (Jurkat), and murine thymocytes, using the whole-cell patch-clamp method. Nanomolar concentrations of charbdotoxin (CTX), a purified peptide component of Leiurus quinquestriatus venom known to block Ca2+-activated K+ channels from muscle, blocked "type n" voltage-gated K+ channels in human T lymphoid cells. The Na+ channels occasionally expressed in these cells were unaffected by the toxin. From the time course of development and removal of K+ channel block we determined the rates of CTX binding and unbinding. CTX blocks K+ channels in Jurkat cells with a Kd value between 0.5 and 1.5 nM. Of the three types of voltage-gated K+ channels present in murine thymocytes, types n and n' are blocked by CTX at nanomolar concentrations. The third variety of K+ channels, "type l," is unaffected by CTX. Noxiustoxin (NTX), a purified toxin from Centruroides noxius known to block Ca2+-activated K+ channels, also blocked type n K+ channels with a high degree of potency (Kd = 0.2 nM). In addition, several types of crude scorpion venoms from the genera Androctonus, Buthus, Centruroides, and Pandinus blocked type n channels. We conclude that CTX and NTX are not specific for Ca2+ activated K+ channels and that purified scorpion toxins will provide useful probes of voltage-gated K+ channels in T lymphocytes. The existence of high-affinity sites for scorpion toxin binding may help to classify structurally related K+ channels and provide a useful tool for their biochemical purification.

To determine whether brief periods of hypoxia could produce hepatic injury, we pretreated Sprague-Dawley rats with phenobarbital, deprived them of food for 24 hr, and then exposed them to various hypoxic mixtures of nitrogen and oxygen for various lengths of time. Rats exposed to 6% oxygen for 15 or more minutes had centrilobular injury, the severity of which was directly related to the length of exposure (r = 0.71). Extrapolation of these data indicated that no injury would occur if exposures were less than 5 min. Experiments using lower concentrations of oxygen did not reveal hepatic injury, probably because death of the animals occurred before the appearance of detectable injury of the liver. Feeding animals before imposition of hypoxia markedly decreased the risk of hepatic injury. Whether patients who are deprived of food preoperatively and whose liver enzymes are induced incur an increased risk of hepatic injury from brief periods of hypoxia remains to be determined.