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Invasive cardiology procedures have changed dramatically over the past 5–10 years. With technological advancement, diagnostic and therapeutic procedures have become broader in scope and complexity, and patient acuity has escalated dramatically. In parallel, the involvement of anesthesiologists has grown. In this chapter, we present an overview of the laboratory environment(s), the evolution and future pathways of current practice(s), cases performed in each venue, and current anesthetic approaches. In this new and changing arena, collaboration and planning between cardiologists and anesthesiologists maximizes patient safety and increases the probability of procedural success. A thorough understanding of the procedure to be performed is required in order for anesthesiologists to define and delineate the extent of their involvement, and is a clear prerequisite for the formulation of a safe and effective anesthetic plan. A common knowledge base and mutual respect for each contributing discipline form the basis for integration of cardiology and anesthesia services in pursuit of optimized patient care.

SummaryGenes disrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise healthy families. Furthermore, during normal brain development, genes are expressed in patterns specific to developmental stage and neuroanatomical structure. We identified de novo mutations in persons with schizophrenia and then mapped the responsible genes onto transcriptome profiles of normal human brain tissues from age 13 weeks gestation to adulthood. In the dorsolateral and ventrolateral prefrontal cortex during fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network significantly enriched for transcriptional coexpression and protein interaction. The 50 genes in the network function in neuronal migration, synaptic transmission, signaling, transcriptional regulation, and transport. These results suggest that disruptions of fetal prefrontal cortical neurogenesis are critical to the pathophysiology of schizophrenia. These results also support the feasibility of integrating genomic and transcriptome analyses to map critical neurodevelopmental processes in time and space in the brain.

Paxbeta is a novel gene family restricted to the bilaterian superphylum Lophotrochozoa. The Paxbeta paired domain is highly diverged from other bilaterian Pax genes, and we were unable to identify an unambiguous sister-group by phylogenetic sequence analysis. However, conservation of a paired domain intron suggests that the Paxbeta genes arose by duplication and divergence from an ancestral Pax2/5/8 gene. We have identified Paxbeta genes in annelids, molluscs, a nemertean, a brachiopod, and a flatworm, indicating that the founding gene duplication occurred before the separation of those taxa and therefore early in the lophotrochozoan radiation. The leech Helobdella has two genes in this family, Hau-Paxbeta1 and -Paxbeta2, which are expressed during embryonic development. Hau-Paxbeta1 is present in the zygote as a localized maternal transcript, and both show dynamic patterns of apparently zygotic expression during later stages. These later expression patterns differ significantly, but both genes are expressed broadly in the mesoderm and also in the central nervous system during organogenesis.

Procedures and interventions in the cardiac catheterization laboratory (CCL) and electrophysiology laboratory (EPL) are more complex and involve acutely ill patients. Safely caring for this growing patient population in the CCL and EPL is now a concern for all anesthesiologists and cardiologists. Anesthesiologists are uniquely trained to care for this complex patient population, allowing the cardiologist to focus on completing the interventional procedure successfully.

Toward Predictable Repair of Regurgitant Aortic Valves: A Systematic Morphology-Directed Approach to Bicommissural RepairGosta B. Pettersson, Adrian C. Crucean, Robert Savage, Carmel M. Halley, Ric...

The Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic polymorphisms that confer susceptibility to schizophrenia among African-Americans by linkage mapping and targeted association analyses. Because deficits in certain dimensions of cognitive ability are thought to underlie liability to schizophrenia, the project also examines cognitive abilities in individuals affected by schizophrenia and their extended family members. This article describes PAARTNERS study design, ascertainment methods and preliminary sample characteristics. We aim to recruit a sample of 1260 African-American families, all of whom have at least one proband with schizophrenia or schizoaffective disorder. The data collection protocol includes a structured Diagnostic Interview for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive assessment, medical records review, and the collection of blood or buccal cells for genetic analyses. We have currently completed study procedures for 106 affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289 probands have completed the best estimate final diagnosis process and 1153 probands and family members have been administered the computerized neuropsychological battery. This project lays the foundation for future analysis of cognitive and behavioral endophenotypes. This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia.

Mitral valve (MV) annuloplasty is the standard surgical technique for the management of ischemic mitral regurgitation (MR). However,or = 1/3 of patients develop recurrent MR after annuloplasty. Therefore, we sought to identify the preoperative echocardiographic parameters that predict annuloplasty failure in patients with ischemic MR. Intraoperative transesophageal echocardiograms from 365 patients who underwent MV repair for ischemic MR were reviewed. Of the 365 patients, 297 (81%) had satisfactory outcomes with2+ MR, and 68 (19%) had recurrent MR (or = 2+) during a mean follow-up of 269 days. The mitral annular parameters, including mitral annular diameter, tethering height, and tethering area of the mitral leaflets, were determined in 3 different echocardiographic views. On multiple logistic stepwise regression analysis, a higher mitral annular diameter, higher tethering area, and higher MR severity were identified as independent predictors for failure of MV repair (p0.0001). In conclusion, these results demonstrated that preoperative echocardiographic findings can be used to identify patients with ischemic MR at increased risk of repair failure. These echocardiographic measurements should be used to guide the cardiologist and cardiac surgeon in the choice of MV repair versus replacement in patients with ischemic MR.

IMPLICATIONS: The authors describe the management of a patient with arrhythmogenic right ventricular dysplasia treated with right ventricular exclusion surgery.

A key element in developing a process to determine knowledge and ability in applying perioperative echocardiography has included an examination. We report on the development of a certifying examination in perioperative echocardiography. In addition, we tested the hypothesis that examination performance is related to clinical experience in echocardiography. Since 1995, more than 1200 participants have taken the examination, and more than 70% have passed. Overall examination performance was related positively to longer than 3 mo of training (or equivalent) in echocardiography and performance and interpretation of at least six examinations a week. We concluded that the certifying examination in perioperative echocardiography is a valid tool to help determine individual knowledge in perioperative echocardiography application.This report describes the process involved in developing the certifying transesophageal echocardiography examination and identifies correlates with examination performance.

Intraoperative transesophageal echocardiography (TEE) has been a valuable tool in cardiac surgery. The TEE probe can easily be inserted after endotracheal intuba tion to provide continuous monitoring and diagnosis during surgery. The role of TEE in the operating room is always expanding. This article examines the role of TEE specifically for cardiopulmonary bypass and perfusion management.

Background Left ventricular dysfunction is often reversed after coronary artery bypass graft (CABG) surgery; however, this change is not easily predicted. The authors hypothesized that functional changes after a low dose of dobutamine (5 microgram. kg-1. min-1) intraoperatively would predict functional changes when complete revascularization was achieved. Methods The authors analyzed 560 segments in 40 patients scheduled for elective CABG surgery for regional wall motion (1-5 scoring system) at four stages: baseline (after induction and intubation), with administration of low-dose dobutamine before cardiopulmonary bypass, after separation from cardiopulmonary bypass (early), and after administration of protamine (late). Two independent observers scored the myocardial regions according to a 16-segment model in multiple imaging planes. For each segment, the response to dobutamine was dichotomized as improved or not improved from baseline and analyzed with logistic regression. The influence of covariates (ejection fraction, myocardial infarction, diabetes mellitus, and beta blockers) was also determined with logistic regression models. P < 0.05 was considered significant. Results Changes in myocardial function after low-dose dobutamine were highly predictive for early (P < 0.0001) and late (P < 0.0001) changes in myocardial function from baseline regional scores. The overall odds ratio for early and late improvement increased by 20.7 and 34.6, respectively, when improvement was observed after low-dose dobutamine was administered. The overall positive predictive value of improved regional wall motion after CABG did not vary with left ventricular ejection fraction, a history of myocardial infarction, or beta blocker use, and it varied little with diabetic status (range, 0.86-0.96) if regional wall motion improved with low-dose dobutamine before CABG. The overall negative predictive value was 0.70; however, the range varied with diabetic status (i.e., lowest in diabetic patients and highest in nondiabetic patients). Conclusion Intraoperative low-dose dobutamine is a reliable method to predict myocardial functional reserve and to determine functional recovery expected after coronary revascularization.

Background The predictive value of electrocardiography (ECG) and coronary angiography for cardioplegia distribution in patients with an occluded right coronary artery was evaluated. Methods Coronary angiograms and ECGs were evaluated in 15 patients with right coronary artery occlusion. Prediction of antegrade cardioplegia distribution was based on ECG evidence of infarction and coronary collateral flow determined from the angiogram. Antegrade and retrograde delivery of cardioplegia was directly assessed in all patients by myocardial contrast echocardiography. Intraoperative transesophageal echocardiographic images of the right ventricular free wall, the apex, and the intraventricular septum were recorded while 4 ml of Albunex (Mallinckrodt Medical, St. Louis, MO) was injected into antegrade and retrograde cardioplegic catheters during cardioplegia delivery. The observed (myocardial contrast echocardiography) cardioplegia distribution was compared to the predicted cardioplegia distribution. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated. Results Eighty seven of 90 (97%) segments were analyzed. Angiography and ECG poorly predicted incomplete cardioplegia distribution. Electrocardiography was a better predictor of inadequate cardioplegia distribution to the right ventricle than was angiography. The negative predicted values of cardioplegia distribution ranged from 20 to 50% for the septum and right ventricle, respectively, with ECG criteria and from 0 to 33% for the septum and apex, respectively, with angiographic criteria. Antegrade cardioplegia delivery was distributed to the right ventricle in 31% of patients, despite 100% occlusion of the right coronary artery; whereas retrograde cardioplegia delivery to the right ventricle occurred 20% of the time. Conclusions In the presence of 100% right coronary artery occlusion, retrograde cardioplegia delivery is not often observed and antegrade delivery of cardioplegia to the right ventricle is not easily predicted. The preoperative angiography and ECG are not predictive of coronary collateral circulation and therefore not predictive of cardioplegia distribution to the right ventricle.

Objective: Intraoperative myocardial contrast echocardiography was used to determine whether the identification of regional myocardial flow patterns during revascularization could predict myocardial contractile function immediately after separation from cardiopulmonary bypass (CPB) and at 1 month after coronary artery bypass grafting (CABG) surgery. Design: A prospective, open-labeled, longitudinal analysis. Setting: Two independent university hospitals. Participants: Twenty patients, during and up to 1 month after CABG. Interventions: The contrast agent Albunex (Mallenckrodt Medical, Inc, St Louis, MO) was injected into the aortic root during CPB. Measurements and Main Results: Myocardial contrast echo-cardiography opacification of flow was graded from intraoperative transesophageal echocardiographic images of the left ventricle in the short-axis, midpapillary view. The same myocardial images were also evaluated for regional wall motion abnormalities at 15, 30, and 60 minutes, 24 hours, 5 to 8 days, and 1 month after CPB. Logistic regression analysis was used to analyze the flow scores and regional function data from identical segments. Regional flow represented by contrast enhancement was assessed in 70% of the myocardial regions (55 of 80 possible segments; 95% confidence interval [CI], 61 to 76). Flow was more easily evaluated in the posterior region (95%) than in the anterior (70%) or septal regions (60%), and least likely evaluated in the lateral regions (50%). Regional wall motion was scored in 84% of the myocardial regions (469 of 560 possible regions). Function (segmental wall motion) was assessed in all regions with equal success. Segmental function and flow scores were matched to the same regions 66% of the time (53 of 80 possible series; 95% Cl, 55 to 76). Regional myocardial contrast flow patterns did not predict myocardial function at 15, 30, or 60 minutes after separation from CPB. However, contrast opacification of flow did predict regional myocardial function at 1 week (p ≤ 0.05) and at 1 month (p ≤0.01) after CABG surgery. The probability that myocardial function would be normal at 1 month was 0.62 when intraoperative flow opacification was abnormal and 0.98 when flow opacification was normal. For patients with normal flow, the estimated odds of having normal myocardial function were 3.33 times those of patients with abnormal flow at 1 week (odds ratio, 3.33; 95% CI, 1.09 to 10.19) and 18.5 timesthose of patients with abnormal flow at 1 month (95% Cl, 2.44 to 140.48). Conclusion: Intraoperative application of myocardial contrast echocardiography to determine regional flow patterns after revascularization may help differentiate conditions of left ventricular systolic dysfunction immediately after separation from CPB for CABG surgery and appear to predict myocardial function at 1 month.

OBJECTIVES: We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling. BACKGROUND: Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance. METHODS: Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation. RESULTS: Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern. After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns. However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling from 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RR interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables. CONCLUSIONS: With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling. Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern.

Objective: To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. Design: This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. Setting: Multicenter (two) independent university hospitals. Participants: 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. Interventions: 2 to 8 mL of Albunex were injected before and after coronary revascularization. Measurements and Main Results: Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL ± 4 (0.25 mL/kg). A single dose of 4.2 ± 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. Conclusion: Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.

Lzf1 and Lzf2 are leech zinc finger (Lzf) genes that are shown to be orthologues to the Drosophila gap gene hunchback (hb). Neither in situ hybridization nor RT-PCR detected Lzf1 transcripts in leech embryos or adults. Lzf2 expression was examined in leech embryos at various stages by in situ hybridization. Lzf2 is expressed continually throughout the early embryonic cleavage divisions, including the period during which the embryo forms stem cells that will give rise to the segmented tissues of the adult. At the time of segmental pattern formation, Lzf2 RNA is expressed uniformly along the length of the segmented trunk in both the ectodermal and mesodermal tissues. This is in contrast to the anteriorly restricted gradient of hb RNA shown to be critical to the normal anteroposterior (AP) patterning of the insect embryo. Thus, this leech orthologue of hb does not appear to play a comparable role in the patterning of the AP axis. In addition, Lzf2 is expressed during organogenesis in segmentally restricted patterns in the central nervous system, the gut, and epidermally derived structures. Lzf2 is the first hb orthologue to be characterized in detail outside of insects and its expression pattern suggests that hb may have acquired a gap gene function in arthropods or insects after their phyletic separation from the annelids.

Objectives. We studied the effects of chronic left ventricular unloading by a ventricular assist device and assessed left ventricular morphologic and histologic changes. Background. The implantable left ventricular assist device has been effective as a “bridge” to cardiac transplantation. Although there are reports documenting its circulatory support, little is known about the effects of chronic left ventricular unloading on the heart itself. Methods. We performed intraoperative transesophageal echocardiography at the insertion and explantation of a HeartMate left ventricular assist device in 19 patients with end-stage heart failure. They were supported by the assist device for 3 to 153 days (mean [±SD] 68±33). Measurements were taken retrospectively to obtain left atrial and ventricular diameters and interventricular septal and posterior wall thicknesses. Histologic examinations were made from the left ventricular myocardial specimens of 15 patients at the times of insertion and explantation for heart transplantation. Insertion and explantation specimens were compared qualitatively (0 to 3 scale) for wavy fibers, contraction band necrosis and fibrosis, with quantitative measurement of minimal myocyte diameter across the nucleus. Results. Left atrial and left ventricular diastolic and systolic diameters decreased immediately after insertion of the left ventricular assist device (from 46 to 35, 63 to 41 and 59 to 36 mm, respectively, all p < 0.001). Left ventricular wall thickness increased from 10 to 14 mm (p < 0.001) for the interventricular septum and from 10 to 13 mm for the posterior wall (p < 0.001). No echocardiographic measurements showed significant subsequent changes at the chronic stage. Myocardial histologic findings demonstrated a reduction in myocyte damage (from 1.9 to 0.5, p < 0.001, for wavy fiber and from 1.3 to 0.2, p < 0.01, for contraction band necrosis) and an increase in fibrosis (from 1.3 to 1.9, p < 0.05), but without significant change in myocyte diameter (from 15.6 to 16.8 μm, p = 0.065). Conclusions.Left ventricular unloading with the implantable assist device induces an immediate increase in wall thickness, consistent with the reduction in chamber size, thereby decreasing wall stress. Chronic unloading allows myocardial healing and fibrosis without evidence for ongoing myocyte damage or atrophy. Left ventricular assist device insertion may have a role in “resting” the ventricle for selected patients with heart failure.

Long-term support on the implantable left ventricular assist device (LVAD) produces structural changes in the recipient's heart. To assess the possibility of heart "recovery" we reviewed the records of 19 HeartMate LVAD recipients to determine structural and left ventricular histologic changes during LVAD support. Intraoperative transesophageal echocardiographic studies were performed in the operating room before LVAD insertion, immediately after LVAD insertion, and at explantation and heart transplantation (mean duration of support, 76 +/- 34 days). The initiation of LVAD pumping led to an immediate decrease (p < 0.001) in left ventricular dimensions, which were not significantly different by the time of device explantation. Left ventricular fractional shortening did not significantly improve during LVAD support (0.07 +/- 0.03 before LVAD; 0.11 +/- 0.10 immediately after LVAD; 0.11 +/- 0.11 before explantation). Histologic specimens showed a significant reduction in the number of wavy fibers, and contraction band necrosis (p < 0.01), both markers of acute myocyte damage. However, myocardial fibrosis increased (p < 0.05). Myocyte diameter increased slightly (p = 0.07). We conclude that implantable LVAD support is associated with immediate changes in ventricular structure. Histologic markers of acute myocyte damage improve, but fibrosis increases. Because the structural changes occur immediately, they do not indicate "recovery" of left ventricular function, but merely changes in loading conditions.

Patients with abdominal aortic aneurysms (AAA) have a high incidence of associated cardiac disease. If a patient presents with both severe coronary artery disease and a large AAA, a staged procedure of cardiac surgery (CS) followed by AAA resection may present too great a risk of aneurysm rupture and death. A combined procedure may be recommended in this circumstance; however, the literature contains only individual successful case reports of such a procedure. A series of 10 patients who underwent CS and AAA repair to define the risks and outcome of this complex patient population is presented. Methods used included a retrospective analysis of hospital chart data from patients undergoing combined CS and AAA resection from 1980 to the present at this institution. The data analyzed included age, sex, chief complaint, past medical history, indications for surgery, abdominal aneurysm size, coronary anatomy, valvular pathology, preoperative left ventricular function, anesthetic agent and dose, order of surgery, prebypass complications, intraoperative complications, cardiopulmonary bypass time, aortic cross-clamp time, abdominal aortic cross-clamp time, blood product use, and postoperative complications. Seven of the 10 patients had a successful outcome (S group), whereas 3 of the 10 patients died postoperatively (D group). The staged procedure of first performing CS and then the AAA resection has a combined operative mortality of 4%. When the nature of both lesions is severe and a combined procedure is necessary, there is an associated in-hospital mortality of approximately 30% at this institution. The S group patients had an unremarkable postoperative course with a relatively short hospital stay when compared to the staged procedure.

The hunchback (hb) gene is a member of the gap class of segmentation genes first identified in the dipteran insect Drosophila melanogastor. The hb gene encodes a C(2)H(2) zinc finger transcription factor whose primary function is to regulate the expression of its target genes along the anteroposterior (AP) axis based on its distribution in the blastoderm embryo. The loss of zygotic hb in Drosophila results in a "gap" in anterior pattern elements that include the loss of labial and thoracic segments in addition to the fusion of the abdominal segments 7 and 8. The hunchback protein is also expressed in the extraembryonic epithelial tissues and the developing nervous system in the zygote. Although the role of hunchback in AP patterning is likely to be an ancestral trait to the insect clade, higher order comparisons of hunchback orthologs suggest that it is a derived trait specific to the arthropod and/or insect lineage. This view is supported by a combination of comparative gene expression data, phylogenetic analyses, and an examination of the evolution of structural domains in the hb protein isolated from annelids, nematodes, and insects. The 3 independent lines of comparative data strongly support the idea that the anterior organizing function of hb originated in the arthropod and/or insect lineage and that its roles in epithelial and CNS patterning are likely to be broadly conserved within protostomes.

Chapter 19 discusses invasive cardiology procedures performed in the cardiac catheterization laboratory (CCL), the electrophysiology laboratory (EPL), and the transesophageal echocardiography laboratory, and which have become the purview of anesthesiologists. Common CCL procedures include the following: diagnostic cardiac catheterizations, percutaneous coronary interventions, peripheral vascular diagnostic and therapeutic procedures, implantation of percutaneous left ventricular assist devices, placement of septal occlusion devices, and percutaneous valve repair or replacement procedures. Common EPL procedures consist of EP studies, atrial and ventricular radiofrequency (RF) ablation procedures, implantation and removal of pacing and cardioverter defibrillator devices, and electrical cardioversion. TEE procedures include trans-esophageal echocardiography (TEE) and combined TEE/direct current cardioversions (DCCV). All of these procedures may require the involvement of anesthesiologists if the patient has significant comorbidities or if the procedure requires that the patient be absolutely still and/or asleep.

A completely implanted total artificial heart (TAH) is under development by Nimbus, Inc., and the Cleveland Clinic Foundation (CCF). Key features of the system include an electrohydraulic energy converter, an automatic control system that produces a Frank-Starling response, and dual ventricles composed of graphite-epoxy and titanium with gelatin blood contacting surfaces. The system is controlled by a single substrate, hybridized microcircuit (the hybrid). Fabrication of the TAH control hybrid has recently been completed and testing begun. Its design emphasizes simplicity, reliability, and efficiency. Particular attention was given to optimizing thermal management. Externally controlled TAH systems have been used in eight in vivo experiments of up to 120 days' duration. In the last two of these experiments, a variable volume device was also implanted with excellent results. In vivo use of the system has demonstrated the Frank-Starling pump response, but the systems quickly reach maximum output with the bovine animal models. Human fitting studies, including adult patients undergoing heart transplantation, demonstrated satisfactory fit of the pump within the pericardium without compression of the vascular structures or chest wall. Measurements of chest circumference, plain chest films, and transesophageal echocardiograms should provide reliable predictions of pump fit in the majority of patients.

MULTIPLE ORGAN transplantation including combined procedures involving the liver and the heart have been reported previously,1-7 but the number of these cases in the literature is small. Severe valvular heart disease not requiring orthotopic heart transplantation may occasionally be encountered in patients with end-stage liver disease (ESLD). Several cases of valvular heart disease requiring either valve repair or replacement secondary to bacterial endocarditis performed subsequent to orthotopic liver transplantation (OLT) have been reported.8-11 Two instances of aortic valve replacement (AVR) for aortic stenosis after liver transplantation have been presented in the literature.12,13 The authors now report the first case of combined AVR and OLT.

Immediate recall and three measures of delayed memory performance were evaluated in 134 healthy adults aged 16-76. Gender of subjects had no Influence on performance for any of the acquisition or retention trials. Age influenced acquisition as memory load began to exceed five to six words, with older subjects exhibiting decreased capacity. There was little loss of information between the immediate and delayed recall trials for any age group. Norms for a 30-min delayed recall trial, commission errors on delayed recall, and delayed recognition using Rey's story recognition procedure are presented, and implications for clinical use are discussed.

We report the expression of Hunchback (Hb)-like protein during embryonic and larval development in two caenogastropods, Crepidula fornicata and Ilyanassa obsoleta. During the cleavage stages of these species, Hb-like protein is uniformly expressed in micromere and macromere nuclei. At gastrulation, gastropod Hb-like protein is expressed in the surface epithelium that undergoes epiboly. During organogenesis, gastropod Hb-like protein is expressed in the developing ciliated structures associated with feeding and locomotion. We find no detectable gradient or regionalization of Hb-like protein in gastropod embryos or larvae that resembles the graded Hb pattern of expression observed in dipteran insect embryos. Rather we found that the spatiotemporal expression profile of gastropod Hb-like protein is nearly identical to the Hb-like patterns obtained from the polychaete Capitella sp. I and is highly similar to those reported for clitellate annelids. Based upon the comparative data collected from both ecdysozoans and lophotrochozoan lineages, our results support the hypothesis that the role of Hb in anteroposterior patterning is a derived trait specific to arthropods, and that the ancestral function of lophotrochozoan Hb-like protein played a role in the formation of the cleavage-stage blastomeres and the gastrula epithelium and in structures associated with larval feeding and locomotion.

M itral valve repair was first suggested in 1902 by Sir Thomas Brunton (1) as a surgical approach to patients with rheumatic mitral valve disease. However, it was not until after the introduction of the heart-lung machine in 1953 by Gibbons (2) that techniques for the repair of pure mitral valve regurgitation were first introduced by Lillehei et al. (3) in 1957. Because of the development of prosthetic valves, however, further investigation into these techniques was not continued until the limitations of mechanical and bioprosthetic valves became apparent and mitral valve repair became a more viable alternative. In the 1970s, the field was revolutionized when Carpentier et al. (4) presented data detailing the anatomic changes in patients with mitral insufficiency and introduced a physiologic classification of the causes of mitral insufficiency. This provided the foundation of our current understanding of the echocardiographic patterns and anatomic mechanisms of mitral valve regurgitation. Both Carpentier et al. (4), in France, and Duran et al. (5), in Spain, developed mitral valve repair techniques primarily for the management of patients with rheumatic mitral disease. These procedures were attractive to surgeons in the United States who foresaw potential benefits for an older patient population with mitral regurgitation as a result of myxomatous degeneration and ischemia (6,7). From the beginning of the 20th century to the turn of the 21st century, mitral valve repair procedures have developed from a surgical suggestion to a therapeutic intervention used in .2000 patients annually in the United States (8). Valve repair for the management of mitral regurgitation offers the advantages of less perioperative morbidity and mortality, preservation of the mitral tensor apparatus with better maintenance of ventricular function, freedom from anticoagulation, long-term durability, and freedom from reoperation (9). However, the surgical valve repair technique is more technically demanding for the surgeon. The development of improved myocardial protection during cardiopulmonary bypass and the technological advancements of intraoperative echocardiography have enhanced the development of innovative surgical techniques for reparative surgery. Both transesophageal and epicardial echocardiography provide an intraoperative safety net that helps to optimize surgical results with transference of real-time information to the surgical team regarding the underlying valve structure, physiologic abnormality, mechanism, and pathologic process. Intraoperative echocardiography has the added advantage of shortening the learning curve for those surgeons who are incorporating the valve repair techniques into their practice, which translates to benefits for patients. The article by Lambert et al. (10) serves as a reminder of the importance of a comprehensive and systematic transesophageal echocardiographic (TEE) evaluation of the mitral valve apparatus in patients undergoing reparative procedures for mitral regurgitation. Their evaluation included a multiplane segment by segment characterization of leaflet structure and mobility, anatomy of the commissure and subvalvular apparatus, annular and ventricular size, and severity and direction of the regurgitant jet. Successful valve repair requires an understanding of the etiology and mechanism of valve regurgitation. This knowledge is a major determinant of the probability of successful repair, which may vary from 98% in patients with a flail middle scallop of the posterior leaflet to 20% in patients with severe rheumatic valvular disease and restricted bileaflet motion. In their prospective study, Lambert et al. (10) report a small population of 13 patients who underwent surgery for significant mitral regurgitation. The mechanism of regurgitation and location of pathology was identified by using this systematic echocardiographic examination in 12 patients (92%) compared with a Accepted for publication February 26, 1999. Address correspondence and reprint requests to Robert M. Savage, MD, FACC, Department of Anesthesiology, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195.

Objectives The primary objective of this study was to analyze perioperative intra-aortic balloon pump (IABP) insertion in patients undergoing cardiac surgery in the authors' institution from 1995 to 2005 and to propose an explanation for changes in use over this period. A secondary objective was to assess patient variables associated with IABP use. Design This is a retrospective study including patients who underwent cardiac surgery between 1995 and 2005. Setting The Cardiothoracic Anesthesia Patient Registry of a single teaching institution was queried to obtain the required information. Participants Thirty thousand two hundred sixty-nine cardiac surgery patients. Interventions Intra-aortic balloon pump insertion before surgery, after cardiopulmonary bypass, or in the cardiovascular intensive care unit was assessed in patients who underwent isolated coronary artery bypass graft surgery, valve surgery, or both. Select patient variables were analyzed for their association with IABP insertion. Transesophageal echocardiography (TEE) examinations, milrinone use, and mortality rates also were determined. Measurements and Main Results Among 30,269 cardiac surgery patients, 1,310 (4.32%) underwent IABP insertion. Combined preoperative, intraoperative, and postoperative IABP use decreased from 7.8% in 1995 to 3.0% in 2005. Simultaneously, the intraoperative use of milrinone increased from 4.8% to 8.8% and postoperative use increased from 5.2% to 7.8%. The number of intraoperative TEE examinations more than doubled from approximately 1,700 to 3,500. The overall mortality for patients with preoperative, intraoperative, and postoperative IABP insertion was 12.6%, 17.5%, and 47.7%, respectively. Conclusions From 1995 to 2005, preoperative, intraoperative, and postoperative IABP use decreased by approximately 60% in cardiac surgery patients. Simultaneously, the use of TEE and milrinone each doubled. Although a cause-effect relationship cannot be established from the present study's observational data, the trends coincide and may be related.

Joseph P. Mathew, MD, FASEKathryn Glas, MD, FASEChristopher A. Troianos, MDPamela Sears-Rogan, MD, FASERobert Savage, MDJack Shanewise, MD, FASEJoseph Kisslo, MD, FASESolomon Aronson, MD, FASEStanton Shernan, MD, FASEfor the Council for IntraoperativeEchocardiography of theAmerican Society ofEchocardiography*

Joseph P. Mathew, MD, FASE, Kathryn Glas, MD, FASE, Christopher A. Troianos, MD, Pamela Sears-Rogan, MD, FASE, Robert Savage, MD, Jack Shanewise, MD, FASE, Joseph Kisslo, MD, FASE, Solomon Aronson, MD, FASE, and Stanton Shernan, MD, FASE, for the Council for Intraoperative Echocardiography of the American Society of Echocardiography, Durham, North Carolina, Atlanta, Georgia, Pittsburgh, Pennsylvania, Washington, DC, Cleveland, Ohio, New York, New York, and Boston, Massachusetts

Current conceptualizations of schizophrenia include neurocognitive impairment, particularly in aspects of attention, memory, and executive functioning. Evaluation of these cognitive abilities typically involves use of comprehensive batteries which may take up to six hours to complete. The current study examined the effectiveness of a briefer battery to detect cognitive impairments usually seen in schizophrenia as established by previous studies using more lengthy and labor intensive protocols. The current study involved 61 outpatients with schizophrenia who were separated into three subgroups: paranoid type (n = 20), undifferentiated type (n = 21), and schizoaffective (n = 20). The majority of the patients were male (61%), African-American (52%), and of low socio-economic status. The mean age was 41.4 years (SD = 8.8), and the mean years of education was 11.7 (SD = 6.8). For the overall sample, results revealed mild to moderate impairments in memory, construction, concept formation, response set maintenance, psychomotor speed, and visual speed of information processing. Post-hoc analyses revealed significant differences between subgroups on Similarities and psychomotor speed, with the undifferentiated group performing more poorly than the paranoid or schizoaffective groups. In conclusion, the current brief battery minimized respondent burden in terms of both time demands and level of task complexity. However, it was also sensitive enough to capture many of the same cognitive weaknesses as those reported when using more labor-intensive neuropsychological test protocols.

The early expression patterns of hunchback protein (T-hb protein) were examined in the oligochaete Tubifex, using an antibody raised to the LZF2 protein in leech. This antibody recognizes a 60-kDa polypeptide in the Tubifex embryo. Before teloblastogenesis, T-hb protein is expressed in every cleavage-stage blastomere. At the completion of teloblastogenesis, the only cells expressing T-hb are a fraction of the micromere-derived epithelial cells. During gastrulation, nuclear T-hb is seen in spreading micromere-derived epithelial cells and also in a subset of ectodermal teloblasts. Comparisons of these results with those from other annelids suggest that hb expression in the early cleavage blastomeres and the micromere-derived epithelium are features highly conserved among annelids. In contrast, hb expression in teloblasts appears to be an innovation evolved in the oligochaetes.

Background: The high mortality rate of congestive cardiac failure, the cost and complications of cardiac transplantation, and the waiting list mortality rate resulting from donor organ scarcity have encouraged the development of surgical techniques as bridges to transplantation or as long-term palliative therapy. Implantable left ventricular assist devices are now routinely used as such a bridge, and within the REMATCH Trial, as permanent palliative devices in nontransplant candidates. These are mechanical managements with myriad mechanical complications and pitfalls. Echocardiography has been extensively used in our institution to detect and diagnose previously documented and hitherto unencountered complications of these procedures. Methods and Results: The role of echocardiography in these procedures, including preoperative patient selection, intraoperative transesophageal echocardiography, and postoperative troubleshooting and late follow-up, is discussed. We describe our clinical echocardiographic approach, which has developed over 91 assist-device procedures. The relative frequency and clinical impact of specific anatomic, physiologic, hemodynamic, and mechanical features are described. New techniques such as the Doppler quantification of assist device inflow obstruction are illustrated, as are the device cannula position, the detection of device valve failure, and the parameters related to the remodeling procedure. Conclusions: Echocardiography in heart failure surgery has proved to be an invaluable tool in the diagnosis and management of mechanical complications. The experience gained in our institution may serve as an aid to new surgical programs treating these critically ill patients. (J Am Soc Echocardiogr 2000;13:754-63.)

Since the introduction of transesophageal echocardiography (TEE) to the operating room in the early 1980s,1-4 its effectiveness as a clinical monitor to assist in the hemodynamic management of patients during general anesthesia and its reliability to make intraoperative diagnoses during cardiac operations has been well established.5-26 In recognition of the increasing clinical applications and use of intraoperative TEE, the American Society of Echocardiography (ASE) established the Council for Intraoperative Echocardiography in 1993 to address issues related to the use of echocardiography in the operating room. In June 1997, the Council board decided to create a set of guidelines for performing a comprehensive TEE examination composed of a set of anatomically directed cross-sectional views. The Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography has endorsed these guidelines and standards of nomenclature for the various anatomically directed cross-sectional views of the comprehensive TEE examination. This document, therefore, is the collective result of an effort that represents the consensus view of both anesthesiologists and cardiologists who have extensive experience in intraoperative echocardiography. The writing group has several goals in mind in creating these guidelines. The first is to facilitate training in intraoperative TEE by providing a framework in which to develop the necessary knowledge and skills. The guidelines may also enhance quality improvement by providing a means to assess the technical quality and completeness of individual studies. More consistent acquisition and description of intraoperative echocardiographic data will facilitate communication between centers and provide a basis for multicenter investigations. In recognition of the increasing availability and advantages of digital image storage, the guidelines define a set of cross-sectional views and nomenclature that constitute a comprehensive intraoperative TEE examination that could be stored in a digital format. These guidelines will encourage industry to develop echocardiography systems that allow quick and easy acquisition, labeling, and storage of images in the operating room, as well as a simple mechanism for side-by-side comparison of views made at different times. ASE/SCA Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography

We are interested in identifying the regulatory genes involved in segmental pattern formation in annelids. The Drosophila segmentation gene hunchback (hb) is critical for the proper anteroposterior development of the fly embryo, but its function outside the diptera is currently unknown. Here, the protein expression pattern of Leech Zinc Finger II (LZF2), a leech orthologue of hb is characterized. In early embryogenesis, LZF2 protein is expressed in a subset of micromeres and is later expressed in the micromere-derived epithelium of the provisional epithelium and prostomium. LZF2 protein is detected in the ventral nerve cord during organogenesis, first in interganglionic muscle cells and later in subsets of neurons in each neuromere of the CNS. The location of immunoreactive cells during development and the similarity of the expression pattern of LZF2 to the expression of the Caenhorhabditis elegans hb homologue hbl-1 suggests that LZF2 plays a role in the morphogenetic movements of leech gastrulation and later in CNS specification but not in anteroposterior pattern formation.

Background. Intraoperative echocardiography is a valuable monitoring and diagnostic technology used in cardiac surgery. This reports our clinical study of the usefulness of intraoperative echocardiography to both surgeons and anesthesiologists for high-risk coronary artery bypass grafting. Methods. From March to November 1995, 82 consecutive high-risk patients undergoing coronary artery bypass grafting were studied in a four-stage protocol to determine the efficacy of intraoperative echocardiography in management planning. Alterations in surgical and anesthetic/hemodynamic management initiated by intraoperative echocardiography findings were documented in addition to perioperative morbidity and mortality. Results. Intraoperative echocardiography initiated at least one major surgical management alteration in 27 patients (33%) and at least one major anesthetic/hemodynamic change in 42 (51%). Mortality and the rate of myocardial infarction in this consecutive high-risk study population using intraoperative echocardiography and in a similar group of patients without the use of intraoperative echocardiography was 1.2% versus 3.8% (not significant) and 1.2% versus 3.5% (not significant), respectively. Conclusions. We conclude that when all of the isolated diagnostic and monitoring applications of perioperative echocardiography are routinely and systematically performed together, it is a safe and viable tool that significantly affects the decision-making process in the intraoperative care of high-risk patients undergoing primary isolated coronary artery bypass grafting and may contribute to the optimal care of these patients.

Objetivo: Estudar a experiência inicial em assistência circulatória ventricular esquerda com o aparelho pneumático implantável Heart Mate® 1000 IP, analisando suas características e aplicações clínicas. Material e Métodos: Entre dez/91 e set/94 (45 meses) 33 pacientes em choque cardiogênico por miocardiopatia isquêmica ou dilatada foram assistidos, com esse aparelho, por um tempo de 0 a 153 dias (média de 76 dias, nos pacientes que chegaram a ser transplantados). O diagnóstico, o tempo de assintência circulatória, os parâmetros hemodinâmicos (índice cardíaco, gradiente transpulmonar, fração de ejeção do ventrículo direito, resistência vascular pulmonar e variação da área do ventrículo direito), assim como as complicações clínicas são apresentados e discutidos. Valores pré e pós implante são apresentados como média +/- desvio padrão e comparados por teste T pareado. Resultados: A melhora hemodinâmica foi estatisticamente significante (p

Pulmonary venous flow measured by pulsed-wave Doppler transesophageal echocardiography reflects the effects of mitral regurgitation on left atrial pressure contour. To assess the relationship between pulmonary venous flow and left atrial pressure in patients with mitral regurgitation under altered loading conditions, we studied 25 patients with 3+ or 4+ mitral regurgitation and a control group by measuring pulmonary venous flow with transesophageal echocardiography and left atrial pressures after administering saline solution (n = 6), nitroglycerin (n = 6), phenylephrine (n = 6), or nitroprusside (n = 7). After administration, the left atrial pressure v wave increased in the group given phenylephrine, concomitant with an increased diastolic flow. In contrast, the left atrial pressure v wave decreased in the group given nitroglycerin, concomitant with a decreased diastolic flow. Changes in diastolic flow were closely related to changes in the left atrial pressure v wave under all loading conditions (r = 0.91; p0.0001). Numeric modeling of left atrial pressure and pulmonary venous diastolic flow corroborated the experimental findings. We conclude that changes in pulmonary venous diastolic flow are closely related to changes in the left atrial pressure v wave in mitral regurgitation, under altered loading conditions.

The posterior leaflet sliding advancement procedure was developed to prevent the occurrence of systolic anterior motion of mitral valve and consequently outflow obstruction after mitral annuloplasty. We present a patient with extremely redundant posterior mitral leaflet in whom outflow obstruction developed despite employment of this procedure. This case underscores the utility of preoperative and intraoperative echocardiography in surgical decision making. Systolic anterior motion can develop in some patients despite this new surgical technique.

In the spawned Xenopus egg, germ plasm is found as cytoplasmic islands spread over a wide cortical region of the vegetal pole. However, by the blastula stage, the same material is found concentrated into a few large blastomeres at the floor of the blastocoel. Components of the germ plasm can be specifically labeled with a fluorescent dye, DiOC6(3), permitting the dynamic movements of germ plasm localization to be followed in live embryos via time-lapse confocal scanning optical microscopy. During the first cell cycle, the small islands initially appear to be fixed to the vegetal yolk mass and to move with it during the cortical rotation. After rotation, the islands appear to be released from the vegetal yolk mass and to begin fusing with one another. During early cleavages, the germ plasm aggregates into large islands at the vegetal pole in a movement dependent on microtubules. Two distinct actions can be discerned: (1) a continuous process of local fusing and (2) periodic surface contraction waves (SCWs) that gather the islands toward the vegetal pole. These SCWs are inhibited by ultraviolet irradiation of the vegetal pole. Near the vegetal pole, germ plasm patches ingress into the embryo's interior along the cleavage furrow in periodic movements contemporaneous with the SCWs.

The Serum Response Element (SRE) is a sequence motif which activates transcription of certain genes in response to factors that stimulate cell proliferation. This motif is found in the promoter of aXenopus laevis cytoskeletal actin gene, which is transcriptionally activated very early in embryonic development. We tested whether the SRE plays a role in the developmentally-timed transcriptional activation of this gene by constructing an SRE replacement mutant and studying its transcription after microinjection intoXenopus embryos. Normal amounts of actin mRNA are transcribed at the normal time in development from this mutant, suggesting that the SRE is not the sole determinant of temporal specificity of actin gene transcription in the embryo.