Enabling dual cellular destinations of polymeric nanoparticles for treatment following partial injury to the central nervous system.

Following neurotrauma, oxidative stress is spread via the astrocytic syncytium and is associated with increased aquaporin 4 (AQP4), inflammatory cell infiltration, loss of neurons and glia and functional deficits. Herein we evaluate multimodal polymeric nanoparticles functionalized with an antibody to an extracellular epitope of AQP4, for targeted delivery of an anti-oxidant as a therapeutic strategy following partial optic nerve transection. Using fluorescence microscopy, spectrophotometry, correlative nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy, in vitro and in vivo, we demonstrate that functionalized nanoparticles are coated with serum proteins such as albumin and enter both macrophages and astrocytes when administered to the site of a partial optic nerve transection in rat. Antibody functionalized nanoparticles synthesized to deliver the antioxidant resveratrol are effective in reducing oxidative damage to DNA, AQP4 immunoreactivity and preserving visual function. Non-functionalized nanoparticles evade macrophages more effectively and are found more diffusely, including in astrocytes, however they do not preserve the optic nerve from oxidative damage or functional loss following injury. Our study highlights the need to comprehensively investigate nanoparticle location, interactions and effects, both in vitro and in vivo, in order to fully understand functional outcomes.

Annular and leaflet augmentation in Noonan's syndrome with dysplastic pulmonary valve.

Two patients with dysplastic pulmonary valves associated with Noonan's syndrome successfully underwent leaflet augmentation with pericardial membrane and annular enlargement with preservation of valve competence. Both patients are doing well at 36 and 37 months, respectively, postoperatively. Echocardiography and clinical assessment showed gradients of 12 and 16 mmHg, respectively, and negligible pulmonary valve insufficiency. The surgical technique is simple and provides an attractive alternative in patients with dysplastic pulmonary valve and small pulmonary orifice and annulus.

Effects of race, with or without gender, on operative mortality after coronary artery bypass grafting: a study using The Society of Thoracic Surgeons National Database.

BACKGROUND: Although gender is known to be an independent predictor of 30-day operative mortality (OM) after coronary artery bypass grafting, the purpose of this study was to determine whether race-alone or in combination with gender-affects OM. METHODS: For 1994 to 1996, The Society of Thoracic Surgeons database records for 441,542 coronary artery bypass grafting-only procedures were analyzed. Baseline annual multivariate models were built. Gender and race were added to each model. Risk-adjusted OM rates were then calculated for race, gender, and their combination. Patients were also stratified into groups of comparable predicted OM to allow for a direct comparison of risk-matched Caucasians and non-Caucasians. RESULTS: Of the procedures, 28.2% were on women and 8.5% on non-Caucasians. Overall, OM was 3.29%. Multivariate risk-adjusted OM varied by gender and race (p < 0.10). Risk-adjusted OM rates (with 95% confidence intervals) were 4.0% (3.9% to 4.1%) for females and 3.2% (3.2% to 3.3%) for males. Risk-adjusted OM rates were 3.9% (3.7% to 4.1%) for non-Caucasians and 3.3% (3.2% to 3.3%) for Caucasians. Among equally risk-matched Caucasians and non-Caucasians, non-Caucasians had significantly higher (p < 0.005) mortality among the lower risk subgroups (up to 10% predicted OM) but not among the higher risk subgroups. CONCLUSIONS: Race and gender are independent predictors of adverse outcome following coronary artery bypass grafting, holding all other risk factors constant.

Late mediastinal shift after repeated aspiration of postpneumonectomy seroma.

Development of a postoperative seroma is a frequent complication after muscle-sparing thoracotomy. We describe an unusual case of late mediastinal shift in a patient in whom our original plan to perform a limited muscle-sparing thoracotomy was abandoned. The procedure was converted to a standard posterolateral incision to perform a pneumonectomy for a large central carcinoid tumor with extrabronchial extension. Fluid that accumulated in her pneumonectomy space presumably shifted into the dissected tissues of her chest wall, and was then drained repeatedly by her local physician in the time interval between 2 weeks and 3 months after surgery.

Assessing quality in cardiac surgery: why this is necessary in the twenty-first century.

The cost and high-profile nature of coronary surgery means that this is an area of close public scrutiny. As much pioneering work in data collection and risk analyses has been carried out by cardiac surgeons, substantial information exists and the correct interpretation of that data is identified as an important issue. This paper considers the background and history of risk-adjustment in cardiac surgery, the uses of quality data, examines the observed/expected mortality ratio and looks at issues such as cost and reactions to outliers. The conclusion of the study is that the continuation of accurate data collection by the whole operative team and a strong commitment to constantly improving quality is crucial to its meaningful application.

9:45-10:00. Superimposition of EBCT Determined Coronary Calcium Deposits onto Myocardial PET Perfusion Images by Rubidium-82 and Nitrogen-13 Ammonia for Assessment of Flow Limiting Defects.

Calcium localization by Electron Beam CT (EBCT) in the coronary arteries is becoming an important non-invasive method for screening asymptomatic patients for early coronary atherosclerosis. However, the relationship between coronary artery calcium deposits and myocardial perfusion abnormalities has not been established. We have developed software to superimpose location of coronary calcium by EBCT onto PET myocardial perfusion images, so that we can determine the role of location and amount of calcium in the arteries to flow-limiting perfusion defects by PET.EBCT and PET transaxial images are each first converted to three-dimensional arrays of 1 mm voxels. The resulting two image volumes sets are displayed so that a vertical line can be drawn from the clavicle to the spine for proper rotation of the body. The rotated images are then displayed superimposed and are shifted in the vertical, horizontal, and the long axis directions to co-register the EBCT and PET images. The EBCT images are windowed for calcium Houndsfield numbers and calcium location is added to the PET images as a maximum intensity value in the image. The modified PET image volume is then translated back to the PET data format and reprocessed using cardiac analysis software such that the calcium location is superimposed on the PET myocardial perfusion images.Preliminary results of the PET-EBCT superimposition program correlate with location of coronary calcium by EBCT and PET perfusion defects following stress. This technique may be useful for identifying flow-limiting calcium deposits in the coronary arteries.

Aortic thrombosis after lumbar spine surgery.

A case of distal aortic occlusion after circumferential lumbar spine surgery is presented. The paradoxical clinical findings are discussed.

Surgery for chronic thromboembolic pulmonary hypertension.

The modern era of surgery for chronic thromboembolic pulmonary hypertension (CTEPH) began just over 10 years ago. Until that time pulmonary thromboendarterectomy (PTE) was performed infrequently and essentially at a single medical center (University of California at San Diego-UCSD). It posed a formidable technical challenge and was associated with both high operative mortality (> 20%) and excessive morbidity due to respiratory and multiorgan system failure. Currently PTE is performed at numerous medical centers throughout the world, largely due to the pioneering efforts of those surgeons who developed and perfected the operation at UCSD. Operative mortality rates have fallen, and postoperative complications have become less common. Although no longer simply an autopsy curiosity, CTEPH continues to be an underdiagnosed condition. Increased awareness and better diagnosis will lead to curative surgery in more patients worldwide.

Esophageal Doppler ultrasound monitor versus pulmonary artery catheter in the hemodynamic management of critically ill surgical patients.

BACKGROUND: The pulmonary artery (PA) catheter has been used to determine hemodynamic indices; however, it has recently been criticized. This study was undertaken to evaluate an esophageal Doppler monitor (EDM) as a possible replacement for PA catheter in critically ill, mechanically ventilated patients. METHODS: EDM and PA catheters were placed in patients in the surgical intensive care units (n = 14, 118 matched sets of data). PA catheter and EDM measurements, including corrected flow time (FTc,) a measure of preload, were obtained. Pearson correlation (r) was analyzed to compare PA catheter and EDM measurements, and a nonlinear regression model was used to describe Starling Relationships. RESULTS: Cardiac output correlated between EDM and PA catheter (r = 0.6; p < 0.001). FTc correlated more strongly with cardiac output than did pulmonary capillary wedge pressure. (FTc: r2 = 0.27; p < 0.001; cardiac output: r2 = 0.04; p = 0.06). CONCLUSION: Corrected flow time is a better indicator of preload than pulmonary capillary wedge pressures. EDM seems to be at least as useful as PA catheter in managing the hemodynamic status of critically ill surgical patients.

Tremorgenic indole alkaloids. Studies directed toward the assembly of the A, F, and I rings of penitrem D: observation of an unexpected stereochemical outcome.

[formula: see text] In this Letter we demonstrate the viability of a highly stereoselective tandem Mannich cyclization-grammine fragmentation/addition cascade, critical for assembly of the A and F rings of penitrem D. We also explored simultaneous execution of this tactic with concurrent construction of ring I. Reinvestigation of a model system provided an explanation for the unanticipated stereochemical outcome at C(28).

Impact of gender on coronary bypass operative mortality.

BACKGROUND: In spite of many reports investigating the influence of gender on coronary artery operations, it is still uncertain whether gender is an independent risk factor for operative mortality. A major problem of previous reports has centered around the fact that men and women constitute quite different populations, thereby making direct comparisons difficult. METHODS: The Society of Thoracic Surgeons National Cardiac Surgery Database was used to retrospectively examine 344,913 patients undergoing coronary artery bypass graft operations from 1994 through the most recent data harvest. The operative mortality of male and female patients was compared for a variety of single risk factors and combinations of risk factors. A logistic risk model was used to account for all important patient parameters so that individuals could be stratified into comparable categories allowing for direct comparisons of risk-matched male and female patients. RESULTS: The univariate analysis showed that the 97,153 women carried a significantly higher mortality for each of the risk factors examined. The multivariate analysis and the risk model stratification showed that women had significantly higher mortality as compared to equally matched men in the low- and medium-risk part of the spectrum, but in high-risk patients, there was no difference between male and female mortality. CONCLUSIONS: Gender is an independent predictor of operative mortality except for patients in very high-risk categories.

Mitral valve replacement in Sickle C disease using intraoperative exchange transfusion.

Sickle C (SC) disease is a relatively uncommon hematologic disorder that poses special challenges when the patient requires a major surgical procedure. In particular, those who have a history of hemolytic crises require some type of intervention, usually homologous transfusion, to decrease the level of circulating hemoglobin S (HbS) and prevent intraoperative sickle crisis. We describe a 25-year-old man with SC disease and a history of multiple sickle cell crises who underwent mitral valve replacement using intraoperative exchange transfusion to decrease his HbS level from 53% to 7%.

Prevention of ischemic damage using controlled limb reperfusion.

Following prolonged limb ischemia, a reperfusion injury may occur with the reintroduction of unmodified blood, resulting in tissue loss and, in severe cases, limb loss. We have shown that the reperfusion injury in the heart can be minimized by using controlled reperfusion with a substrate-enriched cardioplegia solution prior to restoring normal blood flow. This article describes two clinical cases in which we used controlled reperfusion in an ischemic limb to prevent limb loss. It demonstrates that a controlled, substrate-enhanced, hypocalcemic, leukodepleted, modified blood reperfusate solution can minimize limb reperfusion damage and improve functional recovery. This preliminary experience is presented to familiarize surgeons with this form of treatment and to describe the solutions and method of administration that can be used to avoid the devastating complications of severe limb ischemia.

Embolization of IMA side branch for post-CABG ischemia.

The existence of a chest wall "steal" of blood away from the myocardium through patent internal mammary artery branches has been hypothesized as a cause of recurrent angina pectoris after coronary artery bypass grafting. Although some authors believe that such a steal is physiologically impossible because coronary flow occurs in diastole and chest wall flow in systole, we recently documented ischemia in the left anterior descending coronary artery distribution before embolization of a large left internal mammary artery first intercostal branch that had been left intact at the time of operation. After embolization of the branch, clinical and objective evidence of ischemia resolved.

Predictors of mortality in pulmonary thromboendarterectomy.

BACKGROUND: The operative mortality associated with surgical thromboendarterectomy of the pulmonary arteries has decreased at the University of California in San Diego with the application of new techniques. For universal performance of the procedure, however, those factors that contribute to the high operative mortality must be identified. We analyzed our results in 34 consecutive patients undergoing pulmonary thromboendarterectomy to determine those preoperative factors that contribute to operative mortality. METHODS: Since 1983, 34 patients with severe, surgically correctable chronic thromboembolic pulmonary hypertension who were judged to be operable by pulmonary arteriography underwent pulmonary thromboendarterectomy. No patient was excluded because of right ventricular failure or hemodynamic severity of disease; the mean pulmonary artery pressure (PAP) was 54 mm Hg, the mean pulmonary vascular resistance (PVR) was 1,094 dynes.s.cm-5, and all patients were in New York Heart Association functional class III or IV. RESULTS: Postoperative course was characterized either by swift recovery (mean length of stay, 13 days) or by rapid demise resulting from pulmonary or right ventricular failure, or both (overall operative mortality, 23%). In survivors, the mean PAP, PVR, cardiac output, and New York Heart Association functional class were significantly improved (p < 0.05). Patients who died had a significantly greater mean preoperative PAP than did those who survived (62.1 +/- 1.2 versus 49.5 +/- 2.3 mm Hg; p < 0.01) and significantly higher PVR (1,512 +/- 116 versus 949 +/- 85 dynes.s.cm-5; p < 0.01). In addition, both a PVR of more than 1,100 dynes.s.cm-5 and a mean PAP of more than 50 mm Hg could accurately predict operative mortality: operative mortality was six times greater in patients with a preoperative PVR of greater than 1,100 dynes.s.cm-5 (41% versus 5.85%) and almost five times greater in those with a mean PAP of greater than 50 mm Hg (37% versus 8%). No intraoperative factors, including the use or duration of circulatory arrest, affected outcome. CONCLUSIONS: Patients with severe hemodynamic disease (PVR > 1,100 dynes.s.cm-5 and PAP > 50 mm Hg) have a high likelihood of operative mortality and perhaps should not undergo pulmonary thromboendarterectomy, except at institutions where the operation is performed frequently.

Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of hypocalcemic versus normocalcemic blood cardioplegia.

OBJECTIVES: The ideal cardioplegic calcium (Ca+2) concentration in newborns continues to be debated. Most studies examining cardioplegia calcium concentrations have been done with a nonclinical model (i.e., isolated heart preparation), the results of which may not be clinically applicable, and they have not examined the effect of calcium concentration in a clinically relevant stressed (hypoxic) heart. METHODS: Twenty neonatal piglets 5 to 18 days old were placed on cardiopulmonary bypass, and their aortas were crossclamped for 70 minutes with hypocalcemic or normocalcemic multidose blood cardioplegic infusions. Group 1 (n = 5; low Ca+2, 0.2 to 0.4 mmol/L) and group 2 (n = 5; normal Ca+2, 1.0 to 1.3 mmol/L) were nonhypoxic (uninjured) hearts. Ten other piglets were first ventilated at an FiO2 of 8% to 10% (O2 saturation 65% to 70%) for 60 minutes (i.e., causing hypoxia) and then reoxygenated at an FiO2 of 100% with cardiopulmonary bypass, which produces a clinically relevant stress injury. They then underwent cardioplegic arrest (as described above) with a hypocalcemic (n = 5, group 3) or normocalcemic (n = 5, group 4) blood cardioplegic solution. Myocardial function was assessed with pressure volume loops and expressed as a percentage of control values. Coronary vascular resistance was measured during each cardioplegic infusion. All values were reported as the mean +/- standard error. RESULTS: In nonhypoxic hearts (groups 1 and 2), good myocardial protection was achieved at either concentration of cardioplegia calcium, as demonstrated by preservation of postbypass systolic function (104% vs 99% end-systolic elastance), minimally increased diastolic stiffness (152% vs 162%), no difference in myocardial water (78.9% vs 78.9%), and no change in adenosine triphosphate levels or coronary vascular resistance. Low-calcium blood cardioplegia solution repaired the hypoxic reoxygenation injury in stressed hearts (group 3), resulting in no statistical difference in myocardial function, coronary vascular resistance, or adenosine triphosphate levels compared with nonhypoxic hearts (groups 1 and 2). Conversely, when a normocalcemic cardioplegia solution was used in hypoxic hearts (group 4), there was marked reduction in postbypass systolic function (49% +/- 4% end-systolic elastance; p < 0.05), increased diastolic stiffness (276% +/- 9%; p < 0.05), increased myocardial water (80.1% +/- 0.2%; p < 0.05), rise in coronary vascular resistance (p < 0.05), and lower adenosine triphosphate levels compared with groups 1, 2, and 3. CONCLUSIONS: This study demonstrates that, in the clinically relevant, intact animal model, good myocardial protection is independent of cardioplegia calcium concentration in nonhypoxic (noninjured) hearts; hypoxic (stressed) hearts are extremely sensitive to the cardioplegic calcium concentration; and normocalcemic cardioplegia is detrimental to neonatal myocardium subjected to a preoperative hypoxic stress.

Integrated cardioplegia allows complex valve repairs in all patients.

BACKGROUND: Traditionally, most surgeons have taken adversarial positions with respect to whether cardioplegia should be given warm or cold, antegrade or retrograde, continuous or intermittent. Because each method has weaknesses, myocardial protection is compromised when only one method is employed. It is our contention that an "integrated" approach that combines all of the aforementioned principles will improve myocardial protection, allowing the time needed for complex valve repairs. METHODS: Thirty-four patients (25 undergoing complex mitral valve repairs and 9 undergoing Ross procedures) have undergone complex valve repair since we began using an integrated cardioplegic strategy that incorporates all of the techniques mentioned above and is based on the following principles: (1) Cardioplegia is infused antegrade and retrograde, warm and cold. (2) Surgical precision is optimized by a dry, bloodless field using cold intermittent arrest to limit ischemia when visualization is needed. (3) Continuous blood cardioplegia is used when visualization is not problematic, thereby avoiding unnecessary ischemia. RESULTS: Average age was 46 +/- 4 years (range, 9 to 79 years), and 9 patients (26%) were having reoperations. All mitral patients had severe mitral regurgitation, 52% (13/25) had a preoperative ejection fraction less than 0.40, and 40% (10/25) had pulmonary artery pressures greater than 60 mm Hg. In the Ross patients 33% (3/9) had an ejection fraction less than 0.40, including 2 patients who concomitantly underwent complex mitral valve repair. Despite cross-clamp times of 187 +/- 12 minutes (range, 138 to 267 minutes) in the Ross group and 139 +/- 8 minutes (range, 92 to 218 minutes) in the complex mitral valve repair group with a predicted mortality (Parsonnet) of approximately 10%, no patients died, only 5 (15%) required inotropes, none required intraaortic balloon pumping, only 1 (3%) required antiarrhythmics, and the average postoperative hospital stay was 8 days in the mitral repair group and 5 days in the Ross group. CONCLUSIONS: We believe an integrated approach incorporating the strategies of warm and cold blood cardioplegia, antegrade and retrograde delivery, and continuous and intermittent infusion affords better myocardial protection, avoids unnecessary ischemia, facilitates technical ease of operation, and results in a more stable postoperative course. Integrating these modalities into a comprehensive strategy (instead of relying on one) maximizes each method's strength while minimizing weaknesses, thereby allowing surgeons to perform complex valve repairs safely in all patients.