Eliot Rosenkranz

Dendritic Cells in Human Thymus and Periphery Display a Proinsulin Epitope in a Transcription-Dependent, Capture-Independent Fashion

The natural expression of tissue-specific genes in the thymus, e.g., insulin, is critical for self-tolerance. The transcription of tissue-specific genes is ascribed to peripheral Ag-expressing (PAE) cells, which discordant studies identified as thymic epithelial cells (TEC) or CD11c+ dendritic cells (DC). We hypothesized that, consistent with APC function, PAE-DC should constitutively display multiple self-epitopes on their surface. If recognized by Abs, such epitopes could help identify PAE cells to further define their distribution, nature, and function. We report that selected Abs reacted with self-epitopes, including a proinsulin epitope, on the surface of CD11c+ cells. We find that Proins+CD11c+ PAE cells exist in human thymus, spleen, and also circulate in blood. Human thymic Proins+ cells appear as mature DC but express CD8α, CD20, CD123, and CD14; peripheral Proins+ cells appear as immature DC. However, DC derived in vitro from human peripheral blood monocytes include Proins+ cells that uniquely differentiate and mature into thymic-like PAE-DC. Critically, we demonstrate that human Proins+CD11c+ cells transcribe the insulin gene in thymus, spleen, and blood. Likewise, we show that mouse thymic and peripheral CD11c+ cells transcribe the insulin gene and display the proinsulin epitope; moreover, by using knockout mice, we show that the display of this epitope depends upon insulin gene transcription and is independent of Ag capturing. Thus, we propose that PAE cells include functionally distinct DC displaying self-epitopes through a novel, transcription-dependent mechanism. These cells might play a role in promoting self-tolerance, not only in the thymus but also in the periphery.

Substrate enhancement of cardioplegic solution: Experimental studies and clinical evaluation

BACKGROUND The development of myocardial protective strategies depends on a complete understanding of the pathophysiology of myocardial ischemia and reperfusion. This article reviews the rationale for inclusion of metabolic substrates in cardioplegic solutions on the basis of our current understanding of the underlying pathophysiologic pathways and speculates on the inclusion of future additives that await further investigation. METHODS The pathophysiology of myocardial ischemia and reperfusion was evaluated from an extensive review of the pertinent literature. Experimental and clinical studies supporting the inclusion of metabolic substrates in clinical cardioplegic solutions were reviewed and summarized. Speculation on possible future additives to these formulas was made on the basis of encouraging, albeit preliminary, experimental data. RESULTS Sound experimental and clinical evidence supports the inclusion of glucose, amino acids, calcium chelators, and oxygen as fundamental substrate additives to current cardioplegic solutions. Antioxidants, calcium-channel blockers, and tricarboxylic acid cycle intermediates may be of value. Adenosine, potassium-adenosine triphosphate channel modulators, and nitric oxide may join these lists after further research. CONCLUSIONS Substrate enhancement of clinical cardioplegic solutions is based on physiologic principles that have been confirmed in the clinical setting. Further definition of the intricacies of myocardial ischemia and reperfusion promises to expand the current list of additives.

Initial experience with the tandemheart circulatory support system in children

Options for mechanical ventricular assistance in pediatric patients are limited. Extracorporeal membrane oxygenation is used in most cases for short-term support. The TandemHeart circulatory support system is an established device that is used in adult patients to provide short-term ventricular support. In this article, we report three children in whom a TandemHeart ventricular assist device was used for right ventricular support, two after heart transplantation and another for failed Fontan physiology. Herein, we report the novel application of this technology to pediatric patients, and we discuss the lessons learned from its utilization.

Cerebral and somatic oxygen saturation decrease after delayed sternal closure in children after cardiac surgery

OBJECTIVES Delayed sternal closure after pediatric cardiac surgery can temporarily impair cardiac output. Cerebral and somatic regional oxygen saturation measured by using near-infrared spectroscopy (NIRS) have been used as potential surrogates of cerebral and somatic mixed venous oxygen saturation. We hypothesized that cerebral and somatic regional oxygen saturation correlate with indicators of hemodynamic compromise after delayed sternal closure in children undergoing cardiac surgery. METHODS We studied 36 postoperative children (median age, 10 days; range, 1-510 days) undergoing delayed sternal closure 3.7 +/- 2 days after cardiac surgery. Twenty-five had biventricular physiology, whereas 11 had single-ventricle physiology. Cerebral regional oxygen saturation, somatic regional oxygen saturation, and other physiologic parameters (hemodynamic data, respiratory data, blood gas analysis, lactate levels, and inotrope scores) were analyzed at 16 different time points 24 hours before and after sternal closure. One-way analysis of variance and the paired t test were used for statistical comparisons. RESULTS Cerebral and somatic regional oxygen saturation decreased after delayed sternal closure compared with preclosure levels (P = .02 and P = .01, respectively). Higher heart rate (P = .03), lactate levels (P = .02), and left atrial pressure (P = .001) were also noted, suggesting mild hemodynamic compromise. Arterial pressure and inotrope score were unchanged. Somatic regional oxygen saturation returned to preclosure levels earlier in the biventricular group than in the single-ventricle group, whereas cerebral regional oxygen saturation remained decreased after sternal closure with no evidence of return to preclosure levels during the observation period. Oxygen saturation, Pao(2), and Paco(2) levels were unaffected by sternal closure, although greater positive-pressure ventilation was required (P < .01), suggesting reduced lung compliance. CONCLUSION Cerebral and somatic regional oxygen saturation decrease after delayed sternal closure in children recovering from congenital cardiac surgery. These indices are in agreement with other physiologic indicators of cardiac performance, suggesting mild and transient hemodynamic compromise after sternal closure. Cerebral and somatic regional oxygen saturation monitoring might be a useful adjunct during delayed sternal closure.

Successful use of a custom-made paracorporeal total artificial heart as a bridge to retransplantation in adult and adolescent patients.

Because the currently available total artificial hearts are rather bulky, the use of a custom-made paracorporeal total artificial heart constructed with 2 ventricular assist devices is an alternative for children and adults with small stature. This article reports our experience using this system in an adult and a pediatric patient. The advantages and disadvantages of this technique are discussed.

An Adult Patient with Fontan Physiology: A TEE Perspective

Fontan and Baudet described in 1971 the separation of the pulmonary and systemic circulations resulting in univentricular physiology. The evolution of the Fontan procedure, most notably the substitution of right atrial-to-pulmonary artery anastomosis with cavopulmonary connections, resulted in significantly improved late outcomes. Many patients survive well into adulthood and are able to lead productive lives. While ideally under medical care at specialized centers for adult congenital cardiac pathology, these patients may present to the outside hospitals for emergency surgery, electrophysiologic interventions, and pregnancy. This presentation presents a “train of thought,” linking the TEE images to the perioperative physiologic considerations faced by an anesthesiologist caring for a patient with Fontan circulation in the perioperative settings. Relevant effects of mechanical ventilation on pulmonary vascular resistance, pulmonary blood flow and cardiac preload, presence of coagulopathy and thromboembolic potential, danger of abrupt changes of systemic vascular resistance and systemic venous return are discussed.

Venous bullet embolus to the left pulmonary artery

We report a venous bullet embolus into the left pulmonary artery following a gunshot wound to the right chest. The diagnosis and surgical management of migrating venous bullet emboli are reviewed.

Transmyocardial Migration of a Temporary Epicardial Pacing Wire: A Pediatric Case Report

Transmyocardial migration of a retained temporary epicardial pacing wire has been rarely reported in adult patients after heart surgery. We present the case of a child in whom a temporary epicardial pacing wire was discovered incidentally in the right ventricular outflow tract one year after surgical repair of congenital heart disease. The pacing wire was subsequently extracted using the snare method during cardiac catheterization. Clinicians caring for patients after congenital heart surgery should be aware of this uncommon though potentially life-threatening complication.

An adult patient with congenitally corrected transposition of the great arteries.

A26-year-old patient developed a symptomatic pericardial effusion 3 weeks after placement of an automatic implantable cardioversion device and a biventricular pacemaker with an epicardial ventricular lead. His medical history included congenitally corrected transposition of the great arteries (CC-TGA) and chronic congestive heart failure. Consent for this presentation was obtained from the patient. The patient underwent creation of a pericardial window. Because the pericardial fluid appeared sanguineous, transesophageal echocardiography was requested for surgical guidance and surveillance for fluid reaccumulation. The midesophageal (ME) 4-chamber view established situs solitus, because the left atrium, identified by its appendage and pulmonary veins, was to the left of the interatrial septum (Video 1, loop 1; see Supplemental Digital Content 1, http://links.lww.com/AA/A182; see Appendix for video legend). The atrioventricular valve to the left of the interventricular septum was identified as the tricuspid valve (TV) by its apical position and chordal attachment to the septum (Video 1, loop 2, http://links.lww.com/AA/A182), thereby identifying the heavily trabeculated ventricle to the left of the interventricular septum as the morphologic right ventricle (RV). The atrioventricular valve to the right of the interventricular septum was identified as the mitral valve (MV) by its basal position, establishing the ventricle to the right of the interventricular septum as the morphologic left ventricle (LV). The LV morphology was confirmed by its elongated cavity, smooth endocardial surface, and presence of distinct papillary muscles. Maintaining the dextropositioned ventricle in the center of the sector, forward rotation to 51° (modified ME inflowoutflow view) allowed visualization of a fibrous continuity between its inflow and outflow valves (MV and pulmonic), indicative of LV morphology (Video 1, loop 3, http://links.lww.com/AA/A182). Further rotation to the ME long-axis (LAX) view imaged the ventricle to the left of the interventricular septum and identified extensive coarse apical trabeculations and fibrous discontinuity between the TV and aortic valve caused by the presence of the RV infundibulum (conus), characteristic of RV morphology. The aorta was visualized anterior and parallel to the pulmonary artery (PA) (Video 1, loop 4, http://links.lww.com/AA/A182); the main PA was further identified by its branching into the right and left arteries. Rightward rotation of the transducer to the bicaval view confirmed the situs solitus because the right atrium, identified by its appendage, great veins, and the coronary sinus, was to the right of the interatrial septum (Video 1, loop 5, http://links.lww.com/AA/A182). The transgastric short-axis view confirmed the trileaflet structure of the TV (Video 1, loop 6, http://links.lww.com/AA/A182) and allowed the functional assessment of the systemic (morphologic right) ventricle (Video 1, loop 7, http://links.lww.com/AA/A182). The patient tolerated the procedure well and was returned to the ward in satisfactory condition.

Tetralogy of Fallot With Absent Pulmonary Valve and Nonconfluent Pulmonary Arteries: A Management Conundrum

Tetralogy of Fallot with absent pulmonary valve syndrome is a rare form of congenital heart disease. Among the different variations with this rare anomaly is nonconfluent pulmonary artery branches with anomalous origin of the left pulmonary artery from the ductus arteriosus. The authors present one such case which was diagnosed prenatally to have tetralogy of Fallot with absent pulmonary valve and identified postnatally to have nonconfluent pulmonary artery branches in addition. We discuss the conundrum of respiratory management in this patient pre- and postoperatively due to a unique ventilation perfusion mismatch problem, which varies between the two lungs.