Left ventricular dysfunction after open repair of simple congenital heart defects in infants and children: Quantitation with the use of a conductance catheter immediately after bypass

AbstractObjective: Quantification of myocardial injury after the simplest pediatric operations by load-independent indices of left ventricular function, using conductance and Mikro-Tip pressure catheters (Millar Instruments, Inc., Houston, Tex.) inserted through the left ventricular apex. Methods: Sixteen infants and children with intact ventricular septum undergoing cardiac operations had left ventricular function measured, immediately before and after bypass. Real-time pressure-volume loops were generated by conductance and Mikro-Tip pressure catheters placed in the long-axis via the left ventricular apex, and preload was varied by transient snaring of the inferior vena cava. Results: Good quality pressure-volume loops were generated in 13 patients (atrial septal defects, n = 11; double-chambered right ventricle, n = 1; supravalvular aortic stenosis, n = 1; age 0.25 to 14.4 years, weight 3.1 to 46.4 kg). Their mean bypass time was 41 ± 14 minutes and mean aortic crossclamp time 27 ± 11 minutes. End-systolic elastance decreased by 40.7% from 0.34 ± 0.17 to 0.21 ± 0.15 mm Hg-1·ml-1·kg-1 (p < 0.001). There were no significant changes in the slope of the stroke work–end-diastolic volume relationship, end-diastolic elastance, time constant of isovolumic relaxation, and normalized values of the maxima and minima of the first derivative of developed left ventricular pressure. Conclusion: Load-independent indices of left ventricular function can be derived from left ventricular pressure-volume loops generated by conductance and Mikro-Tip pressure catheters during the perioperative period in infants and children undergoing cardiac operations. Incomplete myocardial protection was demonstrated by a deterioration in systolic function after even short bypass and crossclamp times.Ignorance of the cause of postoperative myocardial dysfunction in the immature heart is compounded by the incomplete myocardial protection afforded by current cardioplegic strategies.1,5 Investigations of the mechanisms and treatment of postoperative ventricular dysfunction are hampered by use of nonspecific clinical end points as indirect estimates of ventricular function, for example, requirement for inotropic agents, duration of ventilation, intensive care unit stay, and mortality. These clinical indices are relatively insensitive to changes in ventricular function and necessitate large cohorts of patients to detect even major differences in outcome from differing myocardial protective strategies.To measure left ventricular function optimally during the perioperative period, with its dramatic changes in loading conditions, necessitates the use of load-independent indices of systolic and diastolic function. In infants and children with an intact ventricular septum undergoing cardiac operations (mainly atrial septal defect closure), we report the changes in left ventricular function assessed from the pressure-volume plane with the use of a conductance catheter and Mikro-Tip pressure catheter (Millar Instruments, Inc., Houston, Tex). In animal and human studies the conductance catheter is placed in the long axis of the left ventricle, most commonly through the aortic valve, with the use of retrograde arterial cannulation or aortotomy.6-11 This is clearly impractical in children undergoing bypass procedures, and in this study we report the first clinical use of custom-built miniature catheters placed in the same long axis, but via the left ventricular apex

CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability

International audienceLymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7–/– mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4–positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs