Reduction in Postoperative High-Density Lipoprotein Cholesterol Levels in Children Undergoing the Fontan Operation

Abstract

Despite the emerging relevance of high-density lipoprotein (HDL) in the inflammatory cascade and vascular barrier integrity, HDL levels in children undergoing cardiac surgery are unexplored. As a measure of HDL levels, the HDL-cholesterol (HDL-C) in single-ventricle patients was quantified before and after the Fontan operation, and it was determined whether relationships existed between the duration and the type of postoperative pleural effusions. The study prospectively enrolled 12 children undergoing the Fontan operation. Plasma HDL-C levels were measured before and after cardiopulmonary bypass. The outcome variables of interest were the duration and type of chest tube drainage (chylous vs. nonchylous). The Kendall rank correlation coefficient and the Wilcoxon rank sum test were used. There were 11 complete observations. The median preoperative HDL-C level for all the subjects was 30 mg/dl (range, 24-53 mg/dl), and the median postcardiopulmonary bypass level was 21 mg/dl (range, 14-46 mg/dl) (p = 0.004). There was a tendency toward a moderate inverse correlation (-0.42) between the postcardiopulmonary bypass HDL-C level and the duration of chest tube drainage, but the result was not statistically significant (p = 0.07). In the chylous effusion group, the median postcardiopulmonary bypass HDL-C tended to be lower (16 vs. 23 mg/dl; p = 0.09). After the Fontan operation, the plasma HDL-C levels in children are significantly reduced. It is reasonable to conclude that the reduction in HDL-C reflects reduced plasma levels of HDL particles, which may have pertinent implications in postoperative pleural effusions given the antiinflammatory and endothelial barrier functions of HDL. KeywordsFontan; HDL-C; High-density lipoprotein-cholesterol Since the original description of the Fontan operation by Fontan and Baudet [8] in 1971, the procedure has undergone significant improvements in both the surgical and medical managements. These modifications have allowed a broad cross-section of patients with single-ventricle physiology to undergo successful Fontan palliation with excellent survival rates [1,13]. However, despite low mortality rates, patients who undergo the Fontan operation continue to remain at considerable risk for prolonged postoperative recovery complicated by persistent pleural effusions, ventricular dysfunction, arrhythmias, and protracted mechanical ventilation [18,21].Heart catheterization and echocardiographic evaluations are routinely performed before the Fontan operation in efforts to predict how the lungs and heart will interact. Yet, despite this practice, predicting the early postoperative course remains difficult, and it is becoming increasingly evident that catheterization hemodynamic data are not consistently associated with early postoperative outcomes [5,16]. This suggests the existence of other unexplored variables that place Fontan patients at risk for prolonged postoperative recovery despite acceptable hemodynamic criteria.In recent years, reductions in high-density lipoprotein (HDL) ...

Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle

“…its anti-oxidant and anti-inflammatory properties 37 , and by decreases in HDL-C 9,[38][39][40] . A direct interplay of lipoprotein metabolism and markers for oxidative stress exists: lipoprotein disorders are associated with increased ADMA 41 .…”

Sphingosine 1-Phosphate (S1P) Carrier-dependent Regulation of Endothelial Barrier

“…Indeed, recent findings show that patients with increased endothelial permeability and edema resulting from cardiopulmonary bypass have a reduction in postoperative plasma levels of HDL (38). Furthermore, individuals with high levels of HDL and clinical evidence of heart disease have low levels of S1P in the HDL-containing fraction of serum (39).…”

Targeted metabolomic analysis of serum phospholipid and acylcarnitine in the adult Fontan patient with a dominant left ventricle

“…Besides hyperuricemia and abnormal glucose handling, alterations in cholesterol and lipoprotein metabolism were reported. 13 –17 With that in mind, and extrapolating from findings in HF patients with a biventricular system, where the myocardial energy source switches from metabolism of fatty acids to the metabolism of glucose and ketone bodies, 18 and from findings on the important role as proinflammatory analytes that other lipids metabolised in the liver, especially phospholipids (PL), play in the setting of increased cardiovascular risk, 19 we inferred that patients with a Fontan circulation also would handle lipids anomalously. We thus elected to examine Fontan patients’ serum levels of a variety of PL and acylcarnitines (taking serum acylcarnitine levels as tracking intramitochondrial long-chain fatty acids in the form of their activated acyl-coenzyme-A-esters) and attempted in a homogeneous patient group with a dominant left ventricle (LV) to define patterns that reflect metabolic derangement and that offer promise of better understanding of Fontan physiology.…”