Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry.

BACKGROUND: Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. METHODS: The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. RESULTS: A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival. CONCLUSIONS: Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Chronic exposure to cigarette smoke extract impairs endothelium-dependent relaxation of chicken embryo pulmonary arteries.

Maternal smoking may increase the risk for various adverse neonatal outcomes including persistent pulmonary hypertension of the newborn (PPHN). We investigated whether chronic prenatal cigarette smoke extract (CSE) exposure could produce abnormal vasoreactivity in pulmonary arteries. Daily injections of CSE (diluted in phosphate buffered saline) or vehicle were added to the air cells of fertilized eggs starting on day 5 of the 21-day incubation period of the chicken embryo. On day 19, pulmonary arteries were dissected out and their contractile properties were assessed using small vessel myography. Endothelium-dependent and endothelium-independent vasorelaxations were examined by using acetylcholine (ACh, 10(-8) to 10(-4) M) and sodium nitroprusside (SNP, 10(-8) to 10(-4) M), respectively. The drug concentration inducing 50% of the maximal relaxation was determined for each concentration-response curve and expressed as negative log molar (pD(2)). Exposure to CSE significantly decreased the sensitivity of pulmonary arteries to ACh (pD(2) control group: 7.29 +/- 0.24; pD(2) CSE-exposed group 6.24 +/- 0.12, p < 0.05). SNP elicited similar responses in vessels of both groups at all tested concentrations. In conclusion, chronic prenatal exposure to CSE impaired endothelium-dependent but not endothelium-independent vasodilation in chicken embryo pulmonary arteries. This observation suggests that cigarette smoke components may produce deleterious effects on fetal vascular endothelial vasorelaxant pathways, leading to the development of adverse outcomes such as PPHN.

Effect of cigarette smoke extract on neonatal porcine vascular smooth muscle cells.

RATIONALE: Cigarette smoke exposure in the perinatal period increases the risk of various prenatal and postnatal complications, including sudden infant death syndrome (SIDS) and persistent pulmonary hypertension of the newborn (PPHN). We investigated the cellular effects of cigarette smoke extract (CSE) in the developing vasculature. METHODS: Vascular smooth muscle cells (VSMC) were isolated from neonatal porcine carotid arteries, splenic arteries, and main and resistance pulmonary arteries. Effects of CSE on VSMC proliferation, viability, apoptosis, and media nitrates and nitrites were evaluated. The effects of known constituents of CSE (nicotine, benzopyrene, acrolein, acetaldehyde), aged CSE, CSE with added hemoglobin, devolatilized CSE, CSE with added dithiothreitol (DTT), and reduced glutathione (GSH) on cell proliferation and viability were assessed. RESULTS: CSE caused a dose- and time-dependent decrease in neonatal VSMC numbers isolated from all four sites, mainly as a result of increased cell necrosis and not apoptosis. Nitrates and nitrites were below the threshold of detection. Nicotine and benzopyrene did not affect cell counts, while acrolein and acetaldehyde decreased cell counts in a dose-dependent manner. Addition of hemoglobin, devolatilization, and the addition of DTT or GSH slightly decreased CSE inhibition. CONCLUSIONS: CSE causes necrosis of neonatal VSMC, and this toxicity is mediated mainly by volatile components such as acrolein and acetaldehyde, possibly in association with nitric oxide and carbon monoxide.