β3-Adrenoceptor Antagonist SR59230A Attenuates the Imbalance of Systemic and Myocardial Oxygen Transport Induced by Dopamine in Newborn Lambs

Background In neonates, the increase in O 2 -delivery (DO 2 ) by dopamine is offset by a greater increase in O 2 -consumption (VO 2 ). This has been attributed to β 3 -adrenergic receptors in neonatal brown fat tissue. β 3 receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a β 3 -antagonist, on the balance of systemic and myocardial O 2 -transport in newborn lambs treated with dopamine. Methods Lambs (2-5 days old, n = 12) were anesthetized and mechanically ventilated. Heart rate (HR) and rectal temperature were monitored. VO 2 was measured by respiratory mass spectrometry and cardiac output (CO) by a pulmonary artery transonic flowmeter. Arterial, jugular bulb venous and coronary sinus blood gases and lactate were measured to calculate DO 2 , O 2 extraction ratio (ERO 2 ), myocardial O 2 and lactate extraction ratios (mERO 2 , mERlac). After baseline measurements, lambs were randomized to receive SR59230A at 5 mg/kg iv (SRG) or placebo. Both groups received incremental doses of a dopamine infusion (0-5-10-15-20 mcg/kg/min) every 15 min. Measurements were repeated at the end of each dose. Results After SR59230A infusion, CO and HR trended to decrease ( P = 0.06), but no significant changes occurred in other parameters. Over the incremental doses of dopamine, temperature increased in both groups ( P 0.1). DO 2 trended to a small increase ( P = 0.08). VO 2 increased in both groups ( P < 0.0001) but to a lesser degree in SRG ( P < 0.0001). As a result, ERO 2 increased in both groups ( P < 0.0001), but to a lesser degree in SRG ( P < 0.0001). mERO 2 was lower in SRG ( P = 0.01) with a faster increase ( P < 0.0001). mERlac was higher in SRG ( P = 0.06) with a faster decrease ( P = 0.04). Conclusion Although SR59230A tends to induce an initial drop in CO, it significantly attenuates the rise in VO 2 and hence the imbalance of systemic and myocardial O 2 transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR59230A in cases of cardiac dysfunction and increased VO 2 , observed after cardiac surgery

Chronic Kidney Disease in Congenital Heart Disease Patients: A Narrative Review of Evidence

Purpose of review: Patients with congenital heart disease have a number of risk factors for the development of chronic kidney disease (CKD). It is well known that CKD has a large negative impact on health outcomes. It is important therefore to consider that patients with congenital heart disease represent a population in whom long-term primary and secondary prevention strategies to reduce CKD occurrence and progression could be instituted and significantly change outcomes. There are currently no clear guidelines for clinicians in terms of renal assessment in the long-term follow up of patients with congenital heart disease. Consolidation of knowledge is critical for generating such guidelines, and hence is the purpose of this view. This review will summarize current knowledge related to CKD in patients with congenital heart disease, to highlight important work that has been done to date and set the stage for further investigation, development of prevention strategies, and re-evaluation of appropriate renal follow-up in patients with congenital heart disease. Sources of information: The literature search was conducted using PubMed and Google Scholar. Findings: Current epidemiological evidence suggests that CKD occurs in patients with congenital heart disease at a higher frequency than the general population and is detectable early in follow-up (i.e. during childhood). Best evidence suggests that approximately 30 to 50 % of adult patients with congenital heart disease have significantly impaired renal function. The risk of CKD is higher with cyanotic congenital heart disease but it is also present with non-cyanotic congenital heart disease. Although significant knowledge gaps exist, the sum of the data suggests that patients with congenital heart disease should be followed from an early age for the development of CKD. Implications: There is an opportunity to mitigate CKD progression and negative renal outcomes by instituting interventions such as stringent blood pressure control and reduction of proteinuria. There is a need to invest time, thought and money to fill existing knowledge gaps to improve health outcomes in this population. This review should serve as an impetus for generation of follow-up guidelines of kidney health evaluation in patients with congenital heart disease

Acute kidney injury and renal recovery following Fontan surgeryCentral MessagePerspective

Objectives: Acute kidney injury has been described after Fontan surgery, but the duration and outcomes are unknown. We sought to describe the incidence of and risk factors for acute kidney injury and the phenotype of renal recovery, and evaluate the impact of renal recovery phenotype on outcomes. Methods: All children who underwent a Fontan operation at a single center between 2009 and 2022 were included. Data collected included Fontan characteristics, vasopressor use, all measures of creatinine, and postoperative outcomes. Logistic regression models were used to assess predictors of acute kidney injury and the association between acute kidney injury and outcomes. Results: We enrolled 141 children (45% female). Acute kidney injury occurred in 100 patients (71%). Acute kidney injury duration was transient (<48 hours) in 77 patients (55%), persistent (2-7 days) in 15 patients (11%), more than 7 days in 4 patients (3%), and unknown in 4 patients (3%). Risk factors for acute kidney injury included higher preoperative indexed pulmonary vascular resistance (odds ratio, 3.90; P = .004) and higher postoperative inotrope score on day 0 (odds ratio, 1.13, P = .047). Risk factors for acute kidney injury duration more than 48 hours included absence of a fenestration (odds ratio, 3.43, P = .03) and longer duration of cardiopulmonary bypass (odds ratio, 1.22 per 15-minute interval, P = .01). Acute kidney injury duration more than 48 hours was associated with longer length of stay compared with transient acute kidney injury (median 18 days [interquartile range, 9-62] vs 10 days [interquartile range, 8-16], P = .006) and more sternal wound infections (17% vs 4%, P = .049). Conclusions: Acute kidney injury after the Fontan operation is common. The occurrence and duration of acute kidney injury have significant implications for postoperative outcomes