David P. Nelson

Blockade of selectin-mediated leukocyte adhesion improves postischemic function in lamb hearts

BACKGROUNDnLeukocyte-endothelial interactions appear to have a important role in ischemia/reperfusion injury and are mediated by specific leukocyte and endothelial adhesion molecules. The selectins are adhesion molecules found on leukocytes (L-selectin) and endothelium (P and E selectin) that bind to oligosaccharide ligands containing fucose and sialic acid to mediate leukocyte rolling on the endothelium. Fucoidin is a nontoxic sulfated fucose oligosaccharide derived from seaweed that blocks the selectins.nnnMETHODSnWe tested the effects of fucoidin in an isolated blood-perfused neonatal (age range, 3 to 7 days; mean age, 4.3 days) lamb heart model undergoing 2 hours of cold cardioplegic ischemia. In group F (n = 8) fucoidin (30 mg/L) was added at initial reperfusion. Group C (n = 9) received only cardioplegia with no reperfusion intervention. Isovolumic maximum developed pressure and the maximum positive and negative first derivatives of pressure were measured using a catheter-tip transducer in an intraventricular balloon before ischemia and at 30 minutes of reperfusion. Coronary blood flow, myocardial oxygen consumption, and white blood cell counts in the circulating blood were also measured.nnnRESULTSnPercent recoveries of baseline maximum developed pressure and maximum positive and negative first derivatives of pressure in group F (86% +/- 5%, 81% +/- 10%, and 74% +/- 8%, respectively; mean +/- standard deviation) were higher than in group C (77% +/- 5%, 70% +/- 9%, and 65% +/- 6%; p < 0.05). Group F postischemic coronary blood flow was greater (190% +/- 35%) than in group C (102% +/- 10%; p < 0.05). Recovery of myocardial oxygen consumption in group F (86% +/- 14%) was greater than group C (72% +/- 11%; p < 0.05). Postischemic white blood cell count in group F (88% +/- 4%) was greater than in group C (81% +/- 5%; p < 0.05).nnnCONCLUSIONSnSelectin blockade with fucoidin resulted in better recovery of left ventricular function, coronary blood flow, and myocardial oxygen consumption after cold ischemia, despite a higher circulating white blood cell count. These data support the hypothesis that endothelial-leukocyte interactions play an important role in ischemia/reperfusion and suggest that selectin blockade may be a useful therapeutic strategy.

Myocardial immediate early gene activation after cardiopulmonary bypass with cardiac ischemia-reperfusion

BACKGROUNDnThe inflammatory process after cardiopulmonary bypass is accompanied by alterations in gene expression for various inflammatory mediators.nnnMETHODSnTo analyze differential gene expression after myocardial ischemia-reperfusion, subtraction hybridization was used to discover induction of TIS7/PC4, an immediate early gene heretofore not observed in the heart. This prompted characterization of the related immediate early genes c-fos and c-jun, by Northern analysis and in situ hybridization in human and lamb myocardium subjected to cardiopulmonary bypass with myocardial ischemia. For comparison, we analyzed expression of inducible nitric oxide synthase (iNOS), which requires cytokine-activation, resulting in a delayed response.nnnRESULTSnIn ischemic-reperfused myocardium at endcardiopulmonary bypass, c-fos, c-jun, and TIS7/PC4 were induced, whereas iNOS transcripts were undetectable. Expression patterns of c-fos and c-jun by in situ hybridization were markedly different; myocardial c-fos expression was diffuse and homogeneous, whereas c-jun expression was patchy with areas of intense focal localization.nnnCONCLUSIONSnCardiopulmonary bypass with myocardial ischemia rapidly induces the immediate early genes TIS7/PC4 (discovered by subtraction hybridization), and c-fos and c-jun (precursors to the transcriptional regulator AP-1). Immediate early genes presumably contribute to activation of inflammatory mediators after cardiopulmonary bypass and differences in their tissue expression patterns, as observed for c-fos and c-jun, presumably modulate their effect upon downstream gene activation.

Sialyl LewisX oligosaccharide preserves myocardial and endothelial function during cardioplegic ischemia

BACKGROUNDnNeutrophil adhesion to endothelium contributes to myocardial reperfusion injury after cardiac operation. Initial neutrophil-endothelial interactions involve selectins, which bind Sialyl-LewisX on neutrophils. Blockade of selectin-mediated neutrophil-endothelial interactions with CY-1503, a synthetic analogue of Sialyl-LewisX, might reduce reperfusion injury after myocardial ischemia.nnnMETHODSnThe efficacy of CY-1503 to attenuate global myocardial reperfusion injury was assessed in isolated blood-perfused neonatal lamb hearts that had 2 hours of cold cardioplegic ischemia. CY-1503 (40 mg/L) or saline vehicle was added to blood perfusate before ischemia. Contractile function (developed pressure, dP/dt) and coronary vascular endothelial function (acetylcholine response) were assessed at base line and during reperfusion. Myocardial neutrophil accumulation was assessed by myeloperoxidase quantification.nnnRESULTSnCompared to controls, treatment with CY-1503 improved recovery of all indices of contractile function, preserved coronary vascular endothelial function, and reduced myocardial neutrophil accumulation.nnnCONCLUSIONSnIn isolated neonatal lamb hearts that underwent hypothermic cardioplegic ischemia, CY-1503 administration reduced myocardial neutrophil accumulation and preserved endothelial and contractile function. Selectin blockade of leukocyte-endothelial interactions might attenuate reperfusion injury and enhance myocardial protection during cardiac surgical procedures.

Inhaled nitric oxide improves oxygen saturation in children with pulmonary arteriovenous malformations after the Fontan procedure.

Objective: To report the utility of inhaled nitric oxide to ameliorate excessive hypoxemia in children with pulmonary arteriovenous malformations after the Fontan procedure. Design: Case series. Setting: A tertiary pediatric cardiac intensive care unit in a freestanding childrens hospital. Patients: Three children with complex congenital heart disease and pulmonary arteriovenous malformations who underwent the Fontan procedure. Interventions: The 3 patients all exhibited moderate-to-severe hypoxemia in the immediate postoperative period. The hypoxemia persisted despite mechanical ventilation and oxygen at an Fio2 of 1.0. Inhaled nitric oxide was initiated with immediate and dramatic improvements in oxygen saturation in all patients. All patients were eventually weaned off inhaled nitric oxide. Conclusions: The use of inhaled nitric oxide in patients with pulmonary arteriovenous malformations after having the Fontan procedure improves hypoxemia and may potentially reduce postoperative morbidity, unnecessary testing, and duration of hospital stay.

Improving Communication During Cardiac ICU Multidisciplinary Rounds Through Visual Display of Patient Daily Goals.

Objectives: To improve communication during daily cardiac ICU multidisciplinary rounds. Design: Quality improvement methodology. Setting: Twenty-five–bed cardiac ICUs in an academic free-standing pediatric hospital. Patients: All patients admitted to the cardiac ICU. Interventions: Implementation of visual display of patient daily goals through a write-down and read-back process. Measurements and Main Results: The Rounds Effectiveness Assessment and Communication Tool was developed based on the previously validated Patient Knowledge Assessment Tool to evaluate comprehension of patient daily goals. Rounds were assessed for each patient by the bedside nurse, nurse practitioner or fellow, and attending physician, and answers were compared to determine percent agreement per day. At baseline, percent agreement for patient goals was only 62%. After initial implementation of the daily goal write-down/read-back process, which was written on paper by the bedside nurse, the Rounds Effectiveness Assessment and Communication Tool survey revealed no improvement. With adaptation of the intervention so goals were written on whiteboards for visual display during rounds, the percent agreement improved to 85%. Families were also asked to complete a survey (1–6 Likert scale) of their satisfaction with rounds and understanding of daily goals before and after the intervention. Family survey results improved from a mean of 4.6–5.7. Parent selection of the best possible score for each question was 19% at baseline and 75% after the intervention. Conclusions: Visual display of patient daily goals via a write-down/read-back process improves comprehension of goals by all team members and improves parent satisfaction. The daily goal whiteboard facilitates consistent development of a comprehensive plan of care for each patient, fosters goal-directed care, and provides a checklist for providers and parents to review throughout the day.

Cardiac intensive care for the neonate and child after cardiac surgery.

Purpose of review The focus of postoperative care in the pediatric patient with congenital heart disease has become a reduction in length of stay and morbidity. This review will discuss strategies to achieve this goal and recent studies to support current practices. Recent findings Most agree that prolongation of the length of stay following a cardiac surgery contributes to morbidity. Postoperative feeding difficulty, hyperglycemia, acute kidney injury, fluid overload, and prolonged intubation contribute significantly to length of stay. Summary Postoperative care of the neonate and child following a cardiac surgery remains challenging with limited data to drive our practices. Patients remain at risk for significant morbidity, and future studies should focus on recognizing predictors of morbidity, prevention, and treatment.

Arginine–vasopressin therapy in hypotensive neonates and infants after cardiac surgery: response is unrelated to baseline ventricular function

We hypothesised that infants with ventricular dysfunction after cardiac surgery have impaired haemodynamic response to arginine-vasopressin therapy. We retrospectively reviewed the medical records of neonates and infants treated with arginine-vasopressin within 48 hours of corrective or palliative cardiac surgery who underwent echocardiographic assessment of ventricular function before initiation of therapy. Patients were classified as responders if their systolic blood pressure increased by ⩾10% without increase in catecholamine score or if it was maintained with decreased catecholamine score. Response was assessed 1 hour after maximum upward titration of arginine-vasopressin. A total of 36 children (15 neonates) were reviewed (17 male). The median (interquartile) age was 10.4 weeks (1.1-26.9), and the median weight was 4.3 kg (3.2-5.8). Diagnoses included single ventricle (eight), arch abnormalities (five), atrioventricular septal defect (four), double-outlet right ventricle (three), tetralogy of Fallot (three), and others (13). In all, 12 patients (33%) had ventricular dysfunction. Only 15 (42%) responded favourably according to our definition 1 hour after the target arginine-vasopressin dose was achieved. Ventricular dysfunction was not associated with poor response. The overall mortality was 25%, but mortality in patients with ventricular dysfunction was 42%. Favourable response was associated with shorter ICU stay (9.5 days versus 19.5 days, p=0.01). We conclude that arginine-vasopressin fails to increase blood pressure in ~50% of hypotensive children after cardiac surgery. The response rate does not increase with duration of therapy. Ventricular function does not predict haemodynamic response. The mortality in this group is very high. Prospective comparison of vasopressin with other vasoactive agents and/or inotropes is warranted.