Biomedical subjects

Andrew J Parry

Publications and source records attributed to Andrew J Parry.

13 recordsLinked to original sources

PubMed2006

Changes in myocardial free amino acids during pediatric cardiac surgery: a randomised controlled trial of three cardioplegic techniques.

OBJECTIVE: The developing heart has a much greater dependence on amino acid (AA) metabolism than the adult heart in determining its ischemic tolerance. Blood cardioplegia preserves myocardial free AAs in adult hearts but no clinical studies have looked at the effect of different cardioplegic techniques on intracellular free AAs in the pediatric heart. METHODS: Pediatric patients were randomised to receive intermittent antegrade cold crystalloid (CC), cold blood (CB) or cold blood cardioplegia with a 'hot shot' (CB+HS). Right ventricular biopsies were collected prior to ischemia, at the end of ischemia and 20 min after reperfusion. Amino acid levels were analysed as repeated measures, adjusting for baseline levels. Data were analysed separately for acyanotic and cyanotic patients. RESULTS: Of 103 patients recruited, 32 (22 acyanotic and 10 cyanotic), 36 (24/12) and 35 (25/10), respectively were allocated to CC, CB and CB+HS groups. Cyanotic patients were significantly younger with longer cross-clamp times. In acyanotic patients, there were no significant effects of cardioplegic method on aspartate, glutamine, taurine, alanine or branched chain AA levels (all p>0.05). However, in cyanotic patients, there were significant interactions of cardioplegic method and time (all p<0.05) for all amino acids, with patients allocated to CB+HS having higher levels after reperfusion compared with CC, and patients allocated to CB having intermediate levels. CONCLUSIONS: For cyanotic patients (younger, longer cross-clamp times), CB+HS preserves myocardial free AAs better than CC; CB gives an intermediate effect. In acyanotic patients, AA levels (all p>0.15) and group means were similar both at the end of ischemia and after reperfusion.

Age Factors↗

PubMed2006

Profile of serum S100beta levels during maturation in fetal and neonatal sheep.

Serum levels of the protein S-100beta are dependent on three factors: rate of production, permeability of the blood-brain barrier, and rate of clearance. In the developing fetus and neonate all of these factors change at different rates. This study was performed to determine how serum S-100 levels varied during fetal and early postnatal life. Blood samples were obtained from 41 fetal and neonatal lambs. The blood was separated in a centrifuge and the serum drawn off and assayed for S-100beta using a commercially available radioimunoassay kit. S-100beta did not appear in the blood until halfway through pregnancy. Thereafter, levels steadily increased until 1 month after birth. Following this, S-100beta levels decreased progressively until by 1 year of age, they had reached a plateau. S-100beta levels change significantly with normal fetal and neonatal maturation. Valid interpretation of other data from subjects of similar developmental stage must take into consideration this physiological variation.

Animals↗

PubMed2006

Surgical management of single ostium anomalous coronary artery from pulmonary artery.

A 6-week-old infant presenting in heart failure was suspected on echocardiography of having anomalous origin of the whole coronary circulation from the pulmonary artery arising from a single ostium. This was confirmed at operation, and the child underwent successful correction. The management of cardiopulmonary bypass and myocardial protection in this abnormality is discussed.

Aorta, Thoracic↗

PubMed2006

Free amino acids in hearts of pediatric patients with congenital heart disease: the effects of cyanosis, age, and pathology.

BACKGROUND: The immature heart has a much greater dependence than the adult heart on amino acid transamination in determining its ischemic tolerance. Compared with adult hearts, experimental models of the immature heart have quantified higher resting concentrations of free amino acids (AA) which are depleted by acute hypoxia. However, we have found no clinical studies that have looked at the free AA profile of the immature human heart or the effects of cyanosis, age, and pathology upon this. METHODS: One hundred eighty-one pediatric patients (37 cyanotic, 144 acyanotic) undergoing open-heart surgery were recruited. Myocardial biopsies were collected prior to ischemia and analyzed for free AAs (eg, glutamate, aspartate) using high-performance liquid chromatography. The effects of cyanosis, age, and pathology on amino acid concentrations were estimated by multiple regression modeling with and without controlling for diagnosis; the effects of age and pathology were estimated only in acyanotic children. RESULTS: Alanine concentrations were about 20% higher in cyanotic than acyanotic patients (p = 0.04). Cyanosis was not associated with any other amino acid levels. In acyanotic patients, after controlling for diagnosis, concentrations of glutamate, aspartate, and alanine decreased from birth to about 8 to 10 years, then started to increase again (p < 0.05 for both linear and quadratic terms); concentrations of taurine and the branched chain AAs decreased steadily with increasing age (p < 0.05). There were significant effects of pathology on glutamate (p = 0.006), glutamine (p = 0.003), and branched chain AA (p = 0.004) levels. CONCLUSIONS: There is no evidence that chronic hypoxia depletes endogenous AAs. Young age is associated with higher resting AA levels.

Aging↗

PubMed2006

Invited commentary.

Explore the source record for details and available documents.

Adaptation, Physiological↗

PubMed2005

Randomized comparison between normothermic and hypothermic cardiopulmonary bypass in pediatric open-heart surgery.

BACKGROUND: The purpose of this study is to investigate the effect of cardiopulmonary bypass (CPB) temperature on myocardial reperfusion injury, oxidative stress, and inflammatory response in pediatric open heart surgery. METHODS: Fifty-nine children (median age 78 months; interquartile range, 39-130) undergoing correction of simple congenital heart defects were randomized to receive either hypothermic (28 degrees C) or normothermic (35-37 degrees C) CPB. Troponin I and 8-isoprostane, complement activation C3a, interleukin (IL) -6, -8, and -10, were measured preoperatively, on removal of the aortic cross clamp, 30 minutes, 6, and 24 hours postoperatively. RESULTS: Troponin I and 8-isoprostane were significantly raised, compared to baseline, in both groups, and remained high at 24 hours. Overall, troponin I and 8-isoprostane levels were 37% and 84% higher in the hypothermic than in the normothermic group, respectively (ratio 1.37, 95% CI 1.00 to 1.88, p = 0.053 and 1.84, 95% CI 1.22 to 2.78, p = 0.0045, respectively), and there was no evidence to suggest the treatment effect changed significantly over the time points measured (p = 0.63). Adjusting for aortic cross-clamp time reduced the effect of hypothermia on troponin (p = 0.18) but not on 8-isoprostane levels (p = 0.0028). The C3a, IL-6, and IL-8 release was similar in the two groups. The IL-10 release between the groups changed over time (p = 0.059) and examining differences at individual time points highlighted a statistically significant difference at the end of the cross-clamp time (p = 0.0079). CONCLUSIONS: Normothermic CPB is associated with reduced oxidative stress compared with hypothermic CPB, and similar myocardial reperfusion injury and whole body inflammatory response, in children undergoing open heart surgery. A larger study with clinical outcomes as primary end points is now warranted.

Biomarkers↗

PubMed2005

Spinal anesthesia with an indwelling catheter reduces the stress response in pediatric open heart surgery.

BACKGROUND: Extreme stress and inflammatory responses to open heart surgery are associated with increased morbidity and mortality. Based on both animal and adult human data, it was hypothesized that spinal anesthesia would be more effective at attenuating these responses than conventional high dose intravenous opioid techniques in infants and young children undergoing open heart surgery. METHODS: A prospective randomized controlled clinical trial was performed in 60 children aged up to 24 months undergoing open heart surgery. Patients were randomly assigned to receive either high-dose intravenous opioid or high-dose intravenous opioid plus spinal anesthesia. Spinal anesthesia was administered via an indwelling intrathecal catheter. RESULTS: Spinal anesthesia significantly reduced the stress responses as measured by plasma norepinephrine and epinephrine concentrations (both P < 0.05). Spinal anesthesia reduced plasma lactate concentrations (P < 0.05), but increased fluid requirements during the first postoperative day (P < 0.05). There were no differences in other cardiovascular parameters. CONCLUSIONS: Continuous spinal anesthesia reduces stress responses in infants and young children undergoing cardiac surgery with cardiopulmonary bypass more effectively than high-dose intravenous opioids alone.

Anesthesia, General↗

PubMed2004

Basal metabolic state of hearts of patients with congenital heart disease: the effects of cyanosis, age, and pathology.

BACKGROUND: Experimental models have established numerous myocardial metabolic changes with chronic hypoxia and maturation. We conducted this study to specifically look at the effects of cyanosis, age, and pathology upon the basal metabolic state of the immature human heart. METHODS: One hundred and eighty-one pediatric patients (37 cyanotic, 144 acyanotic) undergoing open heart surgery were recruited. A myocardial biopsy was collected before ischemia and analyzed for adenine nucleotides, purines, and lactate. The effect of cyanosis was estimated by an analysis of age-matched pairs of children with either ventricular septal defects or tetralogy of Fallot, and by multiple regression modeling. The effects of age and pathology were estimated in acyanotic children also by multiple regression modeling (adjustments were made for baseline differences). RESULTS: The only effect of cyanosis was for lactate where the paired t test, and unadjusted and adjusted regression analyses were all consistent (ranging from 1.33 to 1.48 times higher in cyanotic than acyanotic children). The concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) declined with age, whereas the ATP/ADP ratio increased; these associations remained significant even in the adjusted regression analysis. None of the effects of acyanotic pathology were highly significant (p < 0.01), implying that few important metabolic differences were attributable to pathology. CONCLUSIONS: Cyanosis and age are important factors that determine the basal metabolic state of the pediatric heart. Cyanotic patients have higher myocardial lactate concentrations, whereas young age is associated with lower ATP/ADP ratios and higher adenine nucleotide levels.

Adenine Nucleotides↗

PubMed2004

Median sternotomy as an exit procedure in a child with massive pericardial tumor.

Fetuses can survive with complete airway obstruction caused by placental gas exchange until birth when full ventilatory function is required. The authors present a case in which prenatal scans suggested that adequate ventilation would not be achievable because of the presence of an intrathoracic tumor. An EXIT procedure (exutero intrapartum treatment) was therefore performed, which permitted sufficient lung expansion for adequate ventilation.

Adult↗

PubMed2002

Cold blood versus cold crystalloid cardioplegia for repair of ventricular septal defects in pediatric heart surgery: a randomized controlled trial.

BACKGROUND: There is little evidence in the literature on the benefits of cold blood cardioplegia in pediatric cardiac surgery. This study investigates the effects of cold crystalloid versus cold blood cardioplegia on myocardial metabolism, reperfusion injury, and clinical outcomes in patients undergoing ventricular septal defect (VSD) repair. METHODS: Patients were randomly assigned to receive antegrade cold (4 to 6 degrees C) St Thomas's I crystalloid (CCC) or blood (CBC) cardioplegia. Changes in myocardial adenine nucleotides and purine levels were monitored in right ventricular biopsies and postoperative serum troponin I (TnI) and lactate release were measured. RESULTS: Forty patients were randomly assigned to CCC (n = 21; age 21.1 +/- 40.8 months) or to CBC (n = 19; age 27.4 +/- 39.3 months). Patient characteristics were similar in the two groups and there was no mortality. After the ischemic period there was a significant drop in adenosine triphosphate levels compared with control values in the CCC (40.4 +/- 9.9 versus 27.5 +/- 12.5 nmol/mg protein, p = 0.01) but not in the CBC group (40.3 +/- 23.2 versus 37.3 +/- 18.9 nmol/mg protein). The fall was more marked in infants compared with children (40% versus 10%, respectively, p = 0.01). Mean total TnI release was 42% lower in the CBC than the CBC group (95% confidence interval 10% to 62%, p = 0.015). Total TnI release was significantly associated with age (p < 0.001) but as levels in infants in the CBC group were the same as for children, the reduction with age was seen almost entirely in the CCC group. There were no differences in the duration of inotropic support, ventilation time, intensive care unit, or hospital stay in the two groups. CONCLUSION: The use of CBC is associated with less metabolic myocardial ischemic stress and reperfusion injury when compared with CCC in pediatric patients undergoing VSD repair.

Bicarbonates↗

PubMed2002

Cardiac troponin I in neonates undergoing the arterial switch operation.

BACKGROUND: Cardiac troponin I (TnI) is a sensitive and specific marker of myocardial injury, but little is known about its release after complex congenital heart surgery. We investigated whether TnI correlates with early clinical outcome in neonates undergoing the arterial switch operation (ASO) for transposition of the great arteries (TGA). METHODS: Troponin I was measured serially up to 48 hours postoperatively in 31 neonates undergoing the ASO alone (simple TGA) and 9 neonates undergoing the ASO combined with other procedures (complex TGA) (eg, closure of a ventricular septal defect) and correlated with intraoperative and postoperative clinical parameters. RESULTS: There was no mortality. Troponin I peaked at either 4 or 12 hours postoperatively in all patients (median for simple TGA = 3.4 ng/mL, interquartile range 2.4 to 4.6; median for complex TGA = 4.7 ng/mL, interquartile range 3.2 to 6.8, p = 0.20). Peak TnI correlated with the durations of inotropic support (r = 0.54, p < 0.001), ventilation (r = 0.51, p < 0.01), and intensive care unit stay (r = 0.50, p < 0.01). The duration of cardiopulmonary bypass, aortic cross-clamping, and circulatory arrest did not correlate with the peak or total TnI release. The duration of aortic cross-clamping correlated poorly with the duration of inotropic support (r = 0.40, p < 0.05). The complex TGA group had longer aortic cross-clamp times, required more postoperative inotropic support, and had significantly higher total TnI release compared with the simple TGA group. CONCLUSIONS: There are weak but statistically significant correlations between peak TnI and clinical outcome. Complexity of the defect and ischemic times may be as useful to predict outcome in this group of patients.

Biomarkers↗

PubMed2002

Alterations in nitric oxide production in 8-week-old lambs with increased pulmonary blood flow.

Nitric oxide (NO) is an important mediator of pulmonary vascular reactivity, and decreased NO synthase expression has been demonstrated in children with advanced pulmonary hypertension secondary to congenital heart disease and increased pulmonary blood flow. Using aortopulmonary vascular graft placement in the fetal lamb, we have established a unique animal model of pulmonary hypertension with increased pulmonary blood flow. At 4 wk of age, these lambs display an early, selective impairment in agonist-induced NO responses, but an up-regulation of basal NO activity and gene expression. We hypothesized that further exposure to increased flow and/or pressure results in progressive endothelial dysfunction and a subsequent decrease in basal NO production. The objective of this study was to characterize potential later alterations in agonist-induced NO responses and basal NO activity and gene expression induced by 8 wk of increased pulmonary blood flow and pulmonary hypertension. Twenty-two fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt), and were studied 8 wk after delivery. Both in vivo and in isolated pulmonary arteries, the pulmonary vasodilating response to endothelium-dependent agents was attenuated in shunted lambs (p < 0.05), whereas the response to endothelium-independent agents was unchanged. The pulmonary vasoconstricting responses to Nomega-nitro-L-arginine, and lung tissue endothelial NO synthase mRNA, endothelial NO synthase protein, NO synthase activity, and NO(X) levels were all unchanged. These data suggest that the increase in basal NO activity demonstrated after 4 wk of increased pulmonary blood flow is lost by 8 wk of age, whereas the attenuation of agonist-induced responses persists. We speculate that the progressive decrease in basal NO activity participates in the development of pulmonary hypertension secondary to increased pulmonary blood flow.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMedDate not supplied

Pathology-related troponin I release and clinical outcome after pediatric open heart surgery.

BACKGROUND: Perioperative myocardial injury is determined by the ischemic duration, pathology, and preoperative myocardial status. Our aim was to evaluate pathology-related differences in troponin I (TnI) release, a sensitive and specific marker of myocardial injury, and its relation to clinical outcome after pediatric open heart surgery. METHODS: Troponin I was measured serially postoperatively in 133 children undergoing repair of atrial (ASD, n = 41) and ventricular septal defects (VSD, n = 46), and tetralogy of Fallot (TOF, n = 46). The length of the right ventricular outflow tract (RVOT) incision in the latter was classified as either minimum(n = 33) or extended(n = 13). RESULTS: Postoperative TnI levels were lesion specific and did not correlate with clinical outcome for ASDs. Peak TnI correlated with inotropic duration for VSD (r = 0.69, p < 0.0001) and TOF (r = 0.51, p = 0.0004). Significant correlations were also observed for the durations of ventilation (r = 0.64 and 0.36, respectively) and ICU stay (r = 0.60 and 0.55). Younger age (<1 year old) in children with VSDs and an extended incision into the RVOT in TOF were associated with greater TnI release and worse clinical outcome. CONCLUSIONS: Postoperative TnI release is pathology related and reflects myocardial damage from both ischemia-reperfusion injury and direct myocardial trauma.

Child, Preschool↗