Factors Affecting Coronary Flow in Children

Factors Affecting Coronary Flow in Children Elhadi H. Aburawi, MD, MSc, FRCPI, FRCPCH Division of Paediatric Cardiology, Department of Paediatrics, Lund University, Sweden Abstract Background: A number of inborn and exogenous factors influence the flow and function of the coronary arteries with possible consequences on the cardiovascular risk. The regulation of the coronary flow is partly dependent on the functional integrity of coronary endothelial cells, coronary perfusion pressure, and myocardial function. Objectives: To investigate the effects of some of the previously suggested cardiovascular risk factors on coronary flow and function in children. Methods: Blood lipid pattern and concentration of acute phase proteins and their relation to prior infections were studied. The effect of preceding airway infections on the endothelium-dependent vasomotor function of the brachial artery in healthy and type 1 diabetes mellitus children was assessed. Coronary flow was measured with transthoracic Doppler echocardiography before and after non-surgical and surgical treatment of congenital heart defects. Results: Pro-atherogenic changes consisting of decreased circulating levels of high density lipoprotein and albumin were observed in children with past infections. The brachial artery's endothelial vasomotor function was impaired in children with type 1 diabetes, being further affected by preceding mild infections in the upper airways. Compared to controls, coronary flow was increased in patients with left-to-right shunt and coarctation of aorta, and increased further after open heart surgery. In contrast, coronary flow decreased, even if not to normal, after coarctectomy and device closure of atrial septal defect. Cardiac output decreased after open heart surgery but improved after device closure. The coronary flow velocity and velocity time integral decreased with increasing CRP after open heart surgery in particular in those with prolonged aortic cross clamping. Conclusions: Residual pro-atherogenic disturbances in vascular endothelial function, lipid and albumin metabolism may be observed in children with past infections, especially in those with chronic cardiovascular risk factors such as diabetes mellitus. Cardiac malformations and open heart surgery affect negatively the coronary blood flow and cardiac output. LIST OF PUBLICATIONS This thesis is based on the following papers, which will be referred to by the Arabic numerals: 1. Aburawi EH, Grubb A, Raitakari O, Viikari J, Pesonen E. Lowered levels of serum albumin and HDL-cholesterol in children with a recent mild infection. Annals of Medicine. 2006;38:154-160. 2. Aburawi EH, Liuba P, Pesonen E, Yla-Herttuala S, Sjoblad S. Acute respiratory viral infections aggravate arterial endothelial dysfunction in children with type 1 diabetes. Diabetes Care. 2004;27:2733-5. 3. Aburawi EH, Berg A, Liuba P, Pesonen E. Effects of cardio-pulmonary bypass surgery on coronary flow in children assessed with transthoracic Doppler echocardiography. Am J Physiol Heart Circ physiol. 2007 May 4, (Epub ahead of print) 4. Aburawi EH, Berg A, Pesonen E. Coronary blood flow in patients with atrial septal defect before and after surgical versus device closure A transthoracic Doppler echocardiography study. (Submitted to Circulation). 5. Aburawi EH, Liuba P, Berg A, Pesonen E. C-reactive protein and coronary microcirculation in children after open heart surgery A transtoracic Doppler echocardiography study. Cardiology in the Young (in press)

Evaluation of Faculty : Are medical students and faculty on the same page?

Objectives: Student evaluation of individual teachers is important in the quality improvement cycle. The aim of this study was to explore medical student and faculty perceptions of teacher evaluation in the light of dwindling participation in online evaluations. Methods: This study was conducted at the United Arab Emirates University College of Medicine & Health Sciences between September 2010 and June 2011. A 21-item questionnaire was used to investigate learner and faculty perceptions of teacher evaluation in terms of purpose, etiquette, confidentiality and outcome on a five-point Likert scale. Results: The questionnaire was completed by 54% of faculty and 23% of students. Faculty and students generally concurred that teachers should be evaluated by students but believed that the purpose of the evaluation should be explained. Despite acknowledging the confidentiality of online evaluation, faculty members were less sure that they would not recognise individual comments. While students perceived that the culture allowed objective evaluation, faculty members were less convinced. Although teachers claimed to take evaluation seriously, with Medical Sciences faculty members in particular indicating that they changed their teaching as a result of feedback, students were unsure whether teachers responded to feedback. Conclusion: Despite agreement on the value of evaluation, differences between faculty and student perceptions emerged in terms of confidentiality and whether evaluation led to improved practice. Educating both teachers and learners regarding the purpose of evaluation as a transparent process for quality improvement is imperative

Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB

Occurrence of Hypothyroidism, Diabetes Mellitus, and Celiac Disease in Emirati Children with Down’s Syndrome

Objectives: Autoimmune diseases are known to occur in people with Down’s syndrome (DS), especially celiac disease, type 1 diabetes mellitus (DM), and hypothyroidism. Since there are common genetic risk factors involved in the occurrence of these autoimmune disorders, the risks would differ in different populations. We sought to determine the prevalence of type 1 DM, celiac disease, and hypothyroidism in Emirati patients with DS in Abu Dhabi, UAE. Methods: Ninety-two patients with DS were investigated for the presence of anti-thyroid antibodies, antithyroglobulin, and anti-thyroid peroxidase antibodies for hypothyroidism, anti-glutamic acid decarboxylase antibodies for type 1 DM, and anti-tissue transglutaminase immunoglobulin A antibodies for celiac disease. Results: Karyotyping was performed on 89 patients. Eighty-seven had non-disjunction of chromosome 21 (97.8%), one was a mosaic, and one had translocation. Of the patients studied, 19.6% had hypothyroidism, 4.3% had type 1 DM, and 1.1% had celiac disease. Out of the 92 patients studied, 66 (71.7%) did not have any autoimmune disease, 25 (27.2%) had one autoimmune disease, and one (1.1%) had two autoimmune diseases. Conclusions: Celiac disease was the least prevalent autoimmune disease in patients with DS patients, while type 1 DM and hypothyroidism were both significantly associated with DS

TECRL, a new life‐threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT

Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation. A third patient from a consanguineous Sudanese family diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) had a homozygous splice site mutation (c.331+1G>A) in TECRL Analysis of intracellular calcium ([Ca(2+)]i) dynamics in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from this individual (TECRLHom-hiPSCs), his heterozygous but clinically asymptomatic father (TECRLHet-hiPSCs), and a healthy individual (CTRL-hiPSCs) from the same Sudanese family, revealed smaller [Ca(2+)]i transient amplitudes as well as elevated diastolic [Ca(2+)]i in TECRLHom-hiPSC-CMs compared with CTRL-hiPSC-CMs. The [Ca(2+)]i transient also rose markedly slower and contained lower sarcoplasmic reticulum (SR) calcium stores, evidenced by the decreased magnitude of caffeine-induced [Ca(2+)]i transients. In addition, the decay phase of the [Ca(2+)]i transient was slower in TECRLHom-hiPSC-CMs due to decreased SERCA and NCX activities. Furthermore, TECRLHom-hiPSC-CMs showed prolonged action potentials (APs) compared with CTRL-hiPSC-CMs. TECRL knockdown in control human embryonic stem cell-derived CMs (hESC-CMs) also resulted in significantly longer APs. Moreover, stimulation by noradrenaline (NA) significantly increased the propensity for triggered activity based on delayed afterdepolarizations (DADs) in TECRLHom-hiPSC-CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT Patient-specific hiPSC-CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias

Pathophysiology of coronary blood flow in congenital heart disease.

OBJECTIVES: The aim was to investigate the effects of volume and pressure overload and increased coronary perfusion pressure on coronary flow (CF) in congenital heart disease (CHD) patients. BACKGROUND: The effects of CHD on CF are poorly mapped. METHODS: A total of 65 patients with acyanotic CHD and 49 age-matched healthy controls were examined by transthoracic Doppler echocardiography. Posterior descending artery flow was measured in patients with pulmonary valve stenosis (PS) and atrial septal defects (ASDs) i.e. in lesions with right ventricular pressure or volume overload, and left anterior descending artery flow in patients with coarctation of the aorta (CoA) and ventricular septal defect (VSD), in lesions with left ventricular pressure or volume overload. The CF data in each patient group were expressed as the percent of the median for healthy controls from the same age group. RESULTS: The CF values were in VSD 172%, ASD 185%, PS 233%, and CoA 773% patients. In CoA patients body surface area (r=0.90, p<0.0001), systolic blood pressure (r=0.72, p<0.0001), diastolic blood pressure (r=0.77, p<0.0001), systolic wall tension (r=-0.77, p=0.004), and signs of inflammation (log CRP, r=-0.75, p=0.007) correlated with CF. CONCLUSIONS: The increase in CF and velocity was most significant in patients with CoA. In newborns, increased coronary perfusion pressure seems to be the most important factor for increased CF, even if the pressure is not assumed to cause a significant increase in flow over the auto-regulatory range of 70-130mmHg. We also showed that inflammation decreases CF