Gylfi Oskarsson

Normal Coronary Flow Reserve After Arterial Switch Operation for Transposition of the Great Arteries An Intracoronary Doppler Guidewire Study

Background—Recent studies performed with positron emission tomography have suggested that coronary flow reserve (CFR) is moderately to severely reduced after the arterial switch operation (ASO). These findings are of great concern but have not been confirmed by other methods. Methods and Results—Eleven symptom-free children were studied between 4 and 11 (median 6.0) years after the ASO. Flow velocity in the left anterior descending (LAD) and right coronary arteries (RCA) was measured with a 0.014-inch Doppler FloWire (Cardiometrics) before and after intracoronary injection of adenosine (0.5 &mgr;g/kg) and nitroglycerin (5 &mgr;g/kg). CFR was defined as the ratio of hyperemic to basal average peak velocity (APV). The median (range) CFR in the LAD was 3.7 (3.0 to 4.8) and 3.4 (2.9 to 4.8) in the RCA. The increase in APV after intracoronary injection of nitroglycerin was 300% (240% to 420%) in the LAD and 260% (190% to 460%) in the RCA. APV at rest was 15.0 (14.0 to 21.0) cm/s in the LAD and 16.0 (9.6 to 30.0) cm/s in the RCA. A linear relation was found between right ventricular systolic pressure and resting APV in the RCA (r =0.77, P =0.0056), and between resting APV and CFR (r =-0.61, P <0.05) in the RCA. Conclusions—The CFR and coronary vasoreactivity to nitroglycerin in children treated for transposition of the great arteries with the ASO was within normal limits. Increased right ventricular pressure and myocardial hypertrophy can cause increased resting coronary flow velocity in the RCA and affect CFR negatively.

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near‐term fetal lambs (134–138 days) with the ewe under isoflurane‐opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18‐F]Fluoro‐2‐deoxy‐glucose (18‐FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid‐base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) μmol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.

Nordic pulse oximetry screening – implementation status and proposal for uniform guidelines

Pulse oximetry screening of newborn infants increases early detection of critical congenital heart disease and minimises the risk of circulatory collapse before surgery. This study provides an update on the implementation of pulse oximetry screening in the Nordic countries and proposes standardised guidelines.

Coronary Blood Flow in Healthy Neonates: Effects of Left Ventricular Function and Mass

This study used transthoracic echocardiography, including pulsed-wave Doppler, to register coronary flow parameters in 55 healthy neonates. Intraobserver variability was tested in 20 neonates. A Doppler tracing of sufficient quality for analysis was obtained in the left anterior descending coronary artery (LAD) in 53 of 55 studies (96.4% feasibility) and in the right coronary artery (RCA) in 11 of 55 studies (20.0% feasibility). Estimation of intraobserver variability showed coefficients of variation of 7.5–8.0% for diastolic LAD Doppler flow parameters and volume flow but 17.5% for systolic peak flow velocity. Doppler flow parameters were significantly higher in the LAD than in the RCA. Correlation was found between LAD Doppler flow parameters and age, left ventricular (LV) mass, mitral peak early wave velocity as a measure of diastolic LV function, and the aortic velocity time integral/minute as a measure of systolic LV function. This study shows that diastolic LAD Doppler flow parameters and flow volume can be obtained in neonates by transthoracic echocardiography with acceptable reproducibility. In healthy neonates, left coronary flow parameters are linearly related to age, LV mass, and LV systolic and diastolic function. RCA flow parameters in neonates are lower than in the LAD.

Different Responses of Myocardial and Cerebral Blood Flow to Cord Occlusion in Exteriorized Fetal Sheep

Type and duration of fetal asphyxial insult affect the distribution of blood flow to the heart and brain. The purpose of this study was to describe dynamic and quantitative changes in regional myocardial and cerebral blood flow (CBF) during fetal asphyxia induced by total occlusion of the umbilical cord. Eleven exteriorized fetal sheep were subjected to total umbilical cord occlusion and five fetal sheep served as sham controls. Regional blood flow (BF) to the brain and heart was quantified using radioactive microspheres before and after 5 min of occlusion and finally when fetal mean arterial blood pressure had decreased below 25 mm Hg, 9.8 (0.8) [mean (SD)] min after occlusion. Right coronary arterial (RCA) blood flow velocity and carotid BF were registered continuously. Mean values of arterial pH and oxygen content (mL O2/100 mL) were 7.08 (0.11) and 4.4 (2.9) before cord occlusion and decreased to 6.83 (0.05) and 1.4 (0.9) at 5 min after occlusion (p < 0.01, respectively). Carotid BF was significantly below preocclusion values by 2.5 min (p < 0.05), whereas RCA velocity time integral per minute remained above preocclusion values for 9 min. CBF decreased from 316 (24) before cord occlusion to 156 (30) mL/min/100 g at 5 min (p < 0.01), whereas right myocardial BF was maintained at 792 (125) and 751 (183) mL/min/100 g, respectively. CBF decreased rapidly after total cord occlusion whereas myocardial BF increased and was maintained until shortly before cardiac arrest, suggesting the myocardium to be better preserved during this type of insult in already partially asphyxiated fetuses.

Flow dynamics in the left anterior descending coronary artery in infants with idiopathic dilated cardiomyopathy.

Infants with IDC have increased LAD peak flow velocities, velocity-time integrals, and increased LAD flow compared with healthy controls. Although LAD flow is linearly related to LV mass in healthy subjects, a reduced LAD flow corrected for LV mass is observed in infants with IDC. Treatment aimed at improving myocardial perfusion may have benefits for patients with IDC.

Coronary flow and flow reserve in children.

Aortic blood pressure affects coronary blood flow, but within the normal physiological blood pressure range coronary blood flow is constant. The coronary flow is pulsatile, being maximal in the early diastole. There is a smaller systolic flow component. The low systolic pressure in the right ventricle favours systolic flow. The proportion of systolic flow is greater in the right than in the left coronary artery. Heart diseases in children cause several haemodynamic and functional changes that are likely to affect myocardial perfusion. Newborns with severe valvular aortic stenosis may have a retrograde systolic flow in the left coronary artery. Children with dilated cardiomyopathy have a reduced coronary flow related to myocardial mass. Coronary flow reserve (CFR) is defined as the ratio of maximal coronary blood flow, as induced by reactive hyperaemia or administration of vasodilators, divided by resting flow. Coronary flow can normally increase 2.5–4‐fold. CFR is reduced if basal flow is increased due to myocardial hypertrophy, strain or hypoxaemia. Very low CFR values measured with positron emission tomography are reported in neonates with surgically treated congenital heart disease. Measurement of coronary flow velocity with the intracoronary Doppler guide wire may be regarded as a reference or “gold standard” in the evaluation of coronary flow velocity and CFR.

Coronary flow reserve in the newborn lamb: An intracoronary Doppler guide wire study

Recent studies indicate a severely reduced coronary flow reserve (CFR) in neonates with congenital heart disease. The significance of these studies remains debatable, as the ability of the anatomically normal neonatal heart to increase coronary flow is currently unknown. This study was designed to establish normal values for CFR in newborns after administration of adenosine [pharmacologic CFR (pCFR)] and as induced by acute hypoxemia (reactive CFR). Thirteen mechanically ventilated newborn lambs were studied. Coronary flow velocities were measured in the proximal left anterior descending coronary artery before and after adenosine injection (140 and 280 μg/kg i.v.) using an intracoronary 0.014-in Doppler flow-wire. Measurements were made at normal oxygen saturation (Sao2) and during progressive hypoxemia induced by lowering the fraction of inspired oxygen. CFR was defined as the ratio of hyperemic to basal average peak flow velocity. In a hemodynamically stable situation with normal Sao2, pCFR was 3.0 ± 0.5. pCFR decreased with increasing hypoxemia. Regression analysis showed a linear relation between Sao2 and pCFR (R = 0.86, p < 0.0001). Reactive CFR obtained at severe hypoxemia (Sao2 <30%) was 4.2 ± 0.8, and no significant further increase in coronary flow velocity occurred by administration of adenosine. Newborn lambs have a similar capacity to increase coronary flow in response to both pharmacologic and reactive stimuli as older subjects. Administration of adenosine does not reveal the full capacity of the newborn coronary circulation to increase flow, however, as the flow increase caused by severe hypoxemia is significantly more pronounced.

Acute decrease of coronary flow after indomethacin delivery in newborn lambs.

Aim: To document the effects of indomethacin (IND) on coronary flow.

Perinatal adaptive response of the adrenal and carotid blood flow in sheep fetuses subjected to total cord occlusion

OBJECTIVE To investigate the perinatal adaptive response of the adrenal blood flow/adrenal fractional moving blood volume (AFMBV) and carotid blood flow (CBF), in sheep fetuses subjected to severe acute intrauterine hypoxia/asphyxia induced by total cord occlusion. METHODS Adrenal blood flow velocity, AFMBV and CBF were measured in 13 exteriorized fetal sheep; eight of them underwent total umbilical cord occlusion to induce severe acute hypoxia/asphyxia. Five lambs were used as sham controls. Middle adrenal artery pulsatility index (MAAPI) and mean velocity (MAAMV) were recorded with pulsed Doppler ultrasound. AFMBV was estimated using power Doppler ultrasound. CBF was recorded with a transonic flowmeter. In the neonatal period, after resuscitation all lambs were followed for a 4-hour period and AFMBV and CBF were recorded. Mean arterial blood pressure (MABP) and fetal heart rate were recorded continuously. Arterial cortisol levels were measured at the beginning and at the end of the fetal and neonatal periods. RESULTS Following the total cord occlusion, there was a significant reduction in the CBF, MABP, and heart rate and adrenal flow/AFMBV after 2, 4 and 5 min, respectively. Cortisol levels in the asphyctic lambs at the end of the cord occlusion were significantly lower than those in controls. After resuscitation, the asphyctic lambs showed increased AFMBV and cortisol levels, and reduced MABP as compared to control lambs. No differences were found in CBF, MAAPI and MAAMV. Thereafter, no differences were observed between the two groups in any of the studied parameters. At the end of the cord occlusion period, there was a significant correlation between AFMBV and MABP (r=0.69), between AFMBV and CBF (r =0.65) and between CBF and MABP (r=0.89). CONCLUSION During severe acute intrauterine hypoxia, the fetal lamb is able to maintain the blood flow to the brain and the adrenal gland for 3-5 min. Changes in the AFMBV and the CBF were highly correlated to the changes in MABP. Adrenal FMBV and cortisol levels were higher in lamb neonates exposed to severe intrauterine asphyxia.