Coronary Flow Reserve in the Newborn Lamb: An Intracoronary Doppler Guide Wire Study

Abstract

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 g/kg i.v.) using an intracoronary 0.014-in Doppler flow-wire. Measurements were made at normal oxygen saturation (SaO 2 ) 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 SaO 2 , pCFR was 3.0 Ϯ 0.5. pCFR decreased with increasing hypoxemia. Regression analysis showed a linear relation between SaO 2 and pCFR (R ϭ 0.86, p Ͻ 0.0001). Reactive CFR obtained at severe hypoxemia (SaO 2 Ͻ30%) was 4.2 Ϯ 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. Hemodynamic problems in the neonatal period, often related to congenital heart defects, may affect coronary blood flow (1-3). The coronary physiology in newborns has become of greater importance as cardiac surgery for congenital heart defects is increasingly performed in the neonatal period. Coronary flow reserve (CFR) has been found to be useful in evaluating the effects of cardiac disease and pathologic hemodynamic conditions on coronary flow dynamics in adults (4 -6). CFR is defined as the ratio of maximal coronary blood flow, as induced by reactive hyperemia or administration of vasodilators, divided by resting flow (4).Recent studies performed with positron emission tomography (PET) have shown low CFR in neonates and infants with congenital heart disease (1, 7). The significance of these studies remains debatable, as the ability of the anatomically normal neonatal heart to increase coronary flow is currently unknown (1, 7). The objective of this study was to provide normal values for CFR in the normal neonatal heart by administration of adenosine [pharmacologic CFR (pCFR)

Functional and Morphologic Imaging of Coronary Atherosclerosis in Living Mice Using High-Resolution Color Doppler Echocardiography and Ultrasound Biomicroscopy

“…Further, in the same study, the investigators showed an inverse correlation between coronary flow and arteriolar PO 2. Although hypoxic stimuli seem to induce a slight increase of HR in humans, anesthetized mice did not show any HR changes during moderate hypoxia, a phenomenon also known from studies in newborn lambs, which also showed a CFR value around 2 (22). Whether this is attributable to the species difference or to effects of anesthesia is currently not clear.…”

Coronary Flow Reserve Measurement Detects Transplant Coronary Artery Disease in Pediatric Heart Transplant Patients

“…9,11,12 Only a small number of studies have tested CFR in pediatric patients, mainly in patients who have undergone an arterial switch operation, and in neonatal lambs in order to collect reference values for the pediatric population. 13,[21][22][23] Evaluation of epicardial CAV may alternatively be done using intravascular ultrasound (IVUS) studies, although the use of IVUS is limited, especially in smaller pediatric patients, due to the size of the probe. 24,25 Fearon et al showed a good correlation of CFR with IVUS findings, but CFR was, interestingly, abnormal in asymptomatic cardiac transplant patients with normal angiograms, in whom one might speculate about microvasculopathy, which was not evaluated in their study.…”

Scalability and in vivo validation of a multiscale numerical model of the left coronary circulation

“…Indeed, aside from a few published Doppler velocity recordings (47,48), relatively little information about phasic coronary hemodynamics in the newborn is available. Of particular relevance to the design of a newborn coronary circulation model is the hypothesis of Rumberger et al (54,55) that the prominence of the early systolic and diastolic flow transients (and hence the importance of wave propagation) increases with body size due to longer wave transit distances.…”