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Studies in which subcellular systems were used suggest that neonatal myocardium has a sharply limited capacity to metabolize fatty acids. The relationship of these findings to the intact heart was tested on piglets, 8 h to 12 days of age. Left ventricular (LV) performance, O2 consumption (MVO2), and fatty acid (FA) uptake and oxidation were measured. Hearts were perfused at 70 cmH2O pressure with buffer containing 2% bovine serum albumin, insulin (100 microU/ml), 5 mM glucose, and 1.5 mM lactate. 14C-labeled palmitate was added (net FA, 0.5 mM). Washed erythrocytes were used to assure adequate O2 delivery. LV end-diastolic pressure (EDP) was controlled with a fluid-filled balloon. FA oxidation was estimated by measuring 14CO2 production. Hearts less than 24 h (group I, n = 6), those approximately 3 days (group II, n = 5), and those 6-12 days of age (group III, n = 10) were compared. Measurements at a low EDP (2-4 cmH2O) and at a higher EDP (7-9 cmH2O) were compared. At the low EDP, rates of FA oxidation for groups I-III averaged 30.0 +/- 3.0, 31.4 +/- 2.9, and 50.2 +/- 2.6 nmol.min-1.g-1, respectively. These values increased to 43.8 +/- 3.7, 42.6 +/- 2.5, and 63.8 +/- 4.0 nmol.min-1.g-1, respectively, at the higher EDP level (P less than 0.01 for each group). Thus within a few hours of birth, pig hearts are able to oxidize long-chain FA, and the rate of oxidation is linked to mechanical function. However, both the oxidation rate and the percentage of MVO2 accounted for by FA oxidation are greater in older hearts.

The central aortic shunt, consisting of a Gore-Tex (polytetrafluoroethylene) tube (graft) connecting the ascending aorta to the pulmonary artery, is a palliative operation for neonates with cyanotic congenital heart disease. These tubes often have an extended length, and therefore must be angulated to complete the connection to the posterior pulmonary arteries. Thrombosis of the graft is not uncommon and can be life-threatening. We have shown that a viscous fluid (such as blood) traversing a curve or bend in a small-caliber vessel or conduit can give rise to marked increases in wall shear stress, which is the major mechanical factor responsible for vascular thrombosis. Thus, the objective of this study was to use computational fluid dynamics to investigate whether wall shear stress (and shear rate) generated in angulated central aorta-to-pulmonary artery connections, in vivo, can be of magnitude and distribution to initiate platelet activation/aggregation, ultimately leading to thrombus formation. Anatomical features required to construct the computer-simulated blood flow pathways were verified from angiograms of central aortic shunts in patients. For the modeled central aortic shunts, we found wall shear stresses of (80-200 N/m(2)), with shear rates of (16,000-40,000/s), at sites of even modest curvature, to be high enough to cause platelet-mediated shunt thrombosis. The corresponding energy losses for the fluid transitions through the aorta-to-pulmonary connections constituted (70 %) of the incoming flow's mechanical energy. The associated velocity fields within these shunts exhibited vortices, eddies, and flow stagnation/recirculation, which are thrombogenic in nature and conducive to energy dissipation. Angulation-induced, shear stress-mediated shunt thrombosis is insensitive to aspirin therapy alone. Thus, for patients with central aortic shunts of longer length and with angulation, aspirin alone will provide insufficient protection against clotting. These patients are at risk for shunt thrombosis and significant morbidity and mortality, unless their anticoagulation regimen includes additional antiplatelet medications.

There are certainly some levels in all nuclei, and all levels in some nuclei for which the usual treatment of particle transfer reactions, which neglects inelastic effects, is invalid. Here a practical method for taking these effects into account is described. The method is discussed in terms of the (d,p) reaction, but i t has a much broader application than this .

Patients with Fontan-modified, single-ventricle heart frequently have systemic collaterals that increase pulmonary blood flow. Competitive flow from these auxiliary vessels can also elevate pulmonary artery pressure, a process leading to erosion of flow's mechanical energy. An analogous analytical description of mixing fluid streams was used to provide insight into flow energetics associated with systemic-to-pulmonary collaterals in Fontan-type circulation. We find that theoretical pressure increases and flow energy losses due to mixing vary quadratically as the velocity differences of the interacting fluid streams. Moreover, the predicted flow energy loss is shown to depend directly on the resultant pressure increase. Based on studies of aortopulmonary collaterals in patients with Fontan anatomy, we provide an estimate of pulmonary artery pressure elevation and flow energy loss, factors that are of considerable clinical importance.

ABSTRACT. Cardiac effects of the neuropeptide pituitaryAbbreviations adenylate cyclase activating p o l y p e p t i d e -(~~~i~) have not previously been reported. W e investigated the influence of PACAP, vasoactive intestinal polypeptide (68% homology with PACAP) and the B-adrenergic receptor agonist isoproterenol on contractile function and coronary vascular tone in isolated piglet hearts (1 to 5 d of age). Paced (180 beatslmin) isovolumically beating hearts underwent retrograde aortic perfusion a t constant coronary flow (approximately 3 mL. min-' . g-') with an erythrocyte-enriched PACAP, pituitary adenylate cyclase activating polypeptide VIP, vasoactive intestinal polypeptide ISP, isoproterenol IBMX, isobutylmethylxanthine dP/dt,,, maximum rate of change of systolic pressure with respect to time (+), positive (-), negative (hematocrit 15 to 20%)~solution ( 3 7 "~) . ~g o n i s t s were injected into the aortic root of hearts, and the positive (+) and negative (-) changes in maximum rate of change of systolic pressure with respect to time (dP/dtma,) and in PACAP is a newly discovered neuropcptide isolated from the coronary perfusion pressure (that reflected alterations in ovine hypothalamus (1). PACAP is present in two forms: one vascular tone) were measured. PACAP (n = 8,O.l and 0.5 with 27 and the other with 38 N-terminal amino acid residues nmol) increased (+) dP/dt,, from 944 + 59 to 1519 f 206 (2). PACAP has a 68% sequence homology with VIP and appears mm ~g / s and from 867 2 40 to 2010 +: 226 mm ~g / s ( p to be more potent than VIP in stimulating adenylate cyclase in < 0.05); increased (-1 dpldt,, from 11 14 41 to 14-39 + pituitary cells (2). PACAP also has been shown to increase cAMP 9 5 mm ~g and from 999 f 37 to 1668 + 145 mm H~/ S levels in the human neuroblastoma cell line NB-OK (3), the rat ( p < 0.05); and decreased perfusion pressure from 61.4 2 pancreatic acinar cell line AR 4-25 (4), and rat liver cell mem-3.1 to 48.9 2 2.3 mm 1 1~ and from 60.5 + 2.4 to 43.9 branes ( 5 ) . Moreover, high affinity binding sites for PACAP have 2.3 mm H~ (p < 0.05), respectively. comparison, vase-been identified in several organ systems, including the rat lung active intestinal polypeptide (n = 6, 0.1 and 0.5 nmol) (6) and h m a n brain (7). increased (+) dP/dtmn, from 767 +. 53 to 806 + 37 mm Hg/ The ~h~s i o l o g i c role of PACAP has not been elucidated, and from 829 2 94 to 942 8 5 mm ~g /~ (NS); increased although it has been suggested that this peptide may be involved (-) dp/dtma, from 883 2 73 to 926 45 ,,,,,, ~g /~ and in the regulation of vascular smooth muscle tone, in addition to from 923 + 8 2 to 1054 f 78 mm Hg/s (NS); and decreased its presumed role as a hypothalamic, hypophysiotropic hormone perfusion pressure from 57.9 + 4.9 to 50.0 +. 3.6 mm H~ (8 VIP, have been demonstrated in the myocardium and coronary duced positive inotropic, luisitropic, and coronary vasodil-arteries of several adult species (12). The present study, therefore, effects in piglet which may make a was undertaken to inv...

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