bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal relation between neutrophil accumulation and myocardial reperfusion injury
Authors: Smith E. F. , Egan J. W. , Bugelski P. J. , Hillegass L. M. , Hill D. E. , Griswold D. E.
Published: December 2017

Infiltration of polymorphonuclear leukocytes (PMN) is associated with the progression of myocardial infarction and reperfusion injury. However, little is known about the time course of cellular infiltration. To investigate this issue, rats were subjected to 30 min of coronary artery occlusion followed by reperfusion for less than or equal to 96 h. Myocardial injury was determined by measuring the depletion of myocardial creatine phosphokinase activity, and PMN infiltration was assessed by measuring myeloperoxidase (MPO) activity. MPO activity increased from 0.7 U/g tissue in non-operated animals, to a peak of 6.7 +/- 0.8 and 6.4 +/- 1.4 U/g at 6 and 24 h after coronary artery reperfusion, respectively. MPO activity decreased to 3.3 +/- 0.8 U/g at 48 h and 1.1 +/- 0.4 U/g at 96 h, suggesting diminished PMN accumulation. Histological examination confirmed the accumulation and resolution of PMN over the 96-h period. At 24 h, there was a significant linear correlation between infarct size and MPO activity, whereas at 96 h no relationship was found. These data indicate that PMN infiltration occurs early in response to reperfusion injury and persists for only 24 h after initiation of reperfusion. These findings suggest that attempts to moderate inflammatory cell responses to myocardial injury should be administered early after coronary artery reperfusion to limit the accumulation of potentially deleterious inflammatory cells.
Isochronal behavior in left ventricular systolic pressure-wall thickness relations
Authors: Funai J. T. , Thames M. D.
Published: December 2017

Regional left ventricular systolic pressure-thickness relations have been used to assess regional load-insensitive contractility with the assumption that they possess linear isochrones that are fundamental to the time-varying elastance model of global pressure-volume relations. We examined the shape and time-varying behavior of pressure-thickness isochrones in six open-chest canine preparations. Transmural wall thickening (sonomicrometry) and ventricular pressure were altered by abrupt preload alterations during control, dobutamine, and propranolol. In all dogs and interventions, linear isochrones (r2 mean +/- SE = 0.91 +/- 0.11) were found at 5-ms intervals. During control, linear isochrone slope rose monotonically from onset to end of systole. Thickness-axis intercepts also varied continuously in time, but peak intercept and maximal slope were asynchronous. Dobutamine caused a steeper earlier maximum slope and increased slope-intercept asynchrony. Propranolol reduced maximum slope and slope-intercept asynchrony. Isochronal data during early systole were better fitted to a parabolic than to the linear model; however, fits to linear and parabolic models were equally good near end of systole. Linear isochronal behavior exists in systolic pressure-thickness relations especially near end systole and is maintained during modest inotropic alterations.
Mechanism of antihypertensive effect of potassium depletion in renovascular hypertension
Authors: Nolan C. R. , Linas S. L.
Published: December 2017

K depletion (KD) prevents the development of hypertension in two-kidney, one-clip renovascular, hypertension [mean arterial pressure: 110 +/- 5 (KD) vs. 142 +/- 3 mmHg in potassium replete (KR); P less than 0.001]. The protective effect of KD is associated with a 60% decrease in angiotensin II (ANG II) pressor responsiveness and a 40% decrease in ANG II binding to mesenteric artery particles from rats with renovascular hypertension (receptor number 117 +/- 16 in KD vs. 165 +/- 14 fmol/mg protein in KR, P less than 0.05). To determine whether decreases in binding could account for decreases in ANG II pressor responsivity, we measured ANG II binding after bilateral nephrectomy or sustained administration of converting-enzyme inhibitor. Both maneuvers resulted in increases in binding, such that total binding and receptor number were greater than in comparably treated KR rats; e.g., after nephrectomy, receptor number was 215 +/- 26 in KD vs. 98 +/- 12 fmol/mg protein in KR, (P less than 0.01). Despite increased binding, the pressor response to ANG II in KD rats, which were nephrectomized or treated with converting-enzyme inhibitor, was still reduced by 50% compared with comparably treated KR rats. To determine whether the decreased ANG II pressor responsivity of KD was caused by cellular K depletion or to increases in ANG H induced by KD, we administered K to KD, ANG II-deficient rats. ANG II pressor responsivity increased, and total binding and receptor number decreased (KD, ANG II- deficient 246 +/ 22 fmol/mg protein; KD, ANG II-deficient + K 91 +/ 16 fmol/mg protein; P less than 0.005) with K.(ABSTRACT TRUNCATED AT 250 WORDS)
Effective diameter as a determinant of local vascular resistance in presence of vasomotion
Authors: Slaaf D. W. , Vrielink H. H. , Tangelder G. J. , Reneman R. S.
Published: December 2017

The mean resistance of arterioles exhibiting rhythmic changes in diameter (vasomotion) depends on the mean vascular diameter and the amplitude and shape of the vasomotion pattern. The effective diameter, defined as the diameter of a tube with constant diameter and the same vascular resistance as the vessel showing vasomotion, was calculated using Poiseuille's law. The effective diameter was used to compare the results of model calculations of square wave, sinusoidal, and triangular vasomotion patterns with those obtained from rabbit tenuissimus muscle arterioles. Due to the variability of the actual vasomotion waveforms, approximation of the effective diameter using the mean diameter, the relative vasomotion amplitude, and an assumed waveform led to erroneous results. Therefore, effective diameter should be calculated directly from the actual arteriolar diameter tracings to take into account all irregularities in the vasomotion pattern.
Effect of pulmonary perfusion on lung fluid filtration in young lambs
Authors: Teague W. G. , Berner M. E. , Bland R. D.
Published: December 2017

To study the effect of pulmonary perfusion on fluid filtration in the newborn lung, we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine healthy, awake lambs, 2–3 wk old, before and during sustained alterations in pulmonary blood flow. A 12% reduction in cardiac output (from partial occlusion of the inferior vena cava) led to a corresponding decrease in lymph flow, consistent with a reduction in net lung fluid filtration. A 20% increase in pulmonary blood flow (from opening an external shunt between the carotid artery and jugular vein) increased lymph flow by approximately 40%, without a significant change in lymph protein concentration. These findings suggest that lung microvascular surface area expanded in response to increased perfusion, with little or no change in filtration pressure. In five lambs, lung microvascular pressure was increased by inflating a balloon catheter in the left atrium to establish full patency of the pulmonary microcirculation. In the presence of left atrial pressure elevation, increased perfusion through the arteriovenous shunt had no significant effect on pulmonary vascular pressures or lymph flow. Thus, in young lambs, modest changes in pulmonary blood flow may affect lung fluid filtration by altering perfused microvascular surface area; this response is inhibited in the presence of left atrial hypertension.
Stimulation of parabrachial neurons elicits a sympathetically mediated pressor response in cats
Authors: Hade J. S. , Mifflin S. W. , Donta T. S. , Felder R. B.
Published: December 2017

We examined the role of the parabrachial neuronal mass in mediating the pressor response to electrical stimulation of parabrachial nucleus (PBN). In anesthetized cats, 100 mM L-glutamate (L-glu) was microinjected into PBN at sites from which low-intensity (25 microA) electrical stimulation evoked a pressor response. Arterial pressure, heart rate, and, in some animals, renal or phrenic nerve activity were monitored. Microinjection of L-glu caused an increase in arterial pressure that was comparable with that elicited by low-intensity electrical stimulation. Electrical stimulation, and to a lesser extent L-glu microinjection, caused an increase in renal sympathetic nerve activity but no significant change in heart rate. No consistent change in central respiratory drive accompanied the pressor response. These responses were preserved after baroreceptor denervation but were blocked by intravenous administration of the alpha-adrenergic receptor antagonist phentolamine. Microinjection into PBN of 2 mM kainic acid, which selectively depolarizes neurons but spares axons, reversibly blocked the arterial pressure and renal nerve responses to the 25-microA electrical stimulus. We conclude that the pressor response elicited by electrical stimulation of PBN in the anesthetized cat is mediated by cellular elements in PBN, not by fibers of passage. Because phentolamine completely blocked the pressor response, we suggest that it is subserved peripherally by sympathetic alpha-adrenergic rather than humoral (e.g., angiotensin, vasopressin) vasoconstrictor mechanisms. Finally, our data indirectly suggest that PBN stimulation may differentially engage efferent components of the sympathetic nervous system to elicit the pressor response.
Regional variation in pericardial contact pressure in the canine ventricle
Authors: Hoit B. D. , Lew W. Y. , LeWinter M.
Published: December 2017

We studied eight open-chest dogs to determine whether there is regional variation in pericardial contact pressure (PCP). Flat, air-filled balloons were used to measure PCP simultaneously over the lateral walls of the right and left ventricles while cardiac volume was varied by dextran infusion. End-diastolic and mean PCP were significantly higher over the left than right ventricle at high (20.3 +/- 1.0 mmHg) and middle levels (13.7 +/- 0.9 mmHg) of left atrial pressure. At high left atrial pressures, the end-diastolic PCP over the lateral left ventricle was 9.1 +/- 2.4 mmHg compared with 4.3 +/- 2.3 mmHg over the lateral right ventricle (P less than 0.05). At middle levels of left atrial pressures, end-diastolic PCP was 6.2 +/- 3.5 mmHg over the left ventricle and 1.5 +/- 2.4 mmHg over the right ventricle (P less than 0.05). These variations in PCP persisted after severing the pericardial diaphragmatic attachments and after turning the dogs such that one or the other balloon was dependent. Regional distribution of PCP was studied by positioning a single balloon sequentially at multiple ventricular sites. PCP was consistently higher over the lateral wall of the left ventricle than either the anterior or posterior walls of the right or left ventricle. After aortic occlusion, end-diastolic PCP increased more over the left than right ventricle. In contrast, with pulmonary artery occlusion, end-diastolic PCP increased more over the right than left ventricle. Pericardial pressure varies regionally, and a single pericardial pressure may be an oversimplification when used to describe pericardial restraint on the cardiac volume.
Stretch-induced contraction in pulmonary arteries
Authors: Kulik T. J. , Evans J. N. , Gamble W. J.
Published: December 2017

Stretch stimulates contraction of systemic blood vessels, but the response has not been described in pulmonary vessels. To determine whether pulmonary arteries contract when stretched, isolated cylindrical segments of pulmonary arteries were suspended between two parallel wires, stretched, and the active force was generated in response to stretch measured. Eighty-nine percent of segments from small (in situ diameter less than 1,000 microns) feline pulmonary arteries contracted when stretched, and in 65% of these the magnitude of stretch was related to the magnitude of contraction. Large (in situ diameter greater than or equal to 1,000 microns) feline pulmonary arteries did not contract with stretch. Multiple, rapidly repeated stretches resulted in a diminution of active force development. Stretch-induced contraction required external Ca2+ and was abolished by diltiazem (10 microns), but it was not affected by phenoxybenzamine, phentolamine, diethylcarbamazine, or mechanical removal of endothelium. Indomethacin blunted but did not abolish stretch-induced contraction, an effect that may have been nonspecific. This study suggests that stretch can act, probably directly, on smooth muscle in small feline pulmonary arteries to elicit contraction and that it may be a determinant of pulmonary vascular tone. In addition, feline pulmonary arteries are suitable for the in vitro study of stretch-induced contraction.
Sympathetic augmentation of cardiac function in developing hypertension in conscious dogs
Authors: Gelpi R. J. , Hittinger L. , Fujii A. M. , Crocker V. M. , Mirsky I. , Vatner S. F.
Published: December 2017

To determine the alterations in left ventricular (LV) function and the mechanisms involved that occur during the development of perinephritic hypertension, dogs were instrumented with a miniature LV pressure transducer, aortic and left atrial catheters, and ultrasonic crystals to measure LV diameter in the short and long axes and wall thickness. At 2 wk after initiation of perinephritic hypertension, increases (P less than 0.05) were observed in LV systolic pressure, LV end-diastolic pressure, both short- and long-axis end-diastolic diameters, calculated LV end-diastolic volume, stroke volume, global average LV systolic wall stress, first derivative of LV pressure (LV dP/dt), and ejection fraction, whereas mean velocity of circumferential fiber shortening (Vcf) and rate of change of LV short-axis diameter (LV dD/dt) rose but not significantly. At three levels of matched preload and afterload induced by the administration of graded doses of phenylephrine, Vcf, LV dD/dt, and LV dP/dt increased in hypertension compared with the same levels of preload and afterload before hypertension. When the loading conditions in the normotensive and hypertensive dogs were matched, either after ganglionic blockade or beta-adrenergic blockade, both isovolumic and ejection-phase indexes of LV function remained similar before and after hypertension. Thus we conclude that 1) LV function in intact, conscious dogs with early hypertension is enhanced, and 2) the major mechanism for the increase in LV function involves the sympathetic nervous system.
ACh-induced calcium transients in primary cultures of rabbit aortic endothelial cells
Authors: Danthuluri N. R. , Cybulsky M. I. , Brock T. A.
Published: December 2017

Acetylcholine (ACh) causes vascular smooth muscle relaxation by releasing endothelium-derived relaxing factor (EDRF) from endothelial cells (EC). Although a pivotal role for cytosolic free Ca2+ ([Ca2+]i) has been implicated in the generation and/or release of EDRF by various agonists, there is no conclusive evidence showing that ACh increases [Ca2+]i in EC. In the present study, using the Ca2+-sensitive fluorescent indicator fura-2, we show for the first time that ACh (10(-5) M) increases [Ca2+]i six- to sevenfold above prestimulus levels in primary cultures of rabbit aortic EC (RbAEC). ACh effects are dose dependent [effective concentration producing 50% of the maximum response (EC50) approximately 9 X 10(-7) M] and are blocked by atropine, a selective muscarinic receptor antagonist. The [Ca2+]i increase is due both to the mobilization of intracellular Ca2+ and to the influx of extracellular Ca2+. A 5-min incubation of RbAEC with 4 beta-phorbol 12-myristate 13-acetate (10(-7) M) inhibits ACh-induced [Ca2+]i transients, suggesting that the signaling pathway involved in ACh receptor signal transduction may be modulated via protein kinase C. These cultured EC provide a unique in vitro model system for studying mechanisms involved in ACh-induced EDRF release.
Pressor responses to vasopressin in pigs and sheep with DOCA hypertension
Authors: Ling W. D. , Brooks D. P. , Crofton J. T. , Share L. , Bohr D. F.
Published: December 2017

Pressor responses to vasopressin were determined in pigs and sheep during three experimental periods: 1) before deoxycorticosterone acetate (DOCA) treatment, 2) 21 days after DOCA implantation (100 mg/kg) when a stable hypertension had developed, and 3) after reversal of the hypertension by removing the implant in the sheep or by decreasing the dietary sodium intake in the pigs. The infusion of lysine (LVP) or arginine (AVP) vasopressin into pigs and sheep, respectively, resulted in dose-dependent increases in plasma vasopressin concentration. The levels of plasma LVP or AVP achieved by these infusions were not altered in any of the experimental periods. The administration of vasopressin resulted in dose-dependent increases in mean arterial blood pressure. However, pigs required five times more LVP than sheep required AVP to achieve similar pressor responses. The pressor responsiveness to vasopressin was attenuated when either species was made hypertensive. This effect was reversed when normal blood pressure was restored by reducing sodium intake in the pigs or by removing the DOCA implant from the sheep. These data establish that an increased pressor response to vasopressin does not contribute to DOCA hypertension in pigs or sheep.
Vascular development in chick embryos: a possible role for adenosine
Authors: Adair T. H. , Montani J. P. , Strick D. M. , Guyton A. C.
Published: December 2017

We studied the possible role of adenosine in the development of the vasculature using 217 chick embryos. Adenosine (2-32 mumol/day), inosine (16 mumol/day), dipyridamole (0.04-0.4 mumol/day), or aminophylline (400 and 800 micrograms/day) were administered twice each day into the air space on days 11-14. Control embryos received Ringer solution. Whole body vascularity was estimated on day 15 as the whole body structural vascular resistance (SVR), i.e., the hydraulic resistance of the maximally dilated vasculature. Adenosine decreased the SVR in a dose-related manner at the lower dosage amounts but caused a maximum decrease in SVR at the higher dosage amounts averaging 30% below the Ringer control values. Equimolar amounts of adenosine and inosine decreased the SVR by the same extent. Dipyridamole, which potentiates the biological effects of endogenous adenosine, also decreased the SVR in a dose-related manner to values averaging approximately 30% below control. When the effects of endogenous adenosine were blocked by aminophylline, the SVR increased in a dose-related manner to approximately 100% above control at the highest dosage amount. These results suggest that adenosine could have a physiological role in growth regulation of the vascular system in the chick embryo.
Na+-dependent activation of Na+-K+ pump in human myocardium during recovery from acidosis
Authors: Rasmussen H. H. , Cragoe E. J. , ten Eick R. E.
Published: December 2017

In cardiac cells of some species, an intracellular Na+ load and enhanced electrogenic Na+ pumping can develop during recovery from acidosis. We examined whether this can also occur in human heart. Specimens of human right atrial appendage were incubated in cold (2 degrees C) NH4Cl-substituted (for NaCl) Tyrode solution and then transferred to warm (30 degrees C) Na+-Tyrode solution containing 20 mM K+ to induce an intracellular acid load. After transfer, resting membrane potential (Em) transiently hyperpolarized to a maximal level (Emax) of -58.6 +/- 1.3 mV (n = 8), a level significantly (P less than 0.001) more negative than the equilibrium potential for K+. Decreasing K+ conductance with 0.5 mM Ba2+ increased Emax to -74.0 +/- 2.7 mV (n = 6, P less than 0.001), indicating that the hyperpolarization was not due to efflux of NH+4 through K channels. Acetylstrophanthidin (0.5 microM) reduced Emax to -37.5 +/- 3.1 mV (n = 5, P less than 0.001), indicating that an increased level of Na+-K+ pump activity was involved in the hyperpolarization. The Na+-K+ pump-induced hyperpolarization was abolished (Emax = -22.6 +/- 1.6 mV, n = 8, P less than 0.001) by 10 microM 5-(N,N-dimethyl)amiloride and, when the extracellular Na+ concentration was reduced to 50 mM, by 50 mM Li+. These findings suggest that Na+-H+ exchange can produce a Na+ load which then can stimulate electrogenic Na+ pumping in human cardiac cells during recovery from acidosis.
Relative importance of four pressoregulatory mechanisms after 10% bleeding in rabbits
Authors: Katoh N. , Sheriff D. D. , Siu C. O. , Sagawa K.
Published: December 2017

Four physiological mechanisms are known to be important for recovery of arterial pressure (AP) after acute hemorrhage. These are the sino-aortic baroreflex (SA), the vagally mediated cardiopulmonary baroreflex (CP), the renin-angiotensin system (RA), and the vasopressin system (VP). We evaluated in anesthetized rabbits the relative importance of these mechanisms by repeating rapid, 10% arterial hemorrhage (6.5 ml/kg) once before and once after eliminating one of them and comparing the posthemorrhage hypotension. The study was conducted in two series. In the first series, we randomly grouped 24 rabbits into four groups, i.e., a sinoaortic baroreceptor-denervated group (SA) a vagotomized group (CP), a renin-angiotensin-blocked group (RA), and a vasopressin-blocked group (VP). In control conditions, AP fell to 88% at 2 min and 92% at 6 min after completing the hemorrhage. Significantly greater hypotension (e.g., 74% at 6 min) occurred only in the SA group. In the second series, we randomly classified 18 rabbits into three groups, i.e., an autonomic ganglion-blocked group (AB) plus a RA group and a VP group as before. Hypotension significantly greater than control (68% opposed to 91% at 6 min) occurred only in the AB group. We submit that as far as restoration of arterial pressure after rapid, mild hemorrhage in the rabbit is concerned, the arterial baroreceptor reflex system plays a far more important role than the vagally mediated cardiopulmonary baroreflex, the vasopressin system, or the renin-angiotensin system triggered directly by a fall in renal arterial pressure.
Subtype switching of ANP receptors during in vitro culture of vascular cells
Authors: Uchida K. , Mizuno T. , Shimonaka M. , Sugiura N. , Hagiwara H. , Hirose S.
Published: December 2017

Vascular receptors for atrial natriuretic peptide (ANP) have been characterized immunochemically and found to be classified into two subtypes that show differential localization and expression. An antiserum, recognizing the protein core of the receptor, was raised against the purified bovine lung ANP receptor and used for the immunochemical subtyping. ANP receptors solubilized from the bovine jugular vein reacted strongly with the antiserum as well as the homologous lung receptor; however, the receptors from the aorta and carotid artery were recognized only weakly, indicating the presence of two types of ANP receptor in the vascular system. The one that reacts strongly with the antiserum and is distributed mainly in the venous side is termed type I and the other reacting weakly and predominating in the arteries, type II. The two subtypes were also distinguishable in their ligand specificities; the type I receptor showed a remarkably higher affinity for the ANP analogue atriopeptin I than the type II receptor. Surprisingly, similar immunochemical and biochemical analysis of the receptors on cultured vascular smooth muscle and endothelial cells revealed that the arterial cells originally expressing the type II receptor begin to express the type I receptor when cultured in vitro.
Electrical and mechanical responses of rat saphenous vein to short-term pressure load
Authors: Monos E. , Contney S. J. , Cowley A. W. , Stekiel W. J.
Published: December 2017

The magnitude and mechanism of myogenic response of vascular smooth muscle (SM) in rat distal saphenous vein was assessed from SM membrane potential (Em) measured in situ and in vitro with glass microelectrodes and from active and passive stress and strain calculated from changes in vessel diameter measured in vitro via videomicroscopy. Elevation of intraluminal pressure from 2.2 +/- 0.2 (SE) mmHg (control) to 15 +/- 0.8 mmHg for 1 h in a series of in vitro vessel segments perfused with physiological salt solution at 0.2 ml/min induced a maintained and reversible depolarization of 18 +/- 0.9 mV. A 7.6 +/- 0.4-mmHg pressure increase induced a 12.9 +/- 1.2-mV depolarization in a second series. In a third series, 5-mmHg pressure increments induced significant increments in active isometric stress and isobaric strain. Opening an acute, reversible in situ femoral artery to saphenous vein shunt caused a 4- to 5-mmHg venous pressure elevation, a 10-fold increase in venous blood flow, and a 12.1 +/- 0.9-mV venous SM depolarization. Thus a short-term pressure load causes sustained, reversible venous SM cell depolarization both in vitro and in situ, coupled with active strain and stress generation in the vein wall. These results support our hypothesis that SM of peripheral veins can contribute to an intrinsic capacity autoregulation.
Single-beat evaluation of left ventricular inotropic state in conscious dogs
Authors: Lascano E. C. , Negroni J. A. , Barra J. G. , Crottogini A. J. , Pichel R. H.
Published: December 2017

Two competing left ventricular elastic-resistive (ER) models were used to predict parameter values from pressure, volume, and time data of a single ejective beat in conscious dogs during control, enhanced (dobutamine), and decreased (propranolol) inotropic states. The animals were instrumented with three pairs of microcrystals and a transducer to measure intraventricular volume and pressure. Results showed that with the ER nonlinear model (ERNL), parameter values in all animals lay within the physiological range. These were the slope (Emax) and the intercept (V0) of the isovolumic end-systolic pressure-volume relationship (ESPVR), the slope of the end-diastolic pressure-volume relationship (Ed), the time to Emax (Tmax), the normalized time to end of activation (A), and the resistive constant (K). In the two models, the normalized SE of the estimate of data fitting was below 0.2 Emax, as estimated from a single beat, responded to changes in contractility in a significantly more consistent fashion than the slope of ESPVRs (Ees) generated by preload maneuvers in conscious dogs. Single-beat estimated Tmax and K with the ERNL model did also respond consistently to contractility changes, whereas with the elastic resistive linear (ERL) model, K did not reproduce the experimental findings with decreased inotropic state. We conclude that 1) the ERNL model can be employed to assess contractility changes in conscious dogs from data of a single ejective beat, and 2) these changes are better indicated by single-beat estimated Emax than by Ees calculated from conventional ESPVRs.
Ventricular function and fatty acid metabolism in neonatal piglet heart
Authors: Ascuitto R. J. , Ross-Ascuitto N. T. , Chen V. , Downing S. E.
Published: December 2017

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.
Downregulation and desensitization of A1-adenosine receptors in embryonic chicken heart
Authors: Shryock J. , Patel A. , Belardinelli L. , Linden J.
Published: December 2017

Downregulation of cardiac A1-adenosine receptors and desensitization of the negative inotropic response to adenosine were examined 44 h after pretreatment of 15-day-old chick embryos with phenylisopropyladenosine (R-PIA) or vehicle. The number of A1-adenosine receptors, assessed by 125I-aminobenzyladenosine (125I-ABA) binding to crude cardiac membranes, was decreased by 63% (P less than 0.001) after pretreatment of embryos with 1 mumol of R-PIA, from 16.7 +/- 2.4 to 6.2 +/- 1.4 (SD) fmol/mg protein (n = 6). The KD of 125I-ABA binding to the remaining receptors did not differ significantly from control (0.71 +/- 0.45 vs. 0.79 +/- 0.57 nM). A maximally effective concentration of R-PIA (10(-5) M) decreased the developed tension of electrically paced right ventricular (RV) muscle strips from control embryos by 76 +/- 6% (mean +/- SD, n = 7) from its forskolin-stimulated plateau level, whereas the developed tension of strips from R-PIA-pretreated embryos was decreased significantly less, by 38 +/- 4% (P less than 0.001). The potency of R-PIA and the efficacy and potency of carbachol to decrease contractile tension were not changed. The data suggest that chronic exposure of the heart to R-PIA can produce downregulation of A1-adenosine receptors and homologous desensitization of the negative inotropic response to adenosine.
Influence of neutrophil depletion on myocardial function and flow after reversible ischemia
Authors: O'Neill P. G. , Charlat M. L. , Michael L. H. , Roberts R. , Bolli R.
Published: December 2017

We explored the role of polymorphonuclear leukocytes (PMN) in the genesis of contractile dysfunction (myocardial "stunning") and of vascular abnormalities after reversible ischemia. Open-chest dogs underwent a 15-min coronary occlusion and 4 h of reperfusion (REP); treated animals (n = 16) received intravenous goat antiserum against canine PMN, whereas controls received nonimmune goat serum (n = 10) or saline (n = 15). In treated dogs, the average blood PMN levels were 10% of those in saline controls. During ischemia, collateral flow tended to be higher, and paradoxical systolic wall thinning tended to be less in neutropenic dogs, but despite this, recovery of wall thickening after REP was not enhanced in these animals. Similarly, arrhythmias during ischemia or REP did not differ among the three groups. Four hours after REP, both resting and minimal coronary resistance (the latter assessed by adenosine infusion) were higher in the stunned compared with the nonischemic myocardium; these vascular derangements, however, were similar in all three groups. Thus profound neutropenia failed to attenuate mechanical dysfunction, to reduce arrhythmias, and to prevent vascular abnormalities after a 15-min coronary occlusion. Although previous studies have suggested that neutrophils mediate cell death during prolonged ischemia, the present findings suggest that PMN do not contribute importantly to the damage associated with brief, reversible ischemia. The duration of flow reduction may be a critical factor determining whether PMN exacerbate ischemic injury.
Redistribution of coronary microvascular resistance produced by dipyridamole
Authors: Chilian W. M. , Layne S. M. , Klausner E. C. , Eastham C. L. , Marcus M. L.
Published: December 2017

This study assessed the redistribution of coronary microvascular resistance during vasodilation produced by dipyridamole. Measurements of microvascular diameter and pressure in the beating left ventricle of anesthetized cats were accomplished by means of a computer-controlled system that enabled measurements in the beating heart. Resistances of coronary arteries, microvessels, and veins were calculated from the quotients of the pressure gradient across each vascular compartment and myocardial perfusion (radioactive microspheres). Administration of dipyridamole increased coronary blood flow from 1.80 +/- 0.09 to 6.42 +/- 0.31 ml.min-1. g-1 (P less than 0.05). During control conditions, 25 +/- 8% of total resistance occurred in coronary arteries (proximal to 170 microns), 68 +/- 8% of total resistance was in coronary microvessels (between arterioles less than 170 microns in diameter and venules less than 150 microns in diameter), and 7 +/- 7% of resistance resided in veins (distal to 150 microns). There was a significant redistribution (P less than 0.05) of resistance in all vessel classes after dipyridamole: coronary arteries constituted 42 +/- 6%, microvessels contained 27 +/- 5%, and veins had 31 +/- 8% of total coronary resistance. During control conditions, vascular resistance in coronary arteries and microvessels was 17 +/- 4 and 45 +/- 6 mmHg.min.g.ml-1, respectively. During vasodilation, resistance was significantly reduced (P less than 0.05) in both the arterial and microvessel segments to 6 +/- 2 and 4 +/- 2 mmHg.min.g.ml-1, respectively. Venous resistance was not significantly affected during dipyridamole-induced vasodilation. In conclusion, there was a marked reduction of coronary vascular resistance in response to dipyridamole, with the major component accounted for by dilation of microvessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of tissue geometry on initiation of a cardiac action potential
Authors: Joyner R. W. , Ramza B. M. , Tan R. C. , Matsuda J. , Do T. T.
Published: December 2017

We used rabbit ventricular papillary muscles and isolated rabbit ventricular muscle cells to compare the effects of a decrease in cardiac excitability. For the papillary muscles, we defined tissue excitability as the inverse of the current required to initiate a propagated action potential from a local stimulus. For the isolated cells, we defined cellular excitability as the inverse of the current required to initiate a membrane action potential. For papillary muscles, lidocaine with elevated extracellular K+ concentration ([K+]o) decreased maximum rate of rise of membrane potential (Vmax), decreased conduction velocity, and strongly decreased tissue excitability. For the isolated cells, lidocaine with elevated [K+]o decreased Vmax but had little effect on cellular excitability. We interpret our results on the differences of effect on tissue excitability vs. cellular excitability as a consequence of the syncytial nature of the papillary muscle. The cell-to-cell electrical connections produce an electrical load on the locally stimulated region. This electrical load makes the tissue excitability dependent on the amount of inward current that the locally excited cells and the surrounding cells can generate. We simulated these phenomena with numerical solutions of action potential initiation in an isopotential cell compared with a two-dimensional disk of excitable tissue. The simulation results recreate the basic experimental observation that the sensitivity of the current threshold to agents that lower inward current is markedly larger for multidimensional current flow from a source compared with an isopotential system.
Progressive change in collateral blood flow after coronary occlusion in conscious dogs
Authors: Shen Y. T. , Knight D. R. , Canfield D. R. , Vatner S. F. , Thomas J. X.
Published: December 2017

This study used a retrospective analysis of infarcted and salvaged tissue samples to determine the patterns of blood flow changes (radioactive microsphere technique) that occur within the area at risk during the first 24 h after coronary artery occlusion (CAO) in conscious dogs. With the triphenyl tetrazolium chloride (TTC) technique, individual samples were selected and included in either the infarcted (TTC-negative) or salvaged (TTC-positive) group. The infarcted and salvaged samples were paired according to blood flow levels of 0.1-0.2, 0.2-0.3, or 0.3-0.4 ml.min-1.g-1 at either 5 min, 1 h, 3 h, or 6 h after CAO. In tissue samples that were salvaged, blood flow rose progressively, i.e., from 5 min to 1 h, from 1 to 3 h, from 3 to 6 h, and from 6 to 24 h. Blood flow to infarcted tissue rose only in the longest interval, from 6 to 24 h after CAO. When blood flow levels were less than 0.1 ml.min-1.g-1, virtually all the samples were infarcted, whereas corresponding lesser amounts of infarction were observed with increasing blood flow levels after CAO. Thus, in the conscious dog, blood flow rises progressively to salvaged but not infarcted tissue within the area at risk. Except for myocardium with blood flow levels less than 0.1 ml.min-1.g-1, the blood flow levels at any of the time points after CAO could not be used to predict necrosis.
Attenuated response to atrial natriuretic peptide in rats with myocardial infarction
Authors: Kohzuki M. , Hodsman G. P. , Johnston C. I.
Published: December 2017

The natriuretic, diuretic, and hypotensive effects of atrial natriuretic peptide (ANP) were examined in rats 4 wk after myocardial infarction induced by left coronary artery ligation. Synthetic rat ANP (fragment 1-28) was infused intravenously in doses of 0.1, 0.3, and 1.0 micrograms.kg-1.min-1 for 30 min. There was a significant decrease in systolic blood pressure in controls and rats with infarction, although only in control rats was there a significant decrease in diastolic blood pressure. Changes in systolic and diastolic blood pressure were attenuated in rats with infarction compared with controls (P less than 0.01). The diuretic and natriuretic effects of ANP were observed in both groups of rats, but the effects were significantly less in rats with infarction (P less than 0.01). The ANP infusion did not induce significant changes in heart rate or hematocrit in controls or rats with infarction. The results indicate that rats with chronic left heart failure are less sensitive to the natriuretic, diuretic, and hypotensive effects of ANP when compared with controls. The attenuated renal response to ANP may contribute to the impaired sodium and water excretion in chronic heart failure, although other mechanisms are involved.
Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts
Authors: Ambrosio G. , Jacobus W. E. , Mitchell M. C. , Litt M. R. , Becker L. C.
Published: December 2017

It has been proposed that administration of adenine nucleotide precursors might accelerate replenishment of myocardial ATP and "free" ADP, thus improving recovery of depressed contractility of postischemic hearts. To test this hypothesis, Langendorff-perfused rabbit hearts were subjected to 20 min of global ischemia and reperfused for 2 h with normal perfusate (n = 8) or perfusate containing 100 mumol/l of the ATP precursors adenosine (n = 8) or 5-amino-4-imidazolecarboxamide riboside (AICAriboside; n = 8). After reperfusion, developed pressure in untreated hearts averaged 70-80% of base line, whereas ATP content was reduced to approximately 70% of preischemic values. AICAriboside administration did not increase tissue ATP levels or contractility. However, in every heart that received adenosine during reperfusion, ATP content increased from a mean value of 65 +/- 4% of base line to 84 +/- 5% at the end of reperfusion (P less than 0.001). Free ADP also increased in adenosine-treated hearts from 40 to 50% of base line at the beginning of reperfusion, to normal levels by 60 min. However, no improvement in contractility was observed in the hearts that received adenosine. These results support the hypothesis that decreased availability of nucleotide precursors is responsible for depressed ATP levels in postischemic hearts; however, reduced ATP and free ADP levels may not be directly responsible for the depressed function of stunned myocardium.
Inhibition by arachidonate of cerebral arteriolar dilation from acetylcholine
Authors: Kontos H. A. , Wei E. P. , Povlishock J. T. , Kukreja R. C. , Hess M. L.
Published: December 2017

After topical application of arachidonate (200 micrograms/ml) on the brain surface of anesthetized cats equipped with cranial windows, the vasodilator response to topical acetylcholine (10(-7) M) was either abolished or converted to vasoconstriction. This effect of arachidonate was prevented by pretreatment with topical deferoxamine (1 mM) to chelate free iron and inhibit the generation of hydroxyl radical from the Haber-Weiss reaction. Posttreatment with deferoxamine or with the combination of superoxide dismutase and catalase did not reestablish the vasodilator response to acetylcholine. Using a bioassay preparation in which one cranial window served as the donor for endothelium-derived relaxing factor (EDRF) while the other window was used to assay EDRF, we found that arachidonate applied to the donor window inhibited the generation and/or release of EDRF. Arachidonate applied to the assay window did not influence the response to EDRF. The results show that arachidonate interferes with the vasodilator response to acetylcholine, primarily because it inhibits the generation and release of EDRF. This effect is caused by injury to the endothelium induced by hydroxyl radical.
Deleterious effect of ouabain on myocardial function during hypoxia
Authors: Cunningham M. J. , Apstein C. S. , Weinberg E. O. , Lorell B. H.
Published: December 2017

The effect of cardiac glycosides on myocardial function during hypoxia is controversial. Accordingly, we studied left ventricular performance during hypoxia and reoxygenation in the presence of a mildly inotropic, nontoxic dose of ouabain using isolated, isovolumic, buffer-perfused rabbit hearts. After 15 min of hypoxia, left ventricular developed pressure was less in the ouabain-treated group than in controls (35 +/- 4 vs. 55 +/- 3 mmHg, P less than 0.025). Left ventricular end-diastolic pressure (LVEDP) increased more during hypoxia in the presence of ouabain (9 +/- 1 to 32 +/- 7 with ouabain vs. 9 +/- 1 to 14 +/- 3 mmHg without ouabain, P less than 0.005) despite comparable degrees of coronary vasodilatation and myocardial lactate production in the two groups. When coronary flow was abruptly reduced to zero to eliminate the coronary turgor contribution to diastolic pressure, LVEDP after 15 min of hypoxia in the presence of ouabain was greater than that in control hearts that did not receive ouabain (13 +/- 4 vs. 4 +/- 1 mmHg, P less than 0.05), implicating greater diastolic myocardial fiber tension in the ouabain group during hypoxia. With reoxygenation, recovery of developed pressure was less and end-diastolic pressure remained elevated in the ouabain-treated group when compared with controls. We conclude that a modestly inotropic dose of ouabain exacerbates the decrease in diastolic ventricular distensibility induced by hypoxia, worsens the decline in developed pressure during hypoxia, and impairs recovery during reoxygenation.
Effect of umbilical blood flow on transplacental diffusion of ethanol and oxygen
Authors: Wilkening R. B. , Meschia G.
Published: December 2017

We studied the effect of varying umbilical blood flow (F) on transplacental diffusion of ethanol and O2 before and during partial occlusion of the fetal abdominal aorta. At steady state, samples of umbilical and uterine arterial and venous blood were drawn simultaneously from chronically indwelling catheters and analyzed for the concentration of ethanol. O2 capacity, O2 saturation, PO2, PCO2, and pH. A decrease in F from 507 to 289 ml/min (P less than 0.001) was associated with a significant (P less than 0.02) increase of the umbilical-uterine venous ethanol concentration difference. This increase was indicative of a 25% diffusional shunt for ethanol on the fetal side of the placenta. The decrease in F caused a decrease in the umbilical O2 delivery-to-control O2 uptake ratio from 3.1 to values between 2.2 and 0.8 and was associated with a decrease in fetal O2 uptake to values between 94 and 56% of control. Uterine venous PO2 increased in response to the decrease in fetal O2 uptake. Umbilical venous PO2 correlated with uterine venous PO2 (r = 0.8, P less than 0.02). The response of fetal O2 uptake to decrease in umbilical O2 delivery was nonlinear and confirmed previous studies, showing that the normal umbilical O2 delivery rate exceeds approximately twofold the minimum necessary to sustain a normal rate of fetal oxidative metabolism.
Subendocardial infarction produces epicardial parasympathetic denervation in canine left ventricle
Authors: Martins J. B. , Lewis R. , Wendt D. , Lund D. D. , Schmid P. G.
Published: December 2017

Forty dogs underwent anterior descending coronary artery dissection with most having occlusion that was either maintained or reperfused. Study was performed 1-4 days later. Multiple electrodes placed in normal and ischemic zones were used to determine the depth of the epicardial rim overlying a subendocardial infarction. This was done by comparing voltage differential with respect to time (dV/dt) measurements of sequential bipolar electrograms along each needle. By this means, test sites with a rim were documented, and depths of epicardial biopsies for choline acetyltransferase were chosen. Epicardial effective refractory period (ERP) responses to vagal nerve stimulation were measured. In sham-operated controls, vagal stimulation prolonged ERP, and choline acetyltransferase activity was equivalent in all sites. In contrast, dogs with all durations of coronary occlusion and various thicknesses of subendocardial infarction had no significant prolongation of ERP limited to rim sites overlying the infarct during vagal nerve stimulation. Corresponding choline acetyltransferase activity was decreased in rim sites compared with remote areas. In addition, dogs given norepinephrine or physostigmine (to potentiate parasympathetic responses) did not demonstrate significant ERP prolongation with vagal stimulation. Infusion of acetylcholine into the distal ligated coronary artery produced dose-dependent prolongation of ERP in sites overlying the infarct. These data taken together support the hypothesis that subendocardial infarction, regardless of its homogeneity or thickness, produces parasympathetic denervation of the overlying epicardial rim.
Release of NO and EDRF from cultured bovine aortic endothelial cells
Authors: Myers P. R. , Guerra R. , Harrison D. G.
Published: December 2017

The endothelium-derived relaxing factor (EDRF) has recently been reported to be nitric oxide. This study was performed to determine whether the vasorelaxant activity of EDRF could be accounted for by nitric oxide released from cultured endothelial cells. Nitric oxide released from cultured bovine aortic endothelial cells was monitored using a chemiluminescence technique with and without reflux processing of the effluent with a strong reducing environment (1% sodium iodide in glacial acetic acid). In the presence of indomethacin, basally released EDRF was sufficient to relax a bioassay detector vessel (preconstricted with prostaglandin F2 alpha) by 41 +/- 8%. Bradykinin (0.01 microM) and A23187 (10 microM) produced relaxation of the bioassay detector vessel equal to 74 +/- 7 and 69 +/- 13%, respectively. In both the absence and the presence of reflux preprocessing of the cell effluent in a reducing environment, the amount of nitric oxide detected by chemiluminescence was 7-10-fold less than that required to account for the detector vessel relaxation (determined from responses of the detector vessel to standard infusions of authentic nitric oxide). These experiments contradict the view that nitric oxide is the sole or principal EDRF. It is likely that either other nonprostanoid vasodilator substances are released in addition to nitric oxide or that EDRF is a nitric oxide containing or forming compound that is substantially more potent than authentic nitric oxide.