bluuebunny/crossref_metadata_2025 huggingface dataset:
Superior vena caval pressure elevation causes pleural effusion formation in sheep
Authors: Allen S. J. , Laine G. A. , Drake R. E. , Gabel J. C.
Published: December 2017

The effect of superior vena caval pressure (SVCP) elevation on the formation of pleural effusions (PE) was studied in sheep. Through a right thoracotomy, a Silastic cuff was placed around the superior vena cava. Catheters for monitoring SVCP and pulmonary artery pressure (PAP) were also placed. After a 1- to 3-wk recovery period, we measured the SVCP, PAP, cardiac output, and plasma protein concentration (Cp). We then elevated the SVCP to various levels from base line [5.3 +/- 2.6 (SD) mmHg] to 33 mmHg. The cardiac output, PAP, and Cp were remeasured 1–2 h and 24 h after SVCP elevation. At the end of the 24-h period, the animals were killed. The PE volume and pleural fluid protein concentration (Cpl) were measured, and the Cpl/Cp was calculated. PE generally did not occur until the SVCP was elevated above 15 mmHg. To study the effect of the thoracotomy on the subsequent pleural effusion, we studied six additional sheep in which we did not perform a thoracotomy. In these animals, the SVCP was elevated to between 5 and 28 mmHg for 24 h by use of a 16-Fr balloon catheter placed via a left external jugular vein and a right carotid-external jugular shunt. We found that the PE volume, for a given SVCP elevation, was similar to that present in sheep that received a thoracotomy. For all sheep the volume of PE was related to SVCP by the equation PE (ml) = 0.24e0.26SVCP, r = 0.85. In the sheep without a thoracotomy, Cpl/Cp rose with increasing volume of PE. Our data demonstrate that elevation of SVCP greater than 15 mmHg for 24 h results in the formation of PE. The rise in Cpl/Cp with PE volume suggests that filtration through the pleural vessels is not the major contributor to PE formation.
Fast inward current properties of voltage-clamped ventricular cells of embryonic chick heart
Authors: Sada H. , Kojima M. , Sperelakis N.
Published: December 2017

To determine ionic properties of the fast inward current of embryonic chick hearts, whole cell voltage-clamp experiments were carried out on single cardiomyocytes. Ventricular myocytes trypsin dispersed (spherical, 10–15 microns in diameter, 10.7 pF in membrane capacitance) from 16- to 18-day-old embryonic chick hearts were used. Cells were bathed in solutions containing 140 mM Na+ at room temperature of 22 degrees C. Action potentials recorded via patch electrodes were approximately 103 mV in amplitude, -73 mV in resting potential, and 400 ms in duration. The maximum amplitude of the fast inward-current peak was -1.34 nA (-0.126 mA/microF) and the voltage at which the current was maximum was -29 mV. The reversal potential (Vrev) for this inward current was +35 mV. The inward current was sensitive to change in extracellular Na+ concentration ([Na+]o) (18-mV change in Vrev for halved [Na+]o) and to tetrodotoxin (TTX; 10(-6)-10(-5) M). The inactivation time constant (tau h) and the time-to-peak current decreased from several milliseconds at -60 mV to 1 ms at positive potentials. The steady-state inactivation (h infinity) characteristics showed an S-shaped dependence on voltages between -110 and -60 mV, giving about -90 mV for the half-inactivation voltage. The steady-state activation characteristics (m infinity) also showed sigmoidal voltage dependence, and the half-activation voltage was -54 mV. Both h infinity and m infinity curves crossed each other in the vicinity of -73 mV, giving a maximum window conductance (m infinity 3.h infinity) of 0.00044 at -50 mV. Compared with inactivation, the reactivation of the fast inward channel proceeded much more slowly. It was concluded that except for the low current density of embryonic chick ventricular cells the voltage- and time-dependent kinetics of the fast inward current channel were quite similar to those reported for the fast Na+ channels in single myocytes of adult hearts of other animal species.
Sympathetic regulation of cerebral blood flow during seizures in newborn lambs
Authors: Kurth C. D. , Wagerle L. C. , Delivoria-Papadopoulos M.
Published: December 2017

We examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs (3–11 days old) during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow (mean +/- SE ml.min-1.100 g-1) was, respectively, 12 +/- 3 (9%), 71 +/- 12 (21%), 120 +/- 15 (38%), and 54 +/- 5 (14%) greater (P less than 0.05) in the D than in the I hemibrain. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10–39% greater (P less than 0.05) in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10–31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17–27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.
Pentobarbital anesthesia modifies pulmonary vasoregulation after hypoperfusion
Authors: Chen B. B. , Nyhan D. P. , Goll H. M. , Clougherty P. W. , Fehr D. M. , Murray P. A.
Published: December 2017

Our objectives were 1) to investigate the extent to which the pulmonary vascular response to increasing cardiac index after a period of hypotension and hypoperfusion (defined as reperfusion) measured in conscious dogs is altered during pentobarbital sodium anesthesia, and 2) to determine whether pentobarbital anesthesia modifies autonomic nervous system (ANS) regulation of the pulmonary circulation during reperfusion. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise inflation and deflation, respectively, of an inferior vena caval occluder to vary Q in conscious and pentobarbital-anesthetized (30 mg/kg iv) dogs. During pentobarbital anesthesia, controlled ventilation (without positive end-expiratory pressure) allowed matching of systemic arterial and mixed venous blood gases to conscious values. Marked pulmonary vasoconstriction (P less than 0.01) was observed during reperfusion in pentobarbital-anesthetized but not in conscious dogs. Both sympathetic alpha-adrenergic receptor block and total ANS ganglionic block attenuated, but did not abolish, the pulmonary vasoconstriction during reperfusion in pentobarbital-anesthetized dogs. Neither sympathetic beta-adrenergic receptor block nor cholinergic receptor block enhanced the magnitude of the pulmonary vasoconstrictor response to reperfusion during pentobarbital anesthesia. Thus, in contrast to the conscious state, the pulmonary vascular response to reperfusion is characterized by active, non-flow-dependent pulmonary vasoconstriction during pentobarbital anesthesia. This response is primarily, but not exclusively, mediated by sympathetic alpha-adrenergic vasoconstriction and is not offset by either sympathetic beta-adrenergic or cholinergic vasodilation. These results indicate, that, compared with the conscious state, pentobarbital anesthesia modifies pulmonary vasoregulation, during reperfusion following hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial natriuretic factor-induced vasodepression occurs through central nervous system
Authors: Levin E. R. , Weber M. A. , Mills S.
Published: December 2017

To characterize the blood pressure and heart rate effects of atrial natriuretic peptide (ANP) in the brain, we administered 20 micrograms/kg of atriopeptin III in 5 microliters of 0.9 normal saline into the fourth ventricle of awake, freely moving, spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. ANP produced a 13 +/- 1 mmHg decrease in mean arterial blood pressure (MAP) in the SHR (P less than 0.001 vs. base line or saline control, n = 10) and a 9 +/- 2 mmHg decrease in the WKY (P less than 0.02). Heart rate did not change significantly in response to ANP. To determine whether an interaction with the adrenergic nervous system played a role in the effects of ANP, we administered 100 ng yohimbine HCL, an alpha 2-antagonist, by intracerebroventricular injection, 45 min before ANP and completely prevented the ANP-induced decrease in MAP. In contrast, 100 ng intracerebroventricular prazosin, an alpha 1-adrenergic antagonist, had no significant influence on the MAP effect induced by ANP. A third group of SHR was pretreated with intracerebroventricular 6-OH dopamine to deplete central catecholamines or with saline. The rats pretreated with 6-OH dopamine (n = 6) had no significant response to ANP, which was administered 9 days later. This was significantly different from the saline-pretreated control group (n = 6), which responded with a 19 +/- 3 mmHg decrease in MAP (P less than 0.025). These studies indicate that the administration of ANP into the fourth ventricle of the brain decreases the MAP of rats through an interaction with the central alpha 2-adrenergic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Cellular compartmentation in ischemic myocardium: indirect analysis by electron probe
Authors: Walsh L. G. , Tormey J. M.
Published: December 2017

Electron probe microanalysis (EPMA) was carried out directly on myocardial cells and on the myofibrils and the mitochondria within them. A third subcellular compartment, which contains sarcoplasmic reticulum (SR), was measured indirectly. The percent of the total cell calcium content that resides within this "hidden" compartment was calculated from cell data minus weighted myofibril and mitochondria data. This approach was applied to control, ischemic, and reperfused myocardium, and other elements were also quantified. We found that the calcium content of this third compartment is little changed during global ischemia but is markedly depleted after 5 min reperfusion. We conclude that these changes are ascribable to changes in SR function.
Concerning reflex summation
Authors: Greene A. S. , Brunner M. J.
Published: December 2017

A simple, linear, noninteractive model of the reflex control of blood pressure was developed to demonstrate that simple linear addition of the responses of the baroreceptor reflexes can produce observations that appear to have resulted from a redundant control system. Our analysis indicated that common experimental paradigms such as hemorrhage with sequential reflex ablation, which are often used to evaluate reflex interactions, can be simply interpreted. Complex nonlinear interactions need not be postulated to explain data that appear to indicate a redundant control system.
Effects of hypoxia and reoxygenation on maximum rate of early left ventricular filling
Authors: Kusunoki K. , Nakamura Y. , Konishi T. , Kawai C.
Published: December 2017

Left ventricular early filling during hypoxia and reoxygenation was examined in isolated working rat hearts that contracted 300 times/min when perfused with Krebs-Henseleit solution at 37 degrees C. Left ventricular short-axial diameter (LVD = D) was measured with a pair of ultrasonic crystals. The maximum lengthening velocity of LVD [(dD/dt)max] decreased with hypoxia and recovered after reoxygenation (from a control of 20.3 +/- 6.7 to 7.3 +/- 1.7 mm/s after 15 min of hypoxia and to 16.3 +/- 8.1 mm/s after 15 min of reoxygenation; n = 7). However, (dD/dt)max/delta D (where delta D is systolic shortening) showed no significant change with either hypoxia or reoxygenation (from a control of 21.0 +/- 2.9 l/s to 22.2 +/- 2.7 l/s after 15 min of hypoxia and to 22.5 +/- 3.7 l/s after 15 min of reoxygenation; n = 7). Therefore, we concluded that the changes of (dD/dt)max with hypoxia and reoxygenation were caused by the changed systolic shortening and that left ventricular myocardial recoil, expressed by (dD/dt)max/delta D, showed no change with either hypoxia or reoxygenation.
Thoracic duct lymph flow and its measurement in chronically catheterized sheep fetus
Authors: Brace R. A.
Published: December 2017

A method was developed for chronic catheterization of the left thoracic lymph duct at the base of the neck in the sheep fetus, which did not disrupt the other major lymphatic vessels that join the venous circulation at the same location. The lymphatic catheter was connected to a catheter in a jugular vein when lymph flow was not being recorded, so that the lymph continuously returned to the fetal circulation. Special consideration of catheter size to minimize flow resistance and treatment to prevent clotting were required. Individual animals were maintained up to 17 days with lymph flow continuing. In 13 fetuses averaging 128 days gestation (term = 147 days) at the time of catheterization, lymph flow rate was measured for 1 h each day for the first 7 postsurgical days with an on-line computer technique that continuously calculated lymph flow rate. Lymph flow averaged 0.64 +/- 0.17 (SD) ml/min in fetuses weighing 2.3-4 kg and tended to undergo a nonsignificant increase with time. Lymph and plasma protein concentrations did not change with time. In individual fetuses, large spontaneous variations in lymph flow rate occurred over periods of several seconds to a few minutes. Analysis showed that these variations in flow rate were not associated with fetal breathing movements. Thus the present study describes a technique for studying the dynamics of lymph flow in the unanesthetized sheep fetus in utero over a time period limited primarily by the length of gestation. In addition, it appears that thoracic duct lymph flow rate in the fetus per unit body weight averages three to four times that in the adult.
Attenuated microvascular alterations in coarctation hypertension
Authors: Stacy D. L. , Prewitt R. L.
Published: December 2017

Arteriolar vasoconstriction, structural reductions in dilated diameter, and rarefaction have been observed in vascular beds with chronic renal hypertension. To determine their pressure or flow dependence, these functional and structural parameters were studied in the developing and chronic stages of coarctation hypertension in the cremaster muscle, a normotensive skeletal muscle bed that is protected from the effects of elevated microvascular pressures. Hypertension was produced in rats by placing a silver clip around the abdominal aorta above the branches of the renal arteries. In hypertensive rats, resting diameters were reduced in second-order arterioles after 4 and 8 wk, in third-order arterioles after 2, 4, and 8 wk, and in fourth-order arterioles after 4 and 8 wk, vs. controls. Vascular tone was elevated in second-order arterioles after 2, 4, and 8 wk and in third- and fourth-order arterioles after 8 wk in hypertensive rats. No increases in medial-intimal area were found at any stage of hypertension in any arteriolar order. The density of small arterioles (3rd-5th orders) was reduced by 20% in hypertensive rats at 8 wk but was unchanged at the other time periods. These arteriolar alterations, especially the absence of structural reductions in diameter, are attenuated compared with those observed in one-kidney, one-clip hypertension and suggest that most of the arteriolar alterations that occur in renal hypertension are pressure or flow dependent.
Alterations of coronary blood flow and reserve with aging in Fischer 344 rats
Authors: Hachamovitch R. , Wicker P. , Capasso J. M. , Anversa P.
Published: December 2017

To determine whether aging affects the coronary circulation, left and right ventricular coronary blood flow and vascular resistance at rest and after maximal vasodilation were measured by left atrial injection of radioactive microspheres in conscious, unrestrained male Fischer 344 rats at 4, 12, and 20 mo of age. As a function of age, maximal coronary blood flow per 100 g of tissue decreased by 43% in the left ventricle at both 12 and 20 mo, whereas a 44 and a 47% reduction was found in the right side of the heart at the same time intervals. Minimal coronary vascular resistance per 100 g of myocardium increased by 56 and 36% in the left ventricle and by 48 and 44% in the right at 12 and 20 mo, respectively. No change was found in total minimal coronary resistance for either ventricle despite an increase in myocardial mass. Maximal coronary blood flow per 100 g to the endocardium was depressed more than epicardial flow, leading to a 24% reduction in the endocardial-to-epicardial flow ratio at 20 mo. Coronary vascular reserve per 100 g, expressed as the increase in coronary blood flow during maximal coronary vasodilation, was greater in the right than in the left ventricle at all ages. It is concluded that the changes in coronary hemodynamics associated with maturation and aging are comparable with those seen in pressure overload hypertrophy with an increased vulnerability potential of the myocardium to ischemic episodes, particularly of the subendocardial region of the left ventricle.
Alpha 1-adrenergic control of contractility and coronary flow in the perfused rat heart
Authors: Edwards S. J. , Rattigan S. , Colquhoun E. Q. , Lockwood S. C. , Woodcock E. A. , Clark M. G.
Published: December 2017

Prazosin inhibition of phenylephrine plus propranolol (alpha 1-adrenergic agonist combination)-mediated inotropy, oxygen uptake, and coronary vasoconstriction of the perfused rat heart were compared with prazosin binding under identical conditions. Binding studies for the perfused heart indicated a population of high-affinity sites (Kd, 0.41 nM; Bmax, 13.2 pmol/g wet wt). Phenylephrine (50 microM) plus dl-propranolol (10 microM) did not significantly alter binding of 3.9 nM prazosin. The alpha 1-agonist combination mediated a dose-dependent increase in tension development and oxygen uptake and a decrease in coronary flow, each of which was inhibited by prazosin. The concentration of prazosin required for half-maximal inhibition of inotropy and oxygen uptake produced by 50-100 microM phenylephrine was 30-40 nM; no inhibition occurred at 2-3 nM prazosin concentration when binding sites were saturated. One nanomolar prazosin was required for half-maximal inhibition of the flow decrease produced by 10 microM phenylephrine. It is concluded that less than 1% of the alpha 1-binding sites are required for full development of inotropy and that this may result from an excess of binding sites or a small population of low-affinity receptors.
Aberrant baroreceptor mechanotransduction in adult Dahl rats on low-salt diet
Authors: Andresen M. C. , Rudis S. K. , Bee D. E.
Published: December 2017

Single fiber, regularly discharging baroreceptors (n = 118) from adult Dahl salt-sensitive (DS) and salt-resistant (DR) rats on a low-salt diet were studied using an in vitro aortic arch-aortic nerve preparation. Pressure thresholds (Pth) and suprathreshold pressure sensitivities (Sth) were determined from responses to slow ramps of pressure. Pressure-diameter relationships measured in each rat were used to transform Pth and Sth values to their mechanical equivalents in terms of aortic wall strain. DS and DR ages were not different (approximately 50 wk). Despite the low-salt diet, DS tail systolic blood pressures were significantly higher than DR by approximately 25 mmHg. Pth averaged 84 mmHg in DR and 97 mmHg in DS. Sth values were similar in DR and DS (average 1.44 and 1.39 spikes.s-1.mmHg-1 in DR and DS, respectively). Increased variance of baroreceptor properties of DS over DR was a prominent finding and necessitated use of nonparametric statistics. The cumulative distribution of Pth values of DS was significantly different from DR, but Sth values were similar. Thus baroreceptor pressure set points are altered in adult DS, but pressure sensitivity per se is not. The differences in pressure parameters were not eliminated by conversion to their mechanical equivalents. Correlation analysis found only weak relationships between Pth and blood pressure for DS and DR (r less than 0.40). Thus in contrast to previous studies in the spontaneously hypertensive rat model, baroreceptors in adult DS on low salt are characterized by elevated variability and a weaker than expected correlation to the prevailing blood pressure in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Optimal hematocrit for canine gastric oxygenation
Authors: Kiel J. W. , Shepherd A. P.
Published: December 2017

To determine whether an optimal hematocrit exists at which gastric tissue is maximally oxygenated, chambered segments of resting canine stomach were perfused at a constant pressure while hematocrit was decreased in steps from 60 to 10%. The two groups of animals used were a control group and a second group given pentagastrin to elevate metabolic activity. Total blood flow was inversely related to hematocrit in both the control and pentagastrin-treated animals, and arteriovenous oxygen difference was directly related to hematocrit. Consequently, the relationship between gastric oxygen consumption and hematocrit was parabolic in both groups. Therefore, the oxygen uptake vs. hematocrit data from each experiment were fit to a quadratic equation that was used to calculate the maximal oxygen uptake and the optimal hematocrit for each preparation. Both the maximum oxygen uptake and the optimal hematocrit in the pentagastrin-treated group (2.1 +/- 0.4 ml.min-1.100 g-1 and 45.7 +/- 1.4%, respectively) were significantly greater than in the control group (1.5 +/- 0.4 ml.min-1.100 g-1 and 38.2 +/- 0.7%, respectively). We conclude that an optimal hematocrit exists for the oxygenation of gastric tissue and that it is within the normal hematocrit range under resting conditions. However, the optimal hematocrit is slightly higher than normal during periods of increased metabolic activity.
Mechanics and composition of arterioles in brain stem and cerebrum
Authors: Baumbach G. L. , Siems J. E. , Faraci F. M. , Heistad D. D.
Published: December 2017

The goal of this study was to compare mechanics and composition of arterioles in brain stem and cerebrum. We calculated stress and strain of pial arterioles in anesthetized rats from measurements of pial arteriolar pressure (servo-null), diameter, and cross-sectional area of the vessel wall. Composition of pial arterioles was quantitated using point-counting stereology. Before deactivation of smooth muscle with ethylenediaminetetraacetic acid (EDTA), pial arteriolar pressure and diameter were 28 and 30% greater (P less than 0.05) in brain stem than cerebrum. After EDTA, diameter of arterioles was similar in brain stem and cerebrum. Cross-sectional area of the arteriolar wall was 32% greater (P less than 0.05) in brain stem than cerebrum. Stress-strain curves indicated that distensibility of pial arterioles is greater in brain stem than cerebrum. The proportion of nondistensible (collagen and basement membrane) to distensible (elastin, smooth muscle, and endothelium) components was 20% less (P less than 0.05) in brain stem than cerebral arterioles. We conclude that 1) cross-sectional area of the vessel wall in arterioles of comparable size is greater in brain stem than cerebrum, 2) distensibility of arterioles is greater in brain stem than cerebrum, despite greater cross-sectional area of the arteriolar wall in brain stem, and 3) the proportion of elastic components is greater in brain stem than cerebral arterioles, which may contribute to greater arteriolar distensibility in brain stem.
Effect of hemoglobin concentration on critical cardiac output and oxygen transport
Authors: Heusser F. , Fahey J. T. , Lister G.
Published: December 2017

We previously found limited tolerance to acute reduction in cardiac output in lambs at the nadir of their physiological anemia [Am. J. Physiol. 253 (Heart Cir. Physiol. 12): H100-H106, 1987]. To determine the effect of hemoglobin concentration [Hb] on critical cardiac output, critical systemic O2 transport, and peripheral O2 extraction, we performed 31 experiments in 12 one-mo-old lambs at four [Hb] (means +/- SD in g/dl): 7.4 +/- 0.6, 10.5 +/- 0.5, 14.5 +/- 0.5, and 16.5 +/- 0.6. Desired [Hb] was obtained by exchange transfusion with packed red cells or plasma. Cardiac output was reduced by inflation of a balloon-tipped catheter in the right atrium, and critical levels were defined at the point where O2 consumption decreased and/or arterial blood lactate concentration increased in response. With lower [Hb], cardiac output was unchanged, systemic O2 transport was reduced, and fractional O2 extraction was increased, keeping O2 consumption constant at base line. As [Hb] was reduced, critical cardiac output was significantly higher, whereas critical systemic O2 transport was independent of [Hb], as were fractional O2 extraction and mixed venous PO2 at the critical point. Thus peripheral O2 extraction was not affected by changes in [Hb] during progressive decreases in cardiac output. We conclude that 4-wk-old lambs have decreased tolerance to reductions in cardiac output and systemic O2 transport because their relative anemia provides them with a base-line cardiac output and systemic O2 transport close to the critical level.
Dopamine stimulates cAMP production in canine afferent arterioles via DA1 receptors
Authors: Tamaki T. , Hura C. E. , Kunau R. T.
Published: December 2017

Dopamine increases renal blood flow and dilates isolated afferent and efferent arterioles preconstricted with norepinephrine via dopamine 1 (DA1) receptors. DA1-receptor stimulation also results in dopamine-induced elevation of adenosine 3'5'-cyclic monophosphate (cAMP) in dog and rat renal arteries. The present study was undertaken to determine the effects of dopamine on cAMP accumulation in isolated canine superficial cortical afferent arterioles. The effect of Sch 23390, a specific DA1-receptor antagonist, on dopamine-stimulated cAMP accumulation was also examined. Forskolin (10(-5) M), a potent stimulator of adenylate cyclase, produced a greater than 11-fold increase in cAMP production compared with control. Dopamine produced a dose-dependent increase in cAMP accumulation in afferent arterioles at concentrations of 10(-4) M and 10(-6) M, Sch 23390 (2 x 10(-4) M) abolished dopamine (10(-4) M)-stimulated cAMP accumulation in afferent arterioles. The dopamine-induced increase in arteriolar cAMP accumulation was unaffected by propranolol (10(-4) M). Our results suggest that dopamine increases cAMP production in afferent arterioles via the DA1 receptor. Increased cAMP production may be responsible for dopamine-induced vasodilation in the afferent arteriole.
Vascular sensitivity and reactivity to norepinephrine in diabetes mellitus
Authors: Friedman J. J.
Published: December 2017

Vascular sensitivity (VS) and reactivity (VR) of hindquarters, totally isolated from rats made diabetic with 45 mg/kg of streptozotocin (STZ), were determined at 1, 2, 4, 8, and 12 wk post-STZ. Age-matched controls received saline injections and were followed for comparable periods. The hindquarters were perfused at constant flow (8-10 ml/min) with a Tyrode-perfluorocarbon (FC-43)albumin-alpha-globulin solution gassed with 95% O2-5% CO2. Tissues were continuously weighed and venous pressure adjusted to maintain an isogravimetric condition. VS and VR were determined from norepinephrine (NE) dose-response curves generated by infusing stock NE (1 mg/ml) at progressively increasing rates (0.004-0.025 ml/min) into a constant tissue perfusion rate (8-10 ml/min) for sufficient time to reach a plateau (2-3 min). Delivered doses ranged from 0.4 to 2.5 micrograms/ml. VR was established as the perfusion pressure reached in response to 2.5 micrograms/ml NE (Pmax). VS was defined as the delivered NE dose that increased perfusion pressure to 50% of Pmax (ED50). VS increased slightly but significantly (P less than 0.01) by 1 wk post-STZ and remained above control throughout the 12-wk post-STZ period. VR also increased significantly (P less than 0.05) by 1 wk post-STZ and remained above control throughout the 12-wk post-STZ period.
Intraretinal and preretinal PO2 response to acutely raised intraocular pressure in cats
Authors: Alder V. A. , Cringle S. J.
Published: December 2017

The effect of acutely raised intraocular pressure (IOP) on retinal oxygenation has been determined using oxygen-sensitive microelectrodes preretinally and intraretinally. Anesthetized cats were ventilated alternately with one of two oxygen concentrations, 21 or 100%, while the IOP was manipulated via a hydrostatic pressure head connected to the anterior chamber. Preretinal and inner retinal oxygen tension remained stable over a broad range of IOP for air breathing. In contrast, the outer retina was severely affected, with the PO2 reducing as IOP was raised, resulting in some areas becoming anoxic. Outer retinal oxygen consumption was reduced for perfusion pressures less than 50 mmHg. It is postulated that under air-breathing conditions the preretinal and inner retinal oxygen tension was stabilized by the autoregulatory capacity of the retinal circulation. The inability of the choroidal circulation to autoregulate was reflected in the reduction of outer retinal oxygen tension with increasing IOP. With 100% oxygen breathing, increases in IOP caused a significant reduction in PO2 throughout the entire retina and preretinal vitreous. It is proposed that the effect of the autoregulatory capacity of the retinal circulation on retinal oxygenation is reduced in hyperoxia.
Hyperemic response to coronary occlusion during a single diastole in conscious dog
Authors: Sadick N. , Dube G. P. , McHale P. A. , Greenfield J. C.
Published: December 2017

This study determined whether the reactive hyperemic response to a 400-ms diastolic coronary occlusion is dependent on ventricular systole. Studies were obtained on 11 conscious dogs with complete heart block paced at 60 beats/min. A pressure catheter was chronically implanted in the aorta. An electromagnetic flow probe and pneumatic occluder were implanted on the circumflex coronary artery. Three interventions were employed: 1) interruption of pacing for a single beat generating a long diastolic period of 2,000 ms in duration (LDC); 2) introduction of a 400-ms diastolic coronary occlusion early in a long diastole (LD4); and 3) a 400-ms diastolic occlusion during uninterrupted pacing (400R). The rise in diastolic coronary vascular resistance index noted during LDC was inhibited significantly in the last 600 ms of diastole during LD4. Thus an intervening systole is not required for a reactive hyperemic response to a diastolic coronary occlusion. During 400R, the resistance index was lower than that found during LD4. The reactive hyperemic response may be caused by either a myogenic or metabolic mechanism or by both. The greater vasodilatation observed after the postocclusion systole in 400R probably reflects metabolic influences.
Effect of timing of transient diastolic changes in ventricular filling on LV performance in dogs
Authors: Van Hessen M. W. , Schiereck P. , Stokhof A. A. , De Beer E. L. , Hak J. B. , Wesenhagen H. , Bruens M. G. , te Kloeze W. , Crowe A.
Published: December 2017

The influence of acute volume changes during diastole on the contractile state of the left ventricle has been studied in the closed-chest dog. Volume changes were introduced by means of a servo-controlled pump system connected to the left ventricular cavity by an apical cannula. Pressure measurements were made in the left ventricle and aorta. Flow sensors in the mitral valve and around the ascending aorta monitored ventricular inflow and outflow patterns. The ventricular performance was evaluated in terms of the ratio between end-systolic pressure and end-systolic volume (P/Ves). By changing the time of occurrence of the volume interventions from the rapid filling phase of diastole to the atrial contraction phase, the relative contributions of rapid filling and atrial contraction to the mitral flow were changed. When the rapid filling was changed by the volume intervention, the effect on the contractile status of the heart, expressed as the P/Ves value, was small. In contrast, when the volume intervention took place during the atrial contraction phase, the effect on the P/Ves value was much larger. Comparison with muscle fiber experiments suggests that length-dependent calcium sensitivity of troponin and length-dependent conductivity of the sarcolemma are the underlying fundamental mechanisms. Therefore, we conclude that the influence of an intervention in ventricular filling on the inotropic state of the left ventricle is dependent on the timing of the intervention.
Evaluation of long-term variance of left ventricular performance indexes in closed-chest dogs
Authors: Freeman G. L. , Colston J. T.
Published: December 2017

To assess the long-term variance of several parameters of left ventricular performance, we evaluated maximum rate of pressure development (dP/dtmax), ejection fraction, mean velocity of circumferential fiber shortening (VCF), the slope and volume-axis intercept of the end-systolic pressure-volume (PES-VES) relation, the stroke-work end-diastolic volume (SW-EDV) relation, and the dP/dtmax-EDV relation in six chronically instrumented dogs. Each dog was studied five times over a period of 3 wk in the conscious autonomically intact state, after autonomic blockade, and after administration of anesthesia. For each index under each set of testing conditions, a coefficient of variation was determined, defined as (SD/mean) x 100, and expressed as a percent. In conscious autonomically intact dogs, a low day-to-day variance was present in dP/dtmax (6.4%), ejection fraction (6.8%), mean VCF (6.5%), and the slope and volume intercept of the SW-EDV relation (7.2 and 6.2%), whereas higher variance was seen in the slope and intercept of the PES-VES relation (18.1 and 36.1%). The highest variance was present in parameters of the dP/dtmax-EDV relation. Thus dP/dtmax, ejection fraction, and the slope and volume intercept of the SW-EDV relation may be the most reliable indexes for long-term evaluation of left ventricular performance.
Inhibition of rest potentiation in canine ventricular muscle by BAY K 8644: comparison with caffeine
Authors: Hryshko L. V. , Bouchard R. , Chau T. , Bose D.
Published: December 2017

Rest potentiation, believed to be due to increased utilization of sarcoplasmic reticular calcium, was converted to rest depression by BAY K 8644 (1 microM). Plateau height and duration of the postrest beat were enhanced by BAY K 8644, suggesting an enhancement of extracellular calcium entry. Caffeine (3 mM) also produced depression at all rest intervals, although to a lesser extent than BAY K 8644. Compared with BAY K 8644, treatment with caffeine resulted in an elevation of plateau amplitude and a shortening of action potential duration. Action potential configuration changes induced by rest were unaltered by caffeine despite reduction in rest potentiation. Caffeine-induced rest depression was associated with an increase in the time to peak tension. This was not observed with BAY K 8644. Treatment with both caffeine (3 mM) and BAY K 8644 (1 microM) greatly prolonged time to peak tension. Action potential duration and plateau height were either maintained or increased. Less rest depression was observed with the combination than with either agent alone. These results suggest that 1) BAY K 8644 and caffeine inhibit rest potentiation by different mechanisms, and 2) caffeine-induced inhibition of calcium uptake by the sarcoplasmic reticulum may enhance the effect of BAY K 8644-induced increase in calcium influx on the contractile apparatus.
Effects of aging on agonist-activated 86Rb efflux in arteries of Fischer 344 rats
Authors: Cox R. H. , Tulenko T. N.
Published: December 2017

Segments of thoracic aorta (DTA), tail artery (TA), and mesenteric artery branches (MAB) were obtained from male Fischer 344 rats at ages of 1, 2, 6, 12, 24, and 30 mo and were used to determine the effects of aging on agonist-activated 86Rb (and 42K) efflux. At all three arterial sites, basal efflux decreased during development (1-6 mo), but no further changes were observed with aging (6-30 mo). The initial efflux response to 10 microM norepinephrine (NE) in the presence of 1 microM propranolol exhibited either no change (DTA) or an increase (TA and MAB) during development (1-6 mo), but all three sites showed a large decrease during aging (6-30 mo). Changes in the steady-state response to NE paralleled changes in the basal efflux at all ages and arterial sites. The initial efflux response to 75 mM K+-physiological salt solution (PSS) for the DTA in the presence of 1 microM phentolamine and 1 microM propranolol decreased during development followed by an increase during aging, whereas for the TA and MAB, there were no significant changes with age. The steady-state efflux response to K+ decreased during development at all three sites but was increased only for the DTA during aging. The steady-state efflux response to K+ was not altered for the TA and MAB during aging. Efflux responses using 42K were qualitatively similar, but rate constants were quantitatively larger than those with 86Rb at all three arterial sites and at all ages.(ABSTRACT TRUNCATED AT 250 WORDS)
Extent of rapid baroreceptor resetting during first hours of hypertension
Authors: Moreira E. D. , Ida F. , Krieger E. M.
Published: December 2017

Rapid or acute resetting of the aortic baroreceptors was studied in anesthetized rats during the onset and maintenance of hypertension produced by subdiaphragmatic aortic constriction for up to 6 h. After 2 min of hypertension, the systolic threshold pressure for activation of the baroreceptors increased by 33% of the total 27-mmHg increase of the control diastolic pressure. Maximal resetting of 46 and 52% was demonstrable after 20 and 30 min of hypertension. The shifts in pressure threshold were accompanied by parallel shifts in the entire baroreceptor function curves. After 30 min of hypertension, resetting was only partially (60%) reversed within the 30 min of pressure normalization. Resetting did not progress with time. Six hours after aortic constriction, resetting was only 38% (vs. 32% after 30 min). The data indicate that acute or rapid resetting of the aortic baroreceptors reaches a maximum within 20–30 min (40–50%) and remains stable for up to 6 h, with no apparent change in the baroreceptor gain.
DOCA administration and atrial natriuretic factor in dogs with chronic heart failure
Authors: Villarreal D. , Freeman R. H. , Brands M. W.
Published: December 2017

The chronic reserve for the secretion of atrial natriuretic factor (ANF) was studied in conscious dogs with an arteriovenous (a-v) fistula, a model of high-output heart failure. After the first 7 days of marked sodium retention after creation of the a-v fistula, the animals regained sodium balance for the subsequent 3 wk. This compensatory natriuresis occurred in the presence of significant increases in right atrial pressure and was associated with marked and sustained elevations in plasma ANF and with the return of plasma renin and aldosterone to base-line values. The cardiac reserve for ANF secretion was further evaluated in these dogs with compensated high-output heart failure during additional progressive elevations in cardiac filling pressures induced by 3 wk of deoxycorticosterone acetate (DOCA) administration. During the DOCA regimen, plasma ANF increased an additional twofold from its high base line. Arterial blood pressure increased by 6–12 mmHg, and plasma renin activity was suppressed. However, the animals consistently retained sodium, and the high plasma levels of ANF were unable to counterbalance the sodium-retaining actions of DOCA. After termination of DOCA, the dogs exhibited a marked natriuresis, and all the hemodynamic and hormonal parameters returned to pre-DOCA control levels. This longitudinal study demonstrates that the cardiac reserve for chronic ANF secretion is well maintained in dogs with an a-v fistula during progressive cardiac volume overload. The present results suggest that the ANF endocrine system may represent one chronic compensatory mechanism to achieve sodium balance in heart failure when there is concomitant normalization of the renin-aldosterone system.(ABSTRACT TRUNCATED AT 250 WORDS)
Training increases cardiac glucose uptake during rest and exercise in rats
Authors: Kainulainen H. , Virtanen P. , Ruskoaho H. , Takala T. E.
Published: December 2017

The effect of chronic exercise on the regional glucose uptake in the left ventricle of the heart was studied in resting and swimming rats using the 2-deoxyglucose method. The left ventricular glucose uptake of untrained resting controls averaged 1.7 +/- 0.1 mumol.min-1.g protein-1 and that of chronically trained resting rats 3.5 +/- 0.3 mumol.min-1.g protein-1 (P less than 0.001). During a 20-min swimming period the glucose uptake rate of untrained rats was 2.3 +/- 0.1 mumol.min-1.g protein-1 and that of trained rats 3.4 +/- 0.3 mumol.min-1.g protein-1 (P less than 0.01). The subendocardial glucose uptake was 25% higher than the subepicardial uptake in the resting control group, whereas no gradient was observed in the other groups. The product of heart rate and blood pressure during swimming increased by 60-70% in the untrained and trained groups. The increase in total left ventricular glucose uptake and its transmural distribution by training seemed to be independent of the actual oxygen consumption or supply of major alternative myocardial substrates.
Regional hemodynamic and baroreflex effects of endothelin in rats
Authors: Knuepfer M. M. , Han S. P. , Trapani A. J. , Fok K. F. , Westfall T. C.
Published: December 2017

Endothelin is a peptide with potent, long-lasting pressor effects characterized by increases in mesenteric and hindquarters vascular resistance and bradycardia following an initial, transient depressor response. This study examined the mechanisms of action of endothelin on regional hemodynamics in conscious, freely moving rats and on baroreflex sensitivity both in conscious and chloralose-anesthetized rats. The pressor response to endothelin (0.67 nmol/kg) was attenuated by nifedipine (25 micrograms/kg) and augmented by chloralose anesthesia. The bradycardia was attenuated by pentolinium (10 mg/kg), atropine methyl sulfate (0.5 mg/kg), or chloralose anesthesia. Hindquarter vaso-constriction was attenuated by nifedipine, pentolinium, and atropine, whereas mesenteric vasoconstriction was less sensitive to blockade. The vasopressin V1 antagonist, [d(CH2)5Tyr(Me)]-AVP (20 micrograms/kg), indomethacin (5 mg/kg), or verapamil (150 micrograms/kg) did not affect any of these cardiovascular responses. Renal sympathetic nerve activity was reduced similarly in chloralose-anesthetized rats to pressor responses elicited by either phenylephrine or endothelin, and the slope of the baro-reflex function curve after endothelin was similar to that of phenylephrine. These results suggest that endothelin is a potent vasoconstrictor in which its action on visceral and skeletal muscle vasculature is mediated by somewhat different mechanisms. Endothelin does not alter baroreceptor reflex control of sympathetic nerve activity or heart rate.
Cardiovascular effects of dobutamine during exercise in dogs
Authors: Haidet G. C. , Musch T. I. , Friedman D. B. , Ordway G. A.
Published: December 2017

To test the hypothesis that stimulation of adrenergic receptors in the heart is maximal during maximal exercise, and to determine whether generalized stimulation of adrenergic receptors during strenuous exercise produces significant alterations in the normal regional distribution of blood flow that occurs during exercise, we evaluated the cardiovascular effects of the infusion of dobutamine (40 micrograms.kg-1.min-1) in mongrel dogs during treadmill running. During maximal exercise, the dobutamine infusion resulted in a significant (P less than 0.05) increase in heart rate. Exercise capacity, total body O2 consumption (VO2), and maximal arteriovenous O2 difference, however, each were reduced during the infusion of this drug. A concomitant reduction in maximal blood flow to locomotive skeletal muscle occurred. The infusion of dobutamine also resulted in an increase in heart rate at a strenuous level of submaximal exercise. However, unlike during maximal exercise, VO2 was unchanged. Blood flow to locomotive skeletal muscle increased, and there was a concomitant reduction in arteriovenous O2 difference. Blood flow reductions that normally occur in splanchnic circulations during strenuous and during maximal exercise were generally somewhat attenuated during the infusion of this drug. Thus, dobutamine, a sympathomimetic agent, produces significant cardiovascular effects when infused in high doses during exercise. Our results demonstrate that beta-adrenergic receptor reserve exists in the heart during maximal exercise in dogs. In addition, the peripheral responses that occur during the infusion of the drug provide additional evidence that different degrees of adrenergic receptor reserve normally appear to be present within different regional circulations during strenuous and during maximal exercise.
Atrial natriuretic peptide reverses angiotensin-induced venoconstriction in dogs
Authors: Lee R. W. , Gay R. G. , Goldman S.
Published: December 2017

To determine whether atrial natriuretic peptide (ANP) can reverse angiotensin (ANG II)-induced venoconstriction, ANP was infused (0.3 micrograms.kg-1.min-1) in the presence of ANG II-induced hypertension in six ganglion-blocked dogs. ANG II was initially administered to increase mean arterial blood pressure (MAP) 50% above control. ANG II did not change heart rate or left ventricular rate of pressure development (LV dP/dt) but increased total peripheral vascular resistance (TPVR) and left ventricular end-diastolic pressure (LVEDP). Mean circulatory filling pressure (MCFP) increased, whereas cardiac output and venous compliance decreased. Unstressed vascular volume did not change, but central blood volume increased. ANP infusion during ANG II-induced hypertension resulted in a decrease in MAP, but TPVR did not change. There were no changes in heart rate or LV dP/dt. ANP decreased cardiac output further. LVEDP returned to base line with ANP. ANP also decreased MCFP and normalized venous compliance. There was no significant change in total blood volume, but central blood volume decreased. In summary, ANP can reverse the venoconstriction but not the arterial vasoconstriction produced by ANG II. The decrease in MAP was due to a decrease in cardiac output that resulted from venodilatation and aggravation of the preload-afterload mismatch produced by ANG II alone. Because TPVR did not change when MAP fell, we conclude that the interaction between ANG II and ANP occurs primarily in the venous circulation.