bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal circulatory effects of adrenergic stimuli in anesthetized piglets and mature swine
Authors: Buckley N. M. , Brazeau P. , Gootman P. M. , Frasier I. D.
Published: December 2017

The relative maturity of renal circulatory responses to efferent renal nerve stimulation, and to exogenous norepinephrine and isoproterenol, was tested in 62 piglets (1--16 days old) under pentobarbital anesthesia (10--25 mg/kg). Aortic pressure, heart rate, and renal and femoral arterial flows (measured by electromagnetic flow transducers) were recorded simultaneously. Renal vascular resistance was calculated as mean aortic pressure/mean flow. Transection of the renal nerve resulted in decreased renal resistance in all animals. Efferent renal nerve stimulation at increasing frequencies (2--12.5 Hz, at 1.2 ms pulse duration and 1.0 mA current) showed age-dependent differences in the threshold and also in the magnitude of increase in renal resistance. Norepinephrine (0.05--1.0 microgram/kg) caused age-dependent increases in renal resistance. Restoration of renal flow toward control level occurred during the peak pressor effect of norepinephrine only in older piglets. Isoproterenol (0.05--1.0 microgram/kg) did not alter renal resistance consistently in piglets younger than 1 wk. Phentolamine (0.25 mg/kg) attenuated or blocked resistance increases to 0.5 microgram norepinephrine/kg or to renal nerve stimulation at 12.5 Hz in all animals. Propranolol (0.1 mg/kg) attenuated or blocked resistance decreases to 0.1 microgram isoproterenol/kg, which occurred only in older piglets. These results indicate the presence of an active alpha-adrenergic vasoconstrictor mechanism and absence of the beta-adrenergic vasodilator mechanism in the renal circulation of swine at birth.
Regional distribution of blood flow in awake heat-stressed baboons
Authors: Hales J. R. , Rowell L. B. , King R. B.
Published: December 2017

Radioactive microspheres (containing six different nuclide labels) were used to measure blood flow (BF) to most major organs of eight conscious baboons during heat stress. Cardiac output (CO), arterial mean pressure, and arterial PO2, PCO2, and pH did not change, but heart rate increased and stroke volume fell as body temperature increased by as much as 2.56 degrees C. Skin BF increased in all regions sampled so that the fraction of CO distributed to skin (not including feet and hands) increased from 3% (control) to 14%. Increased skin BF was compensated for by decreases in splanchnic (intestines, stomach, pancreas, and spleen) (35%), renal (27%), and possibly muscle BF. There was no change in BF to the brain, spinal cord, coronary, or subcutaneous adipose tissue during heating. Therefore, baboons show a generalized redistribution of BF during heat stress, so that increments in skin BF are provided without increases in CO, whereas man depends on changes in both; despite this latter difference between the baboon and man, the similarity in magnitude of the splanchnic and renal vasoconstriction between the two primates may indicate that the baboon would be a suitable animal model for investigations into mechanisms of changes in regional blood flow in man during heat stress.
Transjugular hepatic vein cannulation in rats with nonisotopic in vivo verification
Authors: Iguchi A. , Burleson P. D. , Szabo A. J.
Published: December 2017

A simple, rapid and relatively atraumatic method for transjugular cannulation of the hepatic vein and for repeated sampling of hepatic venous blood in the rat is described. Preliminary in vivo verification of the cannula's position is proposed, either by using the glucose differential between consecutive samples of the hepatic venous blood and inferior vena cava blood, or more practically, by using the glucose differential between the hepatic venous blood and tail blood obtained simultaneously. The latter procedure is favored because of its technical simplicity.
Cytoplasmic control of DNA synthesis by myocardial nuclei
Authors: Limas C. J.
Published: December 2017

In vitro DNA synthesis by isolated myocardial nuclei declines rapidly during postnatal growth. To study the mechanism(s) responsible for this decline, cytoplasmic extracts (CE) were prepared from isolated rat myocytes at different times after birth. CE from 2-day-old rats stimulated in vitro DNA synthesis by myocardial nuclei from adult (6 mo old) rats (55 +/- 6 pmol[3H]dTMP . mg DNA-1 . 15 min-1 vs. 32 +/- 4 pmol [3H]dTMP . mg DNA-1 . 15 min-1 in untreated controls, P less than 0.01). The ability of cytoplasmic extracts of stimulate DNA synthesis decreased with age, from 73 +/- 9% over controls at age 2 days to 18 +/- 6 at 28 days; adult myocytes were essentially ineffective. Pulse-chase experiments demonstrated that CE-directed DNA synthesis was replicative and discontinuous. CE stimulatory activity was heat-labile, nondialyzable, trypsin-sensitive, and distinct from DNA polymerases. The results indicate that a) adult myocyte nuclei can be induced to synthesize DNA by cytoplasmic extracts from neonatal rats, and b) that absence of regulatory cytoplasmic factor(s) may, in part, explain the age-dependent decline in myocardial DNA synthesis.
Analysis of cardiac kinetics: use of a new photo-optic technique
Authors: Vas R. , Hirsch M. , Diamond G. A. , Tzivoni D. , Pichler M. , Elkayam U. , Forrester J. S.
Published: December 2017

The photokymograph (PKG) is a new noninvasive instrument that can record segmental myocardial wall motion from self-illuminated images such as are produce; by fluoroscopy, cine ventriculography, two-dimensional sonography, and 99mTc scintigraphy. The PKG can be calibrated to provide amplitude of myocardial tissue motion. The recordings of segmental wall motion obtained closely resemble those recorded by established techniques, both during control state and during ischemic episodes. Regression analysis was performed to compare PKG recordings with frame by frame analysis of left ventriculograms (0.98) and with M-mode echo derived from two-dimensional images (r = 0.97). The PKG has some distinct advantages over existing techniques used to analyze segmental wall motion: it is inexpensive, usable simultaneously over multiple areas, analyzes individual beats, and is not restricted to any particular myocardial wall or any particular angle of motion.
Enhanced left ventricular shortening during chronic volume overload in conscious dogs
Authors: LeWinter M. M. , Engler R. L. , Karliner J. S.
Published: December 2017

Prior work with the arteriovenous fistula model indicates that left ventricular performance is at least normal and may be enhanced during chronic volume overload. The present study was undertaken in conscious dogs to determine whether ejection-phase indices of ventricular function are enhanced after 1 mo of volume overload, using an experimental design in which loading conditions could be accounted for and animals were used as their own controls before and after volume overload. We also examined the response of the volume-overloaded left ventricle to an afterload stress and the role of adrenergic stimulation in maintenance of function. Both at rest and during hemodynamically matched conditions, percent shortening (ultrasonic dimension gauges) and mean shortening rates were increased during volume overload. This difference was maintained during phenylephrine-induced blood pressure elevation, although diastolic dimensions increased more in control studies during phenylephrine. Propranolol produced significantly larger reductions in these indices during volume overload than in the control state. Thus, ejection-phase function is enhanced during volume overload, at least in part due to increased adrenergic stimulation.
Prostaglandins and exercise hyperemia of dog skeletal muscle
Authors: Young E. W. , Sparks H. V.
Published: December 2017

The possibility that prostaglandins (PG) contribute to skeletal muscle exercise hyperemia was tested by blocking PG synthesis with indomethacin and by measuring muscle prostaglandin E (PGE) release. The anterior calf muscles of anesthetized dogs were stimulated at frequencies of 1 Hz, 3 Hz, and 6 Hz under conditions of free flow both before and after indomethacin (5 mg/kg). PGE release was elevated from 14.2 +/- 2.4 to 21.8 +/- 3.4 ng . min-1 . 100 g-1 (P less than 0.01) during stimulation at 3 Hz and from 17.5 +/- 5.1 to 39.2 +/- 9.8 ng . min-1 . 100 g-1 (P less than 0.05) during stimulation of 6 Hz. During exercise at 1 Hz, PGE release was not increased. Indomethacin blocked PGE release and the vascular response to arachidonic acid, but caused essentially no changes in blood flow, oxygen consumption, and vascular conductance during exercise at each frequency. Thus, although PGE release is increased during free flow exercise, inhibiting PG synthesis does not alter exercise hyperemia. However, resting vascular conductance is significantly decreased by indomethacin.
Role of adenosine in postocclusion coronary vasodilation
Authors: Kroll K. , Schipperheyn J. J. , Hendriks F. F. , Laird J. D.
Published: December 2017

Coronary vasodilation after brief (less than 15 s) occlusions was studied in closed-chest, anesthetized dogs, using constant-flow perfusion of a large coronary artery. We assumed occlusion duration to be a measure of the concentration of endogeneous adenosine and determined adenosine dose-response curves by varying occlusion duration and measuring the resulting drop in vascular resistance. The curves were compared to dose-response curves measured by continuously infusing adenosine. Both dose-response relations were found to follow the Hill equation for ligand receptor interaction; the slopes of the two curves were not significantly different, and the estimated adenosine accumulation rate in the myocardium was found to be in close agreement with data in the literature, measured by direct tissue assay. The time course of recovery of vascular tone after short occlusions was not very sensitive to flow, at least not for normal flow levels or higher. The results confirm that adenosine accumulation plays an important role in causing postocclusion vasodilation. However, autoregulation of coronary flow based on an adenosine washout mechanism additionally requires tissue clearance to be highly flow dependent for flow levels below normal, but approaches a constant value when flow increases above normal.
Energy and current requirements for ventricular defibrillation using trapezoidal waves
Authors: Geddes L. A. , Bourland J. D. , Tacker W. A.
Published: December 2017

The threshold energy and current required for ventricular defibrillation was determined in dogs ranging in weight from 6.4 to 38 kg and in ponies ranging in weight from 40 to 101 kg. Trapezoidal waves, 10 ms in duration, with 10%, 50%, 70%, and 90% tilt were applied to transchest electrodes. For all values of tilt, the energy and current required increased with body weight. The energy dose (joules per kilogram of body weight) was higher for the heavier animals, whereas the current dose (peak amperes per kilogram of body weight) was essentially the same for dogs and ponies. In both species and for all four waveforms, the percent success increased with increasing energy and current dose. For all four waveforms and for both species, the threshold average current required for defibrillation was between 0.38 and 0.48 A/kg, indicating that average current may be a convenient unit to compare the efficacy of different waveforms.
Effects of current flow on pacemaker activity of the isolated kitten sinoatrial node
Authors: Jalife J. , Hamilton A. J. , Lamanna V. R. , Moe G. K.
Published: December 2017

The dynamic behavior of the cardiac pacemaker in response to single or to periodically repeated perturbations was studied using kitten sinoatrial (SA) nodal strips mounted in a sucrose gap. Sustained stepwise applications of current across the gap produce lasting variations in pacemaker cycle length that depend on current magnitude and polarity, but not on the phase of the pacemaker period at the time of the input. Brief current pulses, whether hyperpolarizing or depolarizing, may abbreviate or prolong the immediately affected cycle depending on their timing. These changes result in phase shifts of the subsequent discharges, but they do not alter the pacemaker period permanently. The phasic effects of brief current pulses can be described by a phase response curve (PRC), which is a plot of the phase shift as a function of the position of the stimulus in the pacemaker cycle. PRCs were constructed for inputs of different polarity and several strengths and durations. The behavior of the sinus nodal pacemaker when interacting with period perturbing inputs, such as vagal stimulation or electrotonic depolarization, can be predicted on the basis of the phase response curve.
Binding of Ca2+ and Na+ to sarcolemmal membranes: relation to control of myocardial contractility
Authors: Philipson K. D. , Bers D. M. , Nishimoto A. Y. , Langer G. A.
Published: December 2017

Studies are presented that relate the calcium binding of isolated sarcolemmal membranes to myocardial contractility. The contractile strength of the perfused rabbit interventricular septum as a function of perfusate calcium concentration is compared with calcium bound to isolated rabbit sarcolemma at the same calcium concentrations. If the calcium-binding incubation medium contains 140 mM sodium chloride, the shapes of these two curves are identical. In another experiment, sarcolemmal calcium-binding data are compared with the results of Tillisch et al. (J. Mol. Cell. Cardiol. 11:137-148, 1979), who studied the response of rabbit papillary muscles to changes in the perfusate sodium concentration. Again a positive correlation between calcium bound and force developed is obtained. The results of experiments, using the isotope 22Na on the binding of sodium to isolated sarcolemmal membranes were subjected to Scatchard analysis. This revealed a single type of sodium receptor. The affinity constant for sodium binding is 110 M-1 and calcium appears to behave as a competitive inhibitor of sodium binding. The experimental results strongly imply a quantitative relationship between sarcolemmal calcium binding and myocardial contractility.
Mechanism of hemodynamic responses to occlusion of the descending thoracic aorta
Authors: Stokland O. , Miller M. M. , Ilebekk A. , Kiil F.
Published: December 2017

To examine left ventricular responses to aortic occlusion, changes in end-diastolic volume (EDV) and end-systolic volume (ESV) were estimated by ultrasonic recordings of myocardial distances in atropinized open-chest dogs. During aortic occlusion EDV and ESV increased equally, systolic left ventricular pressure (LVP) rose by 86 +/- 8 mmHg, and blood flow more than doubled in the superior vena cava and fell by 90% in the inferior vena cava. During combined occlusion of aorta and inferior vena cava, systolic LVP and superior vena cava flow did not rise above control and EDV declined. By infusing 25 +/- 2 ml/kg body wt of blood during combined occlusion, the effects of aortic occlusion could be reproduced; control values before blood infusion were reestablished by withdrawal of only one-third of the infused volume, indicating a shunt line along the spinal column. Thus during aortic occlusion, transfer of blood accounts for the rise in EDV and increased activation of the Frank-Starling mechanism; increased afterload raises ESV as much as EDV in anesthetized dogs not subjected to sympathetic stimulation. Consequently, stroke volume is maintained and systolic LVP increased.
Plasma protein concentration and control of coronary vascular resistance in isolated rat heart
Authors: Avolio A. P. , Spaan J. A. , Laird J. D.
Published: December 2017

Isolated externally paced (300 beats/min) rat hearts were perfused at constant pressure (70 mmHg) using a modified Krebs-Henseleit solution with (n = 52) and without (n = 15) washed bovine red cells. Albumin concentration varied from 1 to 10 g/dl. With increasing albumin concentration in blood-perfused hearts, wet-to-dry weight ratio, peak reactive hyperemic flow, and control geometric resistance were decreased, whereas oxygen consumption, control flow, and minimal geometric resistance remained constant. For plasma-perfused hearts, there was a decrease in both control and peak flow, and the other results were similar to the blood-perfused hearts. These results indicate the following. 1) Increase in interstitial fluid volume is not sufficient to cause a significant increase in minimal vascular resistance. 2) Increase in blood viscosity is compensated by vasodilation maintaining steady flow constant. 3) Minimal vascular resistance is determined by physical geometry of the vascular bed. 4) Regulation of coronary flow is postulated to be achieved by smooth muscle response to interstitial osmolarity, with a negative feedback signal coming from variation of capillary arterial pressure to variations in flow.
The septal artery and its collaterals in dogs with and without circumflex occlusion
Authors: Scheel K. W. , Wilson J. L. , Ingram L. A. , McGehee L.
Published: December 2017

The purpose of this investigation was to study myocardial perfusion and the collateral circulation of the septal artery in dogs without occlusion and to determine the magnitude and time course of septal collateral development with gradual circumflex occlusion. After the dogs with circumflex occlusion for 1 and 3 mo were allowed to develop a prolific collateral circulation under normal physiological conditions, coronary and collateral resistances were determined on an isolated heart preparation with maximal vasodilation. It was found that the septal artery contributes about 25% to the collateral circulation of the major coronary arteries (right, circumflex, and anterior descending). Septal collateral growth increased up to 15 times with circumflex occlusion. Due to the anatomic location of the septal artery, this collateral growth was intramyocardial in contrast to epicardial collaterals. Although there was collateral proliferation to all major coronary vessels, the most significant growth was toward the circumflex, the ischemic vascular bed. Although primary collateralization in the dog is via epicardial collaterals, the septal artery participates in collateral development.
Dissociation of myocardial sodium and potassium alterations in mild versus severe ischemia
Authors: Regan T. J. , Broisman L. , Haider B. , Eaddy C. , Oldewurtel H. A.
Published: December 2017

To determine the relative influence of two levels of ischemia on myocardial cation and water composition as well as cardiac function, intact anesthetized dogs were studied for 1 h using a balloon-tip catheter in the proximal left anterior descending coronary artery. Hemodynamic studies in group A revealed a diminished ejection fraction during mild and severe ischemia associated, respectively, with a 36% and 74% decline in transmural coronary flow. Left ventricular end diastolic pressure rose only after severe ischemia. Greater accumulation of sodium and water and loss of K+ in ischemic tissue was observed in animals with severe ischemia. In group B, intracellular cations and water were estimated on the basis of 51Cr-labeled EDTA distribution. The extracellular space was unaltered at either level of ischemia. During mild ischemia, cell Na+ and H2O were enhanced in the inner and outer layers of myocardium. Despite a 25% reduction in subendocardial blood flow by the labeled microsphere technique, K+ content was normal. After severe ischemia, cell K+ was reduced in inner and outer layers. However, the increase of cell Na+ content substantially exceeded K+, suggesting a major effect on the sodium pump or cell permeability.
Improved phonocardiogram system based on acoustic impedance matching
Authors: Schwartz R. S. , Reeves J. T. , Sodal I. E. , Barnes F. S.
Published: December 2017

We considered that phonocardiographic recording could be improved 1) by minimizing the acoustic impedance mismatch between the precordial tissue and transducer, 2) by optimizing the configuration of the impedance-matching medium and transducer design, and 3) by storing signals in digital form through analog-to-digital conversion of analog recordings made at the bedside. The use of an aqueous coupling medium to improve energy transmission increased signal voltage approximately 100-fold over presently used commercial devices. Further match to the crystal was achieved by a concentrating horn configuration for the aqueous medium. Measured frequency response of the device in the range 1 Hz to 1 kHz was better than two other commercially tested microphones. Inspection of comparative phonocardiograms showed more information from the new device than from the two other commercial devices. Unfiltered digitized signals, using our microphone in normal subjects, demonstrated good beat-to-beat repeatability, but analog filtering to obtain the conventional phonocardiogram showed significant loss of information. The new instrument appears to be superior to those commercial devices tested in recording heart sounds.
Direct pulmonary vascular responses to prostaglandins in the conscious newborn lamb
Authors: Lock J. E. , Olley P. M. , Coceani F.
Published: December 2017

The effects of prostaglandins PGD2, PGE1, PGE2, PGF2 alpha, and PGI2 on pulmonary vascular tone were investigated in normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around right and left pulmonary arteries. Prostaglandins were injected into only one pulmonary artery, and direct effects of the compounds were determined by comparing the flow changes in the injected vs. the uninjected lung. PGD2 and PGF2 alpha were direct pulmonary vasoconstrictors, whereas PGE1, PGE2 and PGI2 were direct pulmonary dilators. Hypoxia augmented the vasodilation of PGE1 and PGI2 and diminished the constriction of PGD2 and PGF2 alpha; it also lowered the threshold for PGI2-induced dilation. While the E-type prostaglandins and PGI2 were both local dilators, they differed in that the systemic dilatory effects of the E-type agents exceeded their pulmonary effects, whereas the opposite occurred with PGI2. These results demonstrate that prostaglandins can act locally on pulmonary vascular smooth muscle tone in vivo and that the level of oxygenation or base-line vascular tone influences the pulmonary vascular responses to the PGs. Among the dilator prostaglandins, PGI2 appears to be more effective on the pulmonary rather than the systemic vascular bed under hypoxic conditions.
Neural effect of digitalis glycosides on gracilis vascular resistance in hypotension
Authors: Garan H. , Powers E. R. , Ruskin J. N. , Powell W. J.
Published: December 2017

This study was undertaken to investigate the effect of intravenous acetylstrophanthidine and digoxin on the gracilis vascular resistance of hypotensive dogs. The gracilis muscle was isolated and separately perfused, but the nerve to the muscle was left intact. Acetylstrophanthidin, 0.5 mg iv, and digoxin, 1.0 mg iv, both produced a sustained vasodilator response in the gracilis vascular bed of all the hypotensive animals (mean arterial pressure 50 mmHg). A short-lasting vasoconstriction preceded the vasodilation in response to acetylstrophanthidin in 6 of the 8 animals. Prior local alpha-adrenergic blockade with phenoxybenzamine did not have any significant effect on vasodilation. Prior local cholinergic receptor blockade with atropine, however, abolished the sustained vasodilator response, thus indicating that the mechanism responsible for this neurogenic effect is cholinergic. In contrast, in the normotensive dogs, the response to intravenously administered digoxin was sustained vasoconstriction, which was abolished by prior local alpha-adrenergic receptor blockade. Thus, the effect of digitalis glycosides on peripheral vascular resistance is importantly affected by the background level of sympathetic activity.
Unsymmetrical alkyl aryl thiourea compounds for use as cerebral blood flow tracers
Authors: Goldman S. S. , Hass W. K. , Ransohoff J.
Published: December 2017

The synthesis and characterization of an homologous series of inert nonvolatile 14C-labeled unsymmetrical alkyl aryl thiourea compounds is described for their use as regional blood flow (rCBF) tracers employing autoradiographic procedures. In alert normocapnic rats the single-pass extraction values into brain for these thioureas were found to be dependent on their respective lipid solubilities ranging from 0.497 for 1-methyl-3-phenylthiourea to 0.730 for 1-butyl-3-phenylthiourea. The commonly used rCBF tracers [14C]antipyrine and [14C]iodoantipyrine had single-pass extraction values of 0.451 and 0.553, respectively. The single-pass extraction value for n-butanol was found to be the same as that for 1-butyl-3-phenylthiourea indicating that both n-butanol and 1-butyl-3-phenylthiourea are mildly diffusion limited at normal rates of flow in rat brain. Since 1-butyl-3-phenylthiourea diffused most readily into rat brain it was chosen as a potentially valuable rCBF tracer. Its brain-blood partition coefficient was found to be 1.09. The plasma distribution of this thiourea in blood varied inversely with the hematocrit, and the compound was freely exchangeable between plasma and erythrocytes. Employing 1-butyl-3-phenylthiourea to measure rCBF and its empirically derived brain extraction values the following flow rates in normocapnic rats were found: 3.2 ml . g-1 . min-1 for cochlear nucleus: 3.0 for inferior colliculus; 2.5 for medical geniculate; 1.9 for pontine gray and hypothalamus; 1.7 for caudate and cerebral cortex; and 1.2 for cerebellar gray and 0.41-0.50 for white matter structures. It was concluded from these studies that 1-butyl-3-phenylthiourea is more advantageous than iodoantipyrine for measuring rCBF, especially in those areas that possess very rapid rates of flow.
Atrial ectopic foci in the canine heart: hierarchy of pacemaker automaticity
Authors: Jones S. B. , Euler D. E. , Randall W. C. , Brynjolfsson G. , Hardie E. L.
Published: December 2017

The sinoatrial node (SAN) and adjacent tissue of the sulcus terminalis were surgically excised in sequential multiple sections to study the location and intrinsic rate of emerging pacemakers in the acute open-chest dog. Under chloralose anesthesia total of 17 ectopic atrial pacemakers emerged in 12 dogs ranging in location from the anterior interatrial band, midsulcus terminalis, and junction of the inferior vena cava-inferior right atrium. Four AV junctional and one idioventricular pacemakers also emerged in these experiments. Each successively inferior focus had a slower rate than the SAN. The average heart rate of the atrial ectopic pacemakers was 73 +/- 4% of the SAN but that the AV junctional pacemakers was 56 +/- 4% of the SAN (P less than 0.05). The greatest reductions in rate were achieved with total excision of the SAN and entire sulcus terminalis, but in only 50% of the animals did this result in a junctional rhythm. The location and rate of atrial ectopic foci support the notion that the AV junctional region is not the fastest pacemaker in the absence of the classically defined SAN and suggest that atrial ectopic pacemakers are intermediate in the hierarchy of cardiac pacemakers in the dog.
Release of autonomic neuromediators by local ventricular electrical stimulation
Authors: Euler D. E.
Published: December 2017

Trains of electrical stimuli were applied to the ventricular epicardium in pentobarbital-anesthetized dogs. The trains, delivered during the absolute refractory period via Walton-Brodie strain gauge arches, resulted in a highly localized potentiation of ventricular contractile force. The magnitude of the potentiation was directly related to the intensity of the trains. The positive inotropic response of either ventricle to trains of stimuli was abolished following chronic cardiac denervation or beta-adrenergic blockade with tolamolol, indicating that the response was probably mediated by the excitation of local sympathetic nerve fibers. Following the elimination of adrenergic influences, a slight negative inotropic response to trains of stimuli was observed in some animals. Administration of atropine blocked the negative inotropic response. When the adrenergic system was intact the administration of atropine resulted in a significant augmentation of the positive inotropic response of both ventricles to trains of stimuli. Thus in addition to norepinephrine release, it also appeared that electrical stimulation of the ventricles resulted in activation of local parasympathetic fibers with subsequent release of acetylcholine.
Cerebral sodium extraction in the dog: a test for extracerebral contamination
Authors: D'Alecy L. G. , Rose C. J. , Sellers S. A. , Manfredi J. P.
Published: December 2017

The single-pass extraction of sodium was measured with and without sympathetic stimulation in dogs anesthetized with alpha-chloralose. A mixture of the test (24Na) and reference ([125I]RISA) substances was injected as a bolus into the common carotid artery. Single-drop samples were taken at approximately 1-s intervals from the sagittal sinus and the temporal sinus while cerebral blood flow was continuously measured at the temporal sinus by the venous outflow technique. The extraction measurements were used to test for extracerebral contamination of venous outflow. The mean integral extraction determined from sagittal sinus samples was 2.2% during control conditions and 3.0% during sympathetic stimulation. The mean temporal sinus extraction of sodium was 6.9% during control and 2.7% during sympathetic stimulation. If true cerebral sodium extraction is assumed to be 1.4% and extracerebral sodium extraction is 60%, then these data indicate that extracerebral contamination is less than 10%.
Dual-path capacitance compensation network for microelectrode recordings
Authors: McGillivray R. , Wald R.
Published: December 2017

Commercially available microelectrode preamplifiers have a built-in capacity compensation circuit. When a shielded cable is utilized to transmit the signal from the microelectrode to the preamplifier the compensative ability of this circuit may be inadequate and may result in a less than desired frequency response. We describe a dual-path capacitance compensation circuit that resolves this problem without impairment of the shielding properties.
Mechanism of reflex control of cardiac contractility by carotid sinus baroreceptors
Authors: Shimizu T. , Bishop V. S.
Published: December 2017

Effects of the carotid sinus baroreflex (CSR) on left ventricular dP/dt, mean arterial pressure (MAP), and heart rate (HR) were examined by changing the pressure in the vascularly isolated carotid sinus in anesthetized cats. When the carotid sinus pressure (CSP) was lowered, a significant increase was observed in dP/dt and MAP. These reflex changes were significantly increased after vagotomy. In vagotomized cats, cardiac sympathectomy attenuated but did not abolish the dP/dt and HR responses to CSR. The MAP response was little affected. The remaining response of dP/dt and HR were virtually abolished by subsequent adrenalectomy or beta-adrenergic blockade. Adrenalectomy reduced the MAP response by 39%. The effect of cardiac sympathectomy or adrenalectomy on the dP/dt response was greater when either procedure was performed in combination with the other. These results indicate that 1) the vagi interact with CSR and 2) both cardiac sympathetic nerves and adrenal secretion of catecholamines contribute to the reflex control of cardiac contractility by CSR in anesthetized cats. However, the relative contribution of either reflex system appears to vary depending on whether the other system in intact.
Cholinergic intervention in intracardiac autonomic nerves in atrioventricular junctional area
Authors: Motomura S. , Iijima T. , Taira N.
Published: December 2017

Cholinergic influence on atrioventricular (AV) junctional rhythm via its intervention in the intracardiac autonomic nerves was investigated in the canine, blood-perfused AV node preparation. Large amounts of acetylcholine (ACh) injected into the anterior septal artery (ASA) caused a rapid increase in the rate of automaticity superimposed on a slow increase. Nicotine given in the ASA caused to a rapid increased superimposed on a slow increase. Large amounts of ACh injected into the posterior septal artery (PSA) caused a slow increase, which was superimposed by a rapid icrease in the presence of l-hyoscyamine. The rapid and slow increases were abolished by dl-propranolol given in the PSA and ASA, respectively. Both types of increases were suppressed by tetrodotoxin (TTX). Nicotine given in the PSA caused a decrease superimposed by a rapid increase, both of which were abolished by TTX. These reslts indicate that cholinergic excitatory intervention induces AV junctional tachycardia via norepinephrine release from sympathetic nerve endings, distributing widely from the proximal to distal portion of the AV junctional area.
Incorporation of adenosine and its metabolites into brain nucleotides
Authors: Winn H. R. , Park T. S. , Curnish R. R. , Rubio R. , Berne R. M.
Published: December 2017

Dogs were subjected to cerebrospinal fluid (CSF) convesity-cisternal perfusion with [U-14C]adenosine, [U-14C]inosine, or [U-14C]hypoxanthine to determine the mechanism of incorporation of these purines into brain adenine nucleotides. After craniotomy, brain tissue was frozen in situ, and the adenine nucleotides were separated by chromatography. A portion of the nucleotide fraction from the brain and [U-14C]purine from CSF were hydrolyzed enzymatically to nucleosides and bases and the specific activities (SA) measured. The pathway of incorporation of adenosine and inosine was determined by comparing the ratio of SA nucleoside to SA base obtained from degraded brain to that obtained from degraded CSF. Adenosine was directly phosphorylated to AMP, but inosine was degraded before incorporation into brain nucleotides. By comparing the SA of the brain nucleotides to that of the purine precursor in the cerebral spinal perfusion fluid, the incorporation of adenosine was found to be sevenfold greater than that of inosine or hypoxanthine. Measurement of the radioactivity in sagittal venous blood during convexity-cisternal perfusion yielded a larger percentage of counts after perfusion with [U-14C]inosine than with adenosine or hypoxanthine. In comparison to other tissues, a unique salvage system thus exists in the brain for adenosine that serves to conserve the adenine nucleotide pool.
Altered renal vascular tone and plasma renin activity due to fastigial and baroreceptor activation
Authors: Koyama S. , Ammons W. S. , Manning J. W.
Published: December 2017

The effects of stimulating the cerebellar fastigial nucleus in altering renal vascular resistance were assessed at three levels of carotid sinus pressure (CSP). In alpha-chloralose-anesthetized, vagotomized, and salt-depleted cats, renal vascular resistance changes were established by perfusing the isolated carotid sinus at high (197 +/- 17 mmHg), medium (117 +/- 8 mmHg), and low (60 +/- 7 mmHg) pressure. The hemodynamic state of the perfused kidney was determined from flow-pressure curves. In relative units, the flow resistance in the renal bed was for low CSP, 2.60 PRU100, for medium CSP, 2.25 PRU100, and for high CSP, 1.22 PRU100. The fastigial pressor response was imposed at each flow-presure determination with or without superior cerebellar peduncle lesions. An increase in the resistance with the fastigial stimulation was noted at each of the three hemodynamic states; 14% at low, 26% at medium, and 22% at high CSP. With increased renal vascular resistance evoked through the baroreflex, there was an increase in plasma renin activity. The rise in plasma renin activity could be attributed in large part to an increase in sympathetic renal nerve activity wherein the fastigial pressor response shared a synergistic action at medium and high carotid sinus pressure. The effect of the fastigial stimulation on renal vascular resistance and renin secretion was abolished by transections of the superior cerebellar peduncles.
Compartmental analysis of circulation of erythrocytes through the rat spleen
Authors: Cilento E. V. , McCuskey R. S. , Reilly F. D. , Meineke H. A.
Published: December 2017

Control, polycythemic, and anemic spleens of Sprague-Dawley rats surgically removed under pentobarbital sodium anesthesia (0.06 mg/g ip) were perfused in vitro by methods similar to those reported by Song and Groom (Am. J. Physiol. 220: 779-784, 1971). Red Blood cell (RBC) washout curves obtained for each group could be described adequately by a series of three exponentials--fast, intermediate, and slow--representing functional compartments in the spleens. Best-fit estimates of the parameters were used to characterize the flow distributions, cellular capacities, and t1/2 for washout of these components. It is thought that the fast compartment represents flow through intrasplenic vessels (including shunts) that bypass the red pulp, the intermediate compartment represents RBCs that flow through less impeded passageways in the red pulp, and the slow compartment consists of more tortuous, convoluted pathways through the red pulp. During polycythemia and anemia, inflow to the intermediate component was decreased, which suggested decreased filtration. In the slow compartment, the shutdown during polycythemia suggested RBC storage whereas during anemia control levels of inflow but increased t1/2 for washout suggested sequestration or erythropoiesis.
Pregnancy blunts pulmonary vascular reactivity in dogs
Authors: Moore L. G. , Reeves J. T.
Published: December 2017

Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.
Contrasting reflexes evoked by chemical activation of cardiac afferent nerves
Authors: Reimann K. A. , Weaver L. C.
Published: December 2017

Afferent neurons within cardiac sympathetic nerves can reflexly excite central sympathetic outflow. However, their contribution to cardiovascular control remains unclear because they are potentially opposed by inhibitory reflexes of cardiac vagal or arterial baroreceptor afferent origin. It was considered that sympathetically mediated, excitatory responses might be more prominent when initiated by chemical stimulation. In chloralose-anesthetized, vagotomized, sinoaortic-denervated cats, epicardial or intracoronary administration of bradykinin or potassium chloride evoked renal nerve excitation and pressor responses mediated by cardiac sympathetic afferent nerves. When upper thoracic sympathetic nerves were severed, and vagal afferent nerves remained intact, bradykinin and potassium chloride produced inhibition of renal nerve activity and depressor responses. When sympathetic and vagal components of cardiac innervation remained intact, these substances produced excitation, inhibition, or no change in sympathetic outflow. Excitation occurred as often as inhibition. A similar pattern was observed when arterial baroreceptor nerves remained intact. These data illustrate that cardiac sympathetic afferent neurons can have significant excitatory influences on the cardiovascular system in spite of opposition by inhibitory afferent groups.
Coronary hemodynamics and oxygen utilization after hematocrit variations in hemorrhage
Authors: Jan K. M. , Heldman J. , Chien S.
Published: December 2017

Twenty closed-chest dogs anesthetized with pentobarbital sodium were used for studying coronary hemodynamics and myocardial oxygen utilization during hemorrhagic hypotension, with the mean arterial pressure maintained constant at 50 mmHg. Variations of hematocrit (Hct) were achieved by exchange of blood with plasma or packed cells. Coronary blood flow (133Xe washout) varied inversely with Hct, whereas cardiac output (indicator dilution) showed a peak value at a Hct of approximately 25%. Coronary, systemic, and pulmonary flow resistances varied in the same direction with Hct, and the relationship was attributable to the change of blood viscosity with Hct. Analyses of vascular hindrance (= resistance/viscosity) suggested that during hemorrhagic hypotension, coronary vasodilation was maintained during variations of Hct. In systemic and pulmonary circulations, however, there were marked increases in vasoconstriction after hemodilution. The optimum Hct for maximum O2 transport was 25% for coronary circulatin and approximately 45% for systemic circulation. The O2 consumption (QO2) in the myocardium increased after hemodilution with a peak value at a Hct of approximately 25%. The QO2 in the total body was constant over a wide range of Hct between 25 and 45%, above and below which the QO2 decreased.
Effects of coronary washout on cardiac function during brief periods of ischemia and hypoxia
Authors: Liedtke A. J. , Nellis S. H.
Published: December 2017

Coronary washout has been shown effective in preserving metabolism during hypoxia, but its impact on mechanical function is unknown. To investigate this, experiments were conducted in a regionally perfused swine heart preparation (n = 19) in which oxygen (O2) delivery was repetitively restricted for short times (3 min) by randomly changing coronary flow (delta Qc) and/or arterial oxygen content (delta O2a) in the perfusion circuit. Recovery periods in each animal were at least 15 min between trials. Changes in metabolism and mechanics were expressed as a function of delta Qc and delta O2a (the two independent determinants) using linear regression equations. Significance and the ranking of importance for the two determinants were estimated by F testing, the t values of the respective regression coefficients, and partial regression analysis. Myocardial oxygen consumption (MVO2) was dependent on both flow and O2 content (MVO2% = 115.8 + 0.8 delta Qc% + 1.1 delta O2a%). However, regional mechanical function, including total shortening (TS) and an index of work (Indexw), was dependent only on arterial O2 content, e.g., TS% = 94.9 + 0.1 delta Qc% + 0.8 delta O2a% and Indexw% = 85.5 + 0.2 delta Qc% + 1.1 delta O2a%. In these latter relationships, O2 content ranked higher than Qc by factors of 7.39:1 and 5.34:1, respectively. Thus it was concluded that coronary washout offers no selective advantages in preserving average regional mechanical function during short-term O2 deprivation.
Improvement by isosorbide dinitrate of exercise-induced regional myocardial dysfunction
Authors: Kumada T. , Gallagher K. P. , Miller M. , McKown M. , White F. , McKown D. , Kemper W. S. , Ross J.
Published: December 2017

Sonomicrometry was used in 10 conscious dogs to measure regional segment length and dynamic wall thickness by telemetry in a zone supplied by the left circumflex coronary artery after implantation of an ameroid constrictor. When coronary obstruction was nearly complete and collaterals had developed (24-42 days), control exercise and exercise runs after oral isosorbide dinitrate were carried out. During control runs, significant increases occurred in hemodynamic parameters, and percent shortening in normal segments increased (P < 0.01). During the repeat runs after isosorbide dinitrate, there were smaller increases in left ventricular systolic and end-diastolic pressures and significantly reduced end-diastolic dimensions. In addition, percent wall thickening and percent segment shortening in the ischemic zone did not deteriorate significantly during exercise. In this animal model, which appears to mimic chronic single-vessel coronary heart disease, isosorbide dinitrate can prevent exercise-induced deterioration of regional myocardial function.
Permeability and model testing of heart capillaries by osmotic and optical methods
Authors: Vargas Fernando F. , Blackshear Gertrude L. , Majerle Randy J.
Published: December 2017

Rabbits were anesthetized with Nembutal; their hearts were removed and perfused with Ringers solution. Osmotic weight transients were then produced by test solute infusion into the perfusate. The rate constant for organ weight change was used to predict test solute venous concentration (Cv) and the distribution volume (V) during an osmotic transient by use of the Johnson and Wilson (6) model for capillary tissue exchange. By use of Cr EDTA, strongly purple in solution, we compared the above predictions with a value of Cv obtained directly by optical measurement of outflow venous concentration and values of V calculated from our measurements of organ weight and the known sucrose distribution volume. The close agreement between both sets of values with a permeability coefficient of 5 x 10-5 cm/s and a volume of distribution of 3.2 ml/10 g heart lead us to conclude that the model used closly represents the conditions of the isolated perfused heart, and that both the osmotic transient and the extraction measurements provide good estimates of organ capillary permeability.
Epinephrine induces Ca2+ uptake in human blood platelets
Authors: Owen N. E. , Feinberg H. , Le Breton G. C.
Published: December 2017

Human blood platelets isolated by albumin density gradient centrifugation take up Ca2+ during 10-6M epinephrine-induced primary aggregation but not during 10-6 M ADP-induced primary aggregation. Platelet uptake of Ca2+ is dose-dependent over a range of 10-7) to 10-5 M epinephrine. Antagonism of the platelet α-receptor by phentolamine (10-6 M) results in inhibition of both epinephrine-stimulated Ca2+ uptake and aggregation. The Ca2+ antagonist verapamil (50 μM) blocks Ca2+ uptake and epinephrine-induced aggregation, but not ADP-induced aggregation. The verapamil inhibition of aggregation is reduced on Ca2+ addition. These results suggest that epinephrine acts to stimulate primary platelet aggregation through a specific receptor interaction that results in a selective increase in platelet membrane permeability to Ca2+.
Rapid radioimmunoassay for serum myoglobin
Authors: Reichlin Morris , Copley Donald P. , Klocke Francis J.
Published: December 2017

A rapid radioimmunoassay for serum myoglobin concentration has been developed, capitalizing on a technique for rapid separation of antibody-bound antigen from free antigen using Sepharose-bound sheep anti-rabbit γ-globulin. Total time required for the assay is 2.75 h, making it suitable for clinical approaches employing myoglobin for rapid identification of patients in the active phase of myocardial injury.