bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Extraluminal Tubular Deposition of Ferrocyanide to Peritubular Perfusion Rate in Cortical and Medullary Nephron Segments of the Rat Kidney
Authors: Coelho J. B. , Chien K. C. H. , Stella S. R. , Bradley S. E.
Published: June 2012

Ferrocyanide can be precipitated in the kidney and retained in microdissected tubules. By means of
14
C-ferrocyanide it is possible to measure nephron glomerular filtration rate, but radioactivity is also detected in tubular segments beyond the reach of filtered ferrocyanide. The present study evaluated this radioactivity with the assumptions that it derives from peritubular capillary and vasa recta blood and that it may be proportional to the perfusion rate to single tubular segments. The findings rule out axial streaming of filtrate and transtubular diffusion of filtered ferrocyanide as factors and therefore point to an extraluminal deposition of ferrocyanide diffusing out of peritubular capillary and vasa recta blood. It was also found that the extraluminal tubular radioactivity is not affected by processing of the tissue, that it decreases from cortex to outer medulla to inner medulla, and that distal convoluted tubules have a greater radioactivity per unit length than the thick ascending limbs at the same level. A comparison with data obtained by others using a method to estimate intrarenal blood flow distribution lends support to the assumption that extraluminal tubular radioactivity is proportional to the capillary perfusion rate to single tubular segments.
Isolation from Rat Diaphragm of a Calcium-Protein Complex Involved in Excitation-Contraction Coupling
Authors: Hajdu Stephen , Posner Christian J. , Leonard Edward J.
Published: June 2012

Rat diaphragms depleted of calcium involved in excitation-contraction (E-C calcium) coupling were tagged with
45
Ca Seventy percent of the
45
Ca was extracted by a 25 m
M
NaHCO
3
-50% glycerol solution. Treatment of the muscles with caffeine, shown previously to release E-C calcium, decreased extractable
45
Ca to about one-fourth of that of control muscles, indicating that a large fraction of the extracted
45
Ca is involved in E-C coupling. On gel filtration, only 10% of the extracted
45
Ca was bound to protein. This figure increased to 30% when procaine (which stabilizes E-C calcium) was present in the extraction solution; total extracted
45
Ca remained unchanged. The results suggest that E-C calcium is extracted from the muscle as a calcium-protein complex and is readily dissociated from the protein unless prevented in part by procaine. Cadmium-115, which is shown to replace
45
Ca at the sites involved in E-C coupling, binds more strongly than
45
Ca When
115
Cd muscles were extracted with glycerol solution containing procaine, all the extracted
ll5
Cd was in protein-bound form. One of the extracted proteins formed a precipitin line which was immunochemicaliy identical with rat plasma cardioglobulin-C when tested in gel against an anti-cardioglobulin-C antiserum. This supports our hypothesis that cardioglobulin is the circulating form of a cell membrane calcium transport system.
Pulmonary Vascular Response to Exercise in the Dog
Authors: Elkins Ronald C. , Milnor William R.
Published: June 2012

The effects of exercise on the pulmonary circulation were studied in seven experiments on five dogs. Pulsatile pulmonary arterial flow and pressure and left arterial pressure were measured by chronically implanted transducers; pulmonary vascular input impedance, resistance, and hydraulic power were computed. The average effects of running on a treadmill at 6.5 mph, as compared with the resting state, were an increase in cardiac output from 2.59 liters/ min to 5.30 liters/ min, a rise in mean pulmonary arterial pressure from 18 mm Hg to 28 mm Hg, and no consistent change in mean left arterial pressure. Pulmonary vascular resistance fell from 482 dyne sec cm at rest to 372 dyne sec cm
-5
during exercise. Characteristic input impedance rose from 147 dyne sec cm-- at rest to 199 dyne sec cm
-5
during exercise, and the oscillations of the impedance modulus with frequency decreased in magnitude. These changes were consistent with passive distention of the pulmonary vessels, decreasing the compliance of the large arteries and improving the impedance match between proximal and distal vessels.
Effects of Catecholamines and Renal Nerve Stimulation on Renin Release in the Nonfilterlng Kidney
Authors: Johnson J. Alan , Davis James O. , Witty Robert T.
Published: June 2012

The mechanisms whereby catecholamines and renal nerve stimulation increase renin secretion were studied in dogs with nonfiltering kidneys. In six dogs, epinephrine was infused into the renal artery at a rate that decreased renal blood flow to half of the control value. Papaverine was then infused into the renal artery to block the decrease in renal blood flow produced by the catecholamine, and the epinephrine infusion was resumed while the papaverine infusion was continued. In this experiment, renin release increased during infusion of epinephrine alone, but no change occurred with epinephrine during papaverine infusion. The protocol for the experiment on six other dogs was similar except that the infused catecholamine was norepinephrine. In this experiment, norepinephrine increased renin release both prior to and during papaverine infusion. In seven dogs, the effect of electrical stimulation of the renal nerves on renin secretion was studied both before and during the infusion of papaverine into the renal artery; renin release increased strikingly both before and during papaverine infusion. It is suggested that epinephrine increased renin secretion in the nonfiltering kidney by an action on the renal arterioles. In contrast, norepinephrine and renal nerve stimulation apparently increased renin secretion in the nonfiltering kidney by a direct effect on the juxtaglomerular cells. These data provide evidence for specific mechanisms of action of epinephrine, norepinephrine, and the renal nerves in renin release.
Influence of Oxygen on Hypothermic Cardiac Standstill in the Heart-Lung Preparation
Authors: BADEER HENRY
Published: June 2012

Administration of pure oxygen to denervated dog heart-lung preparation subjected to hypothermia does not affect the temperature that induces terminal ventricular fibrillation even when the progressive alkalemia that occurs is prevented. It is concluded that hypoxia of the myocardium is not a factor in the terminal cardiac arrest that supervenes in hypothermia of the heart-lung preparation.
The Effect of Hemorrhage on Hepatic Blood Flow and Splanchnic Oxygen Consumption of the Dog
Authors: HAMRICK LADD W. , MYERS J. D.
Published: June 2012

Using the BSP extraction technic, the hepatic blood flow of the dog was found to be reduced markedly following a single massive hemorrhage. However, increase in the arterial hepatic venous-oxygen difference compensated for as much as 75% reduction in flow; hence, splanchnic oxygen consumption was maintained under these circumstances. Significant reduction of splanchnic oxygen consumption occurred only during sustained shock when hepatic blood flow was so seriously diminished that high oxygen extraction could not compensate for the lowered oxygen delivery to the liver.
Validity and Limitations of Rat Mesoappendix Bioassay Studies
Authors: ZWEIFACH BENJAMIN W. , METZ DELILAH B.
Published: June 2012

Bioassay data obtained by the rat mesoappendix method lend themselves poorly to statistical representation. Sufficient reproducibility for quantitative estimation of the titer of vasoactive materials was achieved only with crystalline substances or purified biological extracts. Neither the duration of the displacement of epinephrine reactivity nor the magnitude of the shift in effective constrictor doses of epinephrine provided a satisfactory measure of vasoactivity in blood specimens. A prozone phenomenon, with agents such as Pitressin, histamine and ferritin was encountered with potentiating effects being elicited in high dose ranges and inhibitory effects in low dose ranges.
The Relation of Blood Pressure and Flow to the Development and Regression of Experimentally Induced Pulmonary Arteriosclerosis
Authors: FERGUSON DONALD J. , VARCO RICHARD L.
Published: June 2012

Systemic artery-pulmonary artery shunts have been made in dogs and the relation between pulmonary artery pressure and blood flow and the development of vascular lesions has been studied. Arteriolar medial hypertrophy and intimal proliferation are not necessarily incited by a large blood flow, but such lesions are more readily induced by an end-to-end than by an end-to-side type of shunt. Intimal proliferation is not associated with stainable alterations in elastic tissue or lipid infiltration. Vascular lesions do not readily regress when the inciting factor is removed.
Effect of Hypophysectomy on Electrolyte Excretion in Dogs with Ascites Produced by Thoracic Inferior Vena Cava Constriction
Authors: HOWELL DAVID S. , DAVIS JAMES O. , LAQUEUR GERT L. , CASPER ALFRED
Published: June 2012

Following complete or nearly complete hypophysectomy in dogs with thoracic inferior vena cava constriction, a striking increase in sodium (Na) excretion occurred concomitant with a fall in femoral venous pressure. The previously high venous pressure and renal Na retention were restored by administration of thyrotropin (TSH), growth hormone injection or further constriction of the thoracic inferior vena cava, but adrenocorticotropic hormone (ACTH) was without effect on these functions. The data indicate that pituitary hormones influence the accumulation of ascitic fluid by contributing to the maintenance of an adequate level of venous hypertension.
Sodium Tolerance in Experimental Hypertension
Authors: FRIEDMAN SYDNEY M. , HINKE J. A. M. , HARDWICK DAVID F. , L. FRIEDMAN
Published: June 2012

A sodium tolerance test was applied to rats subjected to three diverse procedures for the production of experimental renal and hormonal hypertension. Sodium tolerance was impaired in all three types of hypertension to the extent that an accelerated excretion of the imposed sodium load occurred, although there was no change in the plasma sodium level. The disturbance was proportional to the height of the blood pressure but occurred even in those treated rats which remained normotensive.
Development of Interarterial Coronary Anastomoses by Chronic Anemia. Disappearance Following Correction of Anemia
Authors: ECKSTEIN RICHARD W.
Published: June 2012

The effect of chronic severe anemia upon functional interarterial coronary anastomoses has been studied in dogs. Retrograde flow measurements at controlled aortic pressures and under conditions of normal viscosity and hemoglobin concentration indicate that severe chronic anemia stimulates growth of collaterals to a significant degree. On the other hand, removal of this stimulus by spontaneous recovery from anemia induces regression of collateral function to control levels.
Oxygen Saturation of Hepatic Blood During Hemorrhagic Shock in the Dog
Authors: SMITH JAMES J. , ROTH DONALD A. , GRACE ROBERT A.
Published: June 2012

During experimental hemorrhagic shock there was a large fall in oxygen saturation of portal, hepatic venous and inferior vena caval blood. Saturation levels were restored to about 90 per cent of the control values after reinfusion of the drawn blood.
Antiarrhythmic Action of Ambonestyl
Authors: LANZONI VINCENT , CLARK BYRON B.
Published: June 2012

The antiarrhythmic activity of Ambonestyl in dogs with persistent ventricular tachycardia is compared with that of procaine amide. The data indicate that Ambonestyl is as effective in suppressing the arrhythmia as procaine amide, but is pharmacologically more specific since it does not depress cardiac conduction, or elevate ventricular electrical threshold, and produces less hypotension.
A Whole Blood Colorimeter for Continuous Registration of Evans Blue Dye Concentration
Authors: FALHOLT W. , KAISER E.
Published: June 2012

A whole blood colorimeter was developed which permits cardiac output determination after the injection of 5 to 15 mg. of Evans blue dye, resulting in maximal excursions of 5 to 11 cm. The apparatus permits sampling of blood through a cardiac catheter and its sensitivity is independent of the oxygen saturation and hematocrit of the blood sampled.
The Effect of Leads Utilized Upon Discrepancies Between Spatial Vectors Recorded by SVEC and by Mean Vector Methods
Authors: SIMONSON ERNST , SCHMITT OTTO H. , BLACKBURN HENRY W.
Published: June 2012

In a former study significant differences were found in the orientation and magnitude of spatial ECG vectors as determined using two different methods. The results presented in this series show that the difference in the leads used account for the major part of these discrepancies and thus emphasize the importance of a standardization of electrode position for spatial vectorcardiography.
Spread of Excitation During Premature Ventricular Systoles
Authors: SCHER A. M. , YOUNG A. C. , Malmgren A. L. , Erickson R. V. , Becker R. A.
Published: June 2012

Premature systoles were elicited at many points in the dog heart and the resultant pattern of excitation plotted in detail with a multipolar electrode and a 16-channel oscilloscope. In premature systoles, most of the mural endocardium is excited by a wave travelling at about 1 meter per second. These results indicate that in a normally originating beat the mural endocardium is excited by branched Purkinje tissue, the elements of which conduct at about 1 meter per second. The transmural velocity of the wave of depolarization in premature systoles is about 0.3 meter per second. No evidence was found for intramural penetration of Purkinje fibers. Intramural potentials recorded on stimulation give some insight into normal intramural potentials.
Specific Avidity of the Heart Muscle to Absorb and Store Epinephrine and Norepinephrine
Authors: RAAB W. , GIGEE W.
Published: June 2012

Circulating epinephrine and norepinephrine are avidly absorbed and stored by the heart muscle but not by skeletal muscle of dogs. Stimulation of the cardiac sympathetic nerves augments myocardial norepinephrine but not epinephrine. Sympatholytic drugs do not diminish, some even increase active catecholamines in heart muscle. The results explain a number of pathophysiologic conditions briefly enumerated.
Cellular Membrane Potentials and Contractility of Normal Rat Atrium and the Effects of Temperature, Tension and Stimulus Frequency
Authors: HOLLANDER PHILIP B. , WEBB J. LEYDEN
Published: June 2012

Simultaneous recording of membrane potentials and contractility in isolated rat atria by means of intracellular micro-electrodes and a sensitive strain gage has been used to establish the normal characteristics of the tissue as well as effects of temperature, stimulus frequency and initial tension on muscle. Preliminary correlations between duration of the action potential and the degree of contraction indicate that the rate of repolarization is of major importance in determination of the contractile response.
A Study of Hydraulics in Simulated Patent Ductus Arteriosus
Authors: RODBARD SIMON , ZAAS ROBERT , COOK WILLIAM
Published: June 2012

A hydraulic model was designed to study the effects of converging streams such as occur in patent ductus arteriosus. The results showed that flow across the fistula was dependent primarily on the resistance at the outlets of the "systemic" as against the "pulmonic" circulation. Even very slight differences in resistance could effect very large shunts. When the left ventricular output was great, the loss across the shunt was relatively unimportant. However, when the left ventricular output was low, most of its flow passed across the shunt and the systemic delivery virtually ceased. This situation became much more severe if the systemic resistance was raised even slightly above that of the pulmonic outflow path.
Coronary Artery Pressure and Strength of Right Ventricular Contraction
Authors: SALISBURY PETER F.
Published: June 2012

Experiments show that the right ventricle is weakened to the point of irreversible failure by decreased coronary artery pressure and also demonstrate that augmented coronary artery pressure can cause a remarkable increment of the right ventricular strength. Both ventricles, even when in otherwise irreversible decompensation, can be restored to full functional competence by various maneuvers which augment coronary blood flow. The studies reported appear to have important clinical applications in the treatment of circulatory disturbances of the right ventricle.
Effect of Premature Depolarization on the Duration of Action Potentials in Purkinje and Ventricular Fibers of the Moderator Band of the Pig Heart: ROLE OF PROXIMITY AND THE DURATION OF THE PRECEDING ACTION POTENTIAL
Authors: GETTES L. S. , MOREHOUSE N. , SURAWICZ B.
Published: June 2012

We compared premature and nonpremature action potentials in Purkinje and ventricular fibers from the moderator band of the pig heart to determine if the duration of premature action potentials depended on factors other than preceding cycle length. In Purkinje fibers, the duration of premature action potentials was cycle-length dependent in responses originating more than 100 msec after the preceding repolarization, but the duration of earlier responses was less than the cycle-length-dependent duration. This cycle-length-independent shortening of premature responses increased with greater proximity to the preceding repolarization and increasing duration of the preceding action potential. In ventricular fibers, the duration of premature action potentials was greater than the cycle-length-dependent duration. This cycle-length-independent lengthening increased as the duration of the preceding action potential increased; it also depended on proximity, being greatest when proximity ranged between 26 and 275 msec. The difference between the durations of simultaneously recorded Purkinje and ventricular action potentials decreased as prematurity increased, but the earliest premature Purkinje action potential was consistently shorter than the simultaneously recorded ventricular action potential. Thus, premature stimulation produced different effects in Purkinje and ventricular fibers. However, in both fibers, the deviation of the duration of premature action potentials from the cycle-length-dependent duration was determined, at least in part, by the duration of the preceding action potential and proximity.
Protocollagen Proline Hydroxylase Activity in Rat Heart During Experimental Cardiac Hypertrophy
Authors: LINDY SEPPO , TURTO HEIKKI , UITTO JOUNI
Published: June 2012

Cardiac hypertrophy was produced in rats by constricting the abdominal aorta subdiaphragmatically. The weight of the left ventricle was significantly elevated 2 days after aortic constriction and was 19% higher than in shamoperated animals at 11 days. The activity of protocollagen proline hydroxylase (PPH), an enzyme participating in collagen biosynthesis, and the hydroxyproline content of the heart muscle were determined. PPH activity was increased at 2 days after aortic constriction and declined thereafter, being still above the control level at 11 days. The hydroxyproline content of the left ventricle was significantly increased at 11 days in hypertrophied heart muscle compared to controls. The present results suggest that in cardiac hypertrophy an early connective tissue activation occurs. Later, this leads to connective tissue accumulation. The increased collagen content may give support to the cardiac muscle contracting against systolic overload.
Effects of Controlling the Velocity of Shortening on Force-Velocity-Length and Time Relations in Cat Papillary Muscle: VELOCITY CLAMPING
Authors: BRUTSAERT DIRK L. , CLAES VICTOR A. , DONDERS JAN J. H.
Published: June 2012

A new technique-velocity clamping-was used to study the effects of a constant total velocity of shortening on the interrelation between force, velocity, length, and time in cat papillary muscle. With decreasing values of clamped total velocity, the duration of the contraction increased but never exceeded the duration of an isometric contraction. Hence these findings confirm that the mode of contraction-isometric or isotonic-has a marked effect on the duration of the contraction. The active state can be prolonged when less shortening occurs and more tension is developed. This phenomenon seems mainly due to the amount of shortening rather than to the velocity of shortening of the muscle. The data were also plotted on a threedimensional graph and compared with velocity-length tracings of afterloaded contractions. The force-length trajectories of the muscle during velocity clamping did not fall on the surface described by the force-velocity-length relations as derived from afterloaded isotonic contractions. This finding could be ascribed to the masking effect of the series elastic component due to the continuous adjusting of the load.
Renal Response to Electrical Stimulation in the Septum and Diencephalon of Rabbits
Authors: JURF AMIN N. , BLAKE WILLIAM D.
Published: June 2012

The septum and diencephalon were electrically stimulated with stereotaxically placed bipolar, concentric electrodes in pentobarbital anesthetized rabbits with one kidney acutely denervated. Transient changes (30-60 seconds) in renal blood flow and urine flow were estimated with electromagnetic flowmeters and drop recorders and persistent changes (20-30 minutes) by clearance techniques. Hypothalamic stimulation, particularly in the perifornical region, caused increased blood pressure, reflex bradycardia (blocked by atropine), and intense renal vasoconstriction in the innervated kidney with a latency of about 2 seconds. In the denervated kidney renal blood flow increased with the rise in blood pressure but after 10-15 seconds decreased, possibly in response to catecholamines released from the adrenal glands. Clearance studies during hypothalamic stimulation showed persistent decreases in renal blood flow, glomerular filtration, maximal tubular transport of glucose and paraaminohippurate, and water and electrolyte excretion in the innervated kidney. The parallel decreases in the maximum tubular transport of glucose and glomerular filtration rate suggest nephron closure rather than flow redistribution as the major component of the response. Ventral thalamic and septal stimulation decreased blood pressure and renal blood flow in the denervated kidney to about the same extent. Ventral thalamic stimulation also decreased renal blood flow in the innervated kidney whereas septal stimulation transiently increased renal blood flow, suggesting inhibition of existing sympathetic vasoconstriction (not blocked by atropine). In clearance studies, effects of septal stimulation on the intact kidney (relative to the denervated kidney) were similar to the effects of acute denervation and consistent with redistribution of intrarenal blood flow.
Pulmonary Alveolar Blood Flow
Authors: FUNG Y. C. , SOBIN S. S.
Published: June 2012

Explicit results concerning blood flow, alveolar blood volume, regional differences, and transit time distribution are derived from the sheet-flow theory and compared with experimental evidence available in the literature. A general consistency is indicated. The theory exhibits in a simple form the effects on flow of the arterial, alveolar, and venous pressures, the alveolar area, the mean path length between arterioles and venules, and the tension in the alveolar membrane, both elastic and surface tension; thus the theory provides a quantitative understanding of a large number of factors.
Thermodynamic Characterization of the Contractile State of the Myocardium
Authors: BLOOMFIELD MARTIN E. , GOLD LOUIS D. , REDDY REDDY V. , KATZ ADOLPH I. , MORENO AUGUSTO H.
Published: June 2012

Definition of the contractile state of the myocardium from force, length, and velocity relationships and measurements of ventricular pressure is a continuum mechanics approach that requires a detailed knowledge of the system under consideration or, in the absence of detailed knowledge, the use of suitable conceptual models. In this paper we proposed a simpler, though still rigorous, approach that required only a general, rather than a detailed, a priori knowledge of the system. Using the theory of thermodynamics, we gained some insight into the physical meaning of the time derivatives of the left ventricular pressure pulse. From integrations and normalizations we obtained power-density functions (energy-averaged power density and power-averaged rate of generation of power density). These functions relating the free energy in the myocardium to the pressure in the blood did not require geometric considerations, and they furnished, to a first approximation, a quantification of the contractile state in a population of 26 normal dogs under anesthesia. Moreover, the functions clearly separated the normal state from abnormal ones created by drug intervention, not only in the same dog, but also in different dogs. The functions appeared to be insensitive to volume loading. In two patients studied before and after surgery, these functions also showed significant changes.
A Steady-State Control Analysis of the Renin-Angiotensin-Aldosterone System
Authors: BLAINE EDWARD H. , DAVIS JAMES O. , HARRIS PATRICK D.
Published: June 2012

This communication develops a steady-state block diagram about the configuration of the renin-angiotensin-aldosterone system in relation to the mineralocorticoid-dependent reabsorption of sodium. Two principal mechanisms appear to be involved in the control of renin secretion. The baroreceptor hypothesis suggests that decreased stretch of the afferent glomerular arteriole produces increased renin secretion. The macula densa theory, on the other hand, suggests that renin secretion responds to alterations either in sodium load or in sodium concentration at the macula densa. These two receptors are presented as parallel feedback pathways which are independently capable of altering renin secretion. This concept of independent receptor function is supported by literature in which one of the receptor pathways was eliminated. The system configuration for the renin-angiotensin-aldosterone system suggests the hypothesis that the vascular receptor controls renin secretion in the autoregulatory range of blood pressure and that macula densa control dominates at pressures below the autoregulatory range. The control system diagram also calls attention to certain unique features of the renin-angiotensin-aldosterone system; it indicates that (1) a chronic low-sodium diet involves changes in both input variables (extracellular fluid volume) and parameters (hepatic blood flow) to maximize sodium reabsorption, (2) thoracic inferior vena cava constriction opens the feedback loop so that the renal receptors do not perceive increases in extracellular fluid volume, (3) congestive heart failure reduces the overall gain of the system, and (4) a small nonhypotensive hemorrhage primarily increases renin secretion through renal sympathetic nerve stimulation.
Biochemical Correlates of Cardiac Hypertrophy
Authors: Skosey John L. , Zak Radovan , Martin Anne F. , Aschenbrenner Vaclav , Rabinowitz Murray
Published: June 2012

The incorporation of [2, 3-
3
H]proline into collagen hydroxyproline and into noncollagenous protein was measured during development of cardiac hypertrophy produced by surgical constriction of the ascending aorta in rats. Heart weight increased sharply during the first 4 days after aortic banding and then slowly rose to a plateau. Free intracellular proline concentration remained unaltered 2 days after banding and increased by 38% on the fifth postoperative day. Specific radioactivity of free proline 3 hours after injection of [
3
H]proline was elevated by 40% on the second postoperative day but was unchanged on the fifth day. Incorporation of [
3
H]proline into collagen hydroxyproline peaked sharply on the second day after aortic constriction (550% above control) in one experiment, and on the fourth day (330% above control) in another. The peak labeling of noncollagenous protein by [
3
H]proline (100% over control) was less than that of collagen. To further evaluate the differences in synthetic response of muscle cells and interstitial cells to increased work load, incorporation of radioactive precursors into myosin, collagen, nuclear DNA, and noncollagenous protein were measured simultaneously, after aortic constriction. Collagen labeling was maximal either on day 2 or 4, depending on the degree of hypertrophy. Labeling of myosin and noncollagenous protein reached a plateau on day 4. Incorporation of [
3
H]thymidine into nuclear DNA peaked on day 7. Thus both muscle cells and connective tissue cells respond independently during cardiac hypertrophy with an increased synthesis of specific proteins.
Effect of Muscle Length on the Force-Velocity Relationship of Tetanized Cardiac Muscle
Authors: Formon Robert , Ford Lincoln E. , Sonnenblick Edmund H.
Published: June 2012

Cat papillary muscles were tetanized with repetitive electrical stimulation in the presence of 10 mM caffeine and 10 mM calcium. Velocities were measured during the plateau of tetanus with quick releases to isotonic loads. The course of isotonic shortening was independent of time in the contraction cycle for at least 2 seconds after the attainment of peak isometric force. The force-velocity relationships were measured at different muscle lengths that had been corrected for series elastic extension. These lengths ranged from 75% to 90% of the passive length from which maximum force was developed. The data were fitted by a least-squares method with hyperbolas described by the Hill equation, each for a constant corrected muscle length. The extrapolated maximum velocities and isometric forces diminished together in almost direct proportion to muscle shortening. Corrections for the load borne by the parallel elastic elements did not significantly change the relationships between isometric force, maximum velocity, and muscle length. The results can be accounted for by two mechanisms: (1) an internal load and (2) deactivation of the contractile elements.
Acute and Chronic Cardiovascular Effects of 6-Hydroxydopamine in Dogs
Authors: Gauthier Pierre , Nadeau Réginald , de Champlain Jacques
Published: June 2012

Acute and chronic cardiovascular effects of repeated injections of 6-hydroxydopamine were studied in unanesthetized dogs. The acute response to initial injections of small doses of 6-hydroxydopamine consisted of an intense sympathomimetic effect characterized by a marked increase in blood pressure and a reflex bradycardia. Three days after the administration of a total dose of 50 mg/kg of 6-hydroxydopamine, significant decreases in heart rate, blood pressure, and total peripheral resistance were observed, but cardiac output remained unchanged. The absence of a response to intravenously injected tyramine, to electrical stimulation of the right stellate ganglion, and to bilateral carotid occlusion was consistent with a state of complete peripheral sympathectomy. Along with the functional impairment of transmission at the sympathetic nerve endings, marked endogenous norepinephrine depletion was observed in the heart, carotid sinus, and spleen. In contrast, endogenous norepinephrine was increased in the stellate ganglion. The response to electrical stimulation of the distal end of the right vagus was not altered by treatment with 6-hydroxydopamine. In anesthetized dogs treated with 6-hydroxydopamine, clamping of the hilar vessels of the adrenal glands for 10 minutes caused hypotension, but the same procedure in normal dogs did not affect blood pressure, demonstrating the importance of the compensatory role of the adrenal medulla in sympathectomized animals. It is concluded that 6-hydroxydopamine can be used effectively to obtain a generalized chemical sympathectomy in unanesthetized dogs and provides a useful means for studying the role of the autonomic nervous system in the regulation of cardiovascular functions.
Protein Synthesis and Amino Acid Transport in the Isolated Rabbit Right Ventricular Papillary Muscle: EFFECT OF ISOMETRIC TENSION DEVELOPMENT
Authors: Peterson Myron B. , Lesch Michael , Ferguson Alan G.
Published: June 2012

To investigate the effects of isometric tension development on myocardial protein metabolism,
14
C-phenylalanine incorporation into protein was studied in the isolated rabbit right ventricular papillary muscle. Amino acid incorporation was linear for 6 hours in resting muscles and was totally inhibited by 10
-3
M cycloheximide and 10
-3
M puromycin. Phenylalanine incorporation into total protein was unaltered by 90 minutes of isometric tension development at peak tension at stimulation rates of 30, 50, or 100/min. Significant increases were noted in muscles stimulated at 50 and 100/min for 180 minutes (P < 0.01). Electrical stimulation, in the absence of isometric tension development, was not responsible for this effect. Passive stretch also appeared to stimulate incorporation, although to a lesser degree than did active tension development. The specific activities of the intracellular phenylalanine pools were identical in control and stimulated muscles. Alpha-aminoisobutyric acid was used to evaluate the effect of tension development on myocardial amino acid transport. Enhanced transport was noted in muscles stimulated isometrically at 30, 50, or 100/min at peak tension. The increased transport ratios could not be solely attributed to active tension development since passive stretch resulted in comparable changes. This study indicates that both passive stretch and tension development are important in regulating myocardial protein synthesis.
Action Potentials in Chick Atria: INCREASED SUSCEPTIBILITY TO BLOCKADE BY TETRODOTOXIN DURING EMBRYONIC DEVELOPMENT
Authors: Pappano Achilles J.
Published: June 2012

Tetrodotoxin (TTX) at a concentration of 1.6 x 10
-7
M blocked intracellularly recorded action potentials in 12- and 18-day-old embryonic chick atria. However, TTX, 1 x 10
-5
M, did not abolish action potentials recorded from cells in 6-day-old atria. TTX-sensitive receptor sites were present in 6-day-old atrial membranes because the toxin depressed the early Na
+
conductance that generated the rapid depolarization phase and the maximum rate of rise of the action potential. TTX at 0.9 x 10
-8
M reduced the maximum rate of rise by 50% in 6-day-old atria, and TTX at 2 x 10
-8
M had the same effect in 12- and 18-day-old preparations. Action potential overshoot changed about 10-20 mv/tenfold variation in external Na
+
concentration in 6-day-old atria in contrast to the change of about 60 mv/decade observed in 18-day-old atria. Moreover, the TTX-resistant action potentials in 6-day-old atria depended primarily on an inward Ca
2+
current because overshoot changed 24 mv/decade variation in external Ca
2+
concentration. The improvement in sodium-electrode properties that occurred during maturation was accompanied by an increase in the maximum rate of rise of the action potential, which averaged 64 v/sec in 6-day-old atria and 94 v/sec in 18-day-old atria. These findings suggested that the early Na
+
conductance mechanism became more critical in generating the action potential in older embryonic atria. These data were consistent with the hypothesis that the membrane density of early conductance sites increased with embryonic age. The TTX resistance of 6-day-old atria depended on an inward Ca
2+
current that generated action potentials after the early Na
+
conductance sites had been blocked by the toxin.
Healing Over and Muscle Contraction in Toad Hearts
Authors: Escobar I. , De Mello W. C. , Pérez B.
Published: June 2012

The influence of temperature, contractures, and Ca
2+
on the processes of healing over and muscle contraction was investigated in toad myocardium by simultaneously measuring the size of the injury potential and the twitch tension. Stimulation with single pulses and electrically induced contractures of short duration (2-3 seconds) markedly increased the rate of healing, and epinephrine (10
-6
g/ml) increased the effectiveness of stimulation. Other results supported the view that the healing process was largely dependent on temperature, since at 15°C or 10°C the rate of healing over was greatly reduced. The effect of temperature was probably related to a reduction in Ca
2+
uptake. A possible change in junctional conductance produced by low temperature probably was not the reason for the decrease in rate of healing. Strontium, which replaces Ca
2+
in the mechanical process, was also a good substitute for Ca
2+
in healing over. The results stress the parallelism between the healing process and the contractile process in heart muscle.
Renal Hemodynamics and Plasma Renin Activity after Renal Artery Constriction in Conscious Dogs
Authors: Harris Robert C. , Ayers Carlos R.
Published: June 2012

Renal hemodynamics and plasma renin activity were studied during acute and chronic renal artery constriction produced by an externally controlled snare in conscious dogs. Renal vascular resistance immediately decreased, then increased to a level above control after approximately 1 hour, and continued to increase until the second day after constriction. Total renal flow rate was unchanged in the first hour, decreased in the second hour, and decreased further between the first and the second day after constriction. Renal artery pressure distal to the snare increased after the initial stenosis but remained below the control level. Changes in renal artery pressure were dependent primarily on renal vascular resistance rather than on aortic blood pressure. Analysis of
133
Xe-clearance curves showed that the fractional weight of and the fractional flow to the fastest-clearing compartment decreased after the first hour and decreased further between the first and the second day after constriction. Plasma renin activity rose immediately, began to drop on the first day after constriction, and was essentially normal by the second day. No parameter changed significantly after the second day, and no hemodynamic factor was consistently correlated with changes in plasma renin activity. These results do not confirm an apparent correlation between renal vasodilation and renin release reported in an earlier study.
Hemodynamics of Early Experimental Renal Hypertension in Dogs
Authors: OVERBECK HENRY W.
Published: June 2012

To investigate the hemodynamics of early experimental renal hypertension, skin and muscle blood flows and intravascular pressures were measured in the isolated, innervated, naturally perfused forelimbs of 44 male mongrel dogs under pentobarbital (35 mg/kg) anesthesia. In addition, venous pressure-volume relationships were studied in temporarily isolated segments of femoral and jugular veins. In 10 dogs (group H-1) one kidney was wrapped in silk 8 days before study; in 12 (H-2) one kidney was wrapped 4 weeks, and a contralateral nephrectomy was done 2 weeks, before study; 22 were prepared as appropriate normotensive controls. A significant rise in mean arterial pressure occurred in groups H-1 and H-2. Compared to corresponding control groups, (1) muscle and skin blood flows in both hypertensive groups were unchanged (
P
>0.1); (2) muscle and skin resistances/100 g limb weight were increased in group H-2 (
P
<0.05); and (3) femoral venous pressure-volume curves were shifted toward the pressure axis (
P
<0.02). These data suggest that in the early stages of experimental renal hypertension in dogs: (1) blood flow in skin and skeletal muscle is not increased; (2) arteriolar resistance is elevated in skin and skeletal muscle; and (3) reduced venous compliance may be present.
Effects of Regression of Atherosclerotic Lesions on the Content and Esterification of Cholesterol by Cell-Free Preparations of Pigeon Aorta
Authors: ST. CLAIR RICHARD W. , CLARKSON THOMAS B. , LOFLAND HUGH B.
Published: June 2012

This study was designed to determine the effect of regression of atherosclerotic lesions on the incorporation of 1-
14
C-oleic acid into phospholipids, triglycerides, and cholesteryl esters and to compare these metabolic alterations with changes in the extent of atherosclerosis and the content of cholesterol and cholesteryl esters in the lesions. Aortic atherosclerosis was produced in White Carneau pigeons by feeding them an atherogenic diet for 1-8 months. The birds were then switched to a cholesterol-free diet for 6 months for the regression phase of the experiment. Following the regression phase, no changes were noted in the atherosclerotic index or the free-cholesterol content of aortas from pigeons that had received the atherogenic diet for 1-5 months; however, a reduction in both of these parameters was seen in aortas from pigeons fed the atherogenic diet for 8 months. There was a marked reduction in the content of cholesteryl esters in the aortas following the regression phase paralleled by a decrease in the rate of cholesterol esterification. No change was seen in the rate of incorporation of fatty acid into phospholipids or triglycerides. These studies suggest that local cholesterol esterification might be of considerable importance in maintaining the large amount of cholesteryl esters found in the atherosclerotic lesion and that changes in the rate of cholesterol esterification are associated with the early events in both progression and regression of atherosclerosis.
Sodium Intake and Vascular Smooth Muscle Responsiveness to Norepinephrine and Angiotensin in the Rabbit
Authors: STREWLER Gordon J. , HINRICHS Kathern J. , GUIOD Linda R. , HOLLENBERG Norman K.
Published: June 2012

The effect of dietary sodium restriction on the responses to norepinephrine and angiotensin was assessed in two vascular smooth muscle preparations in the rabbit. Sodium restriction reduced the response to angiotensin of both the limb vessels in vivo and the aorta in vitro. The response to norepinephrine was potentiated by sodium restriction in both preparations. The effects on angiotensin responsiveness did not appear to be related to tachyphylaxis, changes in extracellular electrolyte composition, or nonspecific depression of smooth muscle function. Probably, the change in sodium intake induced a change in the smooth muscle cell membranes which modified the affinity of their receptors for angiotensin and norepinephrine.
Regulation of the Renal Circulation during Severe Exercise in Normal Dogs and Dogs with Experimental Heart Failure
Authors: MILLARD RONALD W. , HIGGINS CHARLES B. , FRANKLIN DEAN , VATNER STEPHEN F.
Published: June 2012

The role of sympathetic nerves and circulating catecholamines in mediating the renal vascular response to severe exercise was examined in normal dogs and dogs with experimental heart failure, using paired normal and denervated kidneys. In normal dogs, mean arterial blood pressure increased gradually from 97 ± 4 to 137 ± 6 mm Hg, renal blood flow remained at control levels, and renal vascular resistance rose from 0.57 ± 0.04 to 0.84 ± 0.15 mm Hg/ml min
-1
during peak steady-state exercise. The increase in resistance was similar in the denervated renal bed and persisted after alpha-receptor blockade. Exercise in dogs with heart failure increased mean arterial blood pressure slightly from 103 ± 4 to 111 ± 5 mm Hg. In the innervated kidney, blood flow dropped precipitously from 148 ± 6 to 46 ± 9 ml/min, and renal resistance increased from 0.73 ± 0.08 to 3.35 ± 0.53 mm Hg/ml min
-1
. In the denervated kidney, renal blood flow decreased from 174 ± 12 to 120 ± 1 ml/min, and resistance increased from 0.59 ± 0.07 to 0.94 ± 0.09 mm Hg/ml min
-1
. After alpha-receptor blockade, the decrease in flow and the increase in resistance to the denervated kidney were further attenuated. Thus, in normal, healthy dogs, the contribution of adrenergic mechanisms to renal vascular regulation appears to be minimal; blood flow remains constant in the presence of elevated pressure, suggesting that autoregulation is responsible for the elevated renal resistance during exercise. In dogs with experimental heart failure, intense renal sympathetic vasoconstriction prevails throughout exercise; the major portion of this response is neurally mediated, with an additional contribution by circulating catecholamines.
Feedback Regulation of Cholesterol Biosynthesis
Authors: WHITE LAWRENCE W.
Published: June 2012

Regulation of hepatic cholesterol biosynthesis is thought to occur at the step involving formation of mevalonate from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA); this reaction is catalyzed by HMG-CoA reductase. Oral administration of cholestyramine, an agent that interferes with cholesterol reabsorption and is associated with a compensatory increase in hepatic cholesterol synthesis, was used to evaluate feedback regulation of cholesterol biosynthesis. Liver slices and cell-free fractions were prepared from control rats and rats fed 3% cholestyramine for 3-7 days. Cholestyramine feeding was associated with a four- to eightfold increase in incorporation of [
14
C]acetate into cholesterol and mevalonate. However, there was no effect on incorporation of [
14
C]acetate into CO
2
, fatty acids, or acetoacetate or on incorporation of [
14
C]mevalonate into cholesterol, indicating stimulation at an early regulatory site prior to mevalonate formation. In fractionated liver homogenates, incorporation of [
14
C] acetate, [
14
C]acetyl-CoA, and [
14
C]HMG-CoA into mevalonate increased markedly following cholestyramine administration. In the absence of microsomes, incorporation of [
14
C]acetate and [
14
C]acetyl-CoA into HMG was also increased. Changes in incorporation of [
14
C]acetate into HMG, mevalonate, and cholesterol corresponded to changes in product synthesis. I concluded that (1) interruption of the enterohepatic circulation of cholesterol causes a release of feedback inhibition of cholesterol synthesis, (2) mevalonate synthesis catalyzed by HMG-CoA condensing enzyme and HMG-CoA reductase, and (3) HMG-CoA condensing enzyme, by limiting the availability of HMG-CoA, may have an important regulatory function in cholesterol biosynthesis.
Calcium Current Channels Induced by Catecholamines in Chick Embryonic Hearts Whose Fast Sodium Channels are Blocked by Tetrodotoxin or Elevated Potassium
Authors: SHIGENOBU KOKI , SPERELAKIS NICK
Published: June 2012

In isolated ventricles of old (9-19 day) chick embryonic hearts made inexcitable by inactivating the fast sodium channels with either tetrodotoxin (TTX) or elevated external potassium, catecholamines induced slow electrical responses and concomitant contractions within 1-3 minutes. These slow responses had a higher threshold and propagated at a slower velocity than did the normal action potential. They were often graded and quite variable from one region of the heart to another. They were blocked by lanthanum or manganese (1 mM) and showed a dependence on the external calcium level. Strontium and barium could substitute for calcium. The slow channels were not completely inactivated when the external potassium concentration was raised until low membrane potentials of -10 to -25 mv were reached. The catecholamine-induced responses had a shape similar to that of the plateau component of the normal action potential, and cooling affected both in a similar manner. In some cases, slow responses persisted in TTX-blocked hearts even without the addition of exogenous catecholamines. Cyclic 3',5' AMP, dibutyryl cyclic AMP, theophylline, and caffeine partially mimicked the catecholamines, but usually the development of the response to these drugs was much slower. Prostaglandins, ryanodine, and acetylcholine had no effect. The order of effectiveness of the catecholamines was isoproterenol > epinephrine ≥ norepinephrine > dopamine ≥ dopa. Phenylalanine and tyrosine were ineffective. Isoproterenol produced a near-maximal effect at 5 x 10
-7
M. Propranolol blocked the catecholamine-induced effects. In young (2-5 day) hearts, there was no evidence that catecholamines produced a similar effect, and they did not have a positive inotropic action or an effect on the slow sodium channels. The results suggest that catecholamines quickly increase the density of divalent cation channels available in the sarcolemma of older chick hearts, thereby increasing the inward Ca
2-
current and influencing contraction.