bluuebunny/crossref_metadata_2025 huggingface dataset:
Isopotential Body Surface Maps and Their Relationship to Atrial Potentials in the Dog
Authors: KING TERRY D. , BARR ROGER C. , Herman-Giddens G. SCOTT , BOAZ DAVID E. , SPACH MADISON S.
Published: June 2012

The origin of body surface P waves was evaluated in the intact dog by recording body surface isopotential maps and atrial epicardial potential maps. P waves were recorded from 150 points on the body surface, and 80 atrial unipolar electrograms were recorded by means of permanently implanted atrial electrodes during normal sinus rhythm and during atrial pacing. When the atrial pacing sites were changed, the associated shape changes in body surface P waves were highly dependent on the position of the recording sites. Throughout most of the P wave, multiple maxima were present on the body surface, and these were caused by widely separated right and left atrial excitation waves; however, the presence of several simultaneous atrial excitation waves could not be appreciated from the body surface maps when the atrial excitation waves were close to one another. In the last third of atrial excitation there were two maxima on the body surface, one due to atrial excitation waves and the other due to early atrial repolarization. In contrast to the more complicated patterns during excitation, during the P-R segment a single maximum and a single minimum were present on the body surface. The sequence of potential changes on both body surface and atrial epicardium during repolarization was similar to the sequence of excitation except that there was reversed polarity.
Effect of Physical Training on the Mechanical and Metabolic Response of the Rat Heart to Hypoxia
Authors: SCHEUER JAMES , STEZOSKI S. William
Published: June 2012

To study the effects of physical conditioning on cardiac function and metabolism during hypoxia, rats were conditioned by swimming. Their isolated hearts and hearts of sedentary rats were studied under isovolumic conditions and also while performing external work. During isovolumic performance only minimal improvement in hypoxic cardiac performance was observed because of conditioning. While performing external work during hypoxia cardiac output and cardiac work were approximately twice as great in hearts from conditioned rats as in those from sedentary rats. There were also slightly higher peak systolic pressures and mean left ventricular systolic pressures during hypoxia. Oxygen delivery and lactate production during hypoxia were the same in hearts from conditioned and sedentary rats as were myocardial NADH fluorescence, residual high-energy phosphate stores, and myocardial glycogen levels. External efficiency in experiments on working rat hearts was twice as great during hypoxia in hearts from conditioned rats as in those fromsedentary rats. The data suggest that hearts of conditioned rats have enhanced pumping capacity when subjected to hypoxia compared with hearts of sedentary rats. Oxygen delivery and energy formation during hypoxia are not improved in hearts of conditioned animals. The major reason for improved performance appears to be more efficient energy utilization for external cardiac work.
Chronotropic Responses of Human Heart Tissue Cultures
Authors: CHANG T. D. , CUMMING G. R.
Published: June 2012

Three presumptive cardiac tissues from aborted human embryos which ranged in length from 2 mm to 4 mm and in age from 53 days to 71 days were maintained in culture beating rhythmically for 18-88 days. Medium renewal, temperature increases (from 31° to 38°C), and pH increases (from 6.92 to 7.75) raised the pulsation rate. Excess potassium stopped the pulsation. Sympathomimetic drugs increased the pulsation rate, and this action was blocked by the beta-receptor inhibitor, propranolol, suggesting the presence of functioning beta-receptor sites in the heart cells by the end of the second month of development.
Effect of Methylprednisolone on Renal Function and the Zonal Distribution of Blood Flow in the Rat
Authors: deBermudez Lidia , Hayslett John P.
Published: June 2012

The effect of acute and chronic administration of methylprednisolone on renal function was studied in rats with clearance and micropuncture techniques. Although acute administration did not influence renal function, chronic administration for 4 days caused a marked increase in glomerular filtration rate and PAH clearance. The rise in the reabsorption of sodium under these conditions was associated with a disproportionate increase in filtration rate and renal blood flow in deep portions of the cortex. There was no evidence of altered fractional sodium reabsorption in the proximal segment of surface nephrons by micropuncture analysis or in the ascending limb by clearance studies during a water or a solute diuresis.
Numerical Simulation of Conduction Delay in Blocked Purkinje Tissue
Authors: Terry Fred H. , Wennemark James R. , Brody Daniel A.
Published: June 2012

The model used for passive conduction in muscle fibers consisted of a region of nonpropagating fiber of variable length, bounded proximally and distally by normal active tissue. The voltage variation on this fiber was governed by the passive wave equation. This system was analyzed by Fourier series techniques on the digital computer, using a cardiac action potential as the input. With a fixed distal threshold, delays up to 45 msec were simulated by varying the length of nonconducting fiber. Delay time was very sensitive to the extent of the inactive region. Inactive tissue lengths of 1.6 mm and 2.0 mm caused delays of 6.1 msec and 11.7 msec, respectively, but lengths of 2.35 mm and 2.36 mm caused delays of 31.7 msec and 40.0 msec, respectively. Inactive areas longer than 2.37 mm caused complete block. With inactive regions 2.35 mm long, a 5% reduction in distal threshold reduced the delay time 35% and a 5% increase caused complete block. Delay time was also sensitive to variations in the membrane parameters. A 10% reduction in membrane capacitance produced approximately a 10% decrease in delay, but such a reduction in membrane resistance caused approximately a 10% increase in delay. Curves recorded in blocked regions of canine Purkinje fibers were simulated by superimposing nonpropagating potentials from proximal and distal sites. The familiar two-component wave forms and other contour variations were quite realistic in the simulation, demonstrating its effectiveness in predicting voltage variations in nonpropagating Purkinje tissue.
Effect of Hypokalemia and Hypomagnesemia Produced by Hemodialysis on Vascular Resistance in Canine Skeletal Muscle
Authors: Anderson D. K. , Roth S. A. , Brace R. A. , Radawski D. , Hoddy F. J. , Scott J. B.
Published: June 2012

Hemodialysis was used to study the effect of an acute local decrease in plasma [K
+
] or [Mg
2+
] or in both on vascular resistance in skeletal muscle. A dialyzer was placed in the arterial supply of the collateral-free gracilis muscle of the dog and blood flow was held constant while measuring perfusion pressure. Pressure increased linearly with decreased [K
+
] down to 0.2 mEq/liter. A 50% decrease in [K
+
] produced a 12% increase in resistance. Prolonged hypokalemia produced a sustained increase in perfusion pressure and a decreased responsiveness to close arterial injection of norepinephrine. Removal of up to 84% of the plasma Mg
2+
produced no effect, either alone or in conjunction with hypokalemia. When the potassium level of the perfusing blood was changed from normal to hypokalemic during the dilation brought on by simulated exercise, the resistance did not change. In addition, the magnitude of the resistance changes seen during exercise were much greater than could be induced by local changes in plasma [K
+
] alone. It is concluded that hypokalemia produces active constriction of vascular smooth muscle. However, this study fails to lend support to the idea that potassium alone is responsible for exercise dilation.
Mechanisms Regulating Renin Release in Dogs with Thoracic Caval Constriction
Authors: Witty Robert T. , Davis James O. , Shade Robert E. , Johnson J. Alan , Prewitt Russell L.
Published: June 2012

In dogs with chronic thoracic caval constriction, renal denervation was followed by a fall in plasma renin activity from an average of 82.1 ± 1.5 (SE) ng angiotensin/ml of plasma over a 9-day control period to 40.8 ± 2.3 ng/ml for a 13-day period after denervation (
P
< 0.001); normal value was 4.7 ± 0.7 ng/ml. There was no detectable effect of renal denervation on the marked sodium retention. Thus the renal nerves contributed to the high plasma renin activity during caval constriction, but renal innervation was not essential for hypersecretion of renin. In a second group of dogs with caval constriction, the nonfiltering kidney model with a nonfunctional macula densa was produced, and renin secretion was measured before and after papaverine infusion into the left renal artery. Papaverine decreased renin secretion from 1090 ± 185 ng angiotensin/min to 497 ± 140 ng/min (
P
< 0.005). This initial rate of renin secretion of 1090 ng/min was higher than that from a nonfiltering left kidney of 190 ± 50 ng/min in otherwise normal dogs (
P
< 0.001). In a third series of dogs with caval constriction but with filtering kidneys, papaverine produced a similar decrease in renin secretion and an associated increase in sodium excretion. Since papaverine dilated the renal arterioles and the macula densa was nonfunctional in dogs with a nonfiltering kidney, these data support the concept that an intrarenal vascular receptor mediates the elevation in renin secretion in this model with chronic ascites. The striking decrease in renin secretion in response to intrarenal propranolol in dogs with either a filtering or a nonfiltering kidney indicates that a beta receptor is also involved.
Purification and Properties of Angiotensin-Converting Enzyme from Hog Lung
Authors: Dorer Frederic E. , Kahn Joseph R. , Lentz Kenneth E. , Levine Melvin , Skeggs Leonard T.
Published: June 2012

Angiotensin-converting enzyme was purified 1500-fold from a homogenate of hog lungs. The purification procedure included fractionation with ammonium sulfate, inactivation of contaminating enzymes at pH 4.7, batch treatment with CM-cellulose, and chromatography on columns of DEAE-cellulose, hydroxyapatite, and Sephadex G-200. The enzyme was assayed with hippurylglycylglycine and, after pH 4.7 was established, with both hippurylglycylglycine and angiotensin I as substrates. The ratio of activity toward the two substrates remained constant throughout the later stages of purification. The final enzyme preparation, on analytical disc gel electrophoresis, showed one major protein band with the expected ratio of activities toward both substrates. The molecular weight was estimated to be approximately 300,000 by gel filtration. The pH optimums with hippurylglycylglycine and angiotensin I as substrates were 8.4 and 7.5, respectively, and chloride ion was required for optimal activity of the enzyme with both substrates. Hydrolysis of both substrates was inhibited by ethylenediaminetetraacetic acid (EDTA) or the pentapeptide pyroglutamyllysyltryptophanylalanylproline. It would, therefore, appear that a single enzyme, purified in the described manner, hydrolyzes both angiotensin I and hippurylglycylglycine.
Hormonal Control of Cardiac Myosin Adenosine Triphosphatase in the Rat
Authors: Rovetto Michael J. , Hjalmarson Åke C. , Morgan Howard E. , Barrett Michael J. , Goldstein Richard A.
Published: June 2012

Cardiac function was impaired in hearts from hypophysectomized rats. Corresponding to the decrease in performance, myosin from the hearts of these rats exhibited a decreased Ca
2+
-activated ATPase activity. Myosin ATPase activated by K
+
or NH
4
+
was not different in any of the preparations studied. The decreased Ca
2+
-activated ATPase was observed in cardiac myosin but not in red or white skeletal muscle myosin. Treatment with thyroxine, but not with growth hormone, restored cardiac myosin ATPase and performance to normal. Hypothyroidism produced a decrease in cardiac myosin ATPase activity comparable to that seen after hypophysectomy, suggesting that the absence of thyroid hormone was responsible for the alterations. However, hyperthyroidism did not increase ATPase activity above normal values. Adrenalectomy failed to alter myosin ATPase. Anion exchange chromatography of the myosins and addition of various concentrations of Na
+
, Ca
2+
, and Mg
2+
did not abolish the differences in myosin ATPase. The results strongly suggest that the lower myosin ATPase activity in the absence of thyroid hormone was the result of a change in the myosin molecule per se and that the lower enzymatic activity was involved in the lower cardiac performance in these rats.
Substrate Preference and Metabolic Activity of the Aerobic and the Hypoxic Turtle Heart
Authors: Brachfeld Norman , Ohtaka Yoshinaga , Klein Irwin , Kawade Masaka
Published: June 2012

Substrate utilization by the isolated aerobic (Po
2
500 mm Hg) and hypoxic (Po
2
50 mm Hg) turtle (
Pseudemys scripta
) heart was evaluated by retrograde perfusion. During aerobic perfusion, the heart demonstrated active extraction and oxidation of free fatty acid (FFA) even in the presence of exogenous glucose. FFA metabolism was similar to that seen in the mammalian heart and was adequate to meet most of the myocardial energy requirements. When hypoxia supervened, FFA utilization did not compete with, but rather enhanced, concomitant carbohydrate metabolism, and glycogenolysis provided sufficient substrate to meet myocardial energy requirements with little change in observed hemodynamic function. During hypoxia, both rat and turtle demonstrated enhanced myocardial esterification of extracted [1
-14
C]-palmitate into neutral lipid. Exogenous glucose provided the glycerophosphate skeleton for FFA esterification in the hypoxic rat heart; endogenous glycogen served this function in the turtle myocardium. Extraction of glucose by the turtle heart was limited and changed insignificantly during hypoxia. The rat heart increased glucose uptake five-fold during hypoxia. Glycogen stores in turtle heart were tenfold greater than they were in rat heart, and they provided greater metabolic flexibility and permitted the heart to function adequately under environmental conditions that are lethal to the mammal.
Impairment of Red Cell Transit through the Canine Lungs following Injections of Hypertonic Fluids
Authors: Effros Richard M.
Published: June 2012

Rapid injections of hypertonic sucrose, sodium chloride, and urea solutions were given in the jugular veins of anesthetized dogs, and samples of blood were collected from the aorta. Following each of these injections, hemoglobin and plasma protein concentrations in the collected blood declined because fluid was extracted from the lungs. Injections of sucrose and sodium chloride, but not of urea, caused the hemoglobin concentration to fall more than the plasma protein concentration and slowed the movement of labeled red cells relative to that of labeled albumin when these two substances were injected at the same time and site as were the hypertonic solutions. The net flux of plasma through the lungs exceeded that of red cells for several seconds, indicating that plasma might pass around the more slowly moving red cells and through the smaller vessels of the lung. Impairment of red cell movement through the lungs is attributed primarily to red cell dehydration and loss of deformability. Unlike sucrose and sodium chloride, urea rapidly equilibrates between red cells and plasma and can only transiently dehydrate red cells. No impairment of red cell movement was seen after injections of hypertonic solutions of urea.
Spread of Excitation in the Atrioventricular Node of Isolated Rabbit Hearts Studied by Multiple Microelectrode Recording
Authors: van Capelle Frans J. L. , Janse Michiel J. , Varghese P. Jacob , Freud Gerrit E. , Mater Carla , Durrer Dirk
Published: June 2012

The pattern of atrioventricular (AV) nodal activation in isolated rabbit hearts was studied by recording transmembrane action potentials in about 200 AV nodal fibers per heart. A brush electrode consisting of ten microelectrodes was used. Both antegrade and retrograde spread of excitation were mapped: retrograde conduction was not an exact mirror image of antegrade conduction. The major input during antegrade conduction was from the crista terminalis, but the major output during retrograde conduction was through the interatrial septum. Some parts of the AV node were excited without directly participating in either antegrade or retrograde transmission of the impulse. Simultaneous pacing of the atrium and the His bundle generated antegrade and retrograde wave fronts which collided at different levels of the AV node. In this way, cells which transmitted the impulse in both directions were distinguished from those which did not (dead-end pathways). Two types of dead-end pathways were found: type A probably consisted of superficial atrial fibers terminating in the base of the tricuspid valve and type B branched off from cells in the middle node. The shape of the action potential of AV nodal cells strongly depended on the direction of propagation. In some parts of the AV node, the amplitude of the action potential was larger during antegrade activation than it was during retrograde activation; in other parts, the amplitude was smaller during antegrade conduction. The largest amplitudes occurred when wave fronts collided.
Experimental Acute Renal Failure Induced by Uranyl Nitrate in the Dog
Authors: FLAMENBAUM WALTER , MCNEIL JAMES S. , KOTCHEN THEODORE A. , SALADINO ANDREW J.
Published: June 2012

The diminished glomerular filtration rate observed in previous studies of acute renal failure induced by uranyl nitrate has been ascribed to backflow of glomerular filtrate through necrotic tubular epithelium, since renal blood flow was essentially normal. Renal blood flow (
133
xenon washout) and renal function were studied serially for 96 hours after the administration of uranyl nitrate (10 mg/kg, iv) in unanesthetized dogs with chronic renal artery catheters. Inulin clearance and total renal blood flow decreased to 25% and 52% of control, respectively, by 6 hours and remained depressed. By 3 hours, cortical flow decreased to 330±20 ml/min 100 g
-1
(control 507±12 ml/min 100 g
-1
) and outer medullary flow increased to 147±8 ml/min 100 g
-1
(control 97±18 ml/min 100 g
-1
), indicating intrarenal blood flow redistribution. From 6 hours on, these flow components were no longer separable. The ratio of flow in the outer two-thirds of the renal cortex to that in the whole cortex, determined using
85
strontium-labeled microspheres (15µ), decreased to 0.34±0.06 and 0.40±0.04 at 6 and 96 hours, respectively (control 2.21±0.12). Plasma renin activity was 1.8±0.6 ng/ml hour
-1
at 3 hours and remained elevated (control 0.6±0.2 ng/ml hour
-1
). Histological examination revealed minimal tubular change at 6 hours and widespread disruption at 96 hours. The decrease in renal blood flow prior to any significant tubular pathology suggests that alterations in renal hemodynamics, which may be mediated by the renin-angiotensin system, are responsible for the diminished renal function observed in this model of acute renal failure.
Effects of Renal Arterial Infusion of Sodium and Potassium on Renin Secretion in the Dog
Authors: SHADE ROBERT E. , DAVIS JAMES O. , JOHNSON J. Alan , WITTY ROBERT T.
Published: June 2012

The nonfiltering kidney model was used to determine whether sodium or potassium inhibits renin secretion in the absence of a functional macula densa in dogs with thoracic inferior vena caval constriction. The control rate of renin secretion was high, and decreases were readily recognized. After control observations, hypertonic sodium chloride or hypertonic potassium chloride was infused into the renal artery for 1 hour, and renin secretion was measured at 15-minute intervals. An increase in renal venous plasma sodium concentration from 141 to 154-158 mEq/liter caused no change in renin secretion for the first 45 minutes of infusion in dogs with a nonfiltering kidney. In contrast, dogs with thoracic caval constriction but with a filtering kidney showed a striking decrease in renin secretion during intrarenal sodium infusion (3,097 to 1,061 ng angiotensin/min,
P
<0.02). An increase in renal venous plasma potassium concentration from 3.9 to 6.1 mEq/liter in one group of dogs and from 4.9 to 8.3 mEq/liter in a second group also caused no change in renin secretion in the nonfiltering kidney of dogs with thoracic caval constriction. However, in dogs with thoracic caval constriction and a filtering kidney, potassium infusion decreased renin secretion (1,952 to 984 ng angiotensin/min,
P
<0.05). In all experiments, infusion of sodium chloride or potassium chloride failed to produce a significant change in renal blood flow, arterial blood pressure, or inferior vena caval pressure. Therefore, no evidence was obtained for a vascular action or a direct effect of sodium or potassium on the juxtaglomerular cells, and the data are consistent with an action mediated by the renal tubular system.
Renin, Angiotensin II, and Adrenal Corticosteroid Relationships during Sodium Deprivation and Angiotensin Infusion in Normotensive and Hypertensive Man
Authors: MENDELSOHN F. A. O. , JOHNSTON C. I. , DOYLE A. E. , SCOGGINS B. A. , DENTON D. A. , COGHLAN J. P.
Published: June 2012

The responses of plasma renin activity, plasma angiotensin II, plasma aldosterone, cortisol, and corticosterone to sodium deprivation and to angiotensin II infusion (100 ng/min) were measured in 8 normotensive patients and in 17 patients with essential hypertension. Following sodium deprivations, plasma renin activity rose from 0.513 ± 0.100 to 1.029 ± 0.124 ng/ml hour
-1
in normotensive patients and from 0.406 ± 0.077 to 0.629 ± 0.059 ng/ml hour
-1
in hypertensive patients. Plasma angiotensin II did not parallel changes in plasma renin activity: in normotensive patients plasma angiotensin II was unchanged by sodium deprivation (31.8 ± 6.0 compared with 30.1 ± 4.6 pg/ml), but in hypertensive patients it rose from 22.2 ± 3.4 to 36.4 ± 5.1 pg/ml. Plasma aldosterone rose equally in both groups following sodium deprivation (5.8 ± 1.3 to 15.3 ± 2.4 ng/100 ml for normotensive patients and 5.9 ± 1.4 to 14.4 ± 1.6 ng/100 ml for hypertensive patients) and angiotensin infusion (5.8 ± 1.3 to 10.4 ± 2.1 ng/100 ml in sodium-loaded normotensive patients, 15.3 ± 2.4 to 19.6 ± 3.6 ng/100 ml in sodium-deprived normotensive patients, 5.9 ± 1.4 to 11.4 ± 2.7 ng/100 ml in sodium-loaded hypertensive patients, and 14.4 ± 1.6 to 22.2 ± 2.6 ng/100 ml in sodium-deprived hypertensive patients). However, changes in endogenous plasma angiotensin II did not correlate with the rise in plasma aldosterone caused by sodium deprivation, and, despite much larger increases in plasma angiotensin II during angiotensin II infusion, plasma aldosterone showed smaller rises than those accompanying sodium deprivation. Plasma renin activity fell during angiotensin II infusion, in both groups of patients during both sodium loading and sodium deprivation, and, hence, the infusion constitutes a potent feedback inhibition of renin release in normotensive and hypertensive man. Plasma cortisol and corticosterone were unaltered by sodium deprivation but fell significantly with the angiotensin II infusion.
Partition of the Carotid Sinus Baroreceptor Response in Dogs between the Mechanical Properties of the Wall and the Receptor Elements
Authors: KOUSHANPOUR ESMAIL , KELSO DAVID M.
Published: June 2012

The purpose of this investigation was to learn what part of the carotid sinus baroreceptor response is attributable to the gross mechanical properties of the wall and what part to the receptor elements. Static pressure forcings were applied to an isolated dog carotid sinus preparation while baroreceptor nerve activity was recorded; carotid sinus deformation was measured from still photographs taken during the experiment. Pressure-nerve activity data were obtained from four dogs and pressure-deformation data from another five dogs. The average electrical power in the nerve signal was used as the measure of nerve activity, and strain-energy density, a scalar quantity, was selected as the best indicator of the mechanical state of the sinus wall. Strain-energy density was calculated by measuring the circumferential and the longitudinal strains and by estimating the corresponding stresses in accordance with a thin-walled, axially symmetric model. The pressure-nerve activity data followed an S-shaped pattern, but the pressure-strain-energy density data were linear over the pressure range of 50 to 250 mm Hg. A curve of strain-energy density vs. nerve activity constructed from these two graphs, with pressure as the parametric variable, showed a linear relationship between nerve activity and strain-energy density over the pressure range of 75 to 175 mm Hg, but the slope of the curve rapidly went to zero with increasing pressure. We concluded that the nonlinearity in the pressure-nerve activity relationship was primarily due to the inability of the receptor elements to respond to increasing wall strains.
A Feedback Mechanism Responsible for Fixed Coupling in Parasystole
Authors: LEVY MATTHEW N. , LEE MOO H. , ZIESKE HARRISON
Published: June 2012

The ventricles of open-chest anesthetized dogs were stimulated at a constant frequency to simulate ventricular parasystole. When the stimulation frequency was approximately half the spontaneous discharge frequency of the sinoatrial node, the natural pacemaker became synchronized with the artificial pacemaker. During such entrainment, the parasystolic rhythm resembled bigeminy with fixed coupling. Numerous instances of concealed bigeminy were also observed. Characteristic changes in arterial blood pressure always accompanied the repetitive ectopic beats, and these changes in blood pressure, acting mainly through the baroreceptor reflexes, were principally responsible for the synchronization. When the cardiac autonomic neural pathways were interrupted, synchronization usually could not be achieved. The biological feedback control system producing synchronization may be represented as follows. (1) The difference in timing between the firings of the sinoatrial node and the ectopic focus is the coupling interval. (2) This interval is a determinant of the stroke volumes of the premature and the postextrasystolic beats. (3) The stroke volumes affect the arterial blood pressure. (4) The level of blood pressure influences the neural activity in the baroreceptor reflex arc. (5) This activity in turn alters the frequency of the sinoatrial node. (6) Finally, sinoatrial nodal frequency affects the coupling interval to close the feedback loop.
Role of the Frank-Starling Mechanism In Exercise
Authors: HORWITZ LAWRENCE D. , ATKINS JAMES M. , LESHIN STEPHEN J.
Published: June 2012

The mechanisms which determine the response of stroke volume to mild, moderate, and severe exercise were compared in nine dogs running on a level treadmill. The dogs ran for 3-minute periods at 3-4 mph (mild exercise), 6-8 mph (moderate exercise), and 10-14 mph (severe exercise). Heart rate increased from a standing control value of 107 ± 6 beats/min to 191 ± 10 beats/min in mild, 221 ± 8 beats/min in moderate, and 263 ± 9 beats/min in severe exercise. Stroke volume increased 14%, 19%, and 15% for mild, moderate, and severe exercise, respectively. During mild exercise, left ventricular internal diameter decreased at end-systole but was unchanged at end-diastole. During moderate and severe exercise, end-diastolic diameter increased consistently as did left ventricular end-diastolic pressure. It was concluded that, despite extremely high heart rates, stroke volume increased during exercise. The augmentation in stroke volume was due to the combined effects of an increase in contractility, caused by increased sympathetic nervous system activity, and the operation of the Frank-Starling mechanism.
Effects of Training and Detraining on the Distribution of Cholesterol, Triglyceride, and Nitrogen in Tissues of Albino Rats
Authors: WATT EDWARD W. , FOSS MERLE L. , BLOCK WALTER D.
Published: June 2012

The effects of standardized exercise training and detraining on the content of cholesterol, triglyceride, and nitrogen in blood, myocardium, skeletal muscle, and epididymal fat of rats were studied. Forty-eight 90-day-old male rats were randomly assigned to four groups (two control groups, one trained group, and one trained and detrained group). Trained rats were subjected to 8 weeks of moderate running in motor-driven wheels; detraining was effected by discontinuing the running program for 8 weeks. Rats were provided a standard diet and water ad libitum. Trained rats displayed lower body weights and resting bradycardia. Training lowered (
P
<0.01) serum cholesterol, serum triglyceride, and adipose triglyceride levels but had no effect on these lipids in heart or skeletal muscle. These lowered lipid levels persisted after 8 weeks of detraining even though body weight was regained rapidly. Total nitrogen content was higher (
P
<0.01) in myocardial and triceps muscles of both trained and trained-detrained rats. Heart cholesterol and triglyceride levels were unchanged by detraining, but skeletal muscle cholesterol content was lowered. The results indicate that the changes in lipid content associated with training and detraining are tissue specific: reduction occurred in some tissues (serum and adipose tissue), although the lipid content of others (skeletal and heart muscle) was independent of training status, body weight, or circulating lipid levels.
Comparison of Constrictor Responses of the Rabbit Ear Artery to Norepinephrine and to Sympathetic Nerve Stimulation
Authors: WATERSON JOHN G.
Published: June 2012

The perfused isolated rabbit ear artery was used as a vascular model to compare the constrictor responses to exogenous and endogenous norepinephrine. The aim of the study was to estimate the concentrations of norepinephrine reaching the smooth muscle of the artery during sympathetic nerve stimulation. The artery was perfused so that exogenous norepinephrine was introduced exclusively from the adventitial surface; thus, the drug followed a path to the smooth muscle layer similar to that of the endogenous norepinephrine released from the perivascular ring of sympathetic nerves during electrical stimulation of the artery wall. Cocaine was used to remove the influence of neural uptake of norepinephrine on concentrations of the amine reaching the muscle receptor sites. The estimated concentrations of norepinephrine reaching the smooth muscle receptors for each pulse of electrical stimulation ranged from 24.8 ± 5.9 ng/ml (1.47 x 10
-7
M
) to 29.6 ± 7.7 ng/ml (1.75 x 10
-7
M
) over the range of pressure changes from 30 to 100 mm Hg. This finding suggests that the relative sensitivity to endogenous and exogenous norepinephrine is similar at different response levels in this range and that the effect of local factors in the artery on concentrations reaching the smooth muscle is of the same order of magnitude for both endogenous and exogenous norepinephrine.
Stimulation of Aldosterone Secretion by Hemorrhage in Dogs after Nephrectomy and Decapitation
Authors: McCAA ROBERT E. , McCAA CONNIE S. , COWLEY ALLEN W. , OTT COBERN E. , GUYTON ARTHUR C.
Published: June 2012

In eight intact, anesthetized dogs the aldosterone secretory rate averaged 13.8 ± 1.9 ng/min (mean ±
SE
). One hour after nephrectomy and decapitation, the aldosterone secretory rate decreased to 2.3 ± 1.7 ng/min and failed to increase in response to hemorrhage. By 8 hours after surgery, the aldosterone secretory rate had returned to control levels. The serum potassium concentration gradually increased from 3.2 ± 0.5 mEq/liter in the control samples to 5.3 ± 0.5 mEq/liter in the 8-hour samples. Eight hours after nephrectomy and decapitation, the arterial blood pressure was lowered to 70 mm Hg by hemorrhage in six dogs. During the next 3 hours, the aldosterone secretory rate increased from 11.2 ± 2.1 ng/min to 27.3 ± 2.1 ng/min. Associated with the increase in the aldosterone secretory rate following hemorrhage was a further increase in the serum potassium concentration from 5.3 ± 0.5 mEq/liter to 6.8 ± 0.5 mEq/liter. The aldosterone secretory rate did not increase following hemorrhage when the rise in serum potassium concentration was prevented by hemodialysis. These data indicate that normal levels of aldosterone secretion can be maintained in the absence of the renin-angiotensin system and the pituitary secretion of adrenocorticotropic hormone. Also, hemorrhage will greatly enhance aldosterone secretion in the absence of the head and the kidneys but only if the serum potassium concentration is allowed to rise following the hemorrhage.
Influence of Norepinephrine and Digitalis on Myocardial Oxygen Consumption in the Newborn Lamb
Authors: DOWNING S. EVANS , LEE JOHN C. , TAYLOR JAMES F. , HALLORAN KATHERINE
Published: June 2012

The relationships between cardiac performance and oxygen usage were explored in 19 newborn lambs (5 hours to 8 days old), and the influence of inotropic stimulation was studied. A preparation was developed to measure coronary sinus flow and myocardial oxygen consumption (MVo
2
) under controlled hemodynamic conditions. Using a gelatin injection technique, we determined that more than 90% of the measured sinus flow originated from left heart tissue; less than 10% was derived from right ventricular myocardium. Changes in contractility were produced by intravenous infusion of norepinephrine or acetylstrophanthidin. Norepinephrine (1-2.4 µg/min kg
-1
) or acetylstrophanthidin (5 µg/min kg
-1
) produced increases in the maximal rate of rise of left ventricular pressure and large reductions in left ventricular enddiastolic pressure, but the changes in MVo
2
in lambs with constant aortic blood pressure, cardiac output, and heart rate were minimal. Ventricular function curves demonstrated a significant relationship between end-diastolic pressure and MVo
2
(P < 0.01). For a given left ventricular end-diastolic pressure, MVo
2
was approximately 3 ml/min 100 g
-1
left ventricle greater during the infusion of norepinephrine. Therefore, net changes in MVo
2
with inotropic stimulation represented a balance between reciprocal changes in diastolic pressure (and volume) and contractility. The enhanced oxygen cost of increased contractility might be masked by a reduction in heart size (reduced wall stress). Ventricular function was reduced below initial control values following the infusion of norepinephrine in 3 lambs. This reduction correlated with a concomitant reduction in MVo
2
and percent extraction but not with a reduction in flow. Lambs that did not show mechanical depression demonstrated no reduction in MVo
2
. These findings suggest a metabolic basis for catechol dependence which might have special importance for the newborn lamb with its incompletely developed catechol enzyme systems.
Myocardial Performance in Hemorrhagic Shock in the Dog and Primate
Authors: ABEL FRANCIS L. , KESSLER DAVID P.
Published: June 2012

Myocardial performance was investigated in nine dogs and six monkeys during experimental hemorrhagic shock under conditions of constant afterload. Left ventricular function curves were obtained by opening an aorta to left atrial bypass, and simultaneous recordings of stroke volume, peak stroke power, maximal dP/dt, maximal dF/dt, heart rate, atrial pressure and end-diastolic pressure were made. Total plasma catecholamine content was also measured in the monkeys during the control period and at death. The dogs showed a marked increase in performance, in contrast to the control group, 0-2 hours after reinfusion. Performance then deteriorated significantly by 2-4 hours, although it was still comparable to control levels. However, higher atrial and end-diastolic pressures were obtained, and in most cases cardiac failure developed soon thereafter. Two additional dogs were subjected to all stresses except the hypotension for 10 hours without evidence of deterioration. The monkeys did not withstand the surgical procedure as well as the dogs did and survived a maximum of 136 minutes after reinfusion. Catecholamine levels decreased in five of the six monkeys but not below normal levels, which indicates that failure was not due to depletion of myocardial stores. The data are interpreted as direct evidence for a factor(s) seriously depressing myocardial performance during the postinfusion period of experimental hemorrhagic shock in the dog and the monkey despite the high levels of performance in the early postinfusion period and the maintenance of coronary driving pressure and arterial oxygen content.
Angiotensin as a Possible Intrarenal Hormone in Isolated Dog Kidneys
Authors: ITSKOVITZ HAROLD D. , HEBERT LEE A. , MCGIFF JOHN C.
Published: June 2012

The distribution of renal blood flow was measured in isolated blood-perfused dog kidneys using radioactive labeled microspheres. The kidneys were perfused at a constant systolic pressure of 140 mm Hg. For the first 50 minutes of perfusion, flow to the outer zones of the renal cortex was 79±2% (SE) of the total renal blood flow, and inner cortical blood flow accounted for 21±2%. With continued perfusion, inner cortical blood flow increased progressively, reaching 34±3% by 150 minutes--a time when renin substrate was depleted in the perfusates. Infusions of the tetradecapeptide renin substrate (5-50 µg/min) reestablished the fractional distribution of renal blood flow observed in the initial 50 minutes of perfusion, i.e., inner cortical blood flow was reduced significantly from 36±2% to 23±4% (
P
<0.05). In contrast, infusions of angiotensin II (1-10 µg/min) did not reduce the fractional distribution of renal blood flow to the inner cortex. These data provide evidence to support the hypothesis that angiotensin might be formed as an intrarenal hormone which participates in the regulation of deep cortical and medullary vascular resistances. Circulating angiotensin II does not appear to serve a similar function.
Evidence for Uneven Alpha-Receptor Distribution in the Rat Portal Vein
Authors: LJUNG BENGT , BEVAN JOHN A. , SU CHE
Published: June 2012

The smooth muscle of the rat portal vein which supports propagation becomes supersensitive to exogenous
l
-norepinephrine after elimination of the vessel's intramural neuronal uptake mechanism. Such supersensitivity is generally associated with intimate neuromuscular connections. Since the adrenergic vasomotor fibers in the portal vein do not enter the muscle tissue, it has been proposed that muscle cells close to the nerve terminals must determine the response to norepinephrine. With the aim of elucidating the mechanism behind the prejunctional supersensitivity, the total uptake of labeled norepinephrine in the portal vein was analyzed and its distribution within the vessel wall was evaluated directly using isotopically labeled frozen sections. The total uptake of the portal vein, related to its endogenous norepinephrine content, was comparable with that in other vascular and nonvascular tissues. The
3
H-uptake profile of the vessel wall showed that the neurogenic uptake was confined to the narrow adrenergic plexus between the longitudinal and the circular muscle layers. The neuronal uptake mechanism therefore could only influence the concentration of exogenous norepinephrine at muscle cells close to the nerve terminals. These results support the hypothesis that the prejunctional supersenstivity in the rat portal vein indicates that the alpha receptors are located on muscle cells in the vicinity of the adrenergic nerve terminals.
Conduction Block Associated with Transient Depolarizations Induced by Acetylstrophanthidin in Isolated Canine Purkinje Fibers
Authors: SOUNDERS JAMES H. , FERRIER GREGORY R. , MOE GORDON K.
Published: June 2012

Transient depolarizations (TDs) appeared in canine Purkinje tissue but not in cardiac muscle during exposure to 1-2 x 10
-7
g/ml of acetylstrophanthidin. At low levels of toxicity, the TDs were associated with a decrease in threshold and an increase in automaticity. As intoxication progressed, the TDs coincided with transient periods of increased threshold and conduction block. Propagation from muscle to Purkinje tissue was blocked during, but not before or after, the crest of the TDs. As a result of the interaction between temporal and spatial (electrotonic) factors, various patterns of block, including unidirectional block, were observed. At moderate frequencies 2:1 block was demonstrated, but at faster rates 1:1 transmission occurred. At a later stage of toxicity, repetitive stimulation led to progressive depolarization in Purkinje tissue followed by a period of block during which slow repolarization eventually restored excitability and conductivity. In the whole heart, conduction block could permit reentry and could be responsible for the ultimate transition from ventricular tachycardia to ventricular fibrillation.
Transient Depolarizations Induced by Acetylstrophanthidin in Specialized Tissue of Dog Atrium and Ventricle
Authors: HASHIMOTO KEITARO , MOE GORDON K.
Published: June 2012

Isolated preparations of atrial specialized conduction fibers ("plateau" fibers) qualitatively resembled ventricular Purkinje fibers (false tendons) in their response to acetylstrophanthidin. Acetylstrophanthidin in concentrations of 1-3 x10
-7
g/ml caused coupled, frequency-dependent transient depolarizations (TDs) in both types of fiber. In free-running strands of plateau fibers the TDs could reach threshold and generate coupled action potentials, but TDs and automatic responses did not occur in ordinary atrial muscle fibers. TDs were suppressed by elevation of the external potassium concentration. Automatic activity and TDs in atrial plateau fibers were abolished by acetylcholine. Automatic activity was also sometimes suppressed in false tendons by acetylcholine, but TDs and related coupled responses were not influenced.
De Novo Synthesis of Myocardial Adenine Nucleotides in the Rat
Authors: ZIMMER HEINZ-GERD , Trendelenburg Christian , Kammermeier Helmut , Gerlach Eckehart
Published: June 2012

De novo synthesis of adenine nucleotides was measured in rat hearts in situ and in isolated perfused rat hearts under normal conditions and during recovery from asphyxia or ischemia. Using l-
14
C-glycine as the precursor substrate, rates of de novo synthesis were determined from the total radioactivity of adenine nucleotides and from the mean specific activity of intracellular glycine. The rate of de novo synthesis of adenine nucleotides was 8.4±1.42 nmoles/g hour
-1
in the heart in situ and 1.3±0.12 nmoles/g hour
-1
in the isolated perfused heart. De novo synthesis of adenine nucleotides increased almost 100% in the heart in situ and about 580% in the isolated perfused heart during the first hour of recovery from asphyxia or ischemia. This acceleration is regarded as an adaptive process contributing to the postanoxic restoration of normal adenine nucleotide levels. Possible biochemical mechanisms that might be involved in the stimulation of the de novo pathway are a release of feedback inhibition of 5-phosphoribosyl-1-pyrophosphate amidotransferase, an enhanced synthesis of 5-phosphoribosyl-1-pyrophosphate, and an alternate way of 5-phosphoribosyl-amine formation.
Genetic Influence on the Renin-Angiotensin System
Authors: IWAI JUNICHI , DAHL LEWIS K. , KNUDSEN KNUD D.
Published: June 2012

Two strains of rats with opposite, genetically determined predispositions to hypertension were compared. Rats from the hypertension-prone strain had significantly lower plasma and kidney renin activities than did rats from the hypertension-resistant strain. Although renin activities were modified by NaCl intake and blood pressure, significant differences between the two strains were present with all four experimental regimens used: low-NaCl diet, high-NaCl diet, unilateral renal artery constriction, and unilateral renal artery constriction plus contralateral nephrectomy. Therefore, we concluded that renin activities along with blood pressure were modified by genetic influences in these two strains of rats.
Postnatal Changes in Rat Ventricular Function
Authors: HOPKINS SIDNEY F. , MCCUTCHEON ERNEST P. , WEKSTEIN DAVID R.
Published: June 2012

Experiments were designed to assess the intrinsic changes in myocardial function with age and to determine the role of increasing left ventricular mass in this process. Isometric ventricular pressure-volume curves and length-tension curves were measured in isolated perfused rat hearts of different ages and masses. Incremental tension, peak active tension, and peak passive tension were less for 10-day-old hearts than they were for older hearts subjected to proportionately equal increases in length. At resting length, peak active tension developed by hearts at least 16 days old was 78% higher than that developed by 10-day-old hearts, and peak passive tension was 133% higher. There was no significant difference between 16-day-old rats and older rats. Thus, by the sixteenth postnatal day, the heart had developed functional maturity. These functional changes appeared to be related to age rather than to left ventricular mass. Histological studies of the left ventricle showed that, at birth, the myofibrils were disoriented with a high ratio of nonmyofibrillar elements to myofibrillar elements. Within 16-20 days after birth, the structural organization and the ratio of nonmyofibrillar elements to myofibrillar elements were similar to the organization and the ratio found in an adult. Thus a direct relationship existed between the functional properties and the anatomical development of the myocardium. Mass per se was not the sole factor that contributed to improved myocardial function with age.
Depolarization and Action Potential Duration in Cardiac Purkinje Fibers
Authors: ARITA MAKOTO , SURAWICZ BORYS
Published: June 2012

The effect of depolarization on the duration of the action potential was studied in short cardiac Purkinje fibers. Membrane potential was altered by overdriving pacemaker fibers showing spontaneous diastolic depolarization (dog), by injecting constantcurrent pulses through an intracellular microelectrode (sheep), or by voltage clamping (dog). Test action potentials were elicited at the end of 50-300-msec depolarizations by extracellular stimuli in sheep fibers and by cathodal intracellular stimuli in dog fibers. In both species the duration of the test action potential was unchanged by subthreshold depolarization. In fibers showing spontaneous diastolic depolarization, action potential duration was not affected by the take-off potential within the range between -80 and -60 mv. In dog fibers depolarized from the threshold level (about -60 mv), action potential duration was shortened by 14-36%. After stronger depolarization (up to -10 mv), short action potentials could be elicited during the first 100-150 msec. This period coincided with the flow of net inward current. After longer suprathreshold clamps when the net membrane current reversed its polarity, the fibers were not excitable, and the clamp termination was followed by exponential decay of the membrane potentials. Our findings indicate that changes in take-off potential within the range between resting membrane potential and -60 my do not alter action potential duration.
Adrenergic Component of Renin Release Induced by Vasodilating Antihypertensive Drugs in the Rat
Authors: PETTINGER WILLIAM A. , CAMPBELL WILLIAM B. , KEETON KENT
Published: June 2012

The capacity of the vasodilating drugs, minoxidil and hydralazine, for inducing renin release was characterized in rats according to chronology and dose response. Propranolol inhibition of this renin release was also characterized and related to serum levels of propranolol. Minoxidil and hydralazine (1.0 mg/kg) induced sevenfold elevations of serum renin activity. Treatment with propranolol, resulting in plasma propranolol concentrations as low as 50 ng/ml, impaired vasodilatory drug-induced renin release. The propranolol inhibition suggests a beta-adrenergic component to this type of renin release and the potential for a clinically efficacious drug interaction.