bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentiation of Adrenergic Venomotor Responses in Dogs by Cardiac Glycosides
Authors: BRENDER DAVID , VANHOUTTE PAUL M. , SHEPHERD JOHN T.
Published: June 2012

Acetylstrophanthidin, 0.3 to 10 µg/ml, caused contraction of helical strips of the dog cutaneous vein in an organ bath at 37°C. A latent period of 12 to 60 minutes preceded the contraction. During this time, the vein exhibited a progressive increase in response to transmural electric stimulation and added norepinephrine. As the dose of acetylstrophanthidin was increased, the latent period shortened and the increased response during the latent period was potentiated. When the contraction caused by 10 µg/ml was maximal, no additional contraction occurred with electric stimulation; the response to electric stimulation was only partially restored by the repeated washing out of the drug, despite relaxation of the strip to almost base-line tension. Since transmural electric stimulation causes contraction by release of tissue catecholamines, these experiments demonstrate that digitalis glycosides sensitize the cutaneous veins of the dog to adrenergic stimulation. This was confirmed in dogs anesthetized with pentobarbital. Intravenous injections of acetylstrophanthidin and digoxin, in doses too small (12.5 to 15.5 µ/kg) to cause direct constriction of the lateral saphenous vein, potentiated the constriction of this vein caused by electric stimulation of the lumbar sympathetic chain.
Activity and Thermosensitivity of Canine Cutaneous Veins after Inhibition of Monoamine Oxidase and Catechol-O-Methyl Transferase
Authors: VANHOUTTE PAUL M. , SHEPHERD JOHN T.
Published: June 2012

The lateral saphenous vein of the dog was perfused with homologous blood at constant flow. Changes in driving pressure were used to measure active changes in venous tone. Administration of tranylcypromine greatly reduced the activity of monoamine oxidase in the vein and increased its response to electric stimulation of the lumbar sympathetic chain and to norepinephrine infusions. Administration of pyrogallol (a catechol-O-methyl transferase inhibitor) also increased the response of the vein to adrenergic stimulation. These chemicals did not alter the increase in the sensitivity of the venous smooth muscle to sympathetic nerve impulses and infused norepinephrine produced by cooling the perfusate. Thus, the potentiating effect of local cooling on the response of the cutaneous veins to adrenergic stimulation cannot be explained by interference with the local enzymatic inactivation of catecholamines.
Countercurrent Exchange of Heat in the Dog Kidney
Authors: RöED AsbjöRN , AUKLAND KNUT
Published: June 2012

The mechanisms of renal heat clearance were studied in anesthetized dogs by recording renal venous and cortical temperatures during step changes of arterial blood temperature induced by infusion of 0.9% saline of room temperature into the renal artery. The venous thermodilution curves were well described by a three-exponential function with average rate constants: k
1
= 10.4 min
-1
, k
2
= 2.2 min
-1
, and k
3
= 0.59 min
-1
, and intercepts at 34%, 44%, and 22%, respectively. The various components were interpreted as follows:

The slow component mainly represents heat conduction from inner medullary and perirenal tissue as shown by extrarenal temperature recording and by calculating the heat distribution volume. Local cortical recordings showed that cortex is not a homogeneous compartment, and k
2
reflects an average cortical heat clearance, k
1
is much higher than blood flow per gram of tissue in any kidney region and results from heat exchange between intrarenal arteries and veins.

The arteriovenous diffusion of heat explains the higher temperatures observed in the cortex and the renal medulla than in renal venous blood. The arteriovenous thermodilution technique is unsuited for local and total renal blood flow measurements, because of countercurrent diffusion and heat exchange witli perirenal tissue.
Pulmonary Arterial Pulse Wave Velocity and Impedance in Man
Authors: Milnor William R. , Conti C. Richard , Lewis Kenneth B. , O'Rourke Michael F.
Published: June 2012

The differential pressure method of Womersley and McDonald was used to measure instantaneous blood flow in the main pulmonary artery in ten human subjects. Three subjects had normal pulmonary arterial pressures and flows, seven had mitral stenosis and pulmonary hypertension. The spectrum of input impedance versus frequency was similar to that previously reported for the dog and rabbit, with the modulus decreasing from relatively high values at zero frequency to a minimum between 2 and 5 cycles/sec. Characteristic impedance and phase velocity were lower in the normal subjects than in those with pulmonary hypertension (averages, 23 dyne sec cm
-5
and 1.68 m/sec in the normals; 46 dyne sec cm
-5
and 4.77 m/sec in the hypertensives). Hydraulic energy dissipated per unit time by pulsations in the pulmonary bed was usually higher in the hypertensive than in the normal cases, because of the greater stiffness of the pulmonary arteries in the subjects with pulmonary hypertension. The elasticity of the pulmonary arterial tree appears to be as important as the state of the arterioles and capillaries in determining the energy required for pulsatile pulmonary blood flow.
Beta-Receptor Activity in Aorta
Authors: FLEISCH JEROME H. , MOLING HARRIET M. , BRODIE BERNARD B.
Published: June 2012

Helically cut thoracic aortic strips (from rats, rabbits, and guinea pigs) in a state of low to moderate tone and under the influence of alpha-receptor blockade relaxed in response to isoproterenol. Propranolol blocked these relaxations. Helically cut thoracic aortic strips from cats and abdominal aortic strips from rats, rabbits, and cats were not relaxed by isoproterenol. In addition, aortic beta-receptor activity of rats and rabbits decreased with increasing age. The ability of thoracic aortas to be relaxed by isoproterenol was lost when rats were 90 days old and when rabbits were 2 years old. Significant loss of beta-receptor activity was not evident in rat trachea and stomach. Sodium nitrite completely relaxed thoracic and abdominal aortas from all species including thoracic aortas from old rats and rabbits. We conclude: (1) there are species differences in the response of thoracic aortic strips to beta-receptor stimulation; (2) a gradient in beta-receptor activity exists in the aorta with greater activity in the thoracic aorta and a relatively small amount of activity in the abdominal aorta; and (3) aortic beta-receptor activity decreases with increasing age.
Effects of Acute Regional Myocardial Ischemia on Left Ventricular Function in Dogs
Authors: ENRIGHT LEE P. , HANNAH HAMNER , REIS ROBERT L.
Published: June 2012

The immediate functional deficit resulting from acute regional myocardial ischemia was evaluated in 40 anesthetized dogs. Ventricular function curves, maximum dp/dt, isovolumetric force-velocity curves, and peak systolic and resting diastolic length-tension curves were assessed at fixed heart rate and constant aortic pressure before and during occlusion of the anterior descending coronary artery 2 to 3 cm distal to its origin. Mild, moderate, or marked depression of the ventricular function resulted from occlusion of the anterior descending artery, depending upon the anatomy of the intercoronary collateral vessels. Maximum loss of function was apparent 2 minutes after occlusion, and was quantitatively reproducible by reocclusion after an intervening period of unobstructed flow. Resting diastolic length-tension relations were not significantly altered by occlusion of the anterior descending artery. In 12 dogs, force-velocity relations were determined during the inscription of ventricular function curves and in every instance when depressed function was evident from the ventricular function curve, the simultaneously determined force-velocity curve also demonstrated impaired performance. At low preload levels, however, the force-velocity curves inscribed before and during occlusion of the anterior descending artery were not very dissimilar; with increasing ventricular volumes, the force-velocity curve inscribed during coronary artery occlusion progressively shifted downward and to the left of the control curve. Maximum velocity, however, appeared to be unchanged suggesting that this index of contractility is not a satisfactory method for assessing cardiac performance during acute regional myocardial ischemia.
Studies on Left Atrial Automaticity in Dogs
Authors: MIROWSKI M. , LAU SUN H. , BOBB GUSTAVUS A. , STEINER CHARLES , DAMATO ANTHONY N.
Published: June 2012

The site of origin and the sequence of atrial activation were studied in 21 open-chested dogs anesthetized with sodium pentobarbital. Bipolar plunge electrodes were used to record atrial electrograms simultaneously with surface lead II and His bundle electrogram. In sinus rhythm the sinus node was activated first, followed sequentially by Bachmann's bundle, right atrial appendix, left atrial appendix, posterior left atrium, and the proximal portion of the coronary sinus. In 15 dogs left atrial beats and rhythms of various rate were recorded, including instances of left atrial exit block and of rapid left atrial rhythms. In such beats one of the left atrial electrodes was activated first and was followed by Bachmann's bundle, sinus node, proximal portion of the coronary sinus, and by right atrial appendix. Left atrial beats were observed occurring (1) spontaneously; (2) as a result of vagal stimulation; (3) after destruction of the sinus node; (4) during ventricular pacing. Left atrial pacing through the electrode recording initial activity reproduced the sequence and configuration of atrial electrogram similar to that seen in the ectopic left atrial beats. These results demonstrate that in dogs ectopic activity frequently originates in the left atrium.
Mechanically Induced Intravascular and Extravascular Hemolysis in Dogs
Authors: WALLACE HERBERT W. , COBURN RONALD F. , HABBOUSHE FOWZI , BLAKEMORE WILLIAM S. , SHEPARD CAROLYN E.
Published: June 2012

The endogenous production of carbon monoxide and the flow of hemoglobin to and from plasma were measured in 11 anesthetized dogs after pumping blood through an extracorporeal circuit for short periods. Two different pumps were used. In all animals the increase in CO production was greater than could be explained by catabolism of hemoglobin lost from plasma, an average of 11.4 times greater with one pump and 2.49 times greater with the other pump. Evidence is presented that this discrepancy could not be explained by catabolism of heme other than that of hemoglobin, and we therefore concluded that rates of hemoglobin catabolism were much greater than indicated by plasma hemoglobin kinetics and that extravascular hemolysis is a major cause of erythrocyte destruction during mechanically induced hemolysis. Extravascular hemolysis apparently caused an average of 72.9% and 37.2% (with the two pumps) of the total quantity of erythrocytes destroyed during pumping and for 3 hours after pumping.
Morphometric Basis of the Sheet-Flow Concept of the Pulmonary Alveolar Microcirculation in the Cat
Authors: SOBIN SIDNEY S. , TREMER HERTA M. , FUNG Y. C.
Published: June 2012

The purpose of this study was to describe quantitatively the geometric organization of the pulmonary alveolar capillary bed. Conventional representation of these vessels as a tight network of circular cylindrical tubes (tube-flow model) was contrasted with a suggested alternative of a continuous sheet bounded on two sides by endothelium held apart by connective tissue and cellular posts (sheet-flow model). A vascular space-tissue ratio, VSTR, is defined as the ratio of vascular lumen volume to the circumscribing tissue volume. The VSTR was obtained by planimetric measurements. Formulas were developed to relate VSTR to the geometric models. Cat lungs were perfused in situ with liquid silicone elastomer at 25 mm Hg, and the liquid elastomer was allowed to catalyze at 15 or 25 mm Hg static pressure while the airway pressure was maintained at 10 cm H
2
O. After the silicone became solid, the lungs were fixed with formalin-steam, and morphometric analysis was carried out on photographs of frozen sections. The mean values of VSTR of each cat (six lobes) were 0.91 to 0.92, irrespective of intracapillary pressure. These data are consistent with a sheet-flow model. Sheet thickness then becomes a significant variable.
Activation of Lipoprotein Lipase
Authors: WHAYNE THOMAS F. , FELTS JAMES M.
Published: June 2012

Injection of heparin into a number of animal species releases lipoprotein lipase into the circulation. We have studied the effect of heparin added in vitro to the lipase activity in post-heparin serum from six mammalian species. With the exception of man, all animals were studied under anesthesia. Our results demonstrate that only post-heparin serum from the rat developed increasing lipoprotein lipase activity when increasing concentrations of heparin were added to the assay system. Heparin decreased activity in the other species. These results prompted us to test the effect of adding rat serum to post-heparin serum from the other species in the presence of increasing concentrations of heparin. Rat serum stimulated lipoprotein lipase activity markedly. In guinea pigs, post-heparin serum activity increased 2,700% at a heparin concentration of 1.0 U/ml in the assay system. This effect may be related to the extremely low level of high-density lipoprotein in the guinea pig and the presence of a unique high-density lipoprotein in the rat.
Intrarenal Distribution of Blood Flow during Elevation of Ureteral Pressure in Dogs
Authors: CARLSON EDWIN L. , SPARKS HARVEY V.
Published: June 2012

The
85
Kr method was used to determine the effect of elevated ureteral pressure on total cortical and outer medullary nutrient renal blood flow of pentobarbital-anesthetized dogs. Increased ureteral pressure during mild saline diuresis resulted in increased total nutrient blood flow from 316 to 402 ml/100 g/min. Autoradiographs demonstrated that the increased blood flow is confined to the renal cortex and that juxtamedullary cortical and outer medullary flow is unchanged. Elevated ureteral pressure decreased total renal blood flow from 473 to 381 ml/g/min during copious mannitol diuresis. This is due at least partly to decreased cortical blood flow; we were unable to measure juxtamedullary cortical plus outer medullary blood flow during mannitol diuresis. Isolated renal arteries relaxed when placed in a physiologic salt solution containing 70 mM mannitol. Renin release is increased during elevation of ureteral pressure. We concluded that the mechanism for increased renal blood flow during ureteral occlusion selectively involves the nutrient circulation of the renal cortex.
Acceleration of Ventricular Pacemakers by Transient Increases in Heart Rate in Dogs during Ouabain Administration
Authors: WITTENBERG STEPHEN M. , STREULI FRITZ , KLOCKE FRANCIS J.
Published: June 2012

The present experiments describe effects of transient increases in heart rate on ventricular pacemakers during digitalization. Fifteen anesthetized, vagotomized dogs were studied during ouabain infusion or after recovery from ouabain-induced ventricular tachycardia. Vagal stimulation was used to assess baseline ventricular automaticity and 30-second periods of atrial pacing were utilized to evaluate the response of ventricular pacemakers following different increments in rate. After an average dose of 45 ± 3 (SE) µg/kg of ouabain, vagal stimulation unmasked an automatic ventricular focus in 14 animals and pacing was followed by ventricular acceleration in all 15 animals. The Degrees of ventricular acceleration varied directly with the pacing rate. The increment in ventricular rate above the level unmasked by vagal stimulation averaged 59 ± 4% of the increment in atrial rate. At the higher driving rates, a transient postpacing depression was present before the emergence of a rapid ventricular focus. These findings were unaffected by beta-receptor blockade with 4-(2-hydroxy-3-isopropylamino propoxy) acetanilide (AY21,011). The results indicate that transient increases in heart rate may accelerate rather than depress ventricular pacemakers during digitalization.
Vascular Smooth Muscle and the Anisotropy of Dog Carotid Artery
Authors: DOBRIN PHILIP B. , DOYLE JAMES M.
Published: June 2012

Segments of dog carotid artery were held at in-situ length and studied in vitro after excitation of the muscle with norepinephrine and after poisoning of the muscle with potassium cyanide. In-situ length corresponded to a longitudinal strain of .57±.02 relative to the unstretched length. The longitudinal elastic modulus was about 4.1x10
6
dyn/cm
2
at in-situ length and zero transmural pressure. This value was not altered by excitation of the vascular smooth muscle. The longitudinal stress due to traction decreased as the longitudinal stress due to transmural pressure increased, and it was suggested that this interaction underlies the relative constancy of vessel length in situ. The Poisson's ratio between the circumferential and longitudinal directions was about 0.3 and was found to decrease slightly with activation of the vascular muscle. The data for the longitudinal modulus and for Poisson's ratio were used to compute the circumferential elastic modulus. Activation of the muscle increased the circumferential elastic modulus when plotted as a function of circumferential strain. Comparison between the moduli in the two directions revealed that the arterial wall is not isotropic at physiological pressures because the circumferential elastic modulus is greater than the longitudinal modulus. Calculations indicated that assuming isotropy slightly underestimates the true circumferential modulus at small circumferential strains, and greatly overestimates the true circumferential modulus at large circumferential strains. Active smooth muscle has little direct effect on these estimations, but does alter the error by contracting the vessel to smaller strains.
Distribution of Potassium, Sodium, and Chloride in Canine Purkinje and Ventricular Tissues
Authors: VICK ROBERT L. , HAZLEWOOD CARLTON F. , NICHOLS BUFORD L.
Published: June 2012

Cellular resting and action potentials and total tissue concentrations of K
+
, Na
+
, and Cl
-
were measured in canine myocardial and Purkinje tissues. The results with myocardium were consistent with those of others: the total tissue concentration of K
+
was greater than that of Na
+
of Cl
-
In Purkinje tissue, the total tissue concentration of K
+
was relatively low, while that of Na
+
and of Cl
-
was high. Extracellular space was calculated on the basis of four different assumptions about the intracellular concentration of one of the ions: (1) the intracellular concentrations of Cl
-
is zero; (2) the electrochemical equilibrium potential of Cl
-
equals the cellular resting potential; (3) the electrochemical equilibrium potential of K
+
equals the cellular maximum diastolic potential; (4) the electrochemical equilibrium potential of Na
+
equals the reversal of the cellular action potential. In the myocardium, the lowest estimate of extracellular space was 14±2%, and the highest was 18±2%. In the Purkinje tissue, the minimum extracellular space: (1) permitting adequate intracellular K
+
to account for the maximum diastolic potential was 45±3%; (2) consistent with passive distribution of Cl
-
was 61±4%; (3) yielding low enough intracellular concentration of Na
+
to account for the reversal of the action potential was 63±10%. These results suggest that in cardiac Purkinje tissue: (1) the extracellular space is unusually large with respect to that of myocardium and skeletal muscle; (2) intracellular activities of ions do not necessarily equal concentrations; or (3) intracellular space is not necessarily a single compartment.
Flow Estimation by Indicator Dilution (Bolus Injection)
Authors: BASSINGTHWAIGHTE JAMES B. , KNOPP THOMAS J. , ANDERSON DENNIS U.
Published: June 2012

Indicator dilution techniques used for the estimation of flow (F), mean transit time (t), dispersion (σ), and mean transit time volume (V) in the circulation are subject to error when (1) flow is not steady and (2) concentrations are obtained by sampling at a constant rate (time averaging) rather than at rates proportional to the instantaneous flow past the sampling site (volume averaging).

Using a simple descriptive model for indicator transport, the effects of simulated aortic flow or of sinusoidal flow of widely variable frequency were assessed. Errors in estimates of F, t, σ, and V are greater with bolus injections than with constant-rate injections. Errors are roughly proportional to the amplitude of variation in flow. They are maximal when the period of flow fluctuation is similar to the passage time of the dilution curve, which, for the human central circulation, is about the time for one respiratory cycle. With sinusoidal flow between 50% and 150% of the mean flow, errors were at worst up to 60% in F, 30% in t, 50% in σ, and 70% in V, with a bimodal distribution. Errors are minimal at cardiac frequencies. The troublesome lower frequencies can be avoided. Preliminary tests of a method for converting time- to volume-averaged concentrations gave encouraging results.
Patterns of Atrioventricular Conduction in the Human Heart
Authors: WIT ANDREW L. , WEISS MELVIN B. , BERKOWITZ WALTER D. , ROSEN KENNETH M. , STEINER CHARLES , Damato Anthony N.
Published: June 2012

Atrial, His bundle (H), and ventricular electrograms were recorded by an electrode catheter in unanesthetized man. Conduction time through the atrioventricular (A-V) conduction system was subdivided into A-V nodal (A-H interval) and ventricular specialized conduction system (H-V interval). The right atrium was driven at a constant rate and the pattern of A-V conduction of premature atrial test impulses was determined as they occurred progressively earlier in the cardiac cycle. In the type 1 response, conduction delay and block were limited to the A-V node only. The type 2 response was characterized by progressive conduction delay in both the A-V node and ventricular specialized conduction system with block occurring in several instances in the latter. In the type 3 response there was also a progressive delay in A-V nodal conduction time, and a sudden marked delay in conduction in the ventricular specialized conduction system. Conduction block occurred distal to the His bundle depolarization. The relevance of conduction delay and block in the different regions of the A-V conduction system to the full recovery time and the relative, functional, and effective refractory periods of A-V conduction are indicated.
Pyrimidine Nucleotide Synthesis in the Normal and Hypertrophying Rat Heart
Authors: MATSUSHITA SATORU , FANBURG BARRY L.
Published: June 2012

Radioactive orotic acid incorporation into RNA (de novo pathway of pyrimidine nucleotide synthesis) was considerably lower for rat heart than for rat liver in vivo and in vitro.
3
H uridine ("salvage" pathway) was incorporated into heart RNA to a greater extent than
3
H orotic acid, and the labeling with uridine in the heart exceeded that in the liver. Extracts of heart showed little enzymatic conversion of orotic acid to pyrimidine nucleotides in the presence of ATP and ribose-5-phosphate, a condition under which there was good activity in other tissues such as the liver, spleen, and kidney. Addition of phosphoribosylpyrophosphate (PRPP) markedly enhanced orotic acid conversion though it still remained less for heart than for other tissues. These findings indicated that PRPP synthetase activity was low in the heart. Uridine kinase activity in the heart was similar to that in the liver. Uridine kinase appeared to be rate limiting in the "salvage" pathway. Aortic constriction produced an increase in uridine kinase activity at 24 hours with a peak at 2 to 6 days (50 to 60% stimulation) after operation, while uridylate kinase, uridine phosphorylase, and orotidine monophosphate pyrophosphorylase activities remained unchanged. The "salvage" pathway appears to play an important role in pyrimidine nucleotide synthesis in the heart, and uridine kinase may be regulatory in this pathway during cardiac hypertrophy.
Circulatory Transport of Iodoantipyrine and Water in the Isolated Dog Heart
Authors: YIPINTSOI TADA , BASSINGTHWAIGHTE JAMES B.
Published: June 2012

The exchanges of
125
I-labeled 4-iodoantipyrine (I-Ap),
14
C-labeled antipyrine (
14
C-Ap), and tritiated water (THO) were studied in isolated blood-perfused, beating, nonworking dog hearts. From a first set of experiments, analysis of externally monitored myocardial clearance curves of I-Ap after its injection into coronary artery blood showed its washout to be flow limited at flows ranging from 0.8 to 3.8 ml. g
-1
. min
-1
. Therefore, these curves can be used for estimating coronary blood flow. In a second set of experiments, coronary sinus dilution curves of simultaneously injected I-Ap and THO were found to be indistinguishable in shape at high coronary flows. At low flows (<1.8 ml. g
-1
. min
-1
), THO curves showed an earlier upslope and higher peak than antipyrine, indicating either a diffusional shunt for water or a larger volume of distribution for antipyrine.
14
C-Ap had a slightly faster washout than I-Ap. The differences are partially attributable either to differences in solubility of I-Ap,
14
C-Ap, and THO in erythrocytes or to differences in their volumes of distribution, and partially to diffusional shunting of water.
Wave Transmission in the Pulmonary Arterial System in Disease in Man
Authors: REUBEN STUART R.
Published: June 2012

Pulmonary capillary blood flow was measured by the nitrous oxide-body plethysmograph technique in 21 patients with valvular heart disease or pulmonary thromboembolism during routine diagnostic cardiac catheterization. The studies were performed with a high-frequency phonocardiogram recorded from the pulmonary area to indicate the pulmonary valve opening at the beginning of right ventricular ejection. The pulmonary artery to capillary flow conduction time was measured from the time of pulmonary valve opening to the foot of the pulmonary capillary flow pulse. The conduction time was greater than 160 msec when the pulmonary artery pressure was normal. The fall in the conduction time in disease indicated elevated pulmonary arterial pulse wave velocity and this correlated well with the level of pulmonary arterial pressure (correlation coefficient 0.92,
P
< 0.001). This suggests that there is a reduced pulmonary arterial distensibility in the chronic pulmonary hypertension of valvular heart disease and thromboembolic disorders.
Comparison of Medial Growth of Human Thoracic and Abdominal Aortas
Authors: WOLINSKY HARVEY
Published: June 2012

Recent morphologic studies of adult mammalian thoracic and abdominal aortic segments have shown that the adult human abdominal aorta deviates significantly from the usual pattern of medial lamellar architecture. In the present study medial growth of these two aortic segments from prenatal life to adulthood was compared in terms of medial architecture and calculated tangential tension levels. During prenatal life, these parameters were very similar in the two segments. However, the postnatal increase in the medial thickness of the thoracic segment was due mainly to the addition of lamellar units which increased in number from 35 to 56; only a minor contribution was made by increased thickness of each unit which changed from 0.012 to 0.017 mm. The converse was true for the abdominal segment; the number of lamellar units increased only from 25 to 28, but lamellar unit thickness increased strikingly from 0.012 to 0.026 mm. Calculated wall stress was similar in the two segments throughout growth, but tension per lamellar unit became disparate in the segments during the first decade of life, culminating in unusually elevated values in the adult human abdominal aortic media.
Contractile Properties of Cardiac Muscle in Hyperthyroidism
Authors: Taylor Roger R. , Burrows Peter
Published: June 2012

Right ventricular papillary muscles from hyperthyroid and normal cats were studied in vitro at 30°C, at contraction frequencies of 12, 30 and 60/min. At 12/min the contractility of hyperthyroid muscles was significantly greater than normal, as indicated by greater velocity of isotonic shortening, isometric tension development, and rate of tension development. Isotonically contracted muscle lengths were smaller and time to peak isometric tension less. At 60/min, velocity of shortening was still greater and time to peak tension less in hyperthyroid muscles, but isometric developed tension, rate of tension development, and isotonically contracted muscle lengths and shortening were not different. Increasing frequency from 12/min to 60/min resulted in immediate positive inotropic responses in both groups, but a smaller response in hyperthyroid than normal muscles. Over subsequent minutes, a slight decrease in contractility occurred in normal muscles but the decrease was significantly greater in hyperthyroid muscles. The difference in response to increasing frequency is attributed to more profound hypoxia in hyperthyroid muscles at high contraction frequencies. Predisposition of the muscle to hypoxia induced by hyperthyroidism then becomes an important determinant of the net effect of hyperthyroidism on myocardial contractility. The experimental situation is analogous to the coexistence, in vivo, of thyrotoxicosis and other conditions predisposing to coronary insufficiency, such as coronary artery disease or ventricular hypertrophy; that hyperthyroidism does not then augment contractile state in respect to tension development or muscle shortening helps explain the occurrence of thyrotoxic heart failure in response to the body's increased requirements for blood flow.
Attenuation of Postganglionic Sympathetic Nerve Activity by L-Dopa
Authors: WHITSETT THOMAS L. , HALUSHKA PERRY V. , GOLDBERG LEON I.
Published: June 2012

In anesthetized dogs and cats, intravenous L-dopa reduced the increase in mean blood pressure in response to bilateral carotid occlusion by 77.5% (
P
<0.01). In the presence of a dopa decarboxylase inhibitor (Ro 4·4602), this effect was absent. Transmission across the superior cervical sympathetic ganglion in the cat was unaltered by the administration of L-dopa. Carotid artery infusion in the dog of 20% of the effective intravenous dose of L-dopa or dopamine failed to inhibit the response to bilateral carotid occlusion. The pressor response to intravenous tyramine in the dog was potentiated (
P
<0.05) by L-dopa. In the dog, the increase in femoral vascular resistance to lumbar sympathetic nerve stimulation was attenuated (
P
<0.05) by L-dopa while the response to intra-arterial norepinephrine was unchanged. Thus, inhibition of postganglionic sympathetic nerve activity is a possible mechanism by which L-dopa impaired the carotid sinus reflex.
Propagation Velocities and Voltage Magnitudes in Local Segments of Dog Myocardium
Authors: SELVESTER R. H. , KIRK W. L. , PEARSON R. B.
Published: June 2012

Propagation velocities and differential voltages of the electromotive surface in the left ventricle were measured in dogs by multipoint bipolar intramyocardial electrodes. The average velocity of propagation in the inner 4 mm of the ventricular wall of dogs was 2.0 mm/msec, which is considerably greater than that in the middle (0.70 mm/msec) or the outer 4 mm (0.40 mm/msec). The average voltage was less in the inner levels of the ventricular wall than in the outer, but significantly different from zero. This fact indicates a definite but lesser contribution per unit volume than from the outer levels. The propagation of the electromotive surface through the ventricular wall was consistently from endocardium to epicardium with no significant areas propagated in the reverse direction. These data disagree with the hypothesis that certain levels in the wall of the heart and certain regions of the heart are electrocardiographically silent. In dogs, and to a greater degree in humans, small infarcts anywhere in the heart can be expected to produce significant and discernible changes in surface ECGs. The task remains to refine and validate criteria for the diagnosis of infarct in these areas. When viewed from within the myocardium, the waveforms observed in bipolar intramyocardial electrodes are inconsistent with the dipole layer hypothesis as a model of the electromotive surface of ventricular depolarization in the heart.
Redistribution of Cortical Blood Flow during Renal VasodNatation in Dogs
Authors: MCNAY JOHN L , ABE YOUICHI
Published: June 2012

We studied the distribution of cortical blood flow during renal vasodilation induced by four maneuvers; reduction of perfusion pressure, intraarterial infusion of acetylcholine, and diuresis induced by ethacrynic acid or mannitol. Dogs were anesthetized with pentobarbital and urinary losses replaced. Bloodflow of the denervated kidney was measured by an electromagnetic flowmeter,and distribution of renal cortical blood flow analyzed by the radioactive microsphere technique. Acetylcholine caused progressively greater proportional vasodilation from superficial to deep cortex. The resulting pattern of flow redistribution was nearly identical to that observed in response to reduced perfusion pressure (autoregulation). Since the same pattern of heterogeneous cortical response was elicited by two qualitatively different stimuli, we propose that it reflects differential responsiveness of individual cortex zones. Ethacrynic acid redistributed flow in a different pattern, augmenting the proportion to the middle, but not the juxtamedullary cortex. High urine flow was excluded as a nonspecific basis for this difference, since acetylcholine produced its usual pattern of redistribution during the ethacrynic acid-induced diuresis. Additionally, ethacrynic acid-induced flow redistribution was not secondary to high urine flow per se, since mannitol diuresis did not significantly alter distribution of flow.
Effect of Hematocrit and Inertial Losses on Pressure-Flow Relations in the Isolated Hindpaw of the Dog
Authors: BENIS ANTHONY M. , USAMI SHUNICHI , CHIEN SHU
Published: June 2012

The effect of hematocrit on pressure-flow relations was studied in the perfused isolated hindpaw of the dog. Blood and suspensions of erythrocytes (RBC) in albumin-Ringer solution, hematocrit range of 0 to 80%, were used as perfusates. Flow resistance was found to increase markedly with hematocrit. No significant difference was found between pressure-flow data obtained with blood and RBC in albumin-Ringer solution when comparisons were made at comparable hematocrits, indicating negligible effect of RBC aggregation when blood was the perfusion fluid. Computations of flow resistance relative to cellfree perfusate indicated that non-Newtonian viscosity, as well as vessel distensibility, contributed to the nonlinearity of pressure-flow curves. Perfusion of paws with two Newtonian fluids of different viscosities allowed computation of inertial pressure losses under conditions of steady flow. At physiological perfusion pressures, inertial losses accounted for about 40% of the total pressure drop for cell-free albumin-Ringer solution, and dropped to about 5% for a hematocrit of 50. The results suggest that inertial losses, rather than a Fåhraeus-Lindqvist effect, play an important role in pressure-flow relations in the hindpaw.
Renin Release after Hemorrhage and after Suprarenal Aortic Constriction in Dogs without Sodium Delivery to the Macula Densa
Authors: BLAINE EDWARD H. , DAVIS JAMES O. , WITTY ROBERT T.
Published: June 2012

To study the possible factors that control renin secretion by the kidney, a model has been developed to prevent glomerular filtration in the dog. Ureteral ligation was combined with a 2-hour period of total renal ischemia to induce tubular degeneration and cessation of glomerular filtration. After the surgical procedures, the dogs were maintained for 4 days by peritoneal dialysis. The absence of lissamine green dye in the renal tubules after an intra-aortic injection provided evidence that filtration had ceased. Plasma renin activity was significantly increased in six conscious dogs at 30, 60, and 90 minutes after hemorrhage of 20 ml/kg body weight. In another group of five conscious animals, suprarenal aortic constriction produced increases in plasma renin activity at 30, 60, and 90 minutes that were 3 to 4 times the control values before aortic constriction. Plasma renin substrate concentration did not change significantly after hemorrhage or after aortic constriction. In a third group of five dogs, only the left kidney was subjected to ureteral ligation and renal ischemia. These dogs were anesthetized and renal blood flow was measured with an electromagnetic flowmeter. After hemorrhage (20 ml/kg), renin secretion increased significantly above control levels at 30, 45, and 60 minutes. It is concluded that sodium delivery to the macula densa is not essential for renin secretion.
Interactions of Lanatoside C and Potassium on Atrioventricular Conduction in Rabbits
Authors: WATANABE YOSHIO , DREIFUS LEONARD S.
Published: June 2012

Intra-atrial, intranodal and His-Purkinje conduction times were determined in perfused rabbit hearts. In one series, the concentration of lanatoside C was increased by 0.4 mg/liter every 30 minutes, in the presence of normal (4.5) or high (7.5 mM) K
+
in the perfusion fluid. At high (K
+
) the glycoside produced a greater increase in intra-atrial and His-Purkinje conduction times but caused a smaller increase of intranodal conduction time than at normal (K
+
). Second-degree A-V block always occurred intranodally, but the incidence was lower with high (K
+
). In another series, (K
+
) was increased by 3 mM every 30 minutes, in the absence or presence (0.4, 0.8 or 1.2 mg/liter) of lanatoside C. No difference was seen between hearts treated with lanatoside C and those untreated at the level of (K
+
) producing failure of conduction. At all levels of glycoside, conduction delay caused by high (K
+
) was greatest within the atria, less in the His-Purkinje system and insignificant within the A-V node. Intra-atrial and His Purkinje block were observed but never an intranodal block. It is concluded that (1) cardiac glycoside and high (K
+
) primarily affect different regions of the A-V conducting system, and (2) aggravation of glycoside-induced A-V block by high (K
+
) may result from additional intra-atrial and His-Purkinje block rather than from further depression of intranodal conduction. Electrophysiological mechanisms underlying these interactions were also discussed.
Effects of Altered Smooth Muscle Tone on Aortic Diameter and Aortic Baroreceptor Activity in Anesthetized Rabbits
Authors: AARS HAROLD
Published: June 2012

The possible role of aortic smooth muscle in the regulation of aortic diameter and activity in the aortic baroreceptors was investigated in anesthetized rabbits. Aortic diameter was measured with ultrasonic technique within the intact thorax, and activity recorded in the whole left aortic nerve was quantified by rectification and integration. Blood pressure was changed by bleeding and reinfusion. At comparable blood pressures, norepinephrine (1 to 6 µ/kg.min) produced a 1% to 10% constriction of the aorta, without affecting the pressure-strain elastic modulus (E
P
). After phenoxybenzamine, maximum increases in diameter and E
p
were 17% and 280%, respectively. When related to diastolic diameter, however, E
p
was mostly increased by norepinephrine and reduced by phenoxybenzamine. Baroreceptor activity at comparable pressures remained normal during infusion of norepinephrine, but increased after phenoxybenzamine. However, when compared at equal diastolic diameters, the sensitivity of the receptors to aortic distention was found to be increased by norepinephrine and unaltered by phenoxybenzamine. Increased smooth muscle tone therefore served to maintain a normal relationship between blood pressure and baroreceptor activity, in spite of the simultaneous reduction in aortic diameter. Reduction of smooth muscle tone markedly increased activity in the aortic baroreceptors, due to dilatation of the receptor area.
Disorder in Excitation-Contraction Coupling of Cardiac Muscle from Cats with Experimentally Produced Right Ventricular Hypertrophy
Authors: KAUFMANN RAIMUND L. , HOMBURGER HERMANN , WIRTH HEIKE
Published: June 2012

The contractile and electrical activity of papillary muscles from hypertrophied right ventricles of cats with artificial stenosis of the pulmonary artery was investigated. Contractility was considerably decreased along the entire force-velocity relationship, whereas no measurable alterations could be detected in the electrical activities as recorded by intracellular microelectrodes. By supramaximal Ca
2+
activation, the contractility of both the hypertrophied and the normal control preparations was increased to about the same final value. These findings are consistent with the concept that a disorder in the mechanism of excitation-contraction coupling underlies the depressed contractile state of hypertrophied cardiac muscle. In addition, it could be shown that the increase in volume of each cellular unit is clearly related to the decrease in contractility. This can tentatively be explained by the following assumptions. If the amount of Ca
2+
entering the cell per unit area is not changed in hypertrophy, then in a cell of increased diameter, the amount of Ca
2+
distributed per unit cell volume will be diminished. Since the excitation-contraction coupling of the heart is very sensitive to Ca
2+
, this Ca
2+
deficit should be reflected in a depression of contractility.
Fluid Movement in Occluded Single Capillaries of Rabbit Omentum
Authors: LEE J. S. , SMAJE L. H. , ZWEIFACH B. W.
Published: June 2012

The sequence of transcapillary fluid movement during microocclusion of single capillaries was investigated on the theoretical basis of the Starling hypothesis. For most capillaries studied, the theory agrees reasonably well with the experiments with red cells used as the tags for fluid movement. By analyzing the sequence of the movement of the red cell in one single occlusion, it was possible to calculate the filtration coefficient and the effective pressure. The effective pressure ranged from 28 to 38 cm H
2
O. Since the arterial pressure in the capillary is about 20 to 30 cm H
2
O, the calculations suggest that about 10 cm H
2
O of the effective pressure is contributed by tissue factors, i.e., a negative hydrostatic pressure or a substantial colloidal osmotic pressure in the tissue space or both. The calculated filtration coefficient for the capillaries ranged from 0.01 to 0.07 µ
3
/(sec µ
2
cm H
2
O).
Voltage Dependence and Time Dependence of Contraction in Sheep Cardiac Purkinje Fibers
Authors: GIBBONS W. R. , FOZZARD H. A.
Published: June 2012

Contractile behavior of the sheep cardiac Purkinje fiber was examined under voltage-clamp conditions in Tyrode's solution. For square depolarizing clamps to a given voltage, peak twitch tension depended on clamp duration if the duration was less than 80 to 90 msec, but measurable contractions could be obtained following 2-msec square clamps. Time to peak tension at 37°C remained constant as clamp duration was shortened. Twitch tension also depended on clamp voltage. The voltage at which tension was first seen, the position of the voltage-tension curve on the voltage axis, and the shape of the curve all were altered by a shift in the steady membrane voltage. After a contraction, recovery of the contractile system was voltage-dependent; recovery was complete in approximately 2 seconds if the muscle was repolarized to potentials more negative than -75 mv, and no recovery was found at potentials more positive than -20 mv. Step changes of voltage to potentials just below tension threshold rapidly inactivated the contractile mechanism without development of tension. These results show a voltage dependence and time dependence of the contractile mechanism which may be of considerable importance to understanding excitation-contraction coupling.
Comparison of Directly Measured Left Ventricular Wall Stress and Stress Calculated from Geometric Reference Figures
Authors: BURNS JOHN W. , COVELL JAMES W. , MYERS RICHARD , ROSS JOHN
Published: June 2012

Mean left ventricular wall force was determined with a calibrated transmural auxotonic strain gauge in the left ventricle of six anesthetized, open-chest dogs with intact circulation. The gauge was oriented in the plane of the minor left ventricular equator, midway between the papillary muscles. Left ventricular internal volume was derived from the passive pressure-volume curve of the arrested heart and calculated mean wall stress was derived both from spherical and ellipsoidal reference figures for the left ventricle and compared with measured forces. Control left ventricular end-diastolic pressure averaged 3.0 ± 0.6 mm Hg (SE). At this level of end-diastolic pressure, measured peak wall stress averaged 97.2±14.4 g/cm
2
, whereas calculated peak wall stress averaged 79.3±9.9 and 118.6±12.9 g/cm
2
, for the spherical and ellipsoidal models, respectively. Measured end-diastolic wall force values averaged 9.4±4.5 and 29.2±8.1 g/cm
2
at an end-diastolic pressure of 3.0 and 12.3 mm Hg, respectively. In all cases, stress values calculated from spherical reference figures for the left ventricle were significantly lower than those measured directly. In four other experiments, using right heart bypass, the ventricular septum was exposed and active wall force was determined at two or more sites on the left ventricular minor equator. Wall stress at these sites differed by an average of 15.3%, indicating that stresses around the minor equator are relatively uniform. These studies lend validity to the application of geometric models in the calculation of mean wall stress and favor the application of an ellipsoid for the geometric reference figure.
Biphasic Constrictor Response of the Rabbit Ear Artery
Authors: BEVAN JOHN A. , WATERSON JOHN G.
Published: June 2012

The perfused rabbit ear artery shows a biphasic contractile response to intraluminal norepinephrine and sympathetic nerve stimulation. The peak of the first phase occurs after approximately 10 seconds of exposure to NE, and the second, after 1½ to 2 minutes. The magnitudes of the two responses are similar. The time course of the second phase of contraction is similar to the rate of saturation of the vessel's extracellular space as measured by tissue uptake of tritiated norepinephrine. On the other hand, the first phase of contraction occurs when norepinephrine has penetrated only partly into the media. It is proposed that the two phases of contraction are due to different mechanisms of excitation and that the first phase is associated with excitation of the surface layer of smooth muscle cells with subsequent myogenic propagation of excitation through the thickness of the vessel wall. The second may be related to the local concentration of norepinephrine in the extracellular space of the vessel.