bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of the Cardiovascular Effects of
L
-Dopa in Anesthetized Dogs by Inhibitors of Enzymes Involved in Catecholamine Metabolism
Authors: ROBSON RONALD D.
Published: June 2012

The influence of various enzyme inhibitors on the cardiovascular effects of
L
-dopa (methylester) has been studied to determine the sites of action of the drug or a responsible metabolite.
L
-Dopa, 10 mg/kg, iv, had minor early effects on heart rate and blood pressure in normal dogs, but in animals with inhibition of monoamine oxidase (MAO), it caused tachycardia and severe hypotension of gradual onset. When MAO was inhibited, earlier doses of a dopamine β-oxidase inhibitor (FLA 63) did not significantly modify the effects of
L
-dopa; prior administration of a decarboxylase inhibitor, NSD 1055 or Ro 4-4602, prevented all but the initial effects; selective extracerebral decarboxylase inhibition with MK 486 (
L
-α-hydrazino-α-methyldopa) prevented the tachycardia but not the hypotension.
DL
-
threo
-Dihydroxyphenylserine caused an initial rise in blood pressure in dogs with MAO inhibition, had less pressor activity when peripheral decarboxylase was also inhibited, and in both cases did not cause the hypotension characteristic of
L
-dopa.
L
-Dopa enhanced pressor responses and especially associated bradycardic responses to norepinephrine in dogs with MAO inhibition. This action was prevented by all decarboxylase inhibitors but not FLA 63. Responses to angiotensin were similarly augmented. Thus, MAO inhibition enabled
L
-dopa to induce severe hypotension, which appeared to rely on a central conversion to dopamine; the other effects were probably mediated by peripherally formed dopamine.
Velocity of Shortening of Unloaded Heart Muscle and the Length-Tension Relation
Authors: Brutsaert Dirk L. , Claes Victor A. , Sonnenblick Edmund H.
Published: June 2012

A new technique permits removal of the resting force from the muscle during the course of shortening and study of the maximum velocity of shortening with almost zero load at physiological initial muscle lengths. This unloading has been performed as a sudden unloading to zero total load (zero load clamping), or according to the resting length-tension relations, or according to an arbitrary unloading intermediate between both former modes of unloading. Using these various modes of unloading to zero load during shortening, it has been demonstrated that the maximum velocity of shortening V
max
remains constant between maximum length (l
max
) and a length 12.5% shorter than l
max
. This unique force (zero load)-velocity (V
max
)-length (up to 12.5% below l
max
) relation is independent of die initial muscle length over this range of lengths, independent of the time after the stimulus over the largest portion of the shortening phase, and independent of the sequence of length change and mode of unloading through which it arrived at zero load within this range of lengths.
Intrarenal Hemodynamics in Glycerol-Induced Myohemoglobinuric Acute Renal Failure in the Rat
Authors: Ayer G. , Grandchamp A. , Wyler T. , Truniger B.
Published: June 2012

A modified
138
Xe washout technique was used to study changes in intrarenal hemodynamics during glycerol-induced acute renal failure in the rat. Within 10 minutes after glycerol injection, the flow fraction supplied to component 1 of the washout curve ("cortex A") decreases, reaching minimum values 24 hours afer glycerol (31% of control conditions). Seven days thereafter five of the rats, still uremic, showed cortical flow fractions less than 50% of control values. Nine others had recovered. Twenty-four hours after glycerol, renal blood flow was 27% and increased to 86% of control conditions in the recovered rats 7 days after glycerol.
85
Kr autoradiographs and silicone rubber casts of the renal vasculature demonstrated a severe cortical hypoperfusion at the height of oliguria that gradually disappeared in parallel with the functional recovery of the kidney. These observations, in good agreement with micropuncture data, suggest that oliguria and renal insufficiency in this experimental model are the result of a primary decrease in glomerular filtration rate due to an increased preglomerular resistance.
Excitation Sequences of the Atrial Septum and the AV Node in Isolated Hearts of the Dog and Rabbit
Authors: Spach Madison S. , Lieberman Melvyn , Scott John G. , Barr Roger C. , Johnson E. A. , Kootsey J. Mailen
Published: June 2012

The spread of excitation wave fronts over the atrial septum of puppies, adult dogs, and rabbits was studied in vitro by extracellular measurements with a 50µ-diameter electrode. Wave front spread through the AV node of puppies and rabbits was determined, and the functional location of the junctional region between atrial muscle and the AV node was evaluated during antegrade atrial and retrograde His bundle pacing. For dogs of all ages, the pattern of spread over the septum was greatly affected by the location of the pacemaker site simulating a high or low sinus node position. For all sinus pacing positions, wave fronts spread over the crista terminalis to form a posterior input to the AV node, while the anterior septal wave fronts formed another input. No functional evidence could be found for narrow, specialized inteniodal tracts of fixed location. Rather, wave fronts spread over broad areas creating patterns of simultaneous, multiple wave fronts which corresponded in extent to the gross anatomical landmarks of the septum. Only in this fashion were the findings consistent with the idea of three general routes of intemodal conduction in the dog and two general routes in the rabbit. The position of the functional boundary between atrium and AV node could be accounted for only by overlapping of the two tissues of this region; the boundary shifted between antegrade and retrograde conduction. Antegrade wave fronts within the AV node accelerated from the superior border of the node to the exit at the His bundle; retrograde excitation wave fronts from the His bundle decelerated through the AV node. The amplitude of the atrial wave forms as well as the status of die inputs from the posterior and anterior regions of the atrial septum were found to be important factors in AV node conduction.
A Theory for the Quantification of Transcapillary Exchange in the Presence of Shunt Flow
Authors: Chien Shu
Published: June 2012

A theory is proposed to treat the transcapillary exchange of diffusion-limited substances in the presence of shunt circulation. With the simultaneous use of a nondiffusible indicator to correct for the distribution of intravascular transit and two diffusible indicators with different diffusion coefficients, the triple-indicator method can be used to assess the behavior of the diffusion-limited indicators in the exchange circuit. Application of this theory to data on perfused skeletal muscle allows the calculation of capillary blood flow, indicator extraction, and capillary diffusion capacity in the exchange circuit. The initial extraction of Na and Rb in the exchange circuit before back diffusion occurs shows a biphasic relation to flow rate. As the overall blood flow is increased to 10-15 ml min
-1
100 g
-1
, decrease of indicator extraction is associated with an increase of capillary blood flow and a decrease of diffusion capacity in the exchange circuit. The increase of indicator extraction at higher flows is attributable to an increase of diffusion capacity in the exchange circuit. The biphasic changes in capillary diffusion capacity with blood flow has been attributed to the influences of metabolic factors and distending pressure.
Transcapillary Exchange En the Working Left Ventricle of the Dog
Authors: Ziegler Wilfred H. , Goresky Carl A.
Published: June 2012

Sets of multiple indicator dilution curves were obtained from working hearts of dogs with closed chests. A multiple capillary adaptation of a permeability-limited capillary model which assumes that exchanging material returns to the capillary at its site of escape was tested on these curves. The model has only two lumped parameters: a permeability surface product per accessible extravascular volume, and flow per extravascular volume. Labeled red cells and albumin were used as vascular indicators. The model provided close fits for the curves of diffusion-limited indicators (sucrose, inulin, sulfate, sodium, chloride, and urea), and unique values were obtained for both parameters. The accessible extravascular volume obtained by this method was independent of flow whereas the permeability surface product per accessible extravascular volume (a relatively low value for these indicators) increased with flow. In this first group the outflow patterns varied with the size of the test molecule. For a second group of substances (water, ethanol and antipyrine), the outflow patterns were virtually identical and independent of molecular size (i.e., flow-limited). The modeling did not provide an appropriate description of these curves, and analysis indicated that the exchanging indicator may intercommunicate between capillaries in a random fashion, i.e., that the indicator may not return to each capillary at the same site at which it escaped.
Histamine and interstitial Pulmonary Edema in the Dog
Authors: Pietra G. G. , Szidon J. P. , Leventhal M. M. , Fishman A. P.
Published: June 2012

Histamine, administered to dogs by various routes, produced peribronchial interstitial edema. Using colloidal carbon as an electron-dense tracer, it was shown that bronchial venules had become leaky at the same time that the minute blood vessels of the pulmonary circulation remained unaffected by the histamine. The effect of histamine was rapid and brief in duration: wide interendothelial gaps appeared in the walls of bronchial venules through which blood and tracer escaped into the interstitium. This action of histamine seemed to be related to the presence in the bronchial venular endothelium of abundant cytoplasmic fibrils that presumably have contractile capacity. Water content of the lungs was consistent with morphologic evidence that histamine promoted the accumulation of fluid in the lungs. The same pattern of response was observed after bradykinin or compound 48/80, a mast cell degranulator. In contrast to these three agents, serotonin did not affect bronchial venular permeability to colloidal carbon. Consideration of these observations in the light of the large extent of the bronchial venular plexus, raises the possibility that the bronchial venular system may play an important reabsorptive role under normal circumstances and that it may also be involved in the genesis of certain types of interstitial pulmonary edema.
Absorption and Transport of Digitoxin in the Dog
Authors: Oliver G. Charles , Cooksey John , Witte Charles , Witte Marlys
Published: June 2012

Absorption of digitoxin as its studied in 14 fasted anesthetized dogs after administration of 50 µc of
3
H-digitoxin mixed with 1 mg of unlabeled digitoxin into either the duodenum or stomach. Radioactivity was measured in portal, hepatic, and central venous plasma, thoracic duct lymph, common duct bile and urine for 5 hours after digitoxin was given. Three dogs were given a single intravenous dose of 25 µc of
3
H-digitoxin mixed with 0.5 mg of unlabeled digitoxin, and radioactivity was measured in central venous plasma and thoracic duct lymph. Digitoxin was absorbed rapidly and uniformly from the duodenum and entered the body entirely by way of the portal vein, reaching peak concentrations in portal blood in 1 to 15 minutes. Digitoxin was absorbed erratically from the stomach. No metabolites of digitoxin were observed in selected portal venous samples subjected to thin-layer chromatography. Absorption of orally administered digitoxin into the systemic bloodstream is retarded because of highly efficient hepatic extraction of the drug and subsequent transfer into bile.
A Plasma Humoral Factor of Extrarenal Origin Causing Release of Reninlike Activity in Hypotensive Dogs
Authors: De Vito E. , Wilson C. , Shipley R. E. , Miller R. P. , Martz B. L.
Published: June 2012

Plasma reninlike activity significantly increased in anesthetized and unanesthetized normal dogs after intravenous injection of plasma from nephrectomized and normal dogs that have been made hypotensive by controlled hemorrhage. The injection of plasma from nephrectomized, nonhypotensive dogs or the in vitro incubation of normal plasma with calculated proportions of plasma from nephrectomized, hypotensive dogs did not produce any changes in plasma renin concentration or angiotensin production. These results suggest the presence of renin-releasing factor of extrarenal origin which is produced and circulated in the plasma of dogs subjected to periods of hypotension by means of controlled hemorrhage. A direct or indirect action of the renin-releasing factor on the kidney in association with or in conjunction with one or more of the other mechanisms that have been hypothesized to explain the control of renin release is not as yet known. An alternative hypothesis should also be considered. It is possible that the renin-releasing factor may he an activator of the conversion of prerenin to renin and of its release from the kidney into the bloodstream. The source and chemical nature of the renin-releasing factor are not as yet known.
Role of Cardiac Output and the Autonomic Nervous System in the Antinatriuretic Response to Acute Constriction of the Thoracic Superior Vena Cava
Authors: Schrier Robert W. , Humphreys Michael H. , Ufferman Robert C. , Harbottle Judith A.
Published: June 2012

Studies were performed on anesthetized saline-loaded dogs to delineate the afferent and efferent mechanisms involved in the antinatriuretic response to acute constriction of the thoracic vena cava. The kidneys of the animals were denervated prior to study, and renal perfusion pressure was controlled throughout the experiment. To differentiate between the potential afferent stimuli, increased hepatic venous pressure and decreased cardiac output, the thoracic superior vena cava (TSVC) was acutely constricted to lower cardiac output without increasing hepatic venous pressure. Acute TSVC constriction caused a decrease in sodium excretion qualitatively similar to that resulting from an acute constriction of the thoracic inferior vena cava (TIVC) which generated a comparable decrease in cardiac output. This finding suggests that the afferent limb of the antinatriuretic response to acute constriction of the thoracic vena cava, either TSVC or TIVC, involves diminution in cardiac output, or some consequence thereof, rather than increased hepatic venous pressure. Additional experiments were then performed in animals with pharmacologically-induced autonomic blockade. Autonomic blockade with hexamethonium or phenoxybenzamine abolished the antinatriuretic response to constriction of either the TIVC or TSVC. This finding suggests that the efferent limb of the antinatriuretic response to thoracic vena cava constriction involves sympathetic efferent pathways, either by an intrarenal effect of circulatory catecholamines or by controlling the release of an extrarenal factor influencing sodium reabsorption.
Collision of Excitation Waves in the Dog Purkinje System
Authors: Spach Madison S. , Barr Roger C. , Serwer Gerald S. , Johnson Edward A. , Kootsey J. Mailen
Published: June 2012

The ventricular conduction system of the dog was explored with a 50µ extracellular electrode in an in vitro preparation with an intact right and left ventricular bundle branch system connected at the bundle of His. Two pacing electrodes at opposite ends of a functionally single strand produced collision of excitation waves with a distinctive extracellular wave form (uniphasic and positive instead of biphasic). The only changes in the intracellular potential associated with collision were a decrease in the time constant of the foot and an increase in the maximum rate of rise of the action potential, changes not uniquely produced hy collisions. During pacing at one point, collisions were detected at many places throughout the conduction system. The peripheral Purkinje system consisted of fine strands forming a network of interconnecting swirls, each covering 2-25 mm
2
Collisions were found in all swirls and their sites often shifted with a shift in the pacemaker site. Collisions also shifted in location between basic and premature beats which originated from a single point on the bundle of His.
Circulatory Reflex from Vagal Afferents in Response to Hemorrhage in the Dog
Authors: Pelletier Conrad L. , Edis Anthony J. , Shepherd John T.
Published: June 2012

Experiments were conducted in 35 anesthetized dogs to study the circulatory adjustments, after hemorrhage, mediated by vagal afferents from the cardiopulmonary area. With the aortic baroreceptors and chemoreceptors denervated and carotid baroreceptor and chemoreceptor activity held constant, hemorrhage of 10% of blood volume caused an increase in heart rate and constriction of the resistance vessels of the hindlimb, renal, and mesenteric beds and of the splanchnic venous bed. Vagotomy abolished these responses to hemorrhage, resulting in a greater decrease in blood pressure. With the carotid baroreflex operative, the constriction of the renal and mesenteric resistance vessels and of the splanchnic venous bed were similar to that obtained with only the vagi operative, but the constriction of the hindlimb resistance vessels was much greater and aortic pressure was better maintained. It is concluded that receptors in the cardiopulmonary area, subserved by vagal afferents, exert their main influence on the splanchnic resistance and capacitance vessels and on the renal circulation, whereas the carotid baroreceptors predominantly affect the muscle vessels.
Effect of an Early Atrial Premature Beat on Activity of the Sinoatrial Node and Atrial Rhythm in the Rabbit
Authors: Bonke Flex I. M. , Bouman Lennart N. , Schopman Francien J. G.
Published: June 2012

In the spontaneously beating isolated right atrium of the rabbit, premature beats were elicited by electrical stimulation. When the premature beat was elicited early in the atrial cycle, the postextrasystolic pause had a short duration and the sum of the pre- and postextrasystolic pause was about the same as the duration of a normal spontaneous interval. We have tried to demonstrate, using simultaneous multiple microelectrode impalements of SA node fibers, that by such an early atrial premature beat the atrium could be activated by a reentrant mechanism. The results of our experiments led us to the conclusion that the impulse of the premature beat, elicited early in the atrial cycle, discharges the SA node only fractionally and that the fibers in the neighborhood of the activated area are influenced electrotonically. This causes a change of both the site and the moment of the spontaneous impulse formation. The SA node discharges spontaneously after such an early premature beat. Reentry activation is likely to occur when a series of atrial premature beats is observed. A supraventricular tachvcardia might be caused by repeated atrial discharges following a stimulus very shortly after the atrial refractory period.
The Pulmonary Vein Wedge Pressure in Man
Authors: CONNOLLY DANIEL C. , WOOD EARL H.
Published: June 2012

In 12 patients with atrial septal defect or anomalous pulmonary venous connection, pulmonary vein wedge mean pressure uniformly exceeded mean pressure in the left atrium or pulmonary vein and with one exception was less than mean pressure in the pulmonary artery. There was a positive correlation between pulmonary arteriolar resistance and the difference in pressure between pulmonary artery and pulmonary vein wedge position. The oxygen saturation of blood, withdrawn from the pulmonary vein wedge position, uniformly exceeded that of left atrial and usually also that of pulmonary vein blood.
Effect of Diet on Experimental Hypertension and on the Development of Polyarteritis Nodosa in Rats
Authors: KEMPNER WALTER , PESCHEL ERNST , BLACK-SCHAFFER BERNARD
Published: June 2012

Rats with experimental renal hypertension were fed various diets differing in sodium and protein content. Marked prolongation of life was achieved by rice diet. Polyarteritis nodosa developed, as a result of the experimental procedures, in 23.5 per cent of the animals. Its incidence was closely correlated to sodium ingestion: 4 per cent in rats on low sodium intake, 36 per cent in rats on normal or slightly higher sodium intake. Protein intake showed no effect on incidence of polyarteritis but distinct effect on survival time. Except for one rat where a sarcoma destroyed almost all kidney tissue, no animal on rice diet developed polyarteritis nodosa.
An Attempt to Demonstrate Arterial Pressure-Volume Relationships in the Intact Dog by an Ultra-Rapid Bleeding Technic
Authors: OPDYKE DAVID F. , ZANETTI MARY E. , THOMAS GORDOX B.
Published: June 2012

The response of arterial pressure to very rapid central venous bleeding has been utilized in an attempt to establish an arterial pressure-volume relation in the intact dog. When dogs were bled for a brief period at rates between 200 and 500 cc. per minute the arterial pressure declined as a rectilinear function of the bleeding volume. The compensatory mechanisms of cardiac acceleration and vasoconstriction do not influence this relationship. Abolition of the vasomotor pathways does, however, increase the slope of the blood pressure decline curve. This is explained on the basis of a decrease in the initial volume of the arterial reservoir.
The Problem of Adjusting the Wilson Central Terminal to a Zero of Potential in the Living Human Subject
Authors: BAYLEY ROBERT H. , SCHMIDT ARTHUR E.
Published: June 2012

Evaluation of the potential of the Wilson terminal in 33 normal young adults indicates that its potential is zero about once in every twelve. Weighting of the terminal brought its potential to zero in ⅔ of the subjects and left a very small residual (technical) error in the remainder. The vertical component of the cardiac vector is primarily responsible for the error on the Wilson terminal. A weighted terminal in which the arm resistances are 2.6 times the left leg resistance has a zero potential in 50 percent of a small group of subjects. The residual error on the weighted terminal is at most one-half of that on the Wilson terminal. The eccentric origin of the cardiac vector varies only with respiration. Ordinarily, the zero-potential plane of the antero-posterior component of the cardiac vector passes simultaneously through or just dorsal to the limb electrodes and contributes little to the negative error on the Wilson terminal.
The Influence of
in vitro
Phosphatide upon the Disappearance of Free Cholesterol in Heparinized and Unheparinized Serum Upon Incubation
Authors: WAGNER ARNOLD
Published: June 2012

The disappearance of free cholesterol in incubated serum is inhibited in some lightly heparinized subjects. This inhibition is accentuated when an emulsion of soy bean phosphatides is added to the serum prior to incubation. The combined effect of
in vivo
heparin and
in vitro
phosphatide is the reverse of that produced by added phosphatide alone in unheparinized serum. In a limited number of experiments, the results with crystalline lecithin resembled those produced by soy bean phosphatides, but were more pronounced.
Extraction and Quantitative Characteristics of Actomyosin in Canine Heart Muscle
Authors: BENSON ELLIS S. , HALLAWAY BEN E. , FREIER ESTHER FAY
Published: June 2012

The conditions for quantitative extraction of actomyosin from dog heart ventricular muscle were studied. By use of appropriate techniques and conditions, yields of actomyosin comparable to those found by others for a variety of muscles were obtained. The method used could be standardized to give reproducible values with both fresh and frozen muscle. Actomyosin so obtained retained its characteristic properties as evidenced by its viscosity response to ATP and its enzymatic activity.
Effect of the Finite Boundary on Potential Distributions in Volume Conductors
Authors: NELSON C. V.
Published: June 2012

A fieldplotting tank which has a negligible boundary error is described. A comparison between measurements made in this tank and a conventional tank shows graphically the effect of a finite boundary. It is shown that the field of two halfshells is identical to a source-sink field at remote points. The method of electrical images for solving boundary-value problems is presented.
Determination of Total Tissue Sodium Concentrations by Use of Radiosodium
Authors: GREEN D. M. , REYNOLDS T. B. , GIRERD R. J.
Published: June 2012

A method has been developed for the estimate of total tissue sodium by direct measurement of radiosodium concentrations in undigested samples. Accuracy is comparable to that of flame photometric estimates on tissue digests; time and cost, about one-quarter as great. The method appears particularly useful for experimental designs requiring multiple tissue sodium measurements.
Effect of Altitude and Cobalt Polycythemia, Hypoxia, and Cortisone on Susceptibility of Rats to Endocarditis
Authors: HIGHMAN BENJAMIN , ALTLAND PAUL D.
Published: June 2012

Rats with polycythemia induced by exposures to simulated high altitudes developed a significantly higher incidence of endocarditis following intravenous bacterial injections than rats with cobalt polycythemia or ground level controls. No increase occurred in altitude rats when polycythemia was prevented by repeated bleedings. These findings suggest that both polycythemia and hypoxia are necessary to explain increased susceptibility of altitude rats. Cortisone increased susceptibility of ground level rats injected with
Streptococcus faecalis
. Unlike altitude exposures, however, cortisone did not render rats susceptible to endocarditis due to
Hemophilus parainfluenza.
Influence of Adenosine Triphosphate, Adenosine Monophosphate and Heparin in Experimental Arteriopathy
Authors: DAVIS OSCAR F. , OESTER Y. T. , FRIEDMAN BERNARD
Published: June 2012

The effects, in rabbits, of heparin, AMP, and ATP against both experimental cholesterol-induced atherosclerosis and epinephrine-thyroxine medial arteriosclerosis, were studied. Heparin and AMP, in general, were ineffective. Marked, statistically significant inhibition of both experimental atherosclerosis and experimental medial arteriopathy was achieved with ATP.
A Procedure for the Quantitative Determination of Protein of the Rat Heart
Authors: SOBEL HARRY , MYERS SARA M. , MARMORSTON JESSIE
Published: June 2012

A procedure has been developed for the quantitative determination of the extractable proteins of the rat heart. Utilizing extraction with a sucrose-versene solution and employing differential centrifugation, followed by extraction with a phosphate-pyrophosphate buffer, low-ionic-strength extractives, a mitochondrial fraction, and high-ionic-strength extractives have been obtained. Electrophoretic analysis has shown five subfractions to be present in the low-ionic-strength extractives and three sub-fractions in the high-ionic-strength extractives.
The Effect of Pitressin on Sodium Tolerance in Experimental Hypertension
Authors: FRIEDMAN SYDNEY M. , HARDWICK DAVID F. , HINKE J. A. M.
Published: June 2012

Rats subjected to diverse hypertension-inducing procedures develop an abnormal sodium tolerance characterized by an accelerated rate of excretion of an administered load. Pitressin reverses this abnormality in sodium tolerance during the period corresponding to the delayed depressor phase of the response to the extract.
Further Studies with Antifoaming Agents in Experimental Pulmonary Edema
Authors: LUISADA ALDO A. , CARDI LUIGI
Published: June 2012

The effect of several antifoaming agents by inhalation in preventing paroxysmal pulmonary edema was tested in a series of rabbits. Three single agents (silicone aerosol, freon, and ethyl alcohol vapor) proved beneficial; their combination did not enhance the beneficial effect. A new agent (silicone aerosol) and a new combination (10 per cent ether in alcohol by aerosol) are now ready for clinical trial.
Nature of the Blood Coagulation Mechanisms in SPCA Plasma
Authors: SEEGERS WALTER H. , ALKJAERSIG NORMA
Published: June 2012

Derivatives of purified prothrombin and substances required for the formation of a derivative have been studied in connection with SPCA deficient plasma. The deficiency can be corrected in vitro with prothrombin derivatives. It is concluded that the SPCA patient cannot convert prothrombin to autoprothrombin and thrombin in the same way as a normal individual, and that the precursor of SPCA is prothrombin.
The Mechanism of Limb Segment Reactive Hyperemia in Man
Authors: WOOD J. EDWIN , LITTER JULIUS , WILKINS ROBERT W.
Published: June 2012

The roles of vasodilator metabolites and/or reduced local intra-arteriolar pressure in producing the reactive hyperemia which follows the sudden release of arterial occlusion were studied. It was found that slight increases of metabolic activity during the period of occlusion increased the reactive hyperemia considerably. Maintenance of intra-arteriolar pressure during arterial occlusion depressed the resultant reactive hyperemia. It was concluded that both factors contribute to the reactive hyperemia. The blood flow "debt" incurred during arterial occlusion was almost invariably "overpaid" during the reactive hyperemia period.
Capillary Permeability to Macromolecules
Authors: WASSERMAN KARLMAN , LOEB LEOPOLD , MAYERSON H. S. , Mackenzie Allen H. , Cummins Arthur S.
Published: June 2012

Small infusions of dextran fractions having average molecular weights ranging from 10,600 to 412,000 yield plasma to lymph concentration ratios which are directly proportional to molecular weight. The concentration gradient for a specific molecular weight, however, decreases as the volume of infusion is increased. This volume effect, explained in terms of stretching of capillary pores, consequently provides less resistance to the passage of macromolecules through the capillary wall. The significance of these results in terms of the conventional pore theory of capillary permeability is discussed.
Effect of Denervation on Diameter and Reactivity of Arteries in the Bat Wing
Authors: WIEDEMAN MARY PURCELL
Published: June 2012

Responsiveness of the arterial vessels to intravenous and topically applied epinephrine was determined before and after denervation. Responsiveness to injected epinephrine increased 14 days after denervation; responsiveness to topically applied epinephrine was unaffected by denervation; arterial vessels remained dilated in excess of three weeks following denervation.
Renin and Acute Circulatory Renal Failure in the Rabbit
Authors: BROWN WILLIAM C.B. , BROWN JEHOIDA J. , GAVRAS HARALAMBOS , JACKSON ALAN , LEVER ANTHONY F. , MCGREGOR JAMES , MACADAM ROBERT F. , ROBERTSON J.IAN S.
Published: June 2012

Plasma renin concentration (PRC) was measured in 25 rabbits before and 6, 24, or 72 hours after subcutaneous injection of glycerol. Renal failure and tubular necrosis developed in most animals and PRC rose sixfold to a maximum at 24 hours. Small insignificant changes of PRC were present at 6 and 72 hours. None of these changes was observed in a control group of nine animals killed 24 hours after an injection of saline. The amount of renin extractable from single superficial glomeruli and from renal cortical tissue was reduced after injection of glycerol. In a second study of 11 anesthetized rabbits, renal venous PRC increased on average from 151 to 1810 units/liter following a 4-hour period of renal artery occlusion. Arterial PRC did not change significantly during this time, but the kidneys showed histological changes of acute tubular necrosis. These experiments are compatible with the suggestion that renin is involved in the pathogenesis of acute circulatory renal failure.
Spinal Sympathetic Cardiocardiac Reflexes
Authors: MALLIANI ALBERTO , PETERSON D. Fred , BISHOP VERNON S. , BROWN ARTHUR M.
Published: June 2012

We studied the reflex changes in myocardial contractility elicited by electrical stimulation of afferent cardiac sympathetic nerve fibers or chemical stimulation of their cardiac endings. Veratridine injected directly into the left coronary artery was the chemical stimulus. The maximum rate of rise of left ventricular pressure, dP/dt max, was used as an index of myocardial contractility. The stimuli evoked increases in dP/dt max in vagotomized cats with or without spinal transection (C1). Electrical stimulation provoked the same effect in vagotomized dogs. Increases in dP/dt max occurred which were independent of changes in heart rate, preload, or afterload. They were reflex in nature since they were abolished by section of the upper thoracic sympathetic rami or cardiac sympathetic nerves. These results are the first demonstration of a cardiocardiac reflex which can be mediated entirely by the spinal cord. Electrical stimulation in vagotomized cats and dogs also produced a reflex increase in arterial blood pressure partly due to sympathetic vasoconstriction.
Inotropic Agents in Hypoxic Cat Myocardium
Authors: KENT KENNETH M. , GOODFRIEND THEODORE L. , MCCALLUM ZENA T. , DEMPSEY PETER J. , COOPER THEODORE
Published: June 2012

The effects of several inotropic agents were investigated in papillary muscle preparations from normal cats and cats that had undergone previous total extrinsic cardiac denervation. The papillary muscles were bathed in a modified Krebs-Ringer's solution which was equilibrated with 95% O
2
-5% CO
2
for the control drug studies or 5% O
2
-5% CO
2
-90% N
2
for the hypoxia studies. This degree of hypoxia produced a 32 ± 3% decrease in tension in papillary muscles from normal cats and a 14 ± 4% decrease in catecholamine-depleted papillary muscles. During hypoxia there was depression of the maximum response to ouabain and norepinephrine with otherwise unchanged dose-response curves. Deterioration of the hypoxic muscles occurred after exposure to norepinephrine concentrations of 5 x 10
-7
M and greater. The dose-response curve for angiotensin II was unchanged by hypoxia. However, during hypoxia, the dose-response curves for two heptapeptide analogues of angiotensin II, 1-des-5-Valand 1-des-5-Ile-angiotensin II, were augmented. The inotropic effects of these analogues under control and hypoxic conditions were the same in the normal and catecholamine-depleted muscles. The potentiation by hypoxia of the inotropic effects of the angiotensin II analogues is unique among the agents studied.
Altered Urinary Kallikrein Excretion in Rats with Hypertension
Authors: MARGOLIUS HARRY S. , GELLER RONALD , JONG WYBREN de , PISANO JOHN J. , SJOERDSMA ALBERT
Published: June 2012

The urinary excretion of kallikrein, an enzyme which cleaves a vasodilator kinin from kininogen substrate, was examined in three types of hypertensive rats. Enzyme activity was measured by both esterase activity (isotopic assay) and bioassay with purified rat urinary kallikrein as a standard. Excretion of kallikrein was found to increase with age in spontaneously hypertensive rats, but levels were lower and stable in normotensive Wistar control animals. Rats with desoxycorticosterone-salt hypertension excreted markedly more, whereas rats with renal hypertension excreted significantly less kallikrein than did control animals. The alterations in kallikrein excretion were unrelated to changes in urine volume and protein excretion. The findings indicate that the kallikrein-kinin system may be involved in different forms of hypertension in the rat.
Elasticity of the Pulmonary Alveolar Sheet
Authors: FUNG Y. C. , SOBIN S. S.
Published: June 2012

An analysis of experimental data on the pulmonary alveolar sheet of the cat shows: (1) As far as elasticity in the plane of the sheet is concerned, the alveolar sheet may be regarded as uniform; the compliance of the posts is the same as that of the membranes. (2) Within a physiological range of positive transmural pressure, the mean thickness of the sheet varies linearly with the pressure. Also, the stress distribution in the alveolar-capillary membrane is nonuniform and nonisotropic. A theoretical sheet thickness-pressure relationship is derived in which the effect of stress resultants (sum of elastic stress and surface tension) is explicitly linked to the compliance of the sheet thickness. The sheet-flow theory then shows that average flow is very sensitive to the arteriole pressure. The flow per alveolar sheet is (1/
C
) (
h

a

4
--
h

v

4
). Here
h

a

and
h

v

are equal to alveolar sheet thickness at the arteriole and venule, respectively. When
art
>
alv
,
h
a
=
h
0
+ α(
art
-
alv
), where
art
is the blood pressure in the sheet at the arteriole,
alv
is the gas pressure in the alveolus, α is the compliance constant for the sheet thickness, and
h
0
is the thickness at Δ = 0. The constant
C
= 4µf Lα/ (SA), where µ is the coefficient of viscosity of blood,
f
is a friction parameter (on the order of 4, depending on the post geometry), L is the average length of the streamlines in the sheet, S is the vascular space-tissue ratio (on the order of 0.9), and A is the sheet area. Comparison of this formula with the experimental results of Roos et al., using
h
0
and α values from Glazier et al., shows reasonable agreement.
Reevaluation of Arterial Constitutive Relations: A FINITE-DEFORMATION APPROACH
Authors: SIMON BRUCE R. , KOBAYASHI ALBERT S. , STRANDNESS D. Eugene , WIEDERHIELM CURT A.
Published: June 2012

The purpose of this investigation was to use the finite-deformation theory of elasticity to interpret pressure-diameter data for in situ canine aortas and other arterial response data reported in the literature. A meaningful mechanical property for arterial tissue was identified as ∂
W
1
/∂
I
, the partial derivative of the strain-energy density function with respect to the first strain invariant. An exponential function was found to characterize the mechanical property ∂W
1
/∂I for all arteries considered. Thin-walled tube stress approximations were found to result in inaccurate values for arterial stresses and incremental elastic mechanical properties. Wave speeds calculated using ∂
W
1
/∂
I
for these arterial tissues agreed well with experimental measurements of wave speeds reported in the literature. Elevated values for strain-energy density were found in the inner arterial tissue layers. These high values for strain energy may contribute to atherogenesis in relatively straight arteries (e.g., the abdominal aorta) subjected to hypertension.
Effect of Hypercapnia on Myocardial Potassium Movement in the Dog
Authors: SPIKER D. G. , SMITH C. W.
Published: June 2012

This investigation tested the hypothesis that uptake of potassium during respiratory acidosis is secondary to the increased catecholamine activity which accompanies hypercapnia. The plasma K
+
concentration of simultaneously drawn arterial and coronary sinus blood samples from dogs was determined under three conditions: (1) hypercapnia (25% CO
2
-75% O
2
), (2) normocapnia (25% N
2
-75% O
2
) + propranolol (a beta-receptor blocker), and (3) hypercapnia + propranolol. The change during hypercapnia from uptake of K
+
to loss of K
+
after administration of propranolol (0.05 mg/kg, iv) was statistically significant. However, the administration of propranolol during normocapnia had no effect on myocardial K
+
movement. Changes in heart rate and myocardial contractility did not explain the change in myocardial K
+
movement during hypercapnia following the administration of propranolol. These data suggest that uptake of K
+
is secondary to the increased catecholamine activity which accompanies hypercapnia.
Comparison of Adrenergic Mechanisms in an Elastic and a Muscular Artery of the Rabbit
Authors: BEVAN J. A. , BEVAN R. D. , PURDY R. E. , ROBINSON C. P. , SU C. , WATERSON J. G.
Published: June 2012

Elastic and muscular arteries are known to differ in function and in the magnitude of their response to vasoconstrictor influences. With the isolated thoracic aorta and ear artery of the rabbit as representative arteries, the morphological, physiological, and pharmacological correlates of these differences have been sought among their presynaptic adrenergic mechanisms. The adrenergic nerve plexus in the ear artery is wider and the nodes are denser than they are in the aorta. There is some evidence consistent with the hypothesis that the thicker the plexus, the greater the reuptake of released transmitter, the smaller the transmitter overflow, and the lower the efficiency of uptake of exogenous norepinephrine. Measurements of fractional release of tritiated norepinephrine suggest that qualitative differences in the adrenergic transmitter storage and release mechanisms may exist between the two vessels. Thus the considerable functional difference between the two vessels is in part, at any rate, a consequence of adrenergic mechanisms which differ both quantitatively and qualitatively from each other.
Capillary, Interstitial, and Cell Membrane Barriers to Blood-Tissue Transport of Potassium and Rubidium in Mammalian Skeletal Muscle
Authors: SHEEHAN R. M. , RENKIN E. M.
Published: June 2012

Blood-tissue transport of
42
K,
86
Rb, and
22
Na was studied in perfused gracilis muscles of dogs to ascertain the influence of capillary wall, interstitial space, and muscle cell membranes on overall transport kinetics. Single-injection and continuous-infusion techniques were used, with T-1824 or
51
Cr-hemoglobin as nondiffusible references. Results were as follows: (1) Extraction (
E
) of the diffusible solutes was incomplete even in the earliest samples of venous outflow. (2) E
Rb
equaled E
K
in the first few samples, but later, as both declined, the ratio of E
Rb
to E
K
became less than one; stable ratios between 0.6 and 0.8 were established in different experiments. (3) E
Na
was initially slightly less than E
Rb
or E
K
but declined much more sharply in successive samples. (4) Steadystate E
Rb
and E
K
decreased with increasing blood flow but maintained a constant ratio. Vasomotion sometimes changed E
Rb
and E
K
but had little effect on their ratio. Local anesthetics (procaine or cocaine) brought the ratio of E
Rb
to E
K
closer to one. Analysis in terms of capillary and interstitial barriers, which do not discriminate between K, Rb, or Na, in series with a muscle cell membrane barrier, which does, leads to the following conclusions. (1) For K, the nondiscriminating barrier (mainly capillary wall) offers about 70% of the total resistance to transport and the discriminating barrier (cell membrane) about 30%. (2) For Rb, each barrier offers half the total resistance. (3) The resting muscle cell membrane is 2.5 times more permeable to K than to Rb. Local anesthetics reduce cell permeability to both ions and decrease this ratio. (4) For Na, resistance at the capillary wall is about 1.3 times that for K or Rb. Resistance at the cell membrane is, of course, very much greater.
Effect of Extrasystoles on Idioventricular Rhythm
Authors: KLEIN HERMAN O. , CRANEFIELD PAUL F. , HOFFMAN BRIAN F.
Published: June 2012

Ventricular extrasystoles exert a variable effect on idioventricular rhythm. The postextrasystolic, or the "returning," cycle may be unchanged, or it may be shorter or longer than the dominant cycle. The factors responsible for these different responses have never been investigated. Therefore, the effect of electrically induced extrasystoles was studied by microelectrode techniques in an in vitro model of idioventricular rhythm consisting of spontaneously firing Purkinje fiber bundles with their attached ventricular segments. Late extrasystoles lengthened the Purkinje returning cycle, primarily by transiently increasing the duration of spontaneous phase-4 depolarization. In contrast, early extrasystoles produced shortening of the returning cycle, primarily because of the marked abbreviation of the duration of the extrasystolic action potential. Other factors affecting the ultimate duration of the Purkinje returning cycle were delineated. The effect of extrasystoles on the electrical activity of the ventricular segments was studied by surface electrograms. This effect was complex and was modified by the direction of propagation of the extrasystole with respect to the pacemaker site and by the degree of conduction delay. Ventricular electrical activity usually reflected the electrical events occurring in the pacemaker cells, but frequent exceptions occurred: the ventricular returning cycle could be prolonged while the corresponding Purkinje returning cycle was shortened and vice versa. "Interpolation" of an extrasystole did not necessarily indicate failure of the extrasystole to discharge the pacemaker site. The effects of extrasystoles on idioventricular rhythm which have been described in the earlier literature are easily understood from the findings of this study.
Effects of Lidocaine, Propranolol, and Sotalol on Ouabain-lnduced Changes in Transmembrane Potential of Canine Purkinje Fibers
Authors: KOERPEL BARRY J. , DAVIS LARRY D.
Published: June 2012

Isolated canine papillary muscle-false tendon preparations stimulated at 95/min were perfused with Tyrode's solution containing ouabain, 2.1 x 10
-7
M. Action potentials of Purkinje fibers were recorded. Initially ouabain increased the slope of phase-4 depolarization. Subsequently it decreased the maximum diastolic potential and the rising velocity of phase 0, the amplitude, and the duration of the action potential. The slope of phase-4 depolarization increased progressively, and eventually the configuration of the action potential changed to resemble that of sinoatrial node fibers. Onset of enhanced phase-4 depolarization was delayed significantly by treatment before exposure to ouabain with lidocaine, 3.7 x 10
-5
M, or propranolol, 2.1 x 10
-5
M, but not with sotalol, 3.2 x 10
-4
M. Enhanced phase-4 depolarization produced by exposure to ouabain was reduced in slope by subsequent treatment with lidocaine or propranolol but not sotalol. Application of lidocaine or propranolol to fibers with action potentials in the configuration characteristic of sinoatrial node fibers returned the contour of the action potentials toward normal; sotalol was not effective in this regard. These results, coupled with the relative effectiveness of these drugs in intact animals with digitalis arrhythmias, support the hypothesis that enhanced phase-4 depolarization of Purkinje fibers is a factor in the production of digitalis-induced ventricular arrhythmias.
Incorporation of the Terminal Phosphate of ATP into Membranal Protein of Rabbit Cardiac Sarcoplasmic Reticulum: CORRELATION WITH ACTIVE CALCIUM TRANSPORT AND STUDY OF THE EFFECTS OF CYCLIC AMP
Authors: Namm Donald H. , Woods Edward L. , Zucker Joan L.
Published: June 2012

The transfer of the terminal phosphate of ATP to a material from the sarcoplasmic reticulum of cardiac muscle which can be precipitated by trichloroacetic acid was studied, and the relationship of this biochemical event to active Ca
2+
transport was examined. A component of the phosphoryl transfer reaction was stimulated specifically by Ca
2+
. Both the phosphorylation of the reticulum and the active sequestering of Ca
2+
were proportional to the Ca
2+
concentration between 10
-7
and 10
-5
M. The time course of both phenomena was similar. These and other observations relating Ca
2+
-dependent phosphorylation of the membrane of the sarcoplasmic reticulum with the activesequestering of Ca
2+
suggest that the phosphoryl transfer reaction may represent the formation of a carrier system which facilitates the inward flux of Ca
2+
against a concentration gradient. Cyclic AMP, theophylline, or the combination of these two agents did not influence the rate or extent of the phosphorylation of the sarcoplasmic reticulum. These results have led us to question the hypothesis that the cardiac sarcoplasmic reticulum is the site of action of cyclic AMP in its role as a mediator of cardiac inotropic effects.