bluuebunny/crossref_metadata_2025 huggingface dataset:
Elasticity of the Pulmonary Alveolar Microvascular Sheet in the Cat
Authors: SOBIN SIDNEY S. , FUNG Y. C. , TREMER HERTA M. , ROSENQUIST THOMAS H.
Published: June 2012

The pulmonary interalveolar capillary bed of the cat has previously been shown to be consistent with a sheet-like endothelium-lined space bridged by avascular endothelium-covered posts. This was termed the sheet-flow model, and blood flow through that space is termed sheet flow. The initial formulation of the sheet-flow theory and model required that sheet thickness be the independent variable. Sheet thickness (
h
) was measured in vertical and horizontal silicone-elastomer-perfused cat lungs over the transmural (alveolar-capillary) pressure (Δ) range of 6.3 to 27 cm H
2
O. A plot of
h
vs. Δ for 2753 individual measurements is linear over the measured pressure range. The regression line is described by h = 4.28 + 0.2191 Δ. Sheet thickness of 4.28 µ at zero pressure is an extrapolated value. The value 0.2191 µ/cm H
2
O is the compliance coefficient (α) of the pulmonary capillary bed. Electron microscopic studies demonstrated that the capillary posts have a highly organized internal structure with abundant collagen and an elastin or elastinlike core. Collagen fibers originate from the alveolar-capillary basement membrane, emerge in a herringbone pattern, and sweep toward the center of the post in a helical array around the elastinlike amorphous and fibrillar core. The unusual compliance of the microvascular blood vessels in the lung can be correlated with the architectural organization within the posts.
Extracellular Potentials Related to Intracellular Action Potentials in the Dog Purkinje System
Authors: SPACH MADISON S. , BARR ROGER C. , SERWER GERALD A. , KOOTSEY J. Mailen , JOHNSON EDWARD A.
Published: June 2012

Simultaneous extracellular and intracellular recordings of normal action potentials, action potentials initiated at a time when the membrane was partially depolarized (by premature beats or elevated extracellular potassium), and action potentials at reduced temperature were made for Purkinje strands from the left ventricle of the dog with a 50µ tungsten extracellur electrode and a special guarded intracellular microelectrode. The peak-to-peak amplitude of the extracellular wave form was proportional to the maximum rate of rise of the intracellular action potential, and the duration of the extracellular wave form was proportional of the duration of the upstroke of the intracellular potential. Wave forms of extracellular potentials were computed from the recorded intracellular potentials with an equation which included the effects of membrane currents away from the point of observation. The computed wave forms accurately reproduced the recorded extracellular wave forms in all cases, and the wave forms were not directly porportional to the second spatial derivative or the second temporal derivative of the intracellular potential. Extracellular potentials are shown to be directly related to the spatial distribution of the intracellular potential and as such are a sensitive index of propagation and a source of information of the kind previously thought to be obtainable only with an intracllular electrode.
Quantification of Intermediate Steps in the Renin-Anglotensin-Vasoconstrictor Feedback Loop in the Dog
Authors: COWLEY ALLEN W. , GUYTON ARTHUR C.
Published: June 2012

The major intermediate steps in the renin-angiotensin-vasoconstrictor feedback loop have been experimentally determined. The quantitative relationships between renal perfusion pressure, renin secretion, arterial renin activity, and systemic arterial blood pressure were determined in dogs in which the cardiovascular control loops of the central nervous system were eliminated by spinal cord destruction and decapitation. Step-decreases in renal perfusion pressure to a single kidney were introduced and maintained constant to open the feedback loop of arterial pressure. Renin activity was measured by radioimmunoassay of angiotensin I. Each decrease of 15 mm Hg in renal perfusion pressure between pressures of 100 and 50 mm Hg elevated the net secretion of renin nearly 20 ng min
-1
g
-1
kidney an d the arterial renin activity nearly 7.0 ng ml
-1
hour
-1
. Renin secretion and arterial renin activity decreased at perfusion pressures below 50 mm Hg. A bioassay procedure for estimating the rate of angiotensin II formation at various increments of arterial renin activity showed that an increase in renin activity of 10 ng ml
-1
hour
-1
resulted in an increase in the net production of angiotensin II of 5.0 ng kg
-1
min
-1
. The results of these experiments are useful in predicting alterations in the system that follow a decrease in renal artery pressure, and they clarify interactions of the renin-angiotensin system with other homeostatic pressure-regulating systems.
Potassium Deficiency and Cardiac Catecholamine Metabolism in the Rat
Authors: KRAKOFF LAWRENCE R.
Published: June 2012

Norepinephrine metabolism, arterial blood pressure, and electrolytes were studied in rats maintained on either potassium-deficient or control diets. After 3 weeks on the test diets, the arterial blood pressure was significantly lower and the ratio of [Na] to [K] in cardiac tissue was significantly higher in potassium-deficient rats as compared to controls. Ten minutes after intravenous injection of
3
H-norepinephrine the specific activity of cardiac norepinephrine was similar in the control and potassium-deficient groups despite a significant increase in endogenous norepinephrine concentration in the potassium-deficient hearts. But 24 hours after injection, there was a significant increase in
3
H-norepinephrine specific activity, concentration, and content in the potassium-deficient group. Cardiac tissue monoamine oxidase activity was similar in both groups. The increased
3
H-norepinephrine retention and concentration and the decreased arterial blood pressure of the potassium-deficient rate suggest an impairment in norepinephrine release by the sympathetic neurons.
Abnormal Automaticity in Canine Purkinje Fibers Focally Subjected to Low External Concentrations of Calcium
Authors: Sano Toyomi , Sawanobori Tohru
Published: June 2012

The false tendon was isolated from the dog heart and mounted under a partition plate in the center of a chamber which was filled with Tyrode's solution. Two microelectrodes were positioned closely on either side of the plate and inserted into the false tendon. The partition did not alter repolarization of the action potential in normal Tyrode's solution. When EDTA was added to one side of the preparation, a low-plateau potential appeared after repolarization on the other side, which contained normal Tyrode's solution. This change occurred concurrently with a prolongation of the action potential in the calcium-free Tyrode's solution. The low-plateau potential was a reflection of the electrotonic potential from the nearby cells whose action potentials were prolonged. Repetitive firing of the action potential was frequently observed when abrupt differences in repolarization were recorded at close interelectrode distances. These results suggest that differences in repolarization of closely apposed cells can initiate arrhythmias.
Effects of Hypertension on the Lipid Composition of Rat Aortic Intima-Media
Authors: Daly Marie M.
Published: June 2012

Since hypertension intensifies the development of atherosclerosis, effects of hypertension on the lipid composition of aortic intima-media of male rats were studied. Concentrations of cholesterol, both esterified and unesterified, and of phospholipid were increased, and the concentration of triglyceride was decreased in aortas of hypertensive rats maintained on a stock diet. Changes in free cholesterol, phospholipid, and triglyceride are believed to be concomitants of medial hypertrophy, which was pronounced in aortas of hypertensive rats. Changes in esterified cholesterol, however, may be attributable to an influence of plasma lipids on aortic lipids. Cholesteryl ester, quantitatively a minor lipid component of the aorta, shows a larger increase with hypertension than other lipid classes. The resemblance between fatty acid compositions of aortic and plasma cholesteryl esters was strong, and persisted when the composition of plasma cholesteryl esters was altered by diet. These results suggest that most of the aortic esters originated in the plasma, and support the concept that hypertension intensifies the development of atherosclerosis by increasing the net transfer of lipid from plasma to vessel.
Canine Mitral Complex: ULTRASTRUCTURE AND ELECTROMECHANICAL PROPERTIES
Authors: Fenoglio John J. , Pham Tuan Duc , Wit Andrew L. , Bassett Arthur L. , Wagner Bernard M.
Published: June 2012

The mitral complex is a functional entity composed of the annulus, valve leaflets, chordae, and papillary muscles. The mechanical properties of the complex are dependent on the unique structural relations of the collagen in the leaflets and chordae. In the chordae the collagen is arranged in avascular columns. These columns interdigitate between muscle fibers in the papillary muscles, and the collagen is anchored to the myofiber membrane by microfibrils. In the leaflet the chordae are continuous with the dense fibrous tissue, forming a sheet of collagen which merges with the annulus. Within the leaflet there are cardiac muscle fibers in direct continuity with left atrial muscle. Contraction of isolated valve preparations can be initiated by electrical stimulation and is preceded by a propagated depolarization. Action potentials from cells in the middle third of the leaflet have a slow upstroke velocity, prominent plateau, and a characteristic positive afterpotential. Valve muscle electromechanical properties are markedly altered by 1 x 10
-7
M acetylcholine; this concentration has little effect on working left atrial muscle. In preparations containing portions of the left atrium and valve leaflet, the excitation wave spreads into the leaflet after electrical stimulation of the atrial muscle. This suggests that the accompanying contractile event may occur in situ before the initiation of systole.
Circulatory Responses to Graded Stimulation of the Carotid Chemoreceptors in the Dog
Authors: Pelletier Conrad L.
Published: June 2012

The vascular effects of graded stimulation of the carotid chemoreceptors were studied in 13 anesthetized and artificially ventilated dogs, and stimulus-response curves were defined. The carotid bifurcations were isolated and perfused at constant pressure, and the vagi were cut. Autologous blood collected in a reservoir was equilibrated at Po
2
varying from 104 to 34 mm Hg, Pco
2
from 39 to 81 mm Hg, and pH from 7.46 to 6.87 and was used to stimulate the carotid chemoreceptors. Systemic arterial Po
2
, Pco
2
, and pH were kept normal. Reflex increases in aortic blood pressure and in hind-limb perfusion pressure (constant-flow perfusion) were first seen with Po
2
of 70 mm Hg or Pco
2
> 39 mm Hg. The vascular responses increased linearly with lower Po
2
or higher Pco
2
, until tensions of 34 and 71 mm Hg, respectively, were reached. These stimuli caused a reflex dilatation of the perfused saphenous vein that was also proportional to the degree of stimulation. Increasing the pH of the blood perfusing the chemoreceptors decreased these changes by more than 50%; decreases in pH, with normal Po
2
and Pco
2
, caused marked vascular responses, indicating an important role of pH in the activation of the chemoreflex mechanism.
Focal Lesions in the Canine Bundle of His: THEIR EFFECT ON VENTRICULAR EXCITATION
Authors: Watt Thomas B. , Pruitt Raymond D.
Published: June 2012

The alterations in ventricular excitation resulting from production of discrete punctate electrocautery lesions in the canine bundle of His were studied. Electrocardiographic changes were correlated with lesions identified anatomically by microscopic examination of the atrioventricular bundle. Although partial or complete atrioventricular block developed from lesions at several levels of the atrioventricular bundle, changes in the form of the QRS complex appeared only when lesions involved the distal portion of the bundle. Such QRS changes were recorded in 21 of 32 instances when the lesion involved the branching portion of the common bundle but in none of 6 instances when the lesion involved only the nonbranching portion of the common bundle. This study, then, provides evidence for functionally distinct longitudinal fascicles only within the distal portion of the common bundle. The syncytial character of the terminal fascicular (Purkinje) network may minimize the electrocardiographic evidence for such functional specificity within the common bundle.
Ornithine Decarboxylase in Cardiac Hypertrophy in the Rat
Authors: MATSUSHITA S. , SOGANI R. K. , RABEN M. S.
Published: June 2012

Ornithine decarboxylase, a possible rate-limiting enzyme in the synthesis of polyamines, was assayed in hearts of normal rats, sham-operated rats, and rats subjected to aortic constriction. In the hearts of rats with constricted aortas, significantly increased enzyme activity compared with that in the hearts of sham-operated rats was observed 2, 4, 6, and 8 hours and 3, 5, and 10 days after operation, and two peaks in activity occurred--one at 4 hours and the other at 5-10 days. Increased ornithine decarboxylase activity was one of the earliest changes associated with cardiac hypertrophy. The changes in enzyme activity correlated well with the subsequent hypertrophy in the hearts of rats with aortic constriction and with the regression in the hearts of sham-operated rats, suggesting a role for polyamines in the regulation of cardiac growth. The early increase in ornithine decarboxylase activity in hearts of rats with aortic constriction was inhibited by actinomycin D, 8-azaguanine, and cycloheximide, indicating that RNA and protein synthesis are involved in the process. Actinomycin D given 30 minutes after operation or even at the time of aortic constriction failed to inhibit the increase in the enzyme activity, suggesting that the transcription required for the increase occurs early after operation. Cycloheximide given 1 hour before the rats were killed markedly decreased the enzyme activity, and the estimated half-life of cardiac ornithine decarboxylase was comparable to that of the reported short-lived liver ornithine decarboxylase. The study suggests that the synthesis of ornithine decarboxylase is influenced at the stage of transcription by mechanical stress on the myocardium and that polyamines might have a regulatory role in cardiac hypertrophy and regression.
Adenosine Uptake by Canine Heart
Authors: OLSSON Ray A. , SNOW Jerry A. , GENTRY Mary K. , FRICK G. Peter
Published: June 2012

The rate of myocardial adenosine uptake was studied in anesthetized openchest dogs to assess the importance of the process in the regulation of extracellular fluid concentrations of this coronary vasodilator. 8-
14
C-adenosine solutions were infused into the left coronary artery at rates that yielded concentrations in coronary artery plasma of 0.4-13.3 µM. The adenosine uptake rate was calculated as the product of the adenosine infusion rate and the extraction fraction of radioactivity assumed to be adenosine. Uptake appeared to follow Michaelis-Menten kinetics over the range of plasma adenosine concentrations tested, and the apparent values of K
m
and V
max
were 11.6 ± 1.4 (SE) µM and 4.9 ± 0.5 (SE) nmoles/g left ventricle min
-1
, respectively. The K
m
and the tissue activity of dog heart adenosine deaminase were 43 µM and 1.2 µmoles/g left ventricle min
-1
, respectively, and those of adenosine kinase were 0.4 µM and 23 nmoles/g left ventricle min
-1
, values sufficiently different from the parameters of uptake to suggest that the limiting step in uptake is permeation into the cell. Uptake was inhibited by 8-13 µM 6-(
p
-nitrobenzylthio) guanoside, an adenosine analogue that inhibits the facilitated diffusion of a variety of nucleosides in erythrocytes, and by dipyridamole, a compound that inhibits nucleoside uptake in erythrocytes, platelets, and tissue culture cells. Uptake was not inhibited by cardiotoxic doses of ouabain. These findings are evidence against uptake by simple diffusion but are consistent with uptake mediated by a carrier. The rate of cellular adenosine uptake from the extracellular space of the heart appears to be rapid enough to be important in the regulation of myocardial levels of this coronary vasodilator metabolite.
Presence of Adenosine in the Human Term Placenta: DETERMINATION OF ADENOSINE CONTENT AND PATHWAYS OF ADENOSINE METABOLISM
Authors: SIM Meng Kwoon , MAGUIRE M. Helen
Published: June 2012

Adenosine, inosine, and hypoxanthine were isolated from human term placentas by paper chromatography of the dialyzates of aqueous placental homogenates and quantified by ultraviolet spectroscopy. Placentas obtained upon vaginal delivery contained 230 ± 18 nmoles adenosine/g tissue, 300 ± 29 nmoles inosine/g, and 250 ± 19 nmoles hypoxanthine/g. Three prelabor placentas obtained by cesarean section contained 44 ± 3 nmoles inosine/g and 277 ± 22 nmoles hypoxanthine/g, but adenosine was not detected in two of the placentas and was present only at 4 nmoles/g in the third. The activities of placental enzymes catabolizing ATP were determined in homogenates of term placentas. No adenylate deaminase or xanthine oxidase activity was found. Adenosinetriphosphatase, adenylate kinase, and 5'-nucleotidase were more active than were adenosine kinase, adenosine deaminase, and purine nucleoside phosphorylase. The results indicate that in the placenta both the formation of adenosine from adenosine monophosphate and the fate of adenosine, i.e., salvage or catabolism, are influenced by the level of adenosine triphosphate. Possibly, during labor, placental ischemia favors the enzymatic production of adenosine.
Influence of Brief Vagal and Stellate Nerve Stimulation on Pacemaker Activity and Conduction within the Atrioventricular Conduction System of the Dog
Authors: SPEAR JOSEPH F. , MOORE E. NEIL
Published: June 2012

Experiments were performed on open-chest anesthetized dogs to determine the quantitative effects of autonomic nerve stimulation on pacemaker activity and conduction. The lead II electrocardiogram together with bipolar electrograms were recorded from the atria, the His bundles, and the ventricles. The vagi or the stellate ganglia were stimulated in dogs which exhibited either sinus rhythm, ectopic atrial rhythm, junctional rhythm, or ectopic ventricular rhythm. The time courses of the change in heart rate in response to vagal or stellate stimulation were characteristic for each type of rhythm. The characteristic responses of different cardiac pacemaker sites to autonomic influence were demonstrated to be important factors in the production of wandering pacemakers and in the emergence of ectopic beats. Sinus pacemaker activity was more sensitive to modification by autonomic stimulation than was atrioventricular (AV) conduction. However, subliminal autonomic effects on AV transmission were brought out during conduction of premature atrial beats, thereby demonstrating a coupling interval dependency of autonomic influences on AV conduction. The present experiments also showed how fluctuations in autonomic activity could result in Mobitz type II second-degree heart block, pseudosupernormal conduction, and the concertina effect observed in the preexcitation syndrome.
Effect of Sympathetic Nerve Stimulation on Pulmonary Vascular Resistance in the Dog
Authors: KADOWITZ PHILIP J. , HYMAN ALBERT L.
Published: June 2012

The effect of sympathetic nerve stimulation on the pulmonary circulation was studied in a hemodynamically separated dog lung in which blood flow was maintained constant with a pump. Electrical stimulation of the stellate ganglia at 3, 10, and 30 cps produced a significant increase in mean lobar arterial perfusion pressure. Since lobar blood flow and left atrial pressure did not change during nerve excitation, the increase in lobar arterial pressure reflected an increase in vascular resistance across the lung. The increase in pulmonary vascular resistance was dependent on the stimulus frequency, and the time from the onset of stimulation to the attainment of the peak response was inversely related to the stimulus frequency. The response to nerve stimulation was decreased by alpha-receptor blocking agents. Lobar perfusion with a roller pump had an effect similar to perfusion with a piston pump. The response to nerve stimulation was independent of changes in rate, rhythm, and volume of respiration, changes in aortic blood pressure, and changes in airway resistance. The effects of stellate stimulation and of injected norepinephrine on vascular resistance were similar in the hemodynamically separated lobe. In essence, sympathetic nerve stimulation produced an active increase in vascular resistance in the pulmonary circulation, and the contribution of passive factors such as changes in respiration, bronchomotor tone, and bronchial circulation was minimal. Since the response was blocked by phentolamine, the increase in pulmonary vascular resistance in response to nerve stimulation was attributed to activation of alpha receptors in the pulmonary vascular bed by neurally released norepinephrine. These results demonstrate that pulmonary vascular resistance can be increased at stimulus frequencies in the physiological range of discharge for the sympathetic nervous system.
Role of Mineralocorticoids in the Natriuresis of Water Immersion in Man
Authors: EPSTEIN MURRAY , KATSIKAS JAMES L. , DUNCAN DAVID C.
Published: June 2012

The role of aldosterone suppression in mediating the natriuresis of water immersion was assessed in six normal male subjects. All subjects were studied on four occasions while they were in balance on a diet containing 150 mEq of sodium and 100 mEq of potassium daily: during a control period, following deoxycorticosterone acetate (DOCA) treatment for 24 hours (Cont + DOCA), during water immersion to the neck (immersion), and during water immersion following DOCA treatment (Imm + DOCA). Immersion resulted in highly significant increases in the rates of sodium and potassium excretion compared with control beginning in the first hour. Although treatment with DOCA decreased the natriuresis of immersion (
P
< 0.01), the rate of sodium excretion was still three- to fourfold greater during Imm + DOCA than it was during the comparable Cont + DOCA periods (
P
< 0.01). Cessation of water immersion resulted in a marked decrease in urine flow and free water clearance occurring within the initial 30 minutes of recovery (
P
< 0.005). Although the rate of sodium excretion also decreased following cessation of immersion, it continued to exceed both preimmersion values (
P
< 0.01) and the comparable control values throughout the recovery hour (
P
< 0.01). These observations suggest that the natriuresis of immersion cannot be completely accounted for by immersion-induced suppression of aldosterone. The continuing natriuresis occurring despite the progressive volume contraction induced by immersion suggests that the natriuretic stimulus is sufficiently potent to override the compensatory mechanisms which are known to participate in defense of volume homeostasis. Furthermore, the delay in the disappearance of the natriuresis suggests that a humoral factor rather than more rapidly acting hemodynamic and neural mechanisms may mediate the natriuresis.
Venous Relaxation Caused by Acetylcholine Acting on the Sympathetic Nerves
Authors: VANHOUTTE PAUL M. , SHEPHERD JOHN T.
Published: June 2012

Experiments were performed to determine whether acetylcholine affects the sympathetic activation of the cutaneous veins of the dog. Changes in isometric tension of saphenous vein strips were recorded at 37°C in an organ bath. Addition of acetylcholine at 10
-11
to 10
-8
g/ml did not affect basal tension, but larger doses (5 x 10
-8
to 5 x 10
-7
g/ml) caused a contraction of the strips which varied from slight to marked. Acetylcholine at 10
-8
to 10
-7
g/ml caused a further increase in tension when it was added to strips already contracted by norepinephrine, tyramine, KCl, or BaCl
2
; in contrast, similar doses of acetylcholine caused relaxation of strips contracted by liberation of norepinephrine from the nerve terminals by electrical stimulation (1-10 cps). This relaxation was not influenced by propranolol or hexamethonium but was abolished by atropine (10
-8
g/ml). In intact dogs, the lateral saphenous vein was perfused with autologous blood at constant flow. A sustained venoconstriction was induced either by electrical stimulation of the lumbar sympathetic chain or by a continuous infusion of norepinephrine. An infusion of acetylcholine (10
-7
to 10
-6
g/ml min
-1
) relaxed veins constricted by sympathetic stimulation but not those constricted by norepinephrine. Thus, acetylcholine, in doses smaller than those known to have a direct constrictor effect, causes relaxation of cutaneous veins, probably by inhibiting the release of norepinephrine from nerve terminals.
Role of the Sympathetic Nervous System in the Sinus Node Resistance to High Potassium
Authors: VASSALLE MARIO , GREINEDER JÜRGEN K. , STUCKEY JACKSON H.
Published: June 2012

The resistance of sinus node automaticity to high potassium (K) levels was studied in anesthetized dogs by perfusing the sinus node artery with oxygenated Tyrode's solution containing different K concentrations. The following results were obtained. (1) Sinus node automaticity persisted at a K concentration of 21.6 m
M
, although the pacemaker site tended to shift in and out of the node at this concentration. (2) Sinus node dominance at high K concentrations was progressively lost as sympathetic influences were progressively eliminated. (3) Sinus node pacemaker activity was suppressed at a K concentration lower than 21.6 m
M
when calcium was omitted from the perfusion fluid. (4) The pacemaker site shifted consistently from the sinus node towards the atrioventricular node at high K concentrations after the elimination of sympathetic activity (5) The transient sinus tachycardia caused by high K concentrations persisted after bilateral vagotomy. It is concluded that catecholamines participate in the resistance of the sinus node to K, suggesting that the difference in resistance to high K concentrations between the sinus node and Purkinje fibers may, in part, result from the more abundant innervation of the sinus node.
Changes in Microvascular Diameter and Oxygen Tension Induced by Carbon Dioxide
Authors: DULING BRIAN R.
Published: June 2012

Microvascular diameters in the hamster cheek pouch were measured with a Vickers image-shearing eyepiece, and oxygen tension (Po
2
) was measured amperometrically with 2-6µ microcathodes. Perivascular Po
2
was dependent on both the type of microvessel observed and the composition of the solution bathing the tissue. During application of a solution with a mean Po
2
of 17 mm Hg and a Pco
2
of 0 mm Hg, a longitudinal gradient in perivascular Po
2
was observed: Po
2
decreased from 44 ± 2 (
SE
) mm Hg at the large arterioles to 18 ± 2 mm Hg at the capillary origin. Tissue Po
2
was 10 ± 1 mm Hg. Suffusion of the cheek pouch with a solution with approximately the same Po
2
and a Pco
2
of 32 mm Hg resulted in an elevation of perivascular Po
2
at all sites. Large arteriolar Po
2
under these circumstances was 47 ± 2 mm Hg, capillary origin Po
2
was 29 ± 3 mm Hg, and tissue Po
2
was 17 ± 3 mm Hg. CO
2
also produced vasodilation: the average vascular diameter increased 18 ± 7% when the solution Pco
2
was increased from 0 to 32 mm Hg. The tissue showed evidence of regulation of tissue O
2
supply both with and without CO
2
in the suffusion solution. The effects of CO
2
on the distribution of O
2
were compared with the effects of other vasodilators, and it was found that the tissue Po
2
was not consistently changed by the application of the vasodilators, whereas it was elevated 70% by CO
2
. This difference is attributed in part to the effect of CO
2
on the oxyhemoglobin dissociation curve.
Effect of Acute Isovolemic Anemia on Cardiac Output and Estimated Hepatic Blood Flow in the Conscious Dog
Authors: CHAMORRO GASTON , RODRIGUEZ JOSE A. , DZINDXIO BARRY , RAPAPORT ELLIOT
Published: June 2012

The effect of acute isovolemic anemia induced by Dextran 70 exchange (40 ml/kg body weight) on estimated hepatic blood flow, cardiac output, and related variables was studied in 27 experiments on 24 unsedated dogs. Experiments were performed 5-10 days after implantation of an electromagnetic flow transducer around the aorta and catheters in the hepatic vein, jugular vein, and carotid artery. Bromsulphalein infusion was used to measure estimated hepatic blood flows, and electromagnetic measurements of stroke volume and cardiac output were calibrated using a simultaneous dye-dilution curve. With a mean fall in hematocrit from 34.8 to 17.0 ml/100 ml, estimated hepatic blood flow rose from 53.6 ± 15.3 (SD) to 76.3 ± 21.1 ml/min kg
-1
and splanchnic vascular resistance fell from 119 ± 41 to 93 ± 38 mm Hg/liter min
-1
(
P
<0.01). These changes were proportionately smaller than the increase in cardiac output (182 ± 80 to 350 ± 146 ml/min kg
-1
) and the fall in systemic vascular resistance (37.0 ± 4.9 to 21.7 ± 4.9 mm Hg/liter min
-1
), leading to a fall in the ratio of estimated hepatic blood flow to cardiac output from 34.3 to 25.7%. Bromsulphalein extraction ratio was significantly decreased, but Bromsulphalein clearance increased 44%. Splanchnic oxygen consumption did not change. β-receptor blockade in 6 dogs (propranolol 0.5 mg/kg body weight) failed to prevent or attenuate the increase in estimated hepatic blood flow or cardiac output when the blocking agent was given before induction of acute isovolemic anemia. Sixty minutes after accomplishment of anemia, estimated hepatic blood flow and cardiac output had returned toward but not to control levels. Induction of β-receptor blockade in the anemic dog did not influence the effects of time on estimated hepatic blood flow or cardiac output. We concluded that acute isovolemic anemia leads to a significant increase in estimated hepatic blood flow that is essentially independent of β-receptor stimulation.
Distribution of Stresses and of Strain-Energy Density through the Wall Thickness in a Canine Aortic Segment
Authors: VAISHNAV RAMESH N. , YOUNG JOHN T. , PATEL DALI J.
Published: June 2012

In this paper we presented a method for determining the distribution of circumferential (
S
θ
), longitudinal (

S
z

), and radial (

S
r

) stress and of strain-energy density (
W
) in canine aortic segments under physiological loading. Aortic segments from 13 dogs were studied in vitro. Intraluminal pressure and longitudinal force were varied over ranges of 25 to 200 cm H
2
O and 0 to 100 g, respectively, and the external radius and the segment length were measured at each step. A nonlinear theory of large deformation of the aortic tissue based on the assumptions of incompressibility and curvilinear orthotropy was applied to the data. The 3, 7, or 12 constitutive constants of the theory were calculated without using the usual thin-wall assumption. These constants were then used to calculate the distribution of stresses and of
W
. The results indicated that (I)
S
θ
,

S
z

,

S
r

, and
W
were largest in magnitude at the endothelial surface and decreased toward the adventitial surface, (2) the decrease was most marked in the inner third of the vessel wall, (3) in general
S
θ
>

S
z

>
W
>

S
r

, and (4) at a given longitudinal stretch an increase in intraluminal pressure increased
S
θ
,

S
z

, |

S
r

|, and
W
, with the effect being most marked on
S
θ
.
Transcapillary Escape Rate of Albumin and Plasma Volume in Essential Hypertension
Authors: PARVING HANS-HENRIK , GYNTELBERG FINN
Published: June 2012

The transcapillary escape rate of albumin, the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, was determined from the disappearance of intravenously injected
131
I-labeled human serum albumin during the first 60 minutes after the injection in 10 normotensive and 18 hypertensive male subjects. The investigation was preceded by at least 12 hours of fasting and 30 minutes of rest in the supine position. The transcapillary escape rate of albumin was significantly increased in the hypertensive group: it averaged 7.6±1.2 (SD) %/hour compared with 5.6±1.1%/hour in the normotensive group (
P
<0.001). Similar results were obtained for the outflux of albumin, the mass of intravascular albumin that passes to the extravascular space per unit time, when identical intravascular albumin masses were compared (
P
<0.001). A highly significant correlation between the transcapillary escape rate of albumin and blood pressure was found in the hypertensive group (
P
<0.001). Therefore, the increased transcapillary escape rate and the outflux of albumin probably reflected an increase in arteriolar and capillary permeability to albumin. This increase was probably due to the high intra-arterial pressure, which induces constriction in some arteries and dilatation in others and thus allows the high intraluminal pressure to be transmitted distally with distention of the small vessel walls. Finally, a significant reduction in plasma volume was found in the hypertensive subjects (
P
<0.05).
Dependency of Renal Blood Flow on Prostaglandin Synthesis in the Dog
Authors: LONIGRO ANDREW J. , ITSKOVITZ HAROLD D. , CROWSHAW KEITH , MCGIFF JOHN C.
Published: June 2012

Inhibition of prostaglandin synthesis in chloralose-anesthetized dogs reduced renal blood flow, and this reduction closely correlated (r=0.92,
P
<0.01) with a decline in the renal efflux of a substance having the properties of PGE
2
. We used solvent extraction and thin-layer chromatography coupled with parallel bioassay to identify and assay the PGE- and PGF-like substances (expressed as PGE
2
and PGF
2α
equivalents). Either of two antiinflammatory acids, indomethacin or meclofenamate, that inhibited conversion of
14
C-arachidonic acid to prostaglandins in renal homogenates decreased the basal concentration of a PGE-like substance in renal venous blood to 0.06 ± 0.02 ng/ml from a mean control value of 0.34 ± 0.10 ng/ml (
P
<0.01). This change was associated with a mean reduction in renal blood flow of 45% in spite of increased renal perfusion pressure. Femoral blood flow and cardiac output were variably and insignificantly affected. Changes in the renal efflux of a PGF-like substance induced by indomethacin were unrelated to the decline in renal blood flow. Changes in the efflux of a PGE-like substance from the femoral vascular bed were unrelated to the small and variable changes in femoral blood flow. Extrarenal factors, i.e., humoral, nervous, or cardiopulmonary factors, did not account for the decline in renal blood flow produced by the inhibitors of prostaglandin synthesis, since the inhibitors produced identical effects in the isolated blood-perfused canine kidney. We concluded that PGE
2
participates in maintaining renal vascular tone which heretofore has been ascribed to autonomous, intrinsic renal arteriolar activity.
Left Circumflex Coronary Artery Hemodynamics in Conscious Dogs with Congenital Subaortic Stenosis
Authors: PYLE R. LEE , LOWENSOHN HOWARD S. , KHOURI EDWARD M. , GREGG DONALD E. , PATTERSON DONALD F.
Published: June 2012

Coronary arterial hemodynamics were studied in three conscious dogs with congenital fibrous ring-type subaortic stenosis. Flow characteristics were recorded with electromagnetic flow transducers chronically implanted on the circumflex branch of the left coronary artery. Circumflex resting flow (ml/min 100 g
-1
myocardium) was below that previously found in normal dogs studied by the same methods. Phasic coronary flow patterns at rest were abnormal, being characterized by reversed flow throughout most of ventricular systole. The mean reactive hyperemic response after 10 seconds of mechanical occlusion was comparable to that in normal dogs despite the essential absence of systolic forward flow. In one dog, moderate treadmill exercise substantially increased total circumflex flow despite a large increase in reversed circumflex flow.
Evaluation of Several Methods for Computing Stroke Volume from Central Aortic Pressure
Authors: STARMER C. Frank , MCHALE PHILIP A. , COBB FREDERICK R. , GREENFIELD JOSEPH C.
Published: June 2012

Six pulse-contour methods for estimating stroke volume from a single central aortic blood pressure were evaluated in 8 dogs and 17 patients. In the dogs, wide variations in stroke volume, measured with an electromagnetic flowmeter, were obtained by pacing the heart at various rates during a control period and during several pharmacologic interventions. Good correlations existed between measured stroke volume and most estimators when the data from each intervention were analyzed separately. However, regression analysis revealed considerable variation in the individual slopes and intercepts, and thus a poor correlation was obtained when all data for one dog were combined in a single analysis. Similar evaluations were carried out in two groups of patients in whom the pressure-gradient technique was used to measure stroke volume. In the group with minimal variations in hemodynamic status, the correlations between estimated and true stroke volume were reasonably good. In the patients having a wide range of hemodynamic conditions, considerable variation in both slopes and intercepts was observed, and the combined correlation coefficients were generally poor. Although pulse contour methods of estimating stroke volume may work reasonably well over a range of stroke volumes when the variation is induced by a single perturbing agent, none of these methods perform adequately when the variation is induced by multiple perturbing agents; thus their clinical usefulness is markedly limited.
Modifications of the Aortic and Vagal Depressor Reflexes by Hypercapnia in the Rabbit
Authors: OTT NORBERT T. , SHEPHERD JOHN T.
Published: June 2012

Changes in muscle and renal vascular resistances when the traffic in aortic or vagal nerves was interrupted were compared during normocapnia and hypercapnia in rabbits. The rabbits were anesthetized with sodium pentobarbital, paralyzed, and artificially ventilated; the sinus nerves were cut. A hind limb and a kidney were perfused at constant flow with autologous blood. With the vagi cut or cooled, blocking the aortic nerves by cooling caused a 49% and a 28% increase in limb and kidney perfusion pressures, respectively, during normocapnia (end-tidal CO
2
3-4%) and a 56% and a 69% increase during hypercapnia (end-tidal CO
2
8-10%). With the aortic nerves cut or cooled, vagal cold block increased the limb and kidney perfusion pressures 10% and 15%, respectively, during normocapnia and 17% and 61%, respectively, during hypercapnia. These responses were attenuated, especially in the kidney, when one of these pairs of nerves was intact (aortic nerve or vagus) and the other pair was blocked. Thus, hypercapnia augmented the vasodepressor reflexes from the aortic arch and the cardiopulmonary area. The effects of this phenomenon were greater on the renal vascular bed than they were on the muscle vascular bed.
Studies on the Coronary Circulation during Rejection of the Heterotopically Transplanted Dog Heart
Authors: PAOLONI HENRY J. , Wilcken DAVID E. L. , Lykke ATHOL W. J.
Published: June 2012

Coronary blood flow and vascular reactivity were studied at intervals after donor dog hearts were transplanted into the necks of recipient dogs. Coronary blood flow was measured with an electromagnetic flow transducer on the carotid artery of the recipient dog, and coronary vascular reactivity was assessed from the response of the coronary vessels to the vasodilator drugs, dipyridamole and adenosine. During the first 4 days after the transplant, resting coronary blood flow and vascular resistance did not change. Responses to dipyridamole and adenosine were unchanged during the first 2 days but were reduced on the third and fourth days. Increased vascular permeability to circulating Evans blue dye and deposition of colloidal carbon in venules occurred in association with small increases in left ventricular myocardial water content 3 and 4 days after the transplant. These changes indicate that an inflammatory response accompanies the onset of histological evidence of rejection at 3 and 4 days. The reduced vascular reactivity of the transplanted heart at 3 and 4 days may be related to morphological changes in arterioles rather than to gross edema formation during rejection.
Pharmacologic Receptor Activity of Rabbit Aorta
Authors: FLEISCH JEROME H. , KRŽAN MARIJA Č. , TITUS ELWOOD
Published: June 2012

N
-ethylmaleimide (NEM), an alkylating agent that covalently binds sulfhydryl groups, and dithiothreitol (DTT, Cleland's reagent), which reduces disulfide bridges to sulfhydryl groups, affected drug-induced contractions of rabbit aorta. NEM depressed aortic responses to potassium chloride (KCl), norepinephrine, serotonin, histamine, and angiotensin II. This action was attributed to an interaction of NEM with sulfhydryl groups vital to either the membrane function or the contractile apparatus. DTT had minimal effects on responses to KCl, norepinephrine, and serotonin; it potentiated aortic contractions produced by histamine and abolished responses to angiotensin II. Enhancement of the histamine response by DTT was not accompanied by an effect on the histamine-metabolizing enzymes or by an alteration in the K
B
and pA
2
values for pyrilamine. The results suggest that a disulfide bridge plays a prominent role in both histamine and angiotensin receptor activity of rabbit aorta. With regard to the histamine receptor system, two possibilities exist: (1) reduction of a disulfide bridge at some vital point increases receptor activity or (2) the histamine receptor system, normally in a reduced state, is oxidized in the artificial environment of the tissue bath and needs to be reduced to regain full activity.
Influence of Caffeine and Other Inotropic Interventions on the Onset of Unloaded Shortening Velocity in Mammalian Heart Muscle
Authors: HENDERSON ANDREW H. , CLAES VICTOR A. , BRUTSAERT DIRK L.
Published: June 2012

The onset of maximum unloaded shortening velocity was measured in cat papillary muscles by analyzing velocity with respect to time and length after zero load clamps imposed at different times. Unloaded shortening velocity rose rapidly to a constant level by 20% of the time to peak force under all conditions studied except with application of 10 m
M
caffeine, which markedly slowed its onset. Load-clamping experiments showed that the force-velocity-length interrelationship which characterizes shortening remained constant throughout most of shortening except with caffeine, which delayed the onset of steady state. It is suggested that the time course of the force-velocity-length interrelationship usefully describes
velocity active state
, the onset of which can be measured independently of force generation at zero load. In afterloaded contractions, manifestation of velocity active state may be delayed by the slower time course of force generation which precedes shortening. It is concluded that velocity active state normally rises rapidly to a constant level which describes the contractile state. Caffeine slows the onset of velocity active state, and valid time-independent force-peak velocity curves cannot be obtained in the presence of this drug.
Series Elastic and Contractile Elements in Vascular Smooth Muscle
Authors: DOBRIN PHILIP B. , CANFIELD THOMAS R.
Published: June 2012

Segments of dog common carotid artery were excised, cannulated, and restored to in situ length. They were immersed in a Krebs-Ringer's bath and inflated with 100% O
2
under nonoscillating pressure. Diameter was continuously monitored with a linear displacement transducer. The vessel segments were relaxed and then treated isometrically with norepinephrine to excite the muscle. These continuously contracted vessels were subjected to 10- or 25-mm Hg quick release steps to 0 mm Hg. Then the muscle was inactivated with potassium cyanide, and the quick releases were repeated to study the parallel elastic elements. Finally, vessel wall volumes were determined radiographically. Computations were performed to compute series elastic element stiffness for both the Maxwell and the Voigt model of the arterial wall. These experiments indicated that the series elastic element stiffness was dependent on the applied stress and independent of muscle length provided that the vessels were excited at initial strains less than 0.70. Vessels excited isometrically at various initial pressures up to 150 mm Hg yielded identical stress-series elastic element stiffness curves. The computed series elastic element extension at an applied stress of 1.0 x 10
6
dynes/cm was 18.9% for the Hill model and 14.7-17.9% for the Voigt model; these values are percents of the vessel diameter at 0 mm Hg after application of potassium cyanide. The values were reduced to 11.2% for the Maxwell model and 8.6-10.5% for the Voigt model when they were expressed as a percent of the circumferential length associated with the peak in the length-tension curve. Vessels excited isometrically at pressures higher than 150 mm Hg exhibited greater series elastic element extensibility.
Mechanism of Renal Handling of Angiotensin II in the Dog
Authors: OPARIL SUZANNE , BAILIE MICHAEL D.
Published: June 2012

The mechanism of renal handling of angiotensin II was studied in vivo in the renal circulation of the intact anesthetized dog and in vitro in whole blood using
14
C-5-Ile-angiotensin II,
l
-Asp-
125
I-angiotensin II, and
d
-Asp-
125
I-angiotensin II. Seventy-five percent of a 600-pmole bolus of
14
C-angiotensin II was degraded in a single passage through the kidney as measured by radioactive tracer and radioimmunoassay techniques. The metabolic products were
14
C-5-Ile (59%), 5-Ile-8-Phe (15%), and 3-Val-8-Phe (2%); recovery of the injected radioactive material was 99%. The degradation rate of
14
C-angiotensin II in whole dog blood in vitro was only 17%/min. Similar metabolic patterns were seen in vivo and in vitro. Sixty-six percent of the injected
l
-Asp-
125
I-angiotensin II was metabolized, but only 23% of the
d
-Asp-
125
I-angiotensin II was metabolized in a single passage through the kidney. These observations indicate that, under the conditions of these experiments, (1) angiotensin II is rapidly metabolized in the dog kidney by multiple enzymes, including an aminopeptidase, (2) circulating plasma enzymes do not account for the renal handling of angiotensin II, and (3) angiotensin II is not sequestered in the kidney.