bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Passive Elastic Stiffness for Isolated Heart Muscle and the Intact Heart
Authors: MIRSKY ISRAEL , PARMLEY WILLIAM W.
Published: June 2012

A sensitive method was developed for detecting stiffness changes in the left ventricle. Stress-strain relationships (σ--ε) were obtained in the form dσ/dε = kσ +
c
from published studies on eight normal canine hearts, five infarcted canine hearts, and seven isolated cat papillary muscles. Utilizing pressure-volume relationships, the elastic stiffness (dσ/dε) and the stiffness constant (
k
) were also evaluated in patients with normal ventricles, inappropriate hypertrophy, and congestive cardiomyopathy. The
k
values were 35.0 ± 1.7 (isolated muscle, 30°C), 37.3 ± 1.9 (normal canine, 23°C), and 23.9 (infarcted). For the patient groups,
k
and the passive elastic stiffness were 15.8 ± 0.3 and 249 ± 22.4 g/cm
2
for 13 normal patients, 26.4 ± 1.7 and 286 ± 32.0 g/cm
2
for 7 patients with inappropriate hypertrophy, and 20.1 ± 1.2 and 1360 ± 209 g/cm
2
for 6 patients with congestive cardiomyopathy. The results indicate that (1)
k
is sensitive to stiffness changes due to infarction, (2) hypertrophy causes an increase in the value of
k
although elastic stiffness remains within normal limits, and (3)
k
for the intact human heart is lower than it is for isolated muscle.
Length-Tension Relationship of Smooth Muscle of the Hog Carotid Artery
Authors: HERLIHY JEREMIAH T. , MURPHY RICHARD A.
Published: June 2012

The length-tension relationships for arterial smooth muscle were determined using vascular strips teased from the media of hog carotid arteries. Histological examination revealed that the strips were (1) free of adventitia and (2) composed of smooth muscle cells oriented parallel to the long axis of the strips. Measurements from electron micrographs indicated that 60% of the cross-sectional area consisted of smooth muscle. At L
0
(the optimal length for tension development) the total cross-sectional area of the strips varied from 0.3 to 0.8 mm
2
. Potassium-induced depolarization was the most effective stimulus for force development. Norepinephrine and electric field stimulation elicited responses which were 70% and 30%, respectively, of that produced by potassium-induced depolarization. At L
0
the intrinsic load-bearing capacity (P
0
) of the contractile system was 2.22 x 10
6
dynes/cm
2
. Tension development fell off gradually at lengths shorter than L
0
and more rapidly at lengths greater than L
0
. Passive length-tension curves were determined after quick releases from higher to lower lengths to avoid complications arising from tone. Passive tension was negligible at lengths below 0.9 L
0
. At L
0
the passive tension was 10% of P
0
.
Role of Muscular Contraction in the Reflex Vascular Responses to Stimulation of Muscle Afferents in the Dog
Authors: CLEMENT DENIS L. , PELLETIER CONRAD L. , SHEPHERD JOHN T.
Published: June 2012

The effect of stimulation of somatic afferents from muscle was investigated in 24 anesthetized dogs. The carotid sinuses were isolated and kept at constant pressure, the vagi were cut, and the left iliac artery was isolated and perfused at constant flow. Muscle afferents were stimulated by either inserting electrodes into the muscles of the right thigh or stimulating the central end of the right femoral nerve. Muscle stimulation at 5 Hz decreased perfusion pressure in the iliac artery 76 ± 6 mm Hg (mean ± SE ); the decrease was not prevented by paralysis of the stimulated muscles, administration of atropine or antihistamines, or -receptor blockade. Muscle stimulation at 40 Hz increased perfusion pressure in the iliac artery 28 ± 3 mm Hg. This increase was prevented or changed to a depressor response by muscle paralysis. Similar effects were obtained with femoral nerve stimulation. Both depressor and pressor responses persisted after the leg had been skinned and the muscles had been separated from their tendons, but they were abolished by left sympathectomy. Thus, skeletal muscle contraction is necessary for activation of the muscle afferents which cause reflex vasoconstriction but not for activation of those which cause reflex vasodilatation.
Effect of Dietary Sodium Intake on the Intrarenal Distribution of Nephron Glomerular Filtration Rates in the Rat
Authors: COELHO JAIME B.
Published: June 2012

Redistribution of single nephron glomerular filtration rate (SNGFR) between superficial (S) and juxtamedullary (JM) nephrons is thought to participate in the renal adaptation to different levels of dietary sodium intake. This possibility was examined using the Hanssen technique which measures SNGFR as the
14
C-ferrocyanide content of microdissected nephrons factored by the mean plasma concentration following a 12-second infusion. Rats from the same litter were placed on a low-sodium (0.8 mEq/day) or a high-sodium (9 mEq/day) diet. The distribution of SNGFR was measured as the S/JM (mean of S nephrons/mean of JM nephrons) SNGFR ratio. In spite of an eightfold change in sodium excretion, there was no significant change in the S/JM SNGFR ratio (low sodium - high sodium: -0.0033 ± 0.048 [
SE
],
P
> 0.9). Seven rats that were not littermates were maintained on a standard diet but drank saline (13 mEq sodium/day); carotid and ureteral catheterization and the duration of the diet (3-14 weeks) had no effect on the S/JM SNGFR ratio (
P
> 0.1), which was similar to that of nine rats maintained on a standard diet with water for drinking (3 mEq sodium/day). The value of the S/JM SNGFR ratios were 0.77 and 0.83, respectively. These variations in dietary sodium intake appeared to have no detectable effect on the intrarenal SNGFR distribution.
Myocardial Nucleotide Synthesis from Purine Bases and Nucleosides
Authors: NAMM DONALD H.
Published: June 2012

14
C-Labeled adenosine, inosine, hypoxanthine, and adenine were extracted by the isolated rat heart in amounts proportional to their concentration in the perfusion medium between 0.05 and 5 µM. With each of the precursor materials, nearly all of the radioactivity retained by the heart was identified as acid-soluble nucleotide. Nucleotide formation from the four isotopic precursors occurred at similar rates when the concentration of the precursors was below 1 µM. Above this concentration, the heart appeared to utilize adenosine for nucleotide synthesis at rates three to five times those for the other purines. Several experimental approaches were employed to determine the predominant enzymatic routes in the rat heart for the conversion of the nucleosides adenosine and inosine to nucleotides. The results indicated that adenosine was directly phosphorylated to 5'-adenosine monophosphate by a nucleoside kinase. Inosine appeared to proceed to the nucleotide, at least partially, through an initial conversion to hypoxanthine.
Effect of Hematocrit and Colloid-Induced Changes in Blood Viscosity on Renal Hemodynamics and Renin Release in the Dog
Authors: McDONALD KEITH M.
Published: June 2012

This study compared the effects on the kidney of two major determinants of blood viscosity, the hematocrit and the plasma colloid content. In anesthetized dogs, blood viscosity was raised 30% by increasing hematocrit or infusing isoncotic Dextran 500 while blood volume was kept constant. Neither form of hyperviscosity altered blood pressure, but both forms caused a decrease of about 35% in cardiac output and a comparable rise in total peripheral resistance. Renal blood flow decreased minimally (<10%) in the group of dogs with increased hematocrit but fell more than 30% in the group given Dextran 500. Reciprocal changes occurred in renal vascular resistance. The increase in hematocrit was accompanied by an increase in renin secretion from 146 units/min to 416 units/min (
P
<0.001), but Dextran 500 caused a decrease from 167 units/min to 107 units/min (
P
<0.025). Sodium and potassium excretion both decreased similarly in the two groups. The data suggest that increased hematocrits are accompanied by renal vasodilatation so that renal vascular resistance rises less than blood viscosity. Dextran hyperviscosity, however, causes no compensatory vasodilatation. This difference in renal vascular response might explain the difference in renin secretion; afferent arteriolar dilatation might stimulate renin release during a rise in hematocrit, and the absence of vasodilatation in colloid hyperviscosity might explain its failure to stimulate renin.
Reflex Hemodynamic Responses Initiated from the Thoracic Aorta
Authors: LIOY FRANCO , MALLIANI ALBERTO , PAGANI MASSIMO , RECORDATI GIORGIO , SCHWARTZ PETER J.
Published: June 2012

In anesthetized vagotomized cats with both carotid arteries occluded, stretch of the walls of the thoracic aorta performed without obstructing aortic blood flow induced reflex increases in arterial blood pressure (systolic: 136 ± 4 [
SE
] to 170 ± 7 mm Hg), heart rate (230 ± 10 to 236 ± 11 beats/min), and maximum rate of rise of left ventricular pressure (dP/dt max) (2,337 ± 256 to 3,155 ± 302 mm Hg/sec). In cats with spinal transection (C
1
), similar increases were observed. These responses were abolished by infiltrating the walls of the thoracic aorta with xylocaine. In adrenalectomized cats with intact central nervous systems, reflex responses were reduced but were still statistically significant. Phenoxybenzamine abolished the pressor response but not the increases in heart rate and dP/dt max. Propranolol drastically reduced the increases in heart rate and dP/dt max but not the pressor response. It is concluded that stretch of the thoracic aorta induced an increase in sympathetic activity affecting the heart, the peripheral vessels, and, probably, the adrenal glands through a spinal reflex.
Chronotropic Effects of Ouabain and Heart Rate on Canine Atrium in Vivo
Authors: WITTENBERG STEPHEN M.
Published: June 2012

Positive chronotropic effects from the combination of ouabain administration and rapid stimulation were sought in the atrium and ventricle of ten anesthetized vagotomized dogs with intact atrioventricular conduction during the infusion of ouabain (1 µg/kg min
-1
) until the onset of ventricular tachycardia. Sinus rhythm was interrupted every minute by 15 seconds of atrial pacing at either 150 or 200 beats/min. Positive chronotropic effects were recognized immediately after pacing as (1) early ventricular escape beats during vagal stimulation, (2) early atrial escape beats during vagal stimulation, or (3) blunting of the normal postpacing atrial depression. Positive chronotropic effects were rate dependent in both chambers, but they were seen less often in the atrium than in the ventricle. Early ventricular escape beats occurred in all ten dogs at a pacing rate of 200 beats/min when 69 ± 12% of the dose of ouabain required to induce ventricular tachycardia had been administered. They occurred in six of ten dogs at 150 beats/min after infusion of 81 ± 6% of the dose of ouabain which induces tachycardia. Early atrial escape beats did not occur when the hearts were paced at 150 beats/min. However, they appeared in three of ten dogs paced at 200 beats/min after infusion of 93 ± 5% of the dose of ouabain which induces tachycardia. Blunting of the normal postpacing atrial depression occurred in six of ten dogs at both 150 and 200 beats/ min at 100 ± 4% and 89 ± 5%, respectively, of the dose of ouabain required to induce ventricular tachycardia. Six additional dogs with heart block were paced at an atrial rate of 250 beats/min to facilitate positive chronotropic effects in the atrium with simultaneous ventricular pacing at 60 beats/min to delay the onset of positive chronotropic effects in the ventricle. This procedure allowed more consistent and relatively earlier detection of atrial positive chronotropic effects. In these experiments, early atrial escape beats occurred in five dogs after infusion of 80 ± 3% of the dose of ouabain required to induce ventricular tachycardia, and blunting of the normal postpacing atrial depression occurred in all six dogs after 78 ± 3% of the tachycardia-inducing dose of ouabain had been infused. It was concluded that toxic doses of ouabain induce positive chronotropic effects in the atrium of intact dogs. The effects occur later than do similar effects in the ventricle. Moreover, the positive chronotropic effects are heart rate dependent in both chambers and can be studied by atrial-ventricular; differential rate experiments.
Correlation of Maximum Aortic and Carotid Flow Acceleration in Chronically Instrumented Dogs
Authors: GAMS EMMERAM , HUNTSMAN LEE L. , CHIMOSKEY JOHN E.
Published: June 2012

Peak flow acceleration measured in the common carotid artery was compared with peak flow acceleration measured in the ascending aorta of five chronically instrumented dogs. Electromagnetic flow sensors, myocardial electrocardiographic leads, right atrial catheters, and coronary occluders were implanted through an incision of the chest at the fourth intercostal space and a ventral midline incision of the neck under sterile conditions while the dogs were anesthetized with sodium pentobarbital. Experiments began 10 days after surgery. We investigated the response to exercise, to 60-second occlusions of the circumflex branch, the anterior descending branch, or both branches of the left coronary artery, to induction of short-acting barbiturate anesthesia, and to intravenous infusion of three concentrations each of isoproterenol (0.8, 1.5-3.0, and 4.0 µg/min),
l
-norepinephrine (0.8, 2.0, and 4.0 µg/min), and acetylcholine (0.3-0.5, 0.8-2.0, and 4.0 mg/ min). During coronary occlusion, exercise, and induction of anesthesia, both accelerations changed in the same direction and approximately to the same extent. During isoproterenol infusion, both accelerations increased, but the maximum carotid flow acceleration increased more than did the maximum aortic flow acceleration. When
l
-norepinephrine was infused, the changes were small and were not always in the same direction. When acetylcholine was infused, peak carotid flow acceleration decreased. Peak carotid flow acceleration might be useful as an indirect measure of myocardial mechanical performance during coronary occlusion, anesthesia, and exercise, except during potent peripheral vasodilation like that caused by acetylcholine.
Pathophysiology of Aortic Baroreceptors in Rabbits with Vitamin D Sclerosis and Hypertension
Authors: ANGELL-JAMES JENNIFER E.
Published: June 2012

Calciferol (vitamin D
2
) (50,000-100,000 IU) and calcium lactate (1 g) were added to the normal diet of 22 rabbits for 7-11 days. When mean arterial blood pressure had risen from a control value of 87.2 ± 3.7 mm Hg to an experimental value of 137.8 ± 5.7 mm Hg (11-145 weeks), the aortic arch of 9 of these rabbits was isolated and perfused with Krebs-Henseleit solution. The impulse activity in 75 aortic baroreceptor fibers from the left aortic nerve was studied during nonpulsatile perfusion at different pressures and was compared with the impulse activity in 29 fibers from 17 normal rabbits. The threshold pressures and the pressure at the point of inflection of the curves were lower in these fibers than they were with fibers from normal rabbits. The gradient of the curves relating baroreceptor impulse frequency to aortic pressure was depressed from a normal mean value of 1.19 impulses/sec mm Hg
-1
to 0.61 impulses/sec mm Hg
-1
(
P
< 0.001). A similar depression of the gradient was found in 7 baroreceptor fibers from the right aortic nerve. The change in the sensitivity of the baroreceptors was more closely related to the time interval after the calciferol treatment (
r
=-0.95) than it was to the mean arterial blood pressure (
r
= -0.76). The pressure-volume curves show that it was also related to the decreased distensibility of the aortic arch region. Histologically, the aortic arch region had extensive medial sclerosis with calcification.
Microelectrode Study of Alternating Responses to Repetitive Premature Excitation in Canine Purkinje Fibers
Authors: BANDURA JACK P. , BRODY DANIEL A.
Published: June 2012

Microelectrode studies were performed to produce alternation of coupled beats in the specialized conduction system of the heart and to determine the underlying mechanisms of their production. A typical preparation consisted of a superfused Y-shaped bifurcating segment of canine Purkinje tissue, in which the two branches of the Y were approximately symmetrical and terminated in a functionally communicating bridge of myocardium. Transmembrane potentials were recorded simultaneously from a proximal and a distal location in one branch of the Y. Stimulating the stem of the preparation with 60 pulse pairs/min at a critical coupling interval produced alternation of the coupled beats. Alternate reversal of the proximl-to-distal sequence of activation was observed under these circumstances. This finding probably resulted from alternate antegrade block of the instrumental branch accompanied by retrograde conduction through the accessory pathway offered by the other branch and the common myocardial bridge. The validity of this inference was confirmed by microelectrode exploration and by transection of the retrograde pathway. Analysis of the results demonstrated further that alternating block was also intimately related to the alternation of preceding cycle lengths.
Stimulation of Prostaglandin Biosynthesis by Adenine Nucleotides
Authors: NEEDLEMAN PHILIP , MINKES MARK S. , DOUGLAS JAMES R.
Published: June 2012

Prostaglandin release from various isolated perfused organs is characteristically dependent on the stimulus; thus, certain stimuli caused prostaglandin release in some organs and not in others. Adenosine triphosphate and adenosine diphosphate were potent stimulators of prostaglandin biosynthesis in the kidney, spleen, spleen fat pad, heart, liver and lung; adenosine monophosphate and adenosine were inactive. Epinephrine caused prostaglandin release from the kidney, spleen, and liver, whereas, angiotensin was agonistic in the kidney, spleen, spleen fat pad, and liver. Indomethacin abolished the release (biosynthesis) of prostaglandins from all organs by each agonist.
Force-Velocity and Series Elastic Characteristics of Smooth Muscle from the Hog Carotid Artery
Authors: HERLIHY JEREMIAH T. , MURPHY RICHARD A.
Published: June 2012

The force-velocity and series elastic characteristics of vascular strips from the media of hog carotid arteries were determined using the method of quick release to a known afterload. Shortening velocity was a function of load, and the data could be fitted by a rectangular hyperbola using the Hill equation, (P + a) V = b (P
o
- P), where P is the load, P
o
is the maximum isometric force developed at the optimum muscle length (L
o
), V is velocity, and a and b are constants. The following dynamic constants were obtained for the electrically stimulated strips: estimated maximum shortening velocity for the unloaded muscle (V
max
) = 0.12 L
o
/sec, b = 0.02 L
o
/sec, P
o
= 1.80 kg-wt/cm
2
= 1.76 x 10
6
dynes/cm
2
, and a/P
o
= 0.18. Maximum power output occurred at a load of 0.28 P
o
. The stress-strain curve for the series elastic component could be approximated by the simple exponential equation, stress = 0.034e
058 strain
. The extension of the series elastic component at P
o
was 7.2% of L
o
.
Lipid Composition and Metabolism of Thromboatherosclerotic Lesions Produced by Continued Endothelial Damage in Normal Rabbits
Authors: DAY ALLAN J. , BELL FRANK P. , MOORE SEAN , FRIEDMAN ROBERT
Published: June 2012

Thromboatherosclerotic and fibrous lesions were produced by endothelial damage with polyethylene catheters inserted into the aortas in rabbits on a normal diet. Two weeks after insertion of the catheters, the concentration of both free cholesterol and cholesteryl ester in the thromboatherosclerotic lesions was significantly greater than that in the adjacent normal intima. A further increase in the concentration of free cholesterol and particularly of cholesteryl ester occurred during the remainder of the 4-month study period. Gas-liquid chromatography indicated that the raised thromboatherosclerotic lesions contained more cholesteryl oleate and less cholesteryl linoleate than did either the normal intima or the fibrous lesions. The incorporation of [1
-14
C] oleic acid into combined lipid in the aortas incubated in vitro showed that, by 2 weeks, two to three times more oleic acid had been incorporated into cholesteryl ester in the thromboatherosclerotic raised lesions than in the normal intima. A similar increase was demonstrated at 2 and 4 months. When [
32
P] phosphate was used as a precursor, incorporation into lecithin was higher and incorporation into phosphatidyl inositol was lower in the raised lesions than they were in the normal intima. Fibrous lesions did not differ significantly from the adjacent normal intima in their incorporation of either of these precursors into lipid. Therefore, the accumulation of cholesteryl ester in the thromboatherosclerotic lesions resulted in part from synthesis in the arterial wall, which was stimulated by the prominent platelet components of the lesions.
Calcium Requirements for Cardiac Myofibrillar Activation
Authors: SOLARO R. JOHN , WISE ROBERT M. , SHINER JOHN S. , BRIGGS F. NORMAN
Published: June 2012

The amounts of calcium required to achieve various levels of myofibrillar activation in the dog heart were determined by measuring the dependence of myofibrillar calcium binding, myofibrillar adenosinetriphosphatase (ATPase), and isometric tension on free calcium concentration. Myofibrillar ATPase was half-maximal at 2.4 x 10
-6
M free calcium, and tension development was half-maximal at 2.0 x 10
-6
M free calcium. No simple relation between calcium binding and activation was found. For example, between 10
-8
M and 10
-6
M free calcium, an appreciable amount of calcium was bound to the myofibrils, but there was little activation of isometric tension. On the other hand, myofibrillar calcium binding was not saturated at levels of free calcium at which both tension and ATPase were maximal; therefore, it appears that only a portion of the total myofibrillar calcium binding sites control ATPase and tension. Using the information derived from the binding and activation studies together with our determination of the myofibrillar content of the dog heart, 47.5 mg myofibrillar protein/g wet heart, we calculated the calcium required to achieve various levels of myofibrillar activation in the intact ventricle. By this calculation method, development of half-maximal tension required 22.4 µmoles calcium/kg wet heart, and development of maximal isometric tension required 92.8 µmoles/kg wet heart.
Pressures in Cat Mesenteric Arterioles and Capillaries during Changes in Systemic Arterial Blood Pressure
Authors: GORE ROBERT W.
Published: June 2012

An interpretive model of the myogenic autoregulatory response of cat mesenteric arterioles has appeared in the literature; it describes arteriolar dimensional changes during changes in mean systemic arterial blood pressure in terms of tension-radius diagrams (Laplace relationship). The original model assumes that arteriolar pressure is a simple, linear function of systemic blood pressure and that arteriolar pressure is always 40% of systemic blood pressure. The purpose of the present study was to test the validity of these assumptions. Using the isolated, autoperfused mesentery of 14 cats, direct, simultaneous measurements of diameter and pressure were made in microvessels during changes in systemic blood pressure. Diameters and micropressures were recorded with a video filar micrometer system and a servonull transducer, respectively. Control microvascular pressure, dimensional distributions, and stress distributions were established when systemic blood pressure was set at 100 ± 10 (
SD
) mm Hg. Three regions of the arteriolar vasculature were defined and identified for study in terms of these control states. Pressures in the arteriolar regions were a linear function of systemic blood pressure, thus confirming the validity of the previous assumption. Capillary pressures tended not to follow this pattern; pressure in five of eight capillaries sampled was relatively independent of changes in systemic blood pressure between 100 and 40 mm Hg. The apparent constancy of capillary pressure during changes in systemic blood pressure was examined in terms of the modular arrangement of mesenteric microvessels and resistance changes, and the question of physiological regulation of capillary pressure was considered. Data are presented to suggest that a constant capillary pressure in mesentery during changes in systemic blood pressure is primarily the consequence of the vascular geometry peculiar to this tissue.
Effect of Epinephrine on Pressure, Flow, and Volume Relationships in the Systemic Circulation of Dogs
Authors: CALDINI PAOLO , PERMUTT SOLBERT , WADDELL JAMES A. , RILEY RICHARD L.
Published: June 2012

The effect of epinephrine on peripheral circulation was studied in ten anesthetized open-chest dogs. Blood flow and right atrial pressure were independently controlled by a right heart bypass; changes in blood volume could be precisely determined from the changes occurring in the bypass reservoir. At constant blood flow and right atrial pressure, a constant infusion of epinephrine (5.8 µg/kg min
-1
) decreased blood volume by an average of 208 ml. During epinephrine infusion, the ratio of changes in blood volume to changes in blood flow measured at constant right atrial pressure, (Δ
V
/Δ

Q
·

)
Pra
, decreased from 0.226 minutes to 0.153 minutes and the ratio of changes in blood volume to changes in right atrial pressure at constant blood flow, the vascular compliance, decreased from 27.1 ml/cm H
2
O to 20.7 ml/cm H
2
O. Transient changes in blood volume following a step decrease in right atrial pressure at constant blood flow showed that blood was draining from two vascular compartments with different time constants: 0.059 minutes and 0.388 minutes before epinephrine infusion and 0.058 minutes and 0.486 minutes during epinephrine infusion. We analyzed the data using a mathematical model of the peripheral circulation consisting of two compartments with different time constants. The analysis showed that the primary effect of epinephrine on the systemic circulation was to redistribute blood flow away from the compartment with the longest time constant. The reduction in (ΔV/Δ

Q
·

)
pra
and the decrease in blood volume at constant flow and right atrial pressure were essentially determined by the change in flow distribution brought about by a change in arteriolar tone and not by a change in venous tone.
Defective Esterase and Kinin-Forming Activity in Human Fletcher Trait Plasma
Authors: DONALDSON VIRGINIA H. , SAITO HIDEHIKO , RATNOFF OSCAR D.
Published: June 2012

Fletcher trait plasma failed to generate kinin and developed only a small amount of arginine esterase activity at an abnormally slow rate following surface activation. Neither defect was due to a deficiency of Hageman factor (HF, factor XII) or kininogen or to an excessively rapid inactivation of evolving kinin. Pyrex pretreated with Fletcher trait plasma did not generate kinin normally in fresh normal plasma. Fractions rich in prekallikrein prepared from normal, HF-deficient, or plasma thromboplastin antecedent (PTA)-deficient plasma developed kallikrein activity by direct activation during incubation with trypsin or HF fragments formed by digesting partially purified HF with trypsin. In contrast, identical fractions of Fletcher trait plasma did not develop this activity. Although this finding suggested that Fletcher trait plasma was deficient in prekallikrein, materials eluted from Celite that had been incubated in Fletcher trait plasma contained both esterase and kinin-generating activities. Celite eluates prepared from normal and Fletcher trait plasma released kinin from partially purified kininogen equally well. This release was blocked by soybean trypsin inhibitor but not by lima-bean trypsin inhibitor. Therefore, although unfractionated Fletcher trait plasma appears to be functionally and antigenically deficient in normal prekallikrein, it may actually contain a different prekallikrein which is activated by exposure to Celite but not by exposure to activated HF or trypsin.
Computer Model of Cardiac Potential Distribution in an Infinite Medium and on the Human Torso during Ventricular Activation
Authors: D'ALCHÉ PAUL , DUCIMETIERE PIERRE , LACOMBE JACQUES
Published: June 2012

The cardiac electrical field produced by the depolarization of the ventricles of a human heart was simulated with a computer, and the results were presented as isopotential maps. Computations were first done with the heart theoretically immersed in an infinite homogeneous medium and then with it located inside a homogeneous human torso. The principal feature of the model was that only the cardiac regions actually engaged in the depolarization generated an electrical current. Owing to their thinness, these regions could be reduced to the surfaces separating active and inactive cardiac zones at a definite instant. The surfaces used were the isochronal surfaces published by Durrer et al. for the pattern of ventricular excitation in a human heart. The assumption was made that the current flowed perpendicularly and with the same strength at each point on the surfaces. The isopotential maps were drawn on a cylindrical surface surrounding the heart and on the torso. The simulated maps were described in connection with the cardiac activation and compared with experimental maps.
Time Behavior of Series Elasticity in Cardiac Muscle
Authors: MCLAUGHLIN ROBERT J. , SONNENBLICK EDMUND H.
Published: June 2012

Controlled-length quick releases were applied to cat papillary muscle at various times during an isometric contraction to study the series elasticity of cardiac muscle relative to time. Force and length were measured continuously during the course of constant-velocity releases. Series elastic compliance was evaluated from semilogarithmic plots with force referred to plateau levels. The force-extension curve of the series elastic element (SE) was exponential; the compliance of the SE varied with force independently of time. Series elastic compliance relative to time was not altered by changes in initial muscle length. However, when series elastic compliance was measured by extrapolating tension to the end of the release, it appeared to be greater earlier in the twitch. This finding was misleading; it resulted from inadequate release velocities in relation to varying rates of tension redevelopment at different times in the twitch. Force-extension curves of the SE were nearly identical at different initial muscle lengths. Yet, conventional comparisons of series elastic compliance in terms of shortening of the SE between peak tension and preload showed wide variation with initial length, because different portions of the force-extension curve were measured. This problem was avoided by expressing series elastic compliance in terms of the exponential length change (
x
e
) necessary to reduce force by the factor 1/
e
= 0.368 anywhere on the force-extension curve. The average value of
x
e
, in 23 determinations was 1.87 ± 0.26% of initial muscle length; this value is about 25% smaller than that reported previously. Because of the exponential shape of the force-extension curve of the SE, the possibility of substantial series elasticity in myofilament cross-bridges cannot be excluded. However, until convincing evidence is presented to the contrary, it is suggested that the series elasticity of cardiac muscle be regarded as a passive element as it is in the traditional Hill model.
Autoregulation of Single Nephron Filtration Rate in the Presence and the Absence of Flow to the Macula Densa
Authors: KNOX FRANKLYN G. , OTT COBERN , CUCHE JEAN-LOUIS , GASSER JOSIANNE , HAAS JOHN
Published: June 2012

Flow of tubule fluid to the macula densa is part of a proposed feedback loop for autoregulation of glomerular filtration rate. In the present study, autoregulation of single nephron filtration rate was tested in the presence and the absence of flow to the macula densa in the rat. Filtration rates were measured at elevated arterial blood pressures caused by carotid occlusion and vagal section and at reduced renal perfusion pressures caused by partial aortic constriction. Measurements of single nephron filtration rate in the presence and the absence of flow to the macula densa were obtained by complete volume collections from the distal nephron beyond the macula densa and from the proximal tubule, respectively. Mean blood pressure was 130 ± 4 (SE) mm Hg for the initial collections, and renal perfusion pressure was 100 ± 1 mm Hg for the repeat collections (nine rats). Distal single nephron filtration rate was 42 ± 1 nliters/min at elevated perfusion pressure and 41 ± 1 nliters/min at reduced perfusion pressure; proximal single nephron filtration rate was 41 ± 1 nliters/min at elevated perfusion pressure and 41 ± 1 nliters/min at reduced perfusion pressure. Similarly, glomerular filtration rate was 4.6 ± 0.4 ml/min kg
-1
body weight and 4.7 ± 0.3 ml/min kg
-1
body weight at elevated and reduced perfusion pressures, respectively. Additional studies in seven dogs showed good correlation between autoregulation of single nephrons in the absence of flow to the macula densa and autoregulation of the micropunctured kidney. It is concluded that autoregulation of single nephron filtration rate is unaltered by interruption of tubule fluid flow to the macula densa.
Studies on the Cardiomegaly of the Spontaneously Hypertensive Rat
Authors: FARMER BARBARA B. , HARRIS ROBERT A. , JOLLY WALTER W. , VAIL WILLIAM J.
Published: June 2012

Changes in size, morphology, and certain relevant biochemical components of hearts from spontaneously hypertensive and normal Wistar rats were studied comparatively. Groups of rats were killed at stages which represented developing and stable cardiac hypertrophy and approaching cardiac failure. Mitochondrial content was determined by comparing cytochrome oxidase activity per milligram of heart homogenate protein with cytochrome oxidase activity per milligram of heart mitochondrial protein. Based on the relationship of heart weight and body weight found in normotensive rats (hearts weight [mg] = 1.85 x body weight [g] + 287), left ventricular dimensions, and micrographs of left ventricular muscle fibers, hypertrophy of the hearts from the spontaneously hypertensive rats was conclusively demonstrated. Approximately 25% of the total heart protein was mitochondrial in both control and hypertensive rats; the percent increased during the period of rapid growth but subsequently decreased with age. The amount of heart mitochondrial protein was greater for spontaneously hypertensive rats relative to body weight but was not greater relative to heart weight. The maximum increase in heart mitochondria relative to body weight was observed in 6-month-old spontaneously hypertensive rats, whereas the maximum increase in heart weight occurred at 12 months of age. A decrease in heart weight occurred in 17-month-old spontaneously hypertensive rats. No preferential retention of mitochondria was apparent during atrophy induced by starvation in either control or hypertensive rats.
Effects of Obstruction of the Mitral Orifice or Distention of the Pulmonary Vein-Atrial Junctions on Renal and Hind-Limb Vascular Resistance in the Dog
Authors: MASON JAMES M. , LEDSOME JOHN R.
Published: June 2012

This investigation attempted to determine whether stimulation of intrathoracic receptors, including those in the left atrium, is associated with changes in renal vascular resistance. In 19 dogs, the left kidney was perfused at constant pressure and the right hind limb was perfused at constant flow. A partial obstruction of the mitral orifice that increased left atrial pressure by less than 20 cm H
2
O caused tachycardia, hypotension, renal vasodilatation (5% increase in flow), and hind-limb vasoconstriction (10% increase in pressure). A partial obstruction of the orifice that raised left atrial pressure more than 20 cm H
2
O caused tachycardia, hypotension, and more hind-limb vasoconstriction (20% increase in pressure), but renal vascular resistance did not change. After bilateral vagotomy in either the thorax or the neck, partial obstruction of the mitral orifice caused constriction in both the renal and the hind-limb vascular beds. In 10 dogs, localized distention of three pulmonary vein-left atrial junctions caused an increase in heart rate and a small but significant increase in renal blood flow but had no effect on hind-limb vascular resistance. At least a part of the reflex renal dilatation caused by mitral obstruction probably resulted from stimulation of left atrial receptors.
Effect of Ischemia on Capillary Pressure and Equivalent Pore Radius in Capillaries of the Isolated Dog Hind Limb
Authors: DIANA JOHN N. , LAUGHLIN M. HAROLD
Published: June 2012

Measurements were made of filtration coefficients (

L
p

), area per unit path length (
A
/Δ
x
), and equivalent pore radius (

r
p

) in the control state and following severe ischemia (arrested blood flow) for periods of 30 minutes, 1 hour, and 3 hours. The value of

A
s

/Δ
x
for diffusion of all lipid-insoluble substances was not changed after 30 minutes of ischemia, but it was increased after 1 and 3 hours of ischemia. The value of

r
p

calculated from the theory of restricted diffusion yielded values of 34-35 Å for both the control period and after all three periods of ischemia. Combination of hydrodynamic data (

L
p

) and diffusion data (
A
ω
/Δ
x
) yielded values for

r
p

of 23 Å for control and ischemic periods. Measurements of plasma-protein osmotic pressure, tissue-protein osmotic pressure, tissue hydrostatic pressure, and capillary hydrostatic pressure supported the conclusion that extended periods of arrested blood flow did not affect muscle capillary membrane porosity. In 5 of 16 hind limbs, there appeared to be a porosity change following 3 hours of arrested blood flow. This change was demonstrated by a net decrease in plasma-protein osmotic pressure and an increase in

r
p

from 34 Å to 54 Å.

L
p

was not changed after 30 minutes but was increased after 1 hour of ischemia; the increase was associated solely with an increase in capillary surface area. After 3 hours of ischemia, the primary change in 11 of 16 hind limbs was an increase in capillary surface area, although an increase in the size of the pores per unit membrane area could not be rigorously excluded. In 5 hind limbs after 3 hours of ischemia, an increase in

r
p

was the primary change and an increase in capillary surface area was of secondary importance. The data indicate that the edema which occurs subsequent to reperfusion of the vasculature after moderately long periods of severe ischemia results from an increase in capillary hydrostatic pressure augmented by an increase in capillary surface area not associated with an increase in membrane porosity. The rise in capillary pressure for any given arterial or venous pressure involves a decrease in precapillary resistance, but postcapillary resistance does not change for any given flow.
Hypoxic Pulmonary Vasoconstriction in the Rat
Authors: BERKOV STEVEN
Published: June 2012

In isolated blood-perfused rat lungs, brief periods of ventilation hypoxia (2% O
2
) produce pulmonary vasoconstriction. In isolated lungs perfused with a salt-albumin solution, hypoxia produces no pulmonary vasoconstrictor responses in most preparations and only minimal responses in others. Vasoactive agents including angiotensin II, phenylephrine, epinephrine, norepinephrine, bradykinin, histamine, serotonin, and methoxamine were added to the salt-albumin perfusate to determine which substance, if any, was necessary for a pulmonary vasoconstrictor response during hypoxia. The addition of angiotensin II (12-120 nM) to the perfusate during hypoxia resulted in marked pulmonary vasoconstriction in proportion to the amount of angiotensin II added (a maximal response to hypoxia occurred with 120 nM angiotensin II). None of the other agents had the same effect, nor was their vasoactivity dependent on angiotensin II. Angiotensin II augmented the hypoxic response in doses that are themselves subpressor; tachyphylaxis to the direct pressor activity of angiotensin II was not associated with attenuation of the hypoxic response. These results suggest that an action of angiotensin II that is separate from its pressor activity is specifically required for a significant vasoconstrictor response to hypoxia in isolated rat lungs.
Onset of Mechanical Activation of Mammalian Heart Muscle in Calcium- and Strontium-Containing Solutions
Authors: BRUTSAERT DIRK L. , CLAES VICTOR A.
Published: June 2012

The time course of the relationship between force, shortening velocity, and length during shortening was examined in mammalian heart muscle in calcium (Ca)-containing solutions and solutions with strontium (Sr) substituted for Ca by imposing load clamps of various amplitudes at various times during external shortening. The onset of this force-velocity-length relationship was measured by abruptly unloading the muscle at different times to nearly zero external load--by zero load clamping the muscle--under conditions of optimal damping; the subsequent unloaded active muscle shortening velocity was then analyzed with respect to time and length. In Ca- containing solution, the unloaded velocity in the length range around 90% of L
max
rose within 16% of the time required to reach peak isometric force to a maximum level appropriate to a given contractile state. Subsequently, the force-velocity-length relationship was independent of time at any load over a well-determined portion of external shortening. In Sr-containing solution, unloaded active velocity rose much slower to reach a steady state after 30-35% of the time to peak force, and the time independence of the force-velocity-length relationship was delayed until after this time. In Na-free Sr-containing solution, maximum unloaded shortening velocity and the time-independent portion of the force-velocity-length relationship were achieved again within 20% of the time to peak force. The effects of substitution of Sr for Ca thus resemble those of caffeine on mammalian heart muscle. These findings suggest a close relationship between the time course of the force-velocity-length relationship and the degree of activation.
Role of Potassium Ions in the Vascular Response to a Brief Tetanus
Authors: MOHRMAN DAVID E. , SPARKS HARVEY V.
Published: June 2012

Changes in the plasma potassium ion (K
+
) concentration in the venous effluent of isolated dog tibialis cranialis and extensor digitorum longus muscles were measured following 1 second of tetanic exercise (32 impulses/sec) during constant-flow perfusion. After a brief delay, venous plasma K
+
concentration increased to a peak change of 0.23 ± 0.02 mEq/liter and then returned to the control level within 1.5 minutes after the beginning of stimulation, representing a net K
+
loss of 1.7 µEq/100 g muscle. These experiments indicate a very short period of actual tissue-blood K
+
transfer, since the time course of the venous efflux can be explained almost entirely by the distribution of vascular transit times. Our best estimate is that a 1-second tetanus produces an immediate 1.3-2.4-mEq/liter increase in interstitial K
+
concentration which then returns to its control level with a time constant of 6-8 seconds due to rapid cellular reuptake. These K
+
concentration changes have sufficient magnitude and the correct time course to play a significant role in the production of the vascular response to a brief tetanus.
Effect of Beta-Adrenergic Stimulation on Myocardial Adenine Nucleotide Metabolism
Authors: ZIMMER HEINZ-GERD , GERLACH ECKEHART
Published: June 2012

The effects of isoproterenol, propranolol, and compound D600 (α-isopropyl-α-[(
N
-methyl-
N
-homoveratryl)-γ-aminopropyl1-3, 4, 5-trimethoxyphenylacetonitrile) on myocardial adenine nucleotide metabolism were studied in rat hearts in situ. Isoproterenol in doses between 0.1 and 25 mg/kg induced an increase in heart rate concomitant with a significant acceleration in the de novo synthesis of adenine nucleotides (ATP, ADP, and AMP) and a diminution in their concentration. The effects of isoproterenol were antagonized by propranolol (1 and 50 mg/kg), which alone caused a reduction in the de novo synthesis of adenine nucleotides without inducing a change in their concentration. Compound D600 (10 mg/kg) brought about a slight elevation in the concentration of adenine nucleotides but did not influence the rate of de novo synthesis. The isoproterenol-induced diminution in adenine nucleotide concentration was prevented by D600; under these conditions, the acceleration of de novo synthesis was attenuated. These findings indicate that de novo synthesis of myocardial adenine nucleotides in the normal and the isoproterenol-stimulated heart is regulated not only by a feedback mechanism dependent on the concentration of adenine nucleotides but also by β-receptor-mediated alterations in carbohydrate metabolism which can cause changes in the size of the available pool of 5-phosphoribosyl-1-pyrophosphate.
Relationship of Glucose Metabolism to Adrenergic Transmission in Rat Mesenteric Arteries
Authors: MALIK KAFAIT U. , McGIFF JOHN C.
Published: June 2012

The vasoconstrictor response of perfused rat mesenteric arteries to stimulation of sympathetic nerve fibers is markedly potentiated by glucose deprivation; this potentiation is abolished or reduced when glucose or other sugars are added. The augmentation of the vasoconstrictor response to nerve stimulation produced by glucose deprivation presumably results from an increased release of the adrenergic transmitter, since (1) the response to injected norepinephrine is much less affected by glucose deprivation and (2) the increase in the vasoconstrictor response to either adrenergic stimulus produced by inhibition of neuronal reuptake by cocaine is unaltered by glucose deprivation. The inhibitory effect of glucose may involve its metabolite(s). Pyruvic and lactic acids inhibit the vasoconstrictor response to nerve stimulation previously augmented by glucose deprivation but do not affect adrenergic transmission in the presence of glucose. Also, the inhibitory effect of glucose on the potentiated response is abolished by the simultaneous infusion of 2-deoxy-
D
-glucose or iodoacetic acid, inhibitors of glucose metabolism. The inhibitory effect of glucose and its metabolite(s) on adrenergic transmission may also involve changes in the ionic permeability of the nerve terminal. In the absence of glucose, raising the Na
+
and K
+
concentrations affects the vasoconstrictor response differently, namely, Na
+
potentiates and K
+
attenuates the response. These effects are abolished by addition of glucose. In contrast, the effects of increased concentrations of either Ca
2+
(facilitation) or Mg
2+
(inhibition) on neurotransmission are unaffected by removal or restoration of glucose. We conclude that glucose deprivation does not affect adrenergic transmission by acting directly through Ca
2+
. Rather, glucose deprivation decreases pyruvate and possibly other products of glucose metabolism, and these decreases, in turn, alter the concentrations of Na
+
and K
+
within the neuron. These latter changes then enhance the availability of Ca
2+
and, thereby, increase the release of the adrenergic transmitter.