bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Extracellular Potentials
Authors: SPACH MADISON S. , BARR ROGER C. , JOHNSON EDWARD A. , KOOTSEY J. Mailen
Published: June 2012

Extracellular recordings of normal action potentials, action potentials at reduced temperature, and action potentials initiated when the membrane was partially depolarized due to elevated extracellular potassium were made at varying distances from the surface of Purkinje strands of the dog left ventricle. As the electrode was withdrawn from the surface, the time between the positive and negative peaks increased; the amplitude of the simple biphasic wave form decreased markedly at first, and, thereafter, it decreased more gradually. The extracellular wave forms could be described by a single equation for all distances right up to the membrane surface even in the presence of interventions which drastically changed the intracellular potential and the conduction velocity. Wave forms of extracellular potentials at varying distances from the strand were computed from intracellular potentials and showed good agreement with the measured wave forms. Most major bundles in the dog conduction system have polyphasic extracellular wave forms rather than the relatively simple kind characteristic of the single strand. By using the equation that describes how the extracellular potential about a single strand varies as a function of distance, it was shown that the recorded polyphasic wave forms of the bundle studied resulted from the superposition of potentials from a number of asynchronously excited strands situated at varying distances from the recording electrode instead of from an underlying complex intracellular action potential. Extracellular recordings were chosen over intracellular recordings for this study, because they can indicate the presence of more than one excitation wave in a single record, thus permitting the resolution of the sequence of activation of the conduction system to its most elementary level.
Survival of Subendocardial Purkinje Fibers after Extensive Myocardial Infarction in Dogs
Authors: FRIEDMAN PETER L. , STEWART JAMES R. , FENOGLIO JOHN J. , WIT ANDREW L.
Published: June 2012

Alterations in cardiac electrophysiology that accompany myocardial infarction were studied in dogs subjected to a two-stage ligation of the anterior descending coronary artery. A multipolar transmural needle electrode was used to record electrical activity from the in situ infarcted heart 24 hours after coronary occlusion. Bipolar electrograms recorded from subendocardial regions of infarcted myocardium demonstrated the persistence of early, rapid deflections suggesting Purkinje fiber activity; evidence of ventricular muscle activity in the infarct was absent in both subendocardial and intramural electrograms. The infarcted myocardium and the adjacent non-infarcted tissue were then excised and studied with intracellular microelectrodes in vitro. Transmembrane action potentials could be recorded from one or two cell layers of subendocardial Purkinje fibers at all sites within the infarcted region, but no ventricular muscle action potentials were found. Subendocardial Purkinje fibers which survived in the infarct had reduced maximum diastolic potentials, action potential amplitudes, and maximum depolarization velocities compared with normal subendocardial Purkinje fibers; also, action potential durations in these surviving fibers were extraordinarily prolonged. Spontaneous diastolic depolarization was evident in some surviving fibers. Since subendocardial Purkinje fibers that generate abnormal action potentials survive in an infarct, these fibers may participate in the genesis of ventricular arrhythmias that accompany infarction.
Engineering Mechanics for Successive States in Canine Left Ventricular Myocardium
Authors: STREETER DANIEL D. , HANNA WILLIAM T.
Published: June 2012

The relations between end-diastolic (
D
) and end-systolic (
S
) fiber angles (α) and sarcomere lengths (
s
) have been previously studied at different sites in canine left ventricular myocardium. However, no postulates have been advanced for predicting a and s in successive states of the ejection cycle (
D
or S) or at different sites in one state when the semimajor (
Z
) and semiminor (R) axes of the wall surfaces for successive states and the fiber orientations and sarcomere lengths at one site in one state are known. In this study, the myocardial fibers were regarded as the matrix of a myocardial continuum: they are prisoners of the heart wall and must comply with the movements of the wall. Using the same values as in the preceding article, the wall was treated as a nested set of truncated ellipsoidal shells of revolution with shell volumes preserved from
D
to S. Both confocal and nonconfocal configurations were analyzed. In each shell, the fibers were assumed to follow a "helical" path with a constant advance in each turn about the
Z
axis (the simplest possible path). The results of this assumption were compatible with previously reported values of a and s measured at various sites in the left ventricular free wall in states
D
and
S
. These results suggest a postulate for the heart wall: in the beating heart, each muscle fiber changes direction and length uniquely as the wall changes shape.
Reactivity of Vascular Smooth Muscle in Hypertensive Rats
Authors: HOLLOWAY EDWIN T. , BOHR DAVID F.
Published: June 2012

The reactivity of vascular smooth muscle in helical strips from femoral arteries of normotensive, spontaneously hypertensive, renal hypertensive, and deoxycorticosterone acetate-- (DCA-) hypertensive rats was studied. Spontaneous rhythmic contractions occurred in 25 of the 30 strips from the three groups of hypertensive rats and in only 2 of the 10 strips from normotensive rats. Strips from renal and DCA hypertensive rats had lower thresholds to epinephrine and potassium chloride (KCl) than did strips from spontaneously hypertensive and normotensive rats. Lanthanum (2.5 mM) caused contraction of all 10 strips from spontaneously hypertensive rats but failed to cause contraction of any strip from the other three groups of rats. Strontium (5 mM) caused contraction in 8 of 10 strips from spontaneously hypertensive rats but caused contraction in only 7 of the 30 strips from the other three groups. The optimal calcium concentration for tension development in response to a KCl stimulus was approximately twice as high for strips from hypertensive rats as it was for strips from normotensive rats. Strips from DCA-hypertensive rats showed less tachyphylaxis to angiotensin II than did strips from the other three groups of rats. These results quantify our earlier observation that the reactivity of vascular smooth muscle from hypertensive rats is importantly different from that of normotensive rats. In addition, the study delineates individuality in vascular smooth muscle reactivity in different types of experimental hypertension. The results suggest that the cell membrane of the vascular smooth muscle in the hypertensive rat is more labile than that in the normal rat.
Genetic Influence of the Kidneys on Blood Pressure
Authors: DAHL LEWIS K. , HEINE MARTHA , THOMPSON KEITH
Published: June 2012

In two strains of rats with opposite genetic propensities for hypertension, interstrain renal transplants chronically modified the blood pressure of the recipients. The blood pressure of rats with these renal homografts was largely determined by the genotype of the donor kidney rather than by the genotype of the recipient. Kidneys from the hypertension-resistant (R) rats generally had an antihypertensive effect, and kidneys from the hypertension-prone (S) rats had a prohypertensive effect. These effects on blood pressure were most clear-cut in rats maintained on a low-sodium diet, but they were still evident in a modified form in rats on a high-sodium diet. Results from this study and from earlier studies suggest that kidneys from S rats have a greater hypertensinogenic and a smaller antihypertensive capacity than do kidneys from R rats. Therefore the influence of the kidney on blood pressure appears to have genetic determinants. If this finding is applicable to man, it would help to explain the well-established but anomalous observation that one of two individuals who apparently have similar renal disorders can have hypertension when the other does not.
Effects of Agents which Inhibit the Slow Channel on Sinus Node Automaticity and Atrioventricular Conduction in the Dog
Authors: ZIPES DOUGLAS P. , FISCHER JOHN C.
Published: June 2012

A slow ionic current carried by calcium, sodium, or both constitutes transmembrane ionic flow through the slow channel; such a current may be involved in normal action potentials of sinus and atrioventricular (AV) nodal cells. In this study, we investigated the effects of the slow-channel inhibiting agents verapamil, D600, manganous chloride, and lanthanum chloride on sinus node automaticity and AV nodal conduction in open-chest dogs treated with atropine (0.5 mg/kg) and propranolol (1.0 mg/kg). The arteries to the sinus node and the AV node were cannulated and perfused with agents that inhibit the slow current. These agents slowed sinus node discharge rate, depressed AV nodal conduction, and lengthened the effective and the functional AV nodal refractory period. Effects were dose related and reversed with time. His-Purkinje conduction remained normal. Isoproterenol and epinephrine reversed the effects of slow-channel inhibiting agents, but calcium, sodium, glucagon, and phenylephrine did not. Concentrations of propranolol which produced beta-receptor blockade prevented Isoproterenol-induced reversal of the effects of slow-channel inhibitors. We concluded that (1) agents which inhibit the slow channel directly depress sinus node discharge rate and AV nodal conduction, (2) effects of slow-channel inhibiting agents are not mediated through the activation of cholinergic discharge or inhibition of adrenergic discharge, and (3) beta-receptor stimulation reverses these effects.
Role of Central and Peripheral Adrenergic Mechanisms in Neurogenic Hypertension Produced by Brainstem Lesions in Rat
Authors: DOBA NOBUTAKA , REIS DONALD J.
Published: June 2012

Bilateral lesions of the nucleus tractus solitarius (NTS) in rats result in acute fulminating hypertension (NTS hypertension) as a consequence of central deafferentation of baroreceptors. The hypertension is due to increased peripheral resistance and decreased cardiac output. The hypertension is blocked and cardiac output is increased by phentolamine, trimethaphan (Arfonad), and reserpine but not by propranolol. In the present experiment, systemically administered 6-hydroxydopamine (6-OH-DA) did not alter NTS hypertension if the adrenal glands were intact. Adrenalectomy, however, blocked the lesion-induced rise in blood pressure in 6-OH-DA-treated rats. Intracisternally administered 6-OH-DA (600 µg) lowered the concentration of norepinephrine only in the spinal cord and blocked the development of NTS hypertension. Local injection of 6-OH-DA into the lateral hypothalamus did not affect the hypertension. Injection of 6-OH-DA into the NTS resulted in a mild, transient elevation in blood pressure. The results of these experiments demonstrate that (1) NTS hypertension is due to increased sympathetic neural discharge, (2) during NTS hypertension sufficient adrenomedullary catecholamines are released to produce hypertension when sympathetic terminals are destroyed, (3) central noradrenergic neurons participate in the expression of NTS hypertension, and (4) baroreceptors can inhibit the release of adrenal catecholamines.
Senescence and the Renal Vasculature in Normal Man
Authors: HOLLENBERG NORMAN K. , ADAMS DOUGLASS F. , SOLOMON HAROLD S. , RASHID ABDUR , ABRAMS HERBERT L. , MERRILL JOHN P.
Published: June 2012

The xenon washout technique and the renal blood flow response to vasoactive agents or alterations in sodium intake were used to characterize the effect of aging on the renal vasculature in 207 normal human subjects ranging in age from 17 to 76 years. A highly significant, progressive reduction in the mean blood flow, the rapid-component flow rate, and the percent of flow into the rapid-flow (cortical) compartment accompanied advancing age. Because
133
Xe measures flow per unit tissue mass, the results indicated a larger reduction in flow than in mass--the anticipated finding if flow reduction is primary in the genesis of atrophy. Age also reduced the vasodilation consequent to administration of acetylcholine or a sodium load; this finding is consistent with a fixed lesion of the vessels. Responses to angiotensin were not modified by age. Thus, offsetting factors of increased ratio of wall to lumen thickness and smooth muscle atrophy are precisely matched. The findings in this study agree with earlier hypotheses based on morphology that suggest a primary vascular process in the development of age-related renal changes.
Total and Regional Myocardial Blood Flow Measurements with 25µ, 15µ, 9µ, and Filtered 1-10µ Diameter Microspheres and Antipyrine in Dogs and Sheep
Authors: UTLEY JOSEPH , CARLSON EDWIN L. , HOFFMAN JULIEN I. E. , MARTINEZ HUGO M. , BUCKBERG GERALD D.
Published: June 2012

The accuracy of regional myocardial blood flow measurements made with microspheres of different sizes is uncertain. Therefore, we simultaneously injected radioactive microspheres of different sizes into the left atria of dogs and sheep; the microsphere diameters were 25µ, 15µ, 9µ, 1-l0µ, and filtered 1-10µ (most > 7µ). Antipyrine was sometimes simultaneously infused for 15-60 seconds. Myocardial blood flow was altered by hemorrhage, tachycardia, supravalvar aortic constriction, or infusion of methoxamine or adenosine triphosphate; left coronary artery branches were occluded on two occasions. Sometimes the percent of untrapped microspheres was estimated. All sizes of microspheres measured similar total myocardial blood flows when the percent of untrapped microspheres was known. All indicators were distributed identically to the right and left ventricular free walls and septum; ischemic areas had a 1% excess of antipyrine. With any pair of microspheres, the larger had a subendocardial excess except for 25µ microspheres, which were in excess compared with 15µ microspheres in the higher flow layer whether it was subendocardial or subepicardial. The greatest difference for any pair of microspheres was 10.53% of flow in a layer. Antipyrine did not define which size of microspheres measured true regional blood flow, since many previously unemphasized limitations were discovered. Nevertheless, we believe that microspheres 9µ in diameter are probably the best for measuring regional myocardial blood flow.
Renin, Aldosterone, Body Fluid Volumes, and the Baroreceptor Reflex in the Development and Reversal of Goldblatt Hypertension in Conscious Dogs
Authors: LIARD JEAN-FRANCOIS , COWLEY ALLEN W. , MCCAA ROBERT E. , MCCAA CONNIE S. , GUYTON ARTHUR C.
Published: June 2012

The renal artery to a sole remaining kidney was constricted in unanesthetized dogs while renal arterial pressure was recorded distal to the occluder. Following the constriction, mean arterial blood pressure, which was continuously monitored 24 hours a day for 1 week, exhibited a biphasic increase. The first peak in pressure correlated with a large increase in plasma renin activity; the second peak correlated with an increase in plasma volume brought about by positive sodium and water balances. Renin activity was returning to normal when the second peak occurred. Increased drinking played a major role in the positive water balance. Plasma aldosterone concentration was moderately and transiently increased for only a few hours following the constriction. The experiment was repeated in sinoaortic baroreceptor-denervated dogs; apparently, the baroreceptor reflex significantly slows the time course of the arterial blood pressure increase during the first few days of constriction but does not alter the magnitude of the pressure increase after 1 week. After release of renal artery constriction, mean arterial blood pressure decreased progressively over a 3-day period, during which time significant negative sodium and fluid balance occurred. The slow return of the pressure back to normal correlated highly with a decrease in plasma volume. In the baroreceptor-denervated dogs, the initial fall in arterial blood pressure apparently also resulted at least partly from a decrease in plasma renin activity, but this effect was not observed in the intact dogs because the renin activities in these dogs had already decreased to normal prior to constrictor release. The effects of the baroreceptor reflex on the time course of the pressure decrease did not seem to be as significant as those on the time course of the pressure increase.
Microcirculation in the Ventricle of the Dog and Turtle
Authors: TILLMANNS HARALD , IKEDA SHIGEAKI , HANSEN HERBERT , SARMA JONNALAGEDDA S. , FAUVEL JEAN-MARIE , BING RICHARD J.
Published: June 2012

Phasic red cell velocity and diameters of coronary arterioles, capillaries, and venules were measured in the beating turtle and dog heart using high-speed cinematography with transillumination of the left ventricle. In the turtle, arteriolar red cell velocity was diminished during systole, but during diastole arteriolar inflow increased, especially during the rapid and the slow filling period. Capillary and venule red cell velocity was increased during systole, particularly at the time of ejection; however, during diastole red cell velocity declined and the lowest values occurred during isovolumic relaxation. In dog arterioles, capillaries, and venules, the pattern of red cell velocity was similar. Thus, in the turtle and dog, the peak arteriolar red cell velocity occurred in unison with left coronary artery inflow, and the capillary and venule flow pattern followed that of the coronary sinus. The diameters of arterioles, capillaries, and venules in the turtle ventricle all declined about 34% during systole; similar results were obtained in the dog. Capillary arrangement appeared to be predominantly parallel and cocurrent; however, capillary loops with countercurrent flow were occasionally observed. The data on microvascular phasic red cell velocity are consistent with the macroobservations of reduced coronary artery inflow and enhanced coronary sinus outflow during ventricular contraction. The results demonstrate that the shift in the flow pattern occurs at the transition from arterioles to capillaries.
Effects of Norepinephrine on Coronary Circulation and Left Ventricular Dynamics in the Conscious Dog
Authors: VATNER STEPHEN F. , HIGGINS CHARLES B. , BRAUNWALD EUGENE
Published: June 2012

The effects of norepinephrine (0.1 and 1.0 µg/kg, iv) on coronary blood flow and resistance, left ventricular pressure and diameter, dP/dt, (dP/dt)/P, and the velocity (V
ISO
) of myocardial fiber shortening were studied in conscious dogs. When the heart rate was held constant, norepinephrine caused an initial reduction in coronary vascular resistance which was associated with increases in mean arterial blood pressure, systolic left ventricular pressure, end-diastolic diameter, dP/dt, (dP/dt)/P, and V
ISO
. After this brief coronary vasodilator response, a sustained increase occurred in mean coronary vascular resistance (+0.55 ± 0.07 mm Hg/ml min
-1
), and increases persisted in mean arterial blood pressure (+67 ± 7 mm Hg), left ventricular systolic pressure (+74 ± 6 mm Hg), left ventricular end-diastolic pressure (+4 ± 1 mm Hg), left ventricular internal diameter (+1.3 ± 0.3 mm), peak dP/dt (+1660 mm Hg/sec), (dP/dt)/P (+15 ± 2 sec
-1
), and V
ISO
(+11 ± 2 mm/sec); coronary sinus Po
2
decreased. Beta-receptor blockade prevented the inotropic effects of norepinephrine, attenuated the early coronary vasodilator effects, and increased the late vasoconstrictor effects. Alpha-receptor blockade abolished the late coronary vasoconstrictor effects of norepinephrine; only dilatation occurred. In contrast to the effects of norepinephrine in conscious dogs without autonomic blockade , norepinephrine (1.0 µg/kg, iv) failed to produce late coronary vasoconstriction in anesthetized, open-chest dogs; only dilatation occurred. Thus, in the normal, conscious dog, norepinephrine exerts an important coronary vasoconstrictor effect which is sufficiently intense to counteract completely the simultaneous tendency toward metabolic vasodilatation.
Quantitative Studies of Microcirculatory Structure and Function
Authors: ZWEIFACH BENJAMIN W.
Published: June 2012

A systematic study was made of capillary pressures in the microvascular bed of the mesentery of the cat. Simultaneous recordings were made with two micropipettes using a modification of the Wiederhielm servo-null system. All of the measurements were then referred to their specific location in the capillary bed by photographically reconstructing discrete networks. Pressures in different capillary branches within a given network ranged from 40 mm Hg to as low as 24 mm Hg. There was no obvious pattern in the distribution of high-pressure vessels relative to low-pressure vessels. When capillary pressure was measured in a selected vessel and averaged over a period of several minutes, it remained constant (±3 mm Hg), despite much greater fluctuations in the precapillary and postcapillary vessels. A number of different procedures was used to obtain average values for capillary pressure in a given network. Estimates of capillary pressure from venous wedge pressures in the mesentery were related to the actual capillary pressure, but the precise proportionality of the two pressures was not the same in different preparations. Possibly, the estimates of average capillary pressure based on direct measurements were higher than those obtained indirectly from calculations of fluid exchange because other factors affecting the latter were not adequately considered.
A Model of Cardiac Muscle Dynamics
Authors: GROOD EDWARD S. , MATES ROBERT E. , FALSETTI HERMAN
Published: June 2012

A mathematical model is presented describing the time- and length-dependent behavior of cardiac muscle. The model describes a wider variety of experimental data than do previously published models. It incorporates a modification of the Hill equation describing the force-velocity relation. Based on the sliding filament theory, the revised equation includes the effects of finite cross-bridge compliance proposed by A. F. Huxley. The essential simplicity of the Hill equation is retained; however, the model successfully predicts force development during both isometric and isotonic contractions, observed deactivation of the contractile element during isotonic shortening, and the apparent dependence of series elastic stiffness on time after stimulation during quick-release and quick-stretch experiments.
Early and Late Effects of Coronary Artery Occlusion on Canine Purkinje Fibers
Authors: LAZZARA RALPH , EL-SHERIF NABIL , SCHERLAG BENJAMIN J.
Published: June 2012

The electrophysiological characteristics of subendocardial Purkinje and myocardial cells were studied during acute (within 30 minutes) and chronic (after 10 days) phases of myocardial infarction. Endocardial Purkinje and myocardial electrograms were recorded in vivo with bipolar electrodes before and after occlusion of the anterior descending coronary artery. Also, intracellular and extracellular potentials were recorded in vitro from the endocardial surface of infarcted regions of hearts excised during the acute and chronic phases. In the acute phase, Purkinje and myocardial potentials within the ischemic zone deteriorated in vivo, but they were not markedly delayed. Intracellular recordings in vitro showed partial depolarization of both Purkinje and myocardial cells. In the chronic phase, extracellular and intracellular Purkinje potentials recorded in vivo and in vitro from the infarcted zone usually did not differ from normal. No myocardial potentials were recorded from the endocardial surface of the chronic infarcts. Thus, subendocardial Purkinje and myocardial cells are affected early in infarction, but many Purkinje cells survive and return to normal.
A Concurrent Flow Model for Extraction during Transcapillary Passage
Authors: BASSINGTHWAIGHTE JAMES B.
Published: June 2012

A model for capillary-tissue exchange in a uniformly perfused organ with uniform capillary transit times and no diffusional capillary interactions was designed to permit the exploration of the influences of various parameters on the interpretation of indicator-dilution curves obtained at the venous outflow following the simultaneous injection of tracers into the arterial inflow. These parameters include tissue geometric factors, longitudinal diffusion and volumes of distribution of tracers in blood and tissue, hematocrit, volumes of nonexchanging vessels and the sampling system, capillary permeability,
P
. capillary surface area,
S
, and flow of blood- or solute-containing fluid,

F'
s

. An assumption of instantaneous radial diffusion in the extravascular region is appropriate when intercapillary distances are small, as they are in the heart, or permeabilities are low, as they are for lipophobic solutes. Numerical solutions were obtained for dispersed input functions similar to normal intravascular dye-dilution curves. Axial extravascular diffusion showed a negligible influence at low permeabilities. The "instantaneous extraction" of a permeating solute can provide an estimate of

PS/F'
s

, the ratio of the capillary permeability-surface area product to the flow, when

PS/F'
s

lies between approximately 0.05 and 3.0; the limits of the range depend on the extravascular volume of distribution and the influences of intravascular dispersion. The most accurate estimates were obtained when experiments were designed so that

PS/F'
s

was between 0.2 and 1.0 or peak extractions were between 0.1 and 0.6.
Site and Mechanism of Uptake of
3
H-/-Norepinephrine by Isolated Perfused Rat Lungs
Authors: NICHOLAS TERENCE E. , STRUM JUDY M. , ANGELO LYNNE S. , JUNOD ALAIN F.
Published: June 2012

The uptake of
3
H-
l
-norepinephrine was examined in isolated perfused rat lungs, and the mechanism of uptake was compared with that previously found for 5-hydroxytryptamine. Most of the norepinephrine taken up by the lungs was rapidly deaminated and O-methylated, and the metabolic products were subsequently returned to the perfusate. The presence of iproniazid and tropolone markedly inhibited this metabolism; because the metabolites were released from the lungs more rapidly than was norepinephrine itself, these inhibitors appeared to increase the rate of uptake of the amine. The uptake of norepinephrine was a saturable, temperature-dependent process with a

K
m

of 1.11 x 10
-6
M and a
V
max
measured during metabolic inhibition of 2.78 x 10
-9
moles/g min
-1
. Uptake was inhibited by cocaine, imipramine, ouabain, and potassium-free medium as well as by decreasing the sodium concentration or increasing the potassium concentration of the medium. Although normetanephrine reduced the uptake of norepinephrine, metaraminol had no effect. Autoradiography indicated that norepinephrine was taken up into endothelial and smooth muscle cells, but the mechanism of the uptake appeared to combine features characteristic of both extraneuronal and neuronal uptake. The mechanism of uptake of norepinephrine by the lungs is compatible with a sodium-dependent, carrier-mediated transport, but several differences appear to exist between the transport and the site of uptake of norepinephrine and 5-hydroxytryptamine.
Canine Lipoproteins and Atherosclerosis
Authors: MAHLEY ROBERT W. , WEISGRABER KARL H. , INNERARITY THOMAS
Published: June 2012

Characterization of the hyperlipoproteinemia induced by feeding high-cholesterol diets to hypothyroid dogs was undertaken in an attempt to identify a lipoprotein pattern or a specific lipoprotein responsible for the atherosclerosis associated with such hyperlipoproteinemia. Various degrees of hyperlipidemia and atherosclerosis were produced during the diet, which was imposed for 3 months to more than a year. Dogs referred to as hyporesponders did not develop significant atherosclerosis despite plasma cholesterol levels ranging from two to five times normal or up to 750 mg/100 ml. This nonatherogenic hyperlipidemia was characterized by an increase in the LDL (low density lipoprotein) and HDL
c
classes (HDL
c
refers to a broad spectrum of cholesterol-enriched particles which resemble high density lipoproteins). Dogs referred to as hyperresponders developed significant and often complicated atherosclerosis. Their plasma cholesterol levels were in excess of 750 mg/100 ml, and most of the increased cholesterol was present in lipoproteins with density less than 1.006 g/ml. Several classes of lipoproteins were isolated by ultracentrifugation and purified by Geon-Pevikon block electrophoresis. These lipoproteins were characterized with respect to chemical composition, electrophoretic mobility, immunochemical reactivity, electron microscopic size after negative staining, and apoprotein content as determined by polyacrylamide gel electrophoresis. We concluded that the atherogenic hyperlipidemia of the hyperresponders was characterized by an increase in the amount of cholesterol-rich HDL
c
as in the hyporesponders but was distinguished by the appearance of a spectrum of cholesterol-rich lipoproteins in the fraction with a density less than 1.006 g/ml. One of these cholesterol-rich lipoproteins had the properties of β very low density lipoproteins, and the others had those of HDL
c
. We suggest that the spectrum of lipoproteins with density less than 1.006 g/ml represents "remnants" that accumulate because of defective catabolism of lipoproteins synthesized to carry excess of dietary cholesterol.
Urinary Kallikrein Excretion in Normal Man
Authors: MARGOLIUS HARRY S. , HORWITZ DAVID , GELLER RONALD G. , Alexander R. WAYNE , GILL. JOHN R. , PISANO JOHN J. , KEISER HARRY R.
Published: June 2012

The urinary excretion of kallikrein, a renal enzyme that cleaves the potent vasodilator kinin, kallidin, from kininogen, was measured in normal volunteers by three different assays, one of which was a bioassay. When sodium intake was changed from ad libitum or 109 mEq/day to 9 mEq/day, daily kallikrein excretion increased progressively in every subject to a mean maximal value that was 271% of control by day 7; an increase in sodium intake to 259 mEq/day resulted in the return of kallikrein excretion to control values. Urinary excretion of amylase, a protein with a molecular weight similar to that of kallikrein, did not change when sodium intake was changed, but plasma renin activity and aldosterone excretion changed appropriately. In subjects on a constant-sodium (109 mEq/day), constant-potassium (100 mEq/day) diet, fludrocortisone, 0.5 mg/day for 10 days, increased kallikrein excretion to a mean maximal value that was 203% of control. In subjects on a diet containing 9 mEq sodium/day, elevated kallikrein excretion decreased during treatment with spironolactone, 400 mg/day. Rapid administration of water (1 or 2 liters in 30 minutes, orally) or rapid infusion of 2.4 liters of normal saline did not significantly alter urinary kallikrein excretion despite large changes in urine volume or sodium excretion. Thus, kallikrein excretion appears to be directly related to the effective level of circulating sodium-retaining steroid. The findings are consistent with a role for the kallikrein-kinin system in the renal response to sodium-retaining hormones.
Characterization of Anti-Heart Mitochondria Autoantibodies Produced in Dogs following Myocardial Infarction
Authors: KELLEY ROBERT E. , OLSON MERLE S. , PINCKARD R. NEAL
Published: June 2012

A complement-fixing, heart-reactive serum component that develops in dogs following experimental myocardial infarction was characterized with respect to its immunoglobulin nature and its subcellular membrane and organ specificities. The immunoglobulin nature of the heart-reactive serum factor was established by the following evidence: (1) the factor was not removed from the serum following absorption of up to 90% of the first component of dog complement with bovine serum albumin (BSA)-anti-BSA immune precipitates, (2) the serum factor sedimented in the 19S region of sucrose density gradients, and (3) affinity chromatography using a Sepharose column coupled with rabbit anti-dog µ-chain-specific antibody resulted in the removal of nearly all of the heart-reactive substance. The major subcellular autoantigenic locus of the dog heart was determined to be the outer mitochondrial membrane. Serum containing the autoantibody demonstrated a six-fold greater autoantibody titer when outer mitochondrial membrane was used as the test antigen than it did when inner mitochondrial membrane was used. Absorption experiments suggested that the autoantigenic determinants residing on inner and outer mitochondrial membranes were unique to the individual membranes. Significant cross-reaction of the anti-heart autoantibody between heart and skeletal muscle mitochondria was observed, but no cross-reaction was seen with dog liver mitochondrial membranes.
Effect of the thyroid state on the enzymatic characteristics of cardiac myosin. A difference in behavior of rat and rabbit cardiac myosin.
Authors: Yazaki Y , Raben M S
Published: June 2012

The effect of thyroid state on the activity of myosin adenosinetriphosphatase (ATPase) was examined in the rat and the rabbit. Cardiac myosin from thyroxine-treated rabbits showed enzymatic properties characterized by high Ca2plus-activated ATPase activity, low activation energy, lower rate of inactivation at alkaline pH, and no activation by N-ethylmaleimide compared with the same properties in the normal rabbit; thyroidectomy did not affect the enzymatic properties of rabbit cardiac myosin. These findings suggest a difference in the myosin molecule at or near the active site, involving some sulfhydryl groups, between hyperthyroid and euthyroid rabbits. However, rat cardiac myosin showed a pattern of activity in the euthyroid state similar to that of the hyperthyroid rabbit and changed to the euthyroid type after thyroidectomy. These changes were specific for cardiac myosin, since no change was observed in skeletal myosin. It is unlikely that there are major differences in the myosin molecule associated with the two types of activity, since similar proportion and amino acid composition of the subunits of cardiac myosin were observed in the different thyroid states. Thus, we concluded that the administration of thyroxine to the rabbit stimulates the synthesis of new cardiac myosin with altered enzymatic properties and that synthesis of this type of cardiac myosin is maintained by the normal level of thyroid hormone in the rat.
Contractility in mammalian heart muscle; calcium and osmolality.
Authors: Goethals M A , Adèle S M , Brutsaert D L
Published: June 2012

The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, Lmax, at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the Lmax preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at Lmax preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially unaltered by either sucrose or NaCl, except for the high Ca concentrations (above 5 mM) at the higher osmolalities (above 370 mosmoles) especially with sucrose.
Influence of carotid baroreceptors on vascular responses to carotid chemoreceptor stimulation in the dog.
Authors: Mancia G
Published: June 2012

The modification by the carotid baroreceptors of the vascular responses to chemoreceptor stimulation was studied in anesthetized, artificially ventilated, vagotomized dogs. The carotid bifurcations were vascularly isolated and perfused with blood at constant pressures of 134, 215, and 51 mm Hg to cause intermediate, maximal, and minimal inhibition, respectively, of the vasomotor center. At each pressure, stimulation of the carotid chemoreceptors was achieved by perfusion with hypoxic hypercapnic blood. With intermediate inhibition, the chemoreceptor stimulation increased the aortic pressure by 50% and decreased the hind-limb and kidney blood flow (perfusion at constant pressure) by 59% and 19%, respectively. At carotid sinus pressures of 215 and 51 mm Hg, the effects of chemoreceptor stimulation were absent or markedly attenuated. With intermediate sinus pressure, chemoreceptor stimulation decreased the perfusion pressure of the saphenous vein by 27% (perfusion at constant flow). When the sinus pressure was increased to 215 mm Hg, the tone of the vein did not change, but chemoreceptor stimulation was without effect. The present study indicates a central interaction (which may be presynaptic) between the chemoreceptor and baroreceptor inputs such that the vascular responses to chemoreceptor stimulation are inhibited when the carotid sinus activity is maximal or minimal.
Calculations of pulsatile flow through a branch: implications for the hemodynamics of atherogenesis.
Authors: Friedman M H , O'Brien V , Ehrlich L W
Published: June 2012

Numerical simulations of pulsatile blood flow through a symmetrical branch modeling the aortic bifurcation were carried out to assess several hemodynamic theories of atherogenesis by comparing the distribution of hemodynamic variables with that of early lesions in arterial branches. Considerable spatial and temporal variations in wall shear were found when the flow was pulsatile; the highest values occurred at the convex corner on the outer wall of the branch and in the neighborhood of the flow divider tip, and the lowest shears were experienced by the outer wall of the daughter vessel a short distance distal to the corner. Transient flow reversal occurred almost everywhere in the branch, and a transient separated region was found corresponding to the low-shear region in the daughter vessel. The shear profiles and the calculated separated region were influenced to some degree by the extent of flow development at the branch inlet and markedly by the branch area ratio. All of the proposed hemodynamic promoters of atherosclerosis that were examined--high shear, low shear, and separation--were found at sites in the branch where lesions commonly develop. Comparisons with a steady-flow calculation at the same mean flow rate showed that the severity of all of these proposed hemodynamic determinants was increased by pulsatility.
Manganese amd electrogenic phenomena in canine Purkinje fibers.
Authors: Hogan P M , Spitzer K W
Published: June 2012

Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of manganese on membrane electrogenesis. The results indicate that manganese has a calciumlike effect on the excitatory sodium current and inhibitory effects on potassium conductance and slow inward current. The calciumlike effect of manganese on sodium current was reflected through a leftward (toward less negative potentials) and downward shift in the curve relating maximum upstroke velocity to membrane potential. The inhibitory action of manganese on potassium conductance was suggested by the following observations. (1) Manganese caused an initial increase in action potential duration largely due to a lengthening of the plateau and decreases in the rates of phase 3 and terminal repolarization. (2) Manganese increased the rate of diastolic depolarization. (3) Manganes blocked the initial fall in maximum diastolic potential accompanying rapid stimulation. (4) Manganese in high concentrations caused generalized depolarization which was reversed by rapid stimulation and by increased extracellular potassium concentrations. The action of manganese to block slow inward current was indicated by the eventual shortening of the plateau and by the elimination of responses initiated from low levels of membrane potential (less than minus 55 mv). In addition to these effects, manganese also reduced membrane excitability, eliminated arrhythmic beats occurring during low-frequency electrical stimulation, and caused membrane hyperpolarization which was blocked by tetrodotoxin.
Partial versus complete control of blood pressure in the prevention of hypertensive complications.
Authors: Taguchi J , Freis E D
Published: June 2012

The data from the Veterans Administration Cooperative Study on Antihypertensive Agents Prevention of Morbidity Trial were reviewed from the point of view of the importance of normalizing the blood pressure in preventing cardiovascular complications. The treated group of patients was subdivided into three subgroups on the basis of the diastolic blood pressures recorded at the fourth month after randomization as follows: subgroup A, the poorly controlled patients whose diastolic blood pressures were 90 mm Hg or higher, an intermediate subgroup B with diatolic levels of 81 to 89 mm Hg, and subgroup C, the best controlled patients, all of whom exhibited diastolic blood pressures of 80 mm Hg or less. While the incidence of morbid events was slightly higher in subgroup A than in the other subgroups, the differences were not statistically significant. On the other hand, the incidence of morbid events in subgroup A was significantly lower (P less than 0.05) than in the untreated control patients (14.9% in subgroup A vs. 28.9% in the control group). While normalization of blood pressure is a desirable goal of treatment, even partial reduction appears to exert significant therapeutic benefit.
Possible contributions of endogenous prostaglandins to the control of blood pressure.
Authors: Vane J R , McGiff J C
Published: June 2012

Prostaglandins are primarily local or tissue hormones which have their effects at or near the site of release and are metabolized before reaching the arterial circulation. A possible exception is prostaglandin A-2, which has been proposed as a circulating hormone; however, there is no evidence that prostaglandin A-2 is biosynthesized in the mammalian kidney or even in extrarenal tissues. The prostaglandin generated and released in the kidney is predominantly E-2. Some blood vessels also synthesize prostaglandins intramurally, where their local release influences vascular tone and reactivity. Endogenous prostaglandin E-2 production contributes to the regulation of blood pressure by (1) opposing the vasoconstrictor and antidiuretic actions of circulating pressor hormones; (2) braking the release of norepinephrine from vasoconstrictor nerves; and (3) participating in the control extracellular fluid volume through its renal hemodynamic actions.
Vascular responses to prostaglandin F 2 alpha in isolated cat lungs.
Authors: Lonigro A J , Dawson C A
Published: June 2012

Changes in perfusion pressure in response to graded doses of prostaglandin F 2 alpha (PGF 2 alpha) were measured during both forward and retrograde perfusion of isolated cat lungs perfused at a constant flow rate. During forward perfusion, PGF 2 alpha produced a dose-dependent increase in pulmonary artery pressure and a decrease in lung fluid volume. During retrograde perfusion, PGF 2 alpha also produced a dose-dependent increase in perfusion pressure; however, the dose required was fivefold greater than that needed to produce an identical change in pressure during forward perfusion. In addition, during retrograde perfusion, the lung fluid volume increased in response to PGF 2 alpha. These results suggest that the major site of activity of PGF 2 alpha is on the arterial side of the pulmonary vascular bed and that inactivation of PGF 2 alpha by the lung occurs primarily distal to this arterial site of vasomotion. The changes in perfusion pressure in response to PGF 2 alpha were markedly dependent on pH and oxygen tension (Po-2), being abolished by severe alkalosis and potentiated by both acidosis and hypoxia. In contrast, neither serotonin nor norepinephrine exhibited such a pH or Po-2 dependency. Since the ratio of the forward response to the retrograde response was not decreased by alterations of pH or Po-2, their influence on the responses appears to be through interaction at the site of vascular activity rather than through alteration of the rate of prostaglandin inactivation.
Depolarization-induced movement of Mn 2 cations across the cell membrane in the guinea pig myocardium.
Authors: Delahayes J F
Published: June 2012

The effects of Mn-2+-containing solutions on the mechanical and electrical responses of myocardial tissue were studied on guinea pig ventricular strips. At a concentration of 10 mM, Mn-2+ abolished the twitch responses and caused the development of a contracture in stimulated preparations but not in resting or in Ca-2+-depleted preparations. The duration of action potentials was shortened, and dV/dt-max was decreased. In Ca-2+-depleted (0.1 mM), Mg-2+-free medium, Mn-2+ also increased the amplitude of the overshoot; the increase was due to a slow phase of depolarization. Measurement of the Mn-2+ uptake showed an increased influx of these ions in stimulated preparations compared with that in quiescent preparations. These results suggest that Mn-2+ (1) generates a transmembrane current in guinea pig myocardial cells and (2) interferes with the excitation-contraction coupling process at two levels: the cell membrane and an intracellular site.
Pressure drop across artificially induced stenoses in the femoral arteries of dogs.
Authors: Young D F , Cholvin N R , Roth A C
Published: June 2012

Stenoses were artificially induced in 13 large mongrel dogs by implanting small hollow cylindrical plugs in their femoral arteries. The instantaneous pressure drop across the stenosis and the flow rate were measured for a series of stenoses varying in severity from 52.3 to 92.2%. Mean pressure drops ranged from approximately 2 to 30 mm Hg with peak pressure drops ranging from 9 to 53 mm Hg. The pressure drop could be estimated from a relatively simple equation that was originally developed for flow through model stenoses. With this equation, the effects of several factors that contribute to the pressure drop, including stenosis size and shape, artery lumen diameter, blood density, blood viscosity, and velocity and acceleration of flow, could be clearly delineated. For severe stenoses, unsteady flow effects were small and flow could be treated as quasi-steady. Calculations based on data obtained from the dog experiments revealed that the mean pressure drop across a stenosis increased nonlinearly with percent stenosis and showed quantitatively that the value of critical stenosis decreased with increasing demand for blood flow.