bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelets, Fatty Acids and Thrombosis
Authors: HOOK JOHN C. , WARNER EMORY D. , CONNOR WILLIAM E.
Published: June 2012

The sodium salts of stearic, oleic, linoleic and linolenic acids were added to human washed platelet suspensions and platelet-rich citrated plasma. Aggregation of the platelets was measured microscopically and with a turbidimetric method. All of the fatty acids had the ability to produce aggregation when added to washed platelets, but stearic acid, a long-chain saturated fatty acid, was more potent than were the unsaturated acids when added to platelet-rich plasma. Aggregation of platelets by fatty acids required the presence of calcium ions and the aggregation was irreversible. The addition of albumin diminished the aggregating effects of fatty acids, but microscopic aggregates still formed in most instances. Subnormal aggregation was noted when sodium stearate was added to platelet-rich plasma from a patient with a severe deficiency of factor XII (Hageman factor). Thus, fatty acids are now known to have two potential thrombogenic effects: platelet aggregation and the activation of clotting factors involved in the early stages of blood coagulation.
Determination of Regional Cerebral Blood Flow by Inhalation of 133-Xenon
Authors: OBRIST WALTER D. , THOMPSON HOWARD K. , KING HERSCHEL , WANG HSIOH SHAN
Published: June 2012

A method for estimating regional cerebral blood flow is described in which tracer amounts of
133
Xe are inhaled for 2 min and monitored extracranially over the next 45 to 60 min. A three-compartment model used to analyze the resulting clearance curves provided separate blood flows for "gray" and "white" matter, plus a decay constant for a slow third component, believed to arise from extracerebral tissue. The analysis included a correction for recirculation of all three components, based on radioisotope concentration of the expired air or arterial blood. Results from the analysis were compared with those obtained by the more traditional two-compartment approach, using data from 15 healthy young males. Whereas the three-compartment method yielded measurements comparable with those obtained by established techniques (average CBF = 54.7 ml/100 g/min), the two-compartment analysis gave consistently lower values (average CBF = 30.2). Comparison of results based on expired air and arterial sampling suggested that end-expiratory air is a reasonable substitute for arterial blood. Although the
133
Xe inhalation method is technically simpler and less traumatic than other methods, complex analytic treatment of the data is necessitated by the presence of appreciable recirculation and extracerebral contamination.
Effect of Calcium Concentration on the Transmembrane Potentials of Purkinje Fibers
Authors: TEMTE JOHN V. , DAVIS LARRY D.
Published: June 2012

The effects of variation in calcium concentration on the action potential of Purkinje fibers isolated from the dog heart were studied. Action potentials recorded during perfusion with Tyrode solution containing 2.7 mM calcium chloride were compared with those recorded during subsequent perfusion with solutions containing 0.675 (1/4X), 1.35 (1/2X), 5.4 (2X), or 10.8 (4X) mM calcium chloride. In both 1/2X and 1/4X solutions, the time required to repolarize to minus 60 mv and the duration of the action potential were increased. There were significant decreases in the slopes of phases 2 and 3 and the terminal phase of repolarization, while the slope of phase 1 increased. In 2X or 4X solutions, repolarization was speeded mainly by an earlier onset of phase 3. As a result the time to repolarize to minus 60 mv and the duration of the action potential were decreased significantly. The slope of phase 1 decreased significantly in 4X solution. In both high calcium solutions the rate and magnitude of diastolic depolarization increased. It was shown that the rate of the calcium-enhanced diastolic depolarization was dependent on the stimulus rate. The possible role of these changes in transmembrane potential in causing the ventricular arrhythmias following CaCl
2
infusion in intact animals is discussed.
Improved Assay Methods for Renin "Concentration" and "Activity" in Human Plasma
Authors: SKINNER SANDFORD L.
Published: June 2012

Simplified methods are described for the measurement of human plasma renin "concentration" (PRC) and "activity" (PRA) based on the denaturation of renin substrate in which separation and concentration steps are avoided and recovery of renin is complete. In the PRA method effective inhibition of angiotensinase is achieved by warming plasma at pH 4.5 with EDTA followed by dialysis to pH 7.5. Neither renin nor renin substrate is affected by this treatment. In the PRC method, renin substrate is selectively denatured by warming at pH 3.3. After dialysis to pH 7.5 and addition of a standard substrate prepared from nephrectomized sheep, incubation results in a linear increase of pressor material which is assayed without extraction on rat blood pressure against synthetic angiotensin. Specificity is established by nephrectomy and immunological studies. The linear relationship between plasma renin concentration and reaction rate contrasted with the nonlinearity observed with renal renin. The systems are suitable for routine diagnostic use.
Relative Failure of Saturated Fat in the Diet to Produce Atherosclerosis in the Rabbit
Authors: CONNOR WILLIAM E. , ROHWEDDER JAY J. , ARMSTRONG MARK L.
Published: June 2012

Three "saturated" fats of vegetable origin were fed to different groups of rabbits for periods up to 1 year. Cocoa butter and a hydrogenated vegetable oil shortening produced no hypercholesterolemia. Coconut oil feeding increased the serum cholesterol concentrations for 4 months, but a decline to baseline values occurred after 6 months. No gross atherosclerosis occurred in any animal fed coconut oil or the hydrogenated vegetable oil shortening. Slight atherosclerotic lesions were found in 50% of the rabbits fed cocoa butter. Aortic cholesterol content was slightly increased in animals fed coconut oil and cocoa butter. Dietary fats, even when highly saturated, had only a minimal capacity to produce atherosclerosis in the rabbit, a species usually highly susceptible to the induction of atherosclerosis. When a moderate amount of cholesterol was added to the diet, the serum cholesterol levels increased greatly and considerable atherosclerosis resulted.
Regional Redistribution of Blood Flow in the Mature Fetal Lamb
Authors: CAMPBELL A. G. M. , DAWES G. S. , FISHMAN A. P. , HYMAN A. I.
Published: June 2012

Observations on mature fetal lambs delivered under chloralose anesthesia showed that variations in arterial blood gas tensions, caused by ventilation with gas mixtures of differing composition, produced considerable changes in regional systemic blood flows measured with a cannulated electromagnetic flowmeter. Partial asphyxia was associated with a rise in arterial pressure and a reduction in femoral and renal flows; coronary, carotid and superior sagittal venous sinus flows increased owing mainly to coronary and cerebral vasodilatation. Ventilation with air caused an opposite result. The results indicate that a more detailed study of the local and reflex mechanisms controlling vasomotor tone in the mature fetus is necessary.
Contractile State of Cardiac Muscle Obtained from Cats with Experimentally Produced Ventricular Hypertrophy and Heart Failure
Authors: SPANN JAMES F. , BUCCINO ROBERT A. , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

The contractile state of papillary muscles from hypertrophied and from failing right ventricles of cats with pulmonary artery constriction was studied. In muscles from failing hearts, the maximum velocity of shortening, active length-tension curves, and maximum rate of tension development were decreased, while the passive length-tension curves and the time from stimulation to peak tension were normal. The augmentation of isometric tension achieved by paired electrical stimulation, increasing frequency of contraction, and strophanthidin was reduced. In muscle from hearts without failure but with ventricular hypertrophy, there were qualitatively similar depressions of contractile function, although of lesser magnitude. It is concluded that congestive heart failure is associated with extreme quantitative abnormalities of the intrinsic contractile state of each unit of heart muscle, which reflect a depression in the intensity of the active state. Further, ventricular hypertrophy in the absence of failure is associated with a depression of the contractility of each unit of myocardium, while cardiac compensation is maintained by the increase in muscle mass.
The Architecture of the Heart in Systole and Diastole
Authors: ROSS JOHN , SONNENBLICK EDMUND H. , COVELL JAMES W. , KAISER GERARD A. , SPIRO DAVID
Published: June 2012

Techniques for rapid fixation of the canine left ventricle in systole or diastole that have permitted analysis of ventricular geometry under known hemodynamic conditions are described. Six ventricles were arrested at and diastole, 7 at end ejection, and 7 in diastole following acute ventricular overdistension. The architecture of the ventricles was analyzed from measurements of the fixed ventricles and silicone-rubber casts of the ventricular cavities. In ventricles of matched weights, the average reduction, from end diastole to end ejection, of the apex to mitral valve distance was 4.6%, while that from apex to aortic valve was less than 1%. The minor internal equator was reduced by 26%, the midwall radius by 16%, and the outer radius by 8.5%. The ratio of the average end-diastolic volume minus end-systolic volume to the end-diastolic volume (analogous to stroke volume/end-diastolic volume) averaged 59%. The average wall thickness was 28% greater in systolic than in diastolic ventricles. The papillary muscle volume averaged 5.0%e of ventricular volume at end diastole and 14.7% at end systole. The area of the mitral valve orifice averaged 28% less at end systole than at end diastole; this area was 39% more in the hearts subjected to over-transfusion than in those with normal filling pressures. These data provide a framework for construction of a geometric model suitable for use in analyses of the mechanics of left ventricular contraction. Moreover, the methods described offer the possibility of correlating ventricular geometry and ultrastructure with cardiac function in normal and in abnormal hearts.
Interrelationships Between Automaticity and Conduction in Purkinje Fibers
Authors: SINGER DONALD H. , LAZZARA RALPH , HOFFMAN BRAIN F.
Published: June 2012

Microelectrode studies of transmembrane potentials of canine Purkinje fibers show that phase-4 depolarization causes voltage-dependent changes in conduction and responsiveness similar to those occurring during repolarization at comparable levels of potential. Abnormalities ranged from simple slowing of conduction to decrement, unidirectional and bidirectional block, and unexcitability. Reentrant excitation also developed. Significant conduction disturbances usually appeared at -75 to -70 mv; decrement and advanced block at -65 to -60 mv, or below. Because the threshold potential of normal Purkinje cells is approximately -70 mv, depolarization to lower levels implies shifts in this variable toward 0. Determinations of threshold potential confirm such shifts. It may be further inferred that significant abnormalities would most likely occur in fibers in which threshold potential is shifted toward 0 or membrane responsiveness impaired. Alterations in conduction due to phase-4 depolarization provide a reasonable explanation for various peculiarities of cardiac rhythm, including occurrence of conduction disturbances and reentrant rhythms at low heart rates, exit and entry block about parasystolic foci, instability of peripheral Purkinje pacemaakers, and supernormal conduction. Circumstances that enhance phase-4 depolarization are common in diseased hearts, indicating that this mechanism may be a significant factor in human arrhythmias.
Enhancement of Peripheral Alpha-Receptor Stimulation by Blockade of "Silent" Beta Receptors
Authors: BURKS THOMAS F. , COOPER THEODORE
Published: June 2012

Evidence is presented for the existence of "silent" peripheral beta adrenergic receptors with which alpha-receptor stimulants might combine without producing measurable vasodilation. Addition of propranolol (1x10
-7
M) or MJ-1999 (5x10
-6
M) to Krebs solution perfusing canine isolated mesenteric arteries enhanced (1) the pressor responses to intra-arterially administered epinephrine, norepinephrine, and methoxamine and (2) the vasoconstrictor effects of perivascular sympathetic nerve stimulation. Enhancement of the pressor effects of epinephrine and norepinephrine was unaltered during cocaine or guanethidine potentiation. The doses of the beta-receptor blocking agents that enhanced pressor responses in isolated arteries were identical to those required to provide 80 to 100% blockade of the positive inotropic and chronotropic effects of epinephrine and norepinephrine in isolated rabbit hearts. Propranolol and MJ-1999 also enhanced the elevating effects of methoxamine on canine blood pressure. In higher concentrations, propranolol (1x10
-4
M) and MJ-1999 (1x10
-3
M) produced alpha-receptor blockade in the isolated arteries, and propranolol, but not MJ-1999, produced myocardial depression in isolated rabbit hearts.

These data are interpreted as indicating that alpha-receptor stimulants usually combine with both peripheral alpha and beta adrenergic receptors, and blockade of the peripheral beta receptors makes more stimulant available for alpha-receptor stimulation.
Effect of 1-Epinephrine on the Coronary Circulation in Human Subjects with and without Coronary Artery Disease
Authors: SULLIVAN JAY M. , GORLIN RICHARD
Published: June 2012

The effects of intravenous infusion of epinephrine on the coronary circulation of 21 human subjects, 8 with and 13 without coronary artery disease, have been studied. The response to epinephrine was similar in the two groups. Epinephrine increased cardiac output, stroke volume, and systolic ejection rate significantly without significant change in blood pressure. Myocardial O
2
consumption increased in relation to increased kinetics of contraction. Coronary flow increased significantly without change in coronary arteriovenous O
2
difference, suggesting that the vasodilatory response to epinephrine in man is secondary to augmented myocardial metabolic demands.
Plasma Renin in Chronic Experimental Heart Failure and during Renal Sodium "Escape" from Mineralocorticoids
Authors: JOHNSTON C. I. , DAVIS JAMES O. , ROBB CHARLES A. , MACKENZIE JAMES W.
Published: June 2012

A striking increase in the plasma renin level occurred in dogs with low output right heart failure secondary to tricuspid insufficiency and pulmonic stenosis and in three of five animals with high output failure produced by a large arteriovenous fistula. When dogs with a small arteriovenous fistula were given daily injections of DOCA, the renal sodium "escape" phenomenon occurred. In these animals, the level of plasma renin was suppressed during DOCA administration both during the initial period of sodium retention and also later when sodium balance was normal or negative. In contrast, when dogs with a larger arteriovenous fistula but without evidence of cardiac failure were given DOCA, they retained sodium and developed signs of congestive heart failure. However, in these animals with congestion and ascites, in contrast to the dogs that developed spontaneous high output failure, the plasma renin was low. Renin-substrate was unaltered in all of the experimental situations studied except for the decrease observed in dogs with low output right heart failure. In these animals, it seems likely that decreased renin-substrate was secondary to hepatic congestion and liver damage. The renin-angiotensin system does not seem to be related to the "escape" phenomenon, and renin does not appear to be the factor that makes the kidney unusually responsive to mineralocorticoids. Thus, in experimental heart failure the renin-angiotensin system was activated, but in the congestive syndrome produced by DOCA the plasma renin level was suppressed.
Reversibility of Atherosclerosis in Cholesterol-Fed Rabbits
Authors: BORTZ WALTER M.
Published: June 2012

Previous studies have attempted to demonstrate the reversibility of rabbit atherosclerosis after discontinuance of cholesterol feeding or by other measures. These attempts have been largely unsuccessful. In all the studies, atherosclerosis was induced by cholesterol feeding for several months. At the end of these prolonged periods, the animals had advanced aortic lesions. The present study sought to determine whether a shorter exposure to an elevated blood cholesterol might produce lesions that were reversible.

Rabbits were fed cholesterol until their serum levels reached at least 1000 mg/100 ml; cholesterol feeding was then discontinued. Serum cholesterol values rapidly returned to normal levels. Some were killed at the time of discontinuance of the cholesterol diet and the others at periods up to 300 days thereafter. The aortas were removed and analyzed chemically for cholesterol content. The results demonstrate that cholesterol feeding of short duration produces a significant lesion whose cholesterol content may decrease markedly some weeks after the serum cholesterol has returned to normal levels.
A Convection-Diffusion Model of Indicator Transport through an Organ
Authors: PERL WILLIAM , CHINARD FRANCIS P.
Published: June 2012

A model for interpretation of extravascular indicator dilution experiments is proposed, in which the indicator is assumed to enter the blood-tissue exchange region through vascular sources, to equilibrate instantaneously and locally between blood and tissue at the capillary-cell level, and, while maintaining this local equilibration, to be transported to vascular sinks by simultaneous diffusion and convection at a more macroscopic distance level. The model has the mathematical form of the time-dependent Fick diffusion equation to which a convection term was added. The model contains as opposite limiting cases the washout-type models and a recently proposed delayed wave model of the indicator dilution process. The various features of the extravascular indicator outflow pattern-appearance time, modal time, semi-log downslope, and dispersion about the mean-are described in terms of two parameters: (1) a diffusion parameter, square of source-to-sink distance divided by diffusion coefficient of the indicator in the tissue; (2) a convection parameter, the blood flow divided by steady-state solubility volume of distribution of the indicator in the tissue. In contrast to the preceding opposite limiting cases, the present model accounts plausibly for extravascular indicator experiments in dog kidney.
Responses of the Superficial Limb Veins of the Dog to Changes in Temperature
Authors: WEBB-PEPLOE MICHAEL M. , SHEPHERD JOHN T.
Published: June 2012

The lateral saphenous vein of the dog was perfused with homologous blood at constant, flow. Changes in perfusion pressure were used to measure active changes in venous tone. Cooling of the perfusate caused the vein to constrict and warming to relax. Most of the change occurred over the temperature range of 27° to 42°C. The powerful venoconstrictor response to cooling depended on intact sympathetic nerves, since it was reduced by lumbar sympathectomy and largely abolished by alpha-receptor or ganglionic blockade. The response was confined to the vein being cooled. By comparison, cooling the body core when the temperature of the blood in the vein was 37°C caused a generalized constriction of the superficial limb veins. These responses were impaired by anesthetic agents (for example, pentobarbital), by generalized hypoxia, and by arterial hypotension. The data indicate a role for the cutaneous veins in temperature regulation. In the cold, the venous return is directed preferentially to the venae comitantes for heat preservation through countercurrent exchange with the arteries, and in warmth to the superficial veins for heat dissipation.
Constriction of Human Umbillcal Arteries
Authors: ELTHERINGTON L. G. , STOFF J. , HUGHES T. , MELMON KENNETH L.
Published: June 2012

Experiments on perfused segments or isolated rings of human umbilical artery showed that the magnitude of their contraction in response to bradykinin, epinephrine, or serotonin depended on the Po
2
of the perfusing or bathing solution. Constriction to bradykinin varied directly with the O
2
tension and was greatest when the Po
2
was approximately that of umbilical arterial blood during the transition from the fetal to the neonatal period. Catecholamine beta-receptors were not demonstrated (not present or not functional) in the umbilical artery, since there was no vascular response to either isoproterenol or to propranolol. Alpha-receptors were not required for O
2
or bradykinin constriction since these agents constricted the umbilical artery after enough phentolamine had been given to block constriction by norepinephrine. Because of the interaction between O
2
and vasoconstrictor agents the O
2
environment of umbilical vessels must be rigidly controlled in experiments measuring vascular reactivity. Sensitization by O
2
to the effects of chemical substances endogenous to the fetus or mother may play an important role in circulatory adjustments essential for neonatal life.
Measurement of Viscoelastic Properties of Arteries in the Living Dog
Authors: GOW BARRY S. , TAYLOR MICHAEL G.
Published: June 2012

Dynamic elastic moduli (E
dyn
) and viscous moduli (ηω) of the arterial wall were obtained at a number of sites of the systemic vascular tree of living dogs anesthetized with pentobarbital. Constants were calculated using the first harmonics of pressure and diameter obtained from a Fourier analysis of simultaneously recorded pulse waves. The means and standard errors of E
dyn
, in dynes cm
-2
x 10
6
, obtained at mean blood pressures ranging from 87 to 130 mm Hg and pulse frequencies from 1.1 to 2.8 cps were: 3.0±0.33 (9 midthoracic aortas), 9.8±1.2 (7 midabdominal aortas), 11.0 (4 iliac arteries), and 12.3±1.2 (11 femoral arteries). The viscous modulus was approximately 9% of E
dyn
in the midthoracic aorta and approximately 12% of E
dyn
in the abdominal and femoral arteries. Pulse wave velocities calculated from values of E
dyn
and relative wall thickness by the Moens-Korteweg equation agreed with accepted values. A Fourier analysis of pressure and diameter waves was shown to be unsatisfactory for determining the frequency dependence of viscoelastic constants because of anomalous behavior of the viscoelastic parameters. In the midthoracic aorta this behavior may have been partly attributable to artefact; however, there was strong evidence that elsewhere nonlinear pressure and diameter relationships interfered with the accurate determination of the relatively small, higher-order harmonic components.
Sympathetic Innervation of the Developing Rabbit Heart
Authors: FRIEDMAN WILLIAM F. , POOL PETER E. , JACOBOWITZ DAVID , SEAGREN SHIRLEY C. , BRAUNWALD EUGENE
Published: June 2012

The sympathetic innervation of the rabbit heart, as a function of age, was studied by measuring the cardiac concentration of catecholamines and observing the anatomic distribution of sympathetic nerves by the monoamine fluorescense technique. The cardiac concentration of norepinephrine in late gestation was quite low; the levels rose progressively after birth to reach adult levels by about three weeks of age. Similar small amounts of epinephrine were found in the hearts at all ages. Substantially less change in adrenal catecholamines accompanied advancing age. At all ages a close correlation was noted between the norepinephrine levels and the histochemical demonstration of sympathetic innervation. Intensely fluorescent, terminal varicosities were observed within large preterminal nerve trunks only in the youngest animals, suggesting that the sympathetic nerves move into, rather than form within, the heart. Chromaffin cells were observed in the hearts at all ages.
Oxidative Phosphorylation in Mitochondria Isolated from Chronically Stressed Dog Hearts
Authors: STONER CLINTON D. , RESSALLAT MEHDI M. , SIRAK HOWARD D.
Published: June 2012

Oxidative and phosphorylative activities were measured polarographically in mitochondria isolated from the right and left ventricles of normal and chronically stressed dog hearts. Chronic myocardial stress was produced experimentally by surgical procedures (combined tricuspid insufficiency and pulmonary stenosis, pulmonary insufficiency, aortic stenosis, aortic insufficiency, Potts's anastomosis) and by inducing thyrotoxicosis. Experimental stress periods ranged from 332 to 608 days. Some of the dogs had overt symptoms of congestive heart failure at the time they were killed.

Mitochondria isolated from the stressed hearts had abnormally high values for oxidative activity and respiratory control ratios when incubated in the presence of malate-pyruvate. In the presence of succinate, they had either normal or slightly elevated values for oxidative activity and respiratory control ratios. No differences were found between mitochondria from normal and stressed hearts with regard to the efficiency (ADP/O) of oxidative phosphorylation. Estimates of mitochondrial protein per gram of myocardial tissue indicated that the stressed hearts contained normal amounts of mitochondria. The results of this study suggest that the mitochondrial oxidative and phosphorylative capabilities of the chronically stressed myocardium are not impaired.
Fractional Extraction and Transcapillary Exchange during Continuous and Instantaneous Tracer Administration
Authors: YUDILEVICH DAVID L. , RENKIN EUGENE M. , ALVAREZ OSVALDO A. , BRAVO IVÁN
Published: June 2012

The relation between extraction fraction, E, measured by the multiple-tracer, instantaneous intra-arterial injection method and by single-tracer, continuous injection was studied by experiments on gastric wall, liver, and skeletal muscle of anesthetized dogs. E was calculated from ratios of diffusible to nondiffusible tracer concentrations in successive samples of venous blood. Initial extraction, E(0), was the same by instantaneous or continuous injection. E diminished with time due to back-diffusion. In liver, E(0) for water-
3
H, mannitol-
3
H, and glucose-
3
H remained close to unity, indicating that transcapillary transport was flow-limited. E(0) for
22
Na,
36
Cl, and mannitol-
3
H in gastric wall, and for
22
Na and
86
Rb in skeletal muscle were less than unity and decreased with increasing blood flow, indicating diffusion limitation. E for
86
Rb in skeletal muscle eventually reached a plateau level, due to the large "sink" for
86
Rb in cell K. Both E(0) and plateau E for
86
Rb in muscle increased during exercise. Permeability surface products PS were calculated from measured E's and blood flows, Q, by the relation PS = -Q ln (1 - E). Their values suggest that E(0) reflects relative capillary permeabilities to different tracers, but only for capillaries of fastest arteriovenous transit. Plateau E's, such as for
86
Rb in skeletal muscle, represent all the capillaries, but are influenced also by extracapillary barriers.
Early Changes in Energy Metabolism in the Myocardium Following Acute Coronary Artery Occlusion in Anesthetized Dogs
Authors: BRAASCH WOLFGANG , GUDBJARNASON SIGMUNDUR , PURI PRITPAL S. , RAVENS KURT G. , BING RICHARD J.
Published: June 2012

The tissue content of energy-rich phosphates and glycolytic metabolites and the activity of myocardial enzymes were examined in the dog after producing myocardial infarction by ligating branches of the anterior descending and circumflex coronary arteries. The pattern of systolic fiber movement shown by a strain-gauge assembly differentiated ischemic from nonischemic portions of myocardium. In ischemic muscle, 30 minutes after onset of ischemia, creatine phosphate content fell from 8.0 to 1.4 µmoles/g, ATP content fell from 5.8 to 1.5 µmoles/g, lactate content rose tenfold, and α-glycerophosphate content rose fivefold. The content of energy-rich phosphates and glycolytic metabolites did not change much in nonischemic muscle. The activities of myocardial enzymes were assayed in extracts of tissue samples from ischemic and nonischemic muscle 5 to 120 minutes after coronary artery occlusion. The activities of aldolase, lactic dehydrogenase (LDH), glyceraldehydephosphate dehydrogenase, α-glycerophosphate dehydrogenase, malate dehydrogenase (MDH), and 6-phosphogluconate dehydrogenase did not change significantly in ischemic muscle during 2 hours of observation. In nonischemic muscle, phosphofructokinase activity increased 75% 5 minutes after coronary occlusion, followed by an increase in activity of isocitrate dehydrogenase, creatinephosphokinase, MDH, and LDH. The enzymatic changes in nonischemic muscle suggest metabolic changes in nonischemic muscle accompanying compensatory hyperfunction and increased energy requirements of surviving muscle.
Reevaluation of Oxidative Phosphorylation in Cardiac Mitochondria from Normal Animals and Animals in Heart Failure
Authors: LINDENMAYER GEORGE E. , SORDAHL LOUIS A. , SCHWARTZ ARNOLD
Published: June 2012

For an adequate evaluation of mitochondria from diseased hearts, basic characteristics of isolation, storage, media, ultrastructure and type of assay were first determined using mitochondria from normal animals. A proteinase procedure yielded mitochondria from small laboratory animals, with low respiratory control and marked permeability changes. The isolation medium yielding the most stable mitochondria with the highest respiratory control contained 0.18M KCl, 10mM EDTA, and 0.5% to 1% bovine serum albumin at pH 7.2. Heart failure in guinea pigs and rabbits was produced by varying degrees of stenosis of the ascending aorta. An aberration in respiratory control was found in mitochondria from hearts in severe failure. The quantitative differences between normal and experimental respiratory control values were greatest when the highest possible normal respiratory control levels were obtained. The difference between mitochondria prepared by a proteinase method from control and failing hearts was minimal. No changes in oxidative phosphorylation were noted in mitochondria from hearts arrested by nitrogen, suggesting that acute hypoxia does not irreversibly damage energy-liberating reactions. It is concluded that severe heart failure is characterized by defects in mitochondrial oxidative phosphorylation, and that techniques of isolation or assay or both are probably not causing the abnormalities.
Actions of Diphenylhydantoin on the Electrical Properties of Isolated Rabbit and Canine Atria
Authors: STRAUSS HAROLD C. , BIGGER J. THOMAS , BASSETT ARTHUR L. , HOFFMAN BRIAN F.
Published: June 2012

The effects of diphenylhydantoin (DPH), 10
-8
to 10
-4
M, were studied on the various types of cells in the isolated right atrial preparation and on the specialized cells of Bachmann's bundle in atrial preparations obtained from puppies. High concentrations of DPH (10
-4
M) slowed sinoatrial rate but lower concentrations had little effect. These chronotropic effects of DPH were direct. DPH in concentrations above 10
-5
M decreased the slope of phase 4 depolarization in cells in the sinoatrial node and venous automatic tissue. DPH in concentrations of 10
-8
to 10
-6
M had no effect on transmembrane action potentials recorded from any cell studied; concentrations of 10
-4
M, however, prolonged the terminal phase of repolarization. High concentrations (10
-4
M) also prolonged the effective refractory period of Bachmann's bundle and ordinary atrial and perinodal fibers by an average of 10%. DPH markedly increased the dv/dt of phase 0 of the action potential and membrane responsiveness of ordinary atrial and specialized Bachmann's bundle fibers under control conditions and produced more striking increases when these two variables had been decreased by ouabain. DPH was also proved capable of reversing ouabain-induced sinoatrial block. This unique ability of DPH to enhance membrane responsiveness and to improve conduction in the absence of significant effects on the effective refractory period and automaticity of atrial cells suggests that this may be the sole mechanism of its antiarrhythmic action.
Effects of Beta-Receptor Blockade and Glucagon on the Atrioventricular Transmission System in the Dog
Authors: WHITSITT LEIGHTON S. , LUCCHESI BENEDICT R. , Laidlaw Barbara
Published: June 2012

The effects of
dl
-propranolol,
d
-propranolol, and ICI 46037, a quaternary analog of propranolol, on the functional refractory period and conduction time of the atrioventricular transmission system were studied in anesthetized dogs.
dl
-Propranolol, 0.5 mg/kg, prolonged the functional refractory period, increased the conduction time, and reduced the maximum frequency of A-V transmission. Larger doses (5 mg/kg) produced only a small additional depression of A-V transmission. In contrast, neither
d
-propranolol nor ICI 46037, 0.5 mg/kg, depressed A-V transmission. Larger doses of both drugs prolonged both the functional refractory period and the conduction time, the magnitude of the response being quantitatively similar to that produced by increasing the dose of
dl
-propranolol from 0.5 mg/kg to 5 mg/kg.

The intravenous administration of glucagon, 2 µg/kg, promptly restored normal A-V conduction in animals that had received
dl
- or
d
-propranolol, but was ineffective in those which had received ICI 46037. It was concluded that propranolol depresses A-V transmission by both specific (beta-receptor blockade) and nonspecific mechanisms, the former being the more important. In addition, it appears that glucagon is capable of reversing the cardiodepressant action of propranolol on A-V transmission, a finding which may have considerable clinical importance.
Acetylcholinesterase-Containing Nerve Fibers in the Canine Kidney
Authors: MCKENNA OLIVIA C. , ANGELAKOS EVANGELOS T.
Published: June 2012

The distribution of acetylcholinesterase in the canine kidney was studied by the histochemical method of Karnovsky and Roots and compared to the distribution of adrenergic fibers studied with the fluorescence histochemical method of Falck and Hillarp. Specific inhibitors of nonspecific cholinesterase and acetylcholinesterase were used to differentiate between the two enzymes. In the hilus, acetylcholinesterase-containing nerve fibers were found in large bundles lying adjacent to the media of the hilar arteries. In the rest of the kidney, these fibers traveled with the interlobar, arcuate, and interlobular arteries, the afferent arterioles, and the vasa recta in the outer medulla. The outermedullary nerves appeared to originate in the arcuate connective tissue sheath. Acetylcholinesterase-containing nerve fibers were not seen in association with any other structures. The distribution was similar to that of adrenergic fibers although the density of the acetylcholinesterase-containing fibers was less. Two weeks after unilateral renal denervation, no adrenergic nerve fibers could be detected histochemically in the denervated kidney, whereas acetylcholinesterase-containing nerve fibers were found in five out of seven kidneys. Acetylcholinesterase-staining ganglion cells found in the hilus of the unsuccessfully denervated kidneys appeared to be the source of the acetylcholinesterase-containing nerves. On the basis of these observations, it may be concluded that the kidney is innervated by acetylcholinesterase-containing nerves which are independent of the adrenergic nerve supply.
Application of Heated-Film Velocity and Shear Probes to Hemodynamic Studies
Authors: LING SUNG C. , ATABEK H. BULENT , FRY DONALD L. , PATEL DALI J. , JANICKI JOSEPH S.
Published: June 2012

A constant-temperature heated-film anemometer system has been adapted for the detailed study of in-vivo aortic velocity fields. Two types of sensing probes were developed: a velocity probe and a velocity-gradient or fluid shear stress probe. These probes were evaluated for steady and pulsatile flow in rigid circular tubes using both a glycerin-water mixture and blood. Measurements using both devices agreed closely with the values predicted by well established theory. Moreover, the integrated velocity profiles that were measured correlated well with the simultaneously recorded flow values using orifice meter and electromagnetic flowmeter techniques. In-vivo studies were made along the thoracic aortas of anesthetized dogs and pigs. Velocity measurements along the aorta indicated that the velocity profiles are blunt. The flow-pulse forms obtained by the heated-film technique in vivo were also similar in magnitude and contour to those obtained simultaneously from an electromagnetic flowmeter. Fully developed turbulent flow was not observed; however, occasional "eddy" turbulence occurred in the aortic arch of dogs weighing less than 30 kg. Preliminary measurements indicate that peak wall-shear stresses reach values that are approximately one-third that of the endothelial yield stress.
Certain Histological and Chemical Responses of the Vascular Interface to Acutely Induced Mechanical Stress in the Aorta of the Dog
Authors: FRY DONALD L.
Published: June 2012

The purpose of this study is to quantify certain histologic and chemical responses of the intimal tissues in vivo to acutely induced mechanical stresses. Evans blue dye was given to tag serum albumin and an artificial fat emulsion was infused so that altered fluxes of either serum proteins or the artificial chylomicrons across the vascular interface into the intimal region could be detected. Special histologic and photodensimetric techniques were developed to estimate these fluxes as well as the architectural changes in the endothelial cell population. Architectural changes were quantified by doing endothelial cell counts to quantify the "normal" and "abnormal" endothelial cell population density as a function of stress exposure. The stress corresponding to the greatest rate of change of normal to abnormal cell forms is defined as the acute critical yield stress (τ
c
) and was found to average < 420 dynes/cm
2
. Similarly the stress at which the greatest number of cells are being eroded is defined as the erosion stress (τ
e
). The flux of Evans blue dye into the intima increased with pressure or wall strain, with shearing stress, and with increased turbulence. The flux of artificial chylomicrons into the intimal region never occurred in the presence of a normal endothelial cell population and was found to be most heavy in areas of total cellular erosion.
Force-Velocity-Length-Time Relations of the Contractile Elements in Heart Muscle of the Cat
Authors: BRUTSAERT DIRK L. , Sonnenblick Edmund H.
Published: June 2012

The instantaneous force-velocity-length relations of the contractile elements of the cat papillary muscle have been obtained by determining the phase-plane trajectories of velocity of shortening relative to length during isotonic contractions and correcting these measurements for the series elastic extension during the isometric phase of contraction. The load-extension curve of the series elastic component was obtained by quick release. The velocity-length relations for a given load were independent of initial muscle length and largely independent of the time after stimulation. Velocity-length traces at varying lengths diverged only late in contraction because of a fall in the intensity of the active state. Thus the surface created by the instantaneous force-velocity-length relations serves to define a given contractile state for the contractile element of heart muscle. Further, the linear length-tension relations observed for the contractile element permits an estimation of the maximum development of isometric force with the creation of truly hyperbolic force-velocity curves. Limitations of velocities obtained following quick releases have also been noted.
Effect of Replacement of Potassium by Rubidium on the Transmembrane Action Potential and Contractility of Human Papillary Muscle
Authors: PRASAD KAILASH , CALLAGHAN JOHN C.
Published: June 2012

The effects of extracellular rubidium chloride (1, 2, 4, and 8 mM) on simultaneously recorded transmembrane action potentials and contractions of human papillary muscle in potassium-free solutions were investigated. In KCl-free solution, reduction in the duration of the action potential at the 25% and 50% levels of repolarization was associated with an increase in the force of contraction. Exposure of the muscle to rubidium chloride led to an increase in the duration of the action potential at 25% and 50% levels of repolarization associated with a corresponding decrease in the force of contraction. A decrease in the force of contraction was more usually associated with an increase in the duration of the action potential at the 25% level of repolarization than at the 50% level. No appreciable change in the duration of the action potential at the 90% level of repolarization was observed. Increases in the duration associated with corresponding decreases in the force of contraction were concentrationdependent. Rubidium chloride (8 mM) produced a conduction delay and inexcitability in the muscle. It has been suggested that in KCl-free solution the reduction in the duration of the action potential and an increase in the force of contraction were associated with inhibition of membrane ATPase. Also, the increases in the duration of the action potential accompanied by decreases in the force of contraction were associated with rubidium chloride-induced stimulation of membrane ATPase in human myocardium.
Conformational Changes in Myocardial Nuclei of Rats
Authors: BLOOM S. , CANCILLA P. A.
Published: June 2012

Myocardial nuclei have been found to undergo a dramatic change in nuclear conformation during the contraction-relaxation cycle. This was demonstrated with electron micrographs of longitudinally and transversely oriented nuclei in contracted and relaxed fibers of rat myocardium. The contracted fibers had a mean sarcomere length of l.7µ ± 0.1µ (±1 SD), and extended fibers had a mean sarcomere length of 2.1µ ± 0.3µ. The amount of membrane wrinkling was quantified by comparing a straight-line distance of 6.64µ between two points on the nuclear membrane to the distance along the membrane (NML) between the same points. The degree of wrinkling was expressed as "redundancy" which is [(NML - 6.64)/6.64] x 100. Longitudinal sections showed a marked difference in mean length and width in the two populations of nuclei, with an axial ratio of 2.2 in the contracted, and 4.8 in the extended fibers. The most obvious difference between the two populations, however, was the nuclear membrane redundancy, which was 2.1% and 27.0% for the extended and contracted fibers, respectively. Although a difference in nuclear membrane redundancy was clear in longitudinal sections, it was not apparent in transverse sections. It is concluded that during systole myocardial nuclei become longitudinally compressed with folding of the membrane perpendicular to the long axis. The correlation of the change in sarcomere length with the change in nuclear length and membrane redundancy suggests a coupling of the nuclear membrane to some sarcomere segment.
Refractory Period of the Dog's Ventricular Myocardium Following Sudden Changes in Frequency
Authors: JANSE M. J. , VAN DER STEEN A.B.M. , VAN DAM R. TH. , DURRER D.
Published: June 2012

In exposed hearts of anesthetized dogs with total A-V block, a sudden increase or decrease in heart rate changes the duration of refractoriness immediately. A steady state is established only after a few hundred beats. The time course of shortening of the refractory period caused by an increase in driving rate ("on" effect) has the following characteristics. The first beat shortens the refractory period, as determined from strength-interval curves, about 30% of the total shortening; the second beat shortens it 10% more. After the second beat, the rate of change in the duration of the refractory period suddenly becomes slower. Alternation of the refractory period begins with a slightly prolonged refractory period of the third beat and then diminishes rapidly in about the following 10 beats. These changes are in phase throughout the ventricular myocardium.

Following sudden transition to a slower rhythm, the time course of lengthening of the refractory period ("off" effect) is opposite to the "on" effect: the alternation that occurs is less marked. Changes in the duration of the functional refractory period near the stimulus site are parallel to those in the threshold curves.

These results demonstrate a long persistence of the effect on myocardial refractoriness of a previous cardiac frequency.
Fiber Orientation in the Canine Left Ventricle during Diastole and Systole
Authors: STREETER DANIEL D. , SPOTNITZ HENRY M. , PATEL DALI P. , ROSS JOHN , SONNENBLICK EDMUND H.
Published: June 2012

Fiber orientation across the left ventricular myocardial wall has been studied. Specimens were obtained from 18 dog hearts rapidly fixed in situ in systole, in diastole, and in dilated diastole. Fiber orientation was determined across the free wall at eight sites from a T-shaped specimen by measurements with light microscopy in serial paraffin sections. Results indicate: (1) The wall has a well-ordered distribution of fiber angles varying from about 60° (from the circumferential direction) at the inner surface to about -60° on the outer surface. The greatest change in angle with respect to wall thickness occurs at the two surfaces (endocardial and epicardial). (2) Fiber angles did not change significantly during the transition from diastole to systole, despite a 28% increase in wall thickness (except in the papillary muscle root region). (3) The proportion of fibers lying in the sector of fiber angles oriented circumferentially (0±22.5°) to those oriented longitudinally (67.5 to 90° and -67.5 to -90°) is approximately 10:1. This ratio increases toward the base and diminishes toward the apex of the left ventricle. (4) All fiber angles in the lateral wall of hearts in systole increased through the wall by approximately 7° near the base and 19° near the apex relative to their counterparts in diastole, indicating bending or torsion of the left ventricle during contraction.
Mechanism of Hydrocortisone Potentiation of Responses to Epinephrine and Norepinephrine in Rabbit Aorta
Authors: KALSNER STANLEY
Published: June 2012

Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those to norepinephrine. Neither the presence of cocaine nor pretreatment of the rabbits with reserpine impaired the potentiating action of hydrocortisone. Experiments with the oil immersion technique (to prevent loss of amine by diffusion from the tissue) demonstrated that hydrocortisone reduced the rate at which aortic strips inactivated epinephrine, apparently by inhibiting catechol-O-methyl transferase (COMT). Known inhibitors of COMT (U-0521, tropolone, pyrogallol) potentiated responses of aortic strips to epinephrine much more than to norepinephrine and also enhanced responses to isoproterenol and nordefrin to the same extent as did hydrocortisone. Known inhibitors of COMT consistently abolished the enhancing effects of hydrocortisone without materially interfering with potentiation produced by cocaine which is mediated through an independent mechanism unrelated to amine inactivation. Hydrocortisone also abolished the enhancing effects of known COMT inhibitors. It is concluded that hydrocortisone enhances the responses of vascular smooth muscle to epinephrine and norepinephrine by inhibiting a major enzymatic pathway for the inactivation of these amines.