bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering Simulation of the Viscous Behavior of Whole Blood Using Suspensions of Flexible Particles
Authors: Tickner E. Glenn , Sacks Alvin H.
Published: June 2012

Highly flexible model red cells were molded of acrylamide gel and suspended in a mixture of castor oil and diiodomethane to produce a neutrally buoyant fluid suspension in which the particles behaved mechanically very much like living erythrocytes. The various suspensions were permitted to flow down long cylindrical tubes while measurements of flow rate and pressure drop were made for various concentrations. The fluid suspensions were found to exhibit non-Newtonian viscous behavior which agrees very well with that of whole blood under comparable conditions. The fluid suspensions also exhibited a yield stress below which particle motion ceases. The yield stress was found to depend strongly on particle concentration, as is the case for whole blood.
Influence of the Direction of the Atrial Wave Front on A-V Nodal Transmission in Isolated Hearts of Rabbits
Authors: Janse Michiel J.
Published: June 2012

Transmembrane potentials of A-V nodal cells in isolated rabbit hearts were recorded while the route of entry of atrial activity into the A-V node was changed by stimulating the atrium at a high, constant rate on eitherthe crista terminalis or the interatrial septum. Atrial activity arising from the interatrial septum provided a less effective input to the A-V node, as shown by the occurrence of 2 : 1 A-V conduction block, compared to 1 : 1 during driving on the crista terminalis at the same rate. The amplitude and rate of rise of the action potentials of most A-V nodal cells was smaller during driving on the interatrial septum, and many cells developed alarger or smaller "hump" in the repolarization phase, which was absent during stimulation on the crista terminalis. The pattern of A-V nodal excitation during stimulation on the crista terminalis was similar to that during spontaneous sinus rhythm, but was profoundly altered during stimulation on the interatrial septum. The results can be explained by assuming that an atrial wave front coming from the interatrial septum excites the atrial margin of the A-V node asynchronously, resulting in inhoinogeneous conduction within the node, causing longitudinal dissociation. The results show that successful propagation through the A-V node is at least partly determined by the direction of the atrial wave front. This factor may play an important role during atrial fibrillation.
Electrophysiological Actions of Diphenylhydantoin on Rabbit Atria
Authors: JENSEN R. A. , KATZUNG B. G.
Published: June 2012

Isolated rabbit left atrial preparations were perfused with Tyrode's solutions containing 1 to 10 µg/ml (4 x 10
-6
-4 x 10
-5
M) diphenylhydantoin (DPH), 2.6-5.6 mM K
+
, and 154-308 mM Na
+
. Steady-state transmembrane resting and action potentials were recorded from these preparations with glass microelectrodes at stimulation rates ranging from 0.2 to 3/sec. DPH had little or no effect on the relationship between extracellular [K
+
] and membrane resting potential. Action potential overshoot was generally decreased by 5 and 10 µg/ml DPH and increased by 1 µg/ml DPH at stimulation rates of 2 and 3/sec in the presence of increased [K
+
]. DPH and increased [K
+
] acted synergistically to shorten action potential duration (measured at 50% repolarization). The effect of DPH on phase 0 of the action potential (measured as action potential rise time between 10 and 50% and 50 and 90% depolarization) was markedly dependent upon drug concentration, extracellular [K
+
] and stimulation rate. The lowest concentration of DPH (1 µg/ml) usually shortened action potential rise time, particularly when it had been prolonged by increasing extracellular [K
+
]. Conversely, the highest concentration of DPH (10 µg/ml) and increased [K
+
] acted synergistically to prolong action potential rise time (i.e., decrease depolarization rate). When present, the depressant effect of DPH on membrane depolarization was rapidly antagonized by increasing extracellular [Na
+
]. It is proposed that DPH may either enhance or depress (like quinidine) membrane activity in atrial tissue, and that both the direction and magnitude of effect are strongly dependent upon drug concentration, ionic milieu, and heart rate.
Ventricular Nuclei-DNA Relationships with Myocardial Growth and Hypertrophy in the Rat
Authors: GRIMM ARTHUR F. , DE LA TORRE LUIS , LA PORTA MICHAEL
Published: June 2012

Rat ventricles, ranging from 306 to 1999 mg, were obtained from normal animals of different ages and from animals subjected to chronic aortic constriction. The concentration of DNA in the paired ventricles (right and left) was found to be closely related to the concentration of nuclei in the left ventricular papillary muscles. Muscle nuclei represented only 10 to 15% of this population of nuclei. In young animals (phase 1), the total ventricular content of muscle nuclei, nonmuscle nuclei, and of DNA were increasing with ventricular growth. In the adult rat (phase 2), the total ventricular content of DNA and of both muscle and nonmuscle nuclei remained relatively constant with ventricular growth. In the enlarged hearts (phase 3), there was a further increase in total ventricular DNA but there was no further increase in the total number of muscle nuclei. Spectrophotometric studies (Feulgen stain), showed that 88% of the muscle nuclei belonged to a single ploidy class (probably diploid). No relation could be demonstrated between the extent of nuclear polyploidy and the weight of the ventricles. It was concluded that polyploidy was not a significant factor in the increased total DNA of phase 3. The increased ventricular DNA of phase 3 was explained by the proliferation of the nonmuscle nuclei.
Left Ventricular Performance at High End-Diastolic Pressures in Isolated, Perfused Dog Hearts
Authors: MONROE R. G. , GAMBLE W. J. , LAFARGE C. G. , KUMAR A. EDALJI , MANASEK F. J.
Published: June 2012

In the isolated, blood-perfused heart of the dog, left ventricular developed pressure and developed mean wall stress were observed while the ventricle contracted at a constant, nearly isovolumic afterload and while end-diastolic pressure was raised to levels exceeding 100 mm Hg. Coronary perfusion pressure was maintained at the level of the peak systolic pressure. Dilatation of the mitral ring and consequent mitral regurgitation were avoided by left atrial plication. Normalized graphs of percent of peak developed pressure against end-diastolic pressure showed that developed pressure rose abruptly with diastolic pressure, peaked at a diastolic pressure of approximately 30 mm Hg, and declined 14.7% (±0.9 SE) at an end-diastolic pressure of 100 mm Hg. Likewise, developed mean wall stress rose abruptly with diastolic pressure, peaked at a higher diastolic pressure of approximately 50 mm Hg, and declined only 7.5% (±0.8 SE) from this peak at an end-diastolic pressure of 100 mm Hg. Similar findings were observed in hearts acutely depressed with propranolol. Electron micrographs showed sarcomere length to average 2.275µ and 2.300µ in ventricles fixed in diastole while subjected to pressures of 61 and 100 mm Hg, respectively, after potassium arrest, confirming the findings illustrated by the normalized graphs. These observations imply that in the isolated heart of the dog there is no loss of ventricular performance attributable to a descending limb of the Frank-Starling mechanism until the end-diastolic pressure exceeds 60 mm Hg and that this loss is minimal at diastolic pressures as high as 100 mm Hg.
Active Length-Tension Relations Compared in Isometric, Afterloaded and Isotonic Contractions of Cat Papillary Muscle
Authors: TAYLOR ROGER R. , Burrows Peter
Published: June 2012

Isometric, afterloaded and isotonic contractions of cat right ventricular papillary muscle were studied in vitro at 30°C or 37°C. The length to which muscle contracted under a given total load varied directly with initial muscle length. The discrepancies between contracted muscle lengths depended upon load and the inotropic state of the muscle. In control contractions at 12/min, the maximum discrepancy occurred at a load of 0.5 g or 1 g and averaged 0.47 ± 0.04 (
SD
) mm while after acetylstrophanthidin (0.75 µg/ml) the maximum discrepancy occurred between 3- and 5-g load and averaged 0.62 ± 0.07 mm (
P
< 0.001). At low loads acetylstrophanthidin decreased the discrepancy at 0.5-g load from 0.41 ± 0.08 mm to 0.22 ± 0.05 mm (
P
< 0.001). Acetylstrophanthidin increased developed tension at optimum muscle length by 71 ± 23% (
P
< 0.001). Increasing frequency of contraction from 12/min to 60/min induced greater decrease in time to peak tension than occurred with acetylstrophanthidin (30% vs. 15%) but produced little change in either isotonic or isometric contracted length-tension relations. Since the differences between contracted length-tension relations were not influenced by abbreviation of active state induced by frequency changes, it is unlikely that the lesser abbreviation with acetylstrophanthidin was responsible for the changes it produced. Rather, they may be related to the intensity and duration of active state reflecting increased energy release in the contractile process.
Renal Hilar Lymph
Authors: O'MORCHOE CHARLES C. , O'MORCHOE PATRICIA J. , HENEY NIALL M.
Published: June 2012

Renal lymph was collected from single hilar lymphatics in 58 anesthetized dogs (1) to study the mechanism by which lymph production is affected during diuresis and (2) to determine whether a medullary contribution to renal lymph could be defined by changes in the electrolyte concentration of hilar lymph with concomitant alterations in the concentration gradient of the renal medulla. When diuresis was induced by a solute load (mannitol), lymph flow increased by 25 to 300%. On the other hand, when diuresis was induced without such a solute load, lymph flow was either unaffected (mersalyl) or slightly reduced (furosemide). It was concluded that the effect of mannitol on renal lymph flow was mediated primarily through its general effect on extracellular fluid rather than through any specific intrarenal consequence of the diuresis itself.

Control hilar lymph-to-plasma concentration ratios for Na
+
(1.057 ± 0.040), Cl
-
(1.129 ± 0.040) and Ca
2+
(0.770 ± 0.046) but not K
+
(0.0986 ± 0.086) were found to be significantly different from 1.0. Failure of mannitol diuresis to alter significantly the lymph-plasma ratios of Na
+
and Cl
-
provided evidence that the high electrolyte concentrations of the inner medulla were not reflected in hilar lymph. The finding that furosemide abolished the lymph-plasma concentration difference for Na
+
and significantly reduced that for Cl
-
was taken as evidence that the outer medulla was a significant source of renal hilar lymph.
Atrial Electrophysiology in Experimental Hyperthyroidism in Rabbits
Authors: ARNSDORF MORTON F. , CHILDERS RODERICK W.
Published: June 2012

Male rabbits received
l
-thyroxine (250 µg/kg) subcutaneously for 7 days and exhibited marked tachycardia, elevation of protein-bound iodine levels and a 26% mean weight loss. Their hearts were isolated and perfused by the Langendorff technique. In 8 thyroid-treated rabbits the mean heart rate before they were killed and also after 30 minutes of perfusion was much higher than that of 10 controls; threshold in late diastole was lower, and the mean effective refractory period was shorter: 109 msec (95 to 116) as compared with 147 msec (130 to 170). The atrial multiple-response threshold was strikingly lower, and strength-interval curves were shifted to the left without overlap or change in contour. Atropine, 7 µg/liter, did not significantly affect these changes. Acute perfusion of four hearts with
l
-thyroxine (500 µg/liter) produced similar, but less consistent, results. Perfusion with either epinephrine or norepinephrine, regardless of concentration, could not reproduce the changes seen with thyroid treatment. It is concluded that thyroxine profoundly alters electrophysiologic variables of atrial tissue independently of the autonomic nervous system and that these changes are responsible for many cardiac effects of hyperthyroidism, including the enhanced susceptibility to atrial fibrillation in thyrotoxicosis.
Mechanism of Triglyceridemia in Hypercholesterolemic Rabbits
Authors: HUANG C. C. , KAKO K. J.
Published: June 2012

To elucidate mechanisms responsible for the increased plasma triglyceride (TG) which occurs in diet-induced hypercholesterolemia in rabbits, albino rabbits were fed a 3% cholesterol diet for various durations, and the following determinations were carried out: plasma lipid levels; turnover rate of plasma TG (labeled very low density lipoprotein, or glycerol-2-
3
H method); lipoprotein lipase activity of the heart and plasma; fatty acid and acetate incorporation into TG in the liver (homogenates and slices). Plasma levels of both free and esterified cholesterol and phospholipid increased rapidly, while TG increased relatively slowly during cholesterol feeding without change in hepatic TG synthesis. The fractional turnover was, on the other hand, depressed within a week. The decrease in plasma TG in response to a heparin injection was less in hypercholesterolemic rabbits than in normal animals. However, the measured activity of heart lipoprotein lipase of cholesterol-fed rabbits was higher than that of the control group. When the effects of two substrates (very low density lipoprotein from normo- and from hypercholesterolemic plasma) were compared, the apparent activity was lower with the latter. The Degrees of this inhibition was proportional to the amount of cholesterol in the lipoproteins. The inhibition of lipoprotein lipase activity was also observed with the addition of cholesterol to activated Ediol, but not with addition of esterified cholesterol. Lineweaver-Burk plots were constructed using partially purified plasma lipoprotein lipase, and Km values for Ediol, Ediol plus protamine sulphate, and Ediol plus cholesterol were calculated. The presence of cholesterol in the substrate of lipoprotein lipase competitively inhibits the enzyme activity, and this is the mechanism of hyperglyceridemia observed in diet-induced hypercholesterolemic rabbits.
Hypothalamic Control of the Distribution of Cardiac Output in the Unanesthetized Rhesus Monkey
Authors: FORSYTH RALPH P.
Published: June 2012

Regional organ blood flow and resistance changes evoked after 10 minutes of electrical stimulation of pressor areas in the anterior hypothalamus were studied in six unanesthetized, restrained rhesus monkeys. Five other monkeys served as controls. The regional changes produced by stimulus intensities which did not affect systemic arterial pressure, central venous pressure, cardiac output, or pulse rate were similar to those produced by the stimulations at higher levels which significantly increased the levels of these variables. With both low and high levels of stimulation the fractions of cardiac output to skeletal muscle and chest wall were increased 51 and 146% at the expense of the output to the kidneys, skin, stomach, spleen, pancreas, mesentery, and thyroid which decreased 38 to 79%. In each of two monkeys tested, the marked rise in blood flow and vasodilatation of skeletal muscle was only slightly affected by atropine. Therefore, there is at least some hypothalamic control over skeletal muscular vasodilatation in the unanesthetized monkey that is not cholinergically mediated.
Transmission of the Blood Flow Pulse through the Pulmonary Arterial Tree of the Dog
Authors: KARATZAS NICHOLAS B. , NOBLE MARK I.M. , SAUNDERS KENNETH B. , MCLLROY MALCOLM B.
Published: June 2012

We have made simultaneous measurements of the instantaneous flow in the main pulmonary artery using an electromagnetic flowmeter and the pulmonary capillaries using the nitrous oxide body plethysmograph method in six lightly anesthetized and spontaneously breathing dogs. We measured the transmission of the flow wave in the pulmonary arterial tree at a variety of heart rates and during alveolar hypoxia. Fourier analysis enabled us to study transmission in the intact animal in a way similar to that of imposed oscillations of flow in the isolated organ. The amplitude of the pulmonary capillary flow pulse was approximately half that in the main pulmonary artery. There was progressive decrease in amplitude from the first to the fourth harmonic in both the pulmonary arterial and pulmonary capillary flow pulses. Harmonics above the fourth were small and variable in amplitude. Transmission between pulmonary valve and capillaries was independent of heart rate. Hypoxia did not affect transmission. Assuming that the increase in resistance in this instance was due to precapillary vasoconstriction, this finding suggests that other factors may offset the effect of increase in resistance upon transmission.
Role of the Sinus Node in the Mechanism of Cholinergic Atrial Fibrillation
Authors: NADEAU REGINALD A. , ROBERGE FERNAND A. , BILLETTE JACQUES
Published: June 2012

The effect of suppressing sinus rhythm on initiation and maintenance of atrial fibrillation was studied in 17 thoracotomized and artificially ventilated dogs. Atrial fibrillation was evoked by methacholine chloride applied to the right atrium followed by light mechanical stimulation. Episodes of fibrillation were compared before and after sinus rhythm had been suppressed by injection of absolute alcohol or concentrated sodium pentobarbital into the sinus node artery. Sixty-nine control episodes of atrial fibrillation lasting 6.00 ± 0.36 (
SE
) minutes were easily initiated while the heart was in sinus rhythm. The response to methacholine application plus mechanical stimulation depended on the type of escape rhythm obtained after suppression of sinus rhythm. In ten dogs with no sign of supra A-V junctional pacemaker activity, only 50% of the attempts to initiate fibrillation were successful. The 26 episodes of atrial fibrillation observed in this group of animals lasted 0.65 ± 0.23 (
SE
) minutes. In seven other dogs, supra A-V junctional pacemaker activity persisted after injection into the sinus node artery. In these seven dogs, 60% of the attempts at initiating fibrillation were successful, and the 18 episodes of fibrillation lasted 4.44 ± 0.30 (
SE
) minutes. In dogs showing no supra A-V junctional pacemaker activity, a more sustained arrhythmia was obtained after recovery of sinus node activity or during electrical pacing of the right atrial appendage. These observations suggest that the sinus node participates in the mechanism of cholinergic atrial fibrillation and that an equivalent role can be played by a natural or artificial supra A-V junctional pacemaker.
Relative Contributions of the Atrial Systole-Ventricular Systole Interval and of Patterns of Ventricular Activation to Ventricular Function during Electrical Pacing of the Dog Heart
Authors: DAGGETT WILLARD M. , BIANCO JESUS A. , POWELL W. JOHN , AUSTEN W. GERALD
Published: June 2012

In areflexic canine right heart bypass preparations, little difference in ventricular function was observed as a result of atrial pacing, sequential atrioventricular pacing, or atrial-His bundle pacing at an appropriate atrial systole-ventricular systole (As-Vs) interval. Ventricular function was depressed during ventricular pacing and during atrioventricular pacing with an inappropriate As-Vs interval. In areflexic isovolumic left ventricle preparations, ventricular function was depressed during ventricular pacing compared to atrial pacing, and changes in the As-Vs interval during atrioventricular pacing were accompanied by changes in ventricular function only in association with changing patterns of ventricular activation. In animals with heart block under conditions of right heart bypass, wherein changes in the pattern of ventricular activation were precluded during atrioventricular pacing, ventricular function deteriorated pari passu with shortening of the As-Vs interval. These data indicate that both the temporal relation between atrial and ventricular contraction and the pattern of ventricular activation importantly influence ventricular function during cardiac pacing. The marked changes in ventricular function observed as a function of the As-Vs interval, for any given pattern of electrical activation, suggest that the As-Vs interval is the more important determinant of ventricular function during cardiac pacing.
Blood Flow and Tissue Space of the Left Coronary Artery in Man
Authors: KLASSEN GERALD A. , AGARWAL JAI B. , TANSER PAUL H. , WOODHOUSE STANLEY P. , MARPOLE DEREK
Published: June 2012

Using a constant infusion of two indicators, T-1824 bound to albumin and tritiated water, flow and transit time were measured in the left coronary system of intact man. Indicators were infused for 6 minutes into the left coronary artery with sampling from the coronary sinus in a region that drained exclusively the inflow of the left coronary artery and from the brachial artery for recirculation. The degree of heterogeneity of myocardial perfusion could be defined by the time required for the curve to reach a plateau. A correlation coefficient of 0.966 was found between the two indicator-measured blood flows. The average myocardial hematocrit was calculated and found to be similar to the arterial. In the presence of myocardial disease, total flow of the left coronary artery was increased. When this was divided by tissue volume, the blood flow per unit volume of tissue was decreased in the presence of the idiopathic cardiomyopathy.
Augmentation of Myocardial Oxygen Consumption in Hyperthyroid Cats
Authors: SKELTON C. LYNN , COLEMAN HENRY NEAL , WILDENTHAL KERN , BRAUNWALD EUGENE
Published: June 2012

To clarify the effects of hyperthyroidism on myocardial oxygen consumption (VO
2
), a polarographic method was employed to compare the VO
2
of isolated papillary muscles from 13 normal euthyroid cats with that of 11 hyperthyroid cats. Basal VO
2
was greater in the hyperthyroid group (3.03±0.20 vs. 2.36±0.19 SE filter-ing dry wrr
1
· hour
1
,
P
< 0.05). In muscles studied under afterloaded isotonic conditions, hyperthyroidism shifted the forcevelocity curve upward and to the right, with an increase in both extent and velocity of shortening at equivalent loads. These changes in myocardial behavior in hyperthyroidism were associated with an increase in myocardial VO
2
. Isometrically contracting muscles from hyperthyroid animals demonstrated significant increases in both developed tension (6.3±0.7 vs. 4.7±0.4 g/mm
2
,
P
< 0.05) and rate of tension development (32.6±3.5 vs. 19.4±1.5 g/mm
2
· second-
1
,
P
< 0.01), as compared to the euthyroid group. Myocardial VO
2
, expressed per g/mm
2
isometric developed tension, was significantly greater in the hyperthyroid group (0.641±0.09 vs. 0.42±0.04 milliter · mg dry wt-
1
· beat-,
P
< 0.02). Thus, experimental hyperthyroidism augments myocardial VO
2
whether measured in resting or contracting cardiac muscle. This increase can be attributed, at least in part, to $ie altered contractile function of the heart in hyperthyroidism.
Presence of Widened and Multiple Intercalated Discs in the Hypertrophied Canine Heart
Authors: LAKS MICHAEL M. , MORADY FRED , ADOMIAN G. E. , SWAN H. J. C.
Published: June 2012

Fresh tissues were taken for light microscopy from the trabeculae carneae at the right ventricular base, apex, left ventricular base, and apex of four normal canine hearts and nine whose pulmonary artery had been banded for 7 to 48 weeks. After banding, the width of the intercalated disc at the right base, 1.34 ± 0.10 µ (mean ± SE), was greater than at the right apex, 1.02 ± 0.09 µ (
P
<0.002); both were greater than the normals (
P
<0.005 and
P
<0.001). The intercalated discs were wider than corresponding normals in only three hearts at the left base and six at the left apex. The mean widths of the discs correlated positively with both ventricular wall thickness and weight in the right ventricle but not in the left. Structures characterized by two, three, or four transverse segments of discs lying along the same myofibrils, each two of which are separated by 1 to 10 sarcomeres, have been named multiple intercalated discs. In six of the nine hearts whose pulmonary artery was banded, there were more multiple discs per mm
2
at the right base and right apex than in the corresponding normals (
P
<0.02). In five of these, the number of multiple discs per mm
2
was greater at the right base than in the corresponding apex (
P
<0.001). There was no significant increase in the number of multiple discs per mm
2
in either the left base or left apex of the experimental animals compared to controls. After banding the pulmonary artery, tension increases in the right ventricle and this stimulates a broadening of the folds of the discs and then triggers a mechanism for the formation of new sarcomeres, perhaps involving multiple intercalated discs.
Catecholamine Metabolism in Hypertensive Rats
Authors: LOUIS WILLIAM J. , KRAUSS KENNETH R. , KOPIN IRWIN J. , SJOERDSMA ALBERT
Published: June 2012

The possible role of catecholamines in two forms of experimental hypertension in rats was investigated further. Inbred, spontaneously hypertensive (SH) Wistar rats had unchanged endogenous levels of norepinephrine (NE) in the three tissues studied, and a significantly (
P
<0.05) decreased rate of NE synthesis (
14
C-tyrosine technique) in heart and brainstem but not in gut, in comparison to normotensive Wistar rats. Also, the levels of free fatty acids (FFA) and major urinary catecholamine metabolites in plasma revealed no evidence of increased catecholamine turnover or release. Sprague-Dawley rats rendered hypertensive by treatment with desoxycorticosterone acetate and 1% salt had decreased cardiac NE concentration and increased cardiac NE turnover (
3
H-NE technique) and cardiomegaly, confirming the work of others. However, urinary normetanephrine and plasma FFA did not differ from those in normal rats. These and other results fail to support but do not completely exclude a primary role for catecholamines in either type of hypertension.
Role of Specific Glycopeptides of Human Serum Lipoproteins in the Activation of Lipoprotein Lipase
Authors: HAVEL RICHARD J. , SHORE VIRGIE G. , SHORE BERNARD , BIER DENNIS M.
Published: June 2012

Lipoprotein lipase forms an enzyme-substrate complex with fat emulsions in the presence of serum lipoproteins. Lipoproteins of very low density and high density have this property, but the former are much more active per unit weight of protein. In this investigation, the activity, expressed as quantity giving half-maximal rate of production of free fatty acids, of specific glycopeptides isolated from very low density and high density lipoproteins was tested in an incubation mixture containing lipoprotein lipase from cows' milk and 1.8 mg triglyceride per ml. The two major polypeptides of high density lipoproteins were virtually inactive in amounts up to 100 µg per ml. Activity of the unfractionated apoproteins of very low density lipoprotein was similar to that of the native lipoprotein (about 4 µg/ml). Two of its polypeptides were active: one with carboxyl-terminal glutamic acid at 0.45 to 0.60µg/ml and one with carboxyl-terminal alanine at
1.8.2.8
µg/ml. Some preparations of the latter peptide were less active and inhibited at high levels. Three other glycopeptides from very low density lipoprotein were inactive. Low density lipoprotein from subjects with primary biliary cirrhosis and a lipoprotein of density 1.04 to 1.06 from a subject with specific elevation of this fraction, both containing the active glycopeptides, had considerable activity (5 to 11 µg/ml). These studies indicate that specific glycopeptides are required for the action of lipoprotein lipase on emulsified triglycerides and suggest that they are important components of the mechanism for extra-hepatic utilization of plasma triglycerides.
Cardiovascular Effects of Sustained Norepinephrine Infusions in Dogs
Authors: MOSS ARTHUR J. , SCHENK ERIC A.
Published: June 2012

Sustained infusions of norepinephrine (NE) are known to produce deleterious pathophysiologic effects on the circulatory system. The mechanisms responsible for these effects were investigated in 25 dogs; 17 were treated with selective block of alpha receptors by phenoxybenzamine or of beta receptors by propranolol, or by both agents, and then infused with NE (4 µg.kg
-1
.min
-1
) for 4 hours; 8 control animals were given only adrenergic blocking agents. Left ventricular and systemic pressure, cardiac output and arterial blood gases were measured at selected intervals throughout the infusion period, and histologic examinations of the heart and other vital organs were performed at the conclusion of each study. In animals with alpha-receptor blockade, NE infusions were associated with extensive subendocardial hemorrhage and focal myofiber fatty degeneration, yet blood pressure, cardiac output, and derived cardiac work parameters were well maintained. In animals with beta-receptor blockade, NE caused minimal pathologic changes in the heart despite significant reduction in cardiac output, minute and stroke work, and significant increase in left ventricular end-diastolic pressure (LVEDP) and peripheral vascular resistance. In animals receiving combined alpha- and beta-receptor blockade, NE infusions were not associated with significant hemodynamic or morphologic abnormality. These findings indicate: (1) the hemodynamic abnormalities are the result of the action of NE mediated primarily through alpha receptors; (2) the morphologic changes are produced by NE mediated mostly through beta receptors; and (3) the reductions in cardiac output and minute and stroke work and the increase in LVEDP produced by sustained NE infusions are not necessarily a consequence of the pathologic changes which develop in the heart muscle.
Isoproterenol-Induced Myocardial Infarction in Rats
Authors: SAROFF JACK , WEXLER BERNARD C.
Published: June 2012

Mature male rats with isoproterenol-induced myocardial infarction and normal controls were injected intravenously with [1, 2-
3
H] corticosterone (
3
H corticosterone). Blood and tissue samples (liver, brain, adrenal glands, "normal" and necrotic areas of the heart) were collected 15, 30, and 45 minutes after tracer injection. Gross and histopathological changes were noted. The metabolic clearance rate of corticosterone was greater for the experimental group (11.9 liter/day) than in the normal group (8.4 liter/day). The production rate of corticosterone was approximately 4.45 mg/day for both groups of animals. The percent serum protein-binding of corticosterone was lowered from a normal of 70.3 to 56.7 in the group with cardiac necrosis. The data indicated that during myocardial infarction there was a decrease in the synthesis or availability of the corticosteroid-binding globulin. The increased uptake of
3
H corticosterone by the adrenal glands reflected the increased adrenal glandular steroid metabolism as well as depletion of its corticosterone reserve in animals during the stress of cardiac necrosis. There was a greater uptake of
3
H corticosterone by the hearts and brains of the animals with myocardial infarction; but during the acute phase of infarction, there was no selective uptake of
3
H corticosterone by necrotic vs. normal-appearing areas of the heart.
Contributions of Coronary Perfusion Pressure, Metabolic Acidosis and Adrenergic Factors to the Reduction of Myocardial Contractility during Hemorrhagic Shock in the Cat
Authors: SIEGEL HOWARD W. , DOWNING S. EVANS
Published: June 2012

The contributions of metabolic acidosis, coronary perfusion pressure (CPP) and adrenergic support to left ventricular performance during hemorrhagic shock at aortic pressure (AP) of 30 ± 5 mm Hg were evaluated in cats in which AP, cardiac output (CO), and heart rate (HR) were controlled, and arterial pH, Po
2
and Pco
2
were continuously monitored. After 2 hours of shock, the stroke volume (SV), ejected at end-diastolic pressure of 10 cm H
2
O (SV
10
), was irreversibly reduced to 46 ± 4% (P < .001) of initial values (arterial pH 6.93 ± .05). In control animals SV
10
after 2 hours was 86 ± 6% (pH 7.32 ± .07). Eight animals were subject to shock, but their CPP was held at 100 mm Hg. These showed no difference in SV
10
from controls after 2 hours, although the pH had fallen to 6.90 ± .05. Reduction of CPP in these animals without correction of pH resulted in a rapid fall of SV
10
. In 10 animals subjected to shock for 2 hours, the arterial pH was maintained near 7.40 by infusion of Tris buffer. Five showed no greater reduction of SV
10
than the controls, and five became severely depressed. In five cats subjected to beta-receptor blockade, hemorrhagic shock (pH 7.40) produced a rapid fall of SV
10
which initially could be reversed by reelevation of AP. In less than 15 minutes, the SV
10
depression became irreversible. Thus, shock (2 hours) and associated metabolic acidosis is detrimental to ventricular contractility only if CPP is also reduced. The contribution of acidosis may be related to the amount of sympathetic support during shock. With beta-receptor blockade, shock results in a marked reduction in SV
10
, even in the absence of metabolic acidosis.
Renal Blood Flow and Renin Activity in Renal Venous Blood in Essential Hypertension
Authors: BLAUFOX M. DONALD , FROMOWITZ ARTHUR , LEE HYO BOK , MENG CHIEN-HSING , ELKIN MILTON
Published: June 2012

The intrarenal distribution of blood flow measured by the
133
xenon washout method and the renin activity of renal venous blood were determined in 16 patients with early essential hypertension. None of the patients had evidence of systemic disease except for the elevation in blood pressure (> 150/100 mm Hg). Fifteen of the subjects received a controlled sodium diet during 7 to 9 days before study, at the time of renal angiography. An inverse relationship was noted between the cortical component of the renal blood flow and renin activity of renal venous blood (r = 0.64,
P
< 0.02). Renin secretion rates were also calculated in 12 patients confirming the inverse relationship between cortical distribution of blood flow and renin secretion (r = 0.763,
P
< 0.01). The cortical renal blood flow in 10 patients on a low salt intake was 79.6% ± 2.6 (SE) of the total renal blood flow. The cortical blood flow in five patients on a high salt diet was 87.6% ± 1.9 (SE); the statistical difference between the two groups is significant (
P
< 0.05). A direct relationship was noted between cortical blood flow and the logarithm of the 24-hour urinary sodium excretion from the day preceding the study (r = 0.54,
P
< 0.05). Renin secretion rate and renin in renal venous blood were directly correlated (r = 0.813,
P
< 0.01). Changes in corticomedullary distribution of flow were inversely related to the changes in cortical distribution. The degree of reduction of cortical renal blood flow correlated with the degree of increase in renin secretion and in renin activity in renal venous blood. Our data are compatible with reduced cortical renal blood flow mediating renin release or vice versa. Either mechanism would result in more efficient conservation of salt and water by the kidney.
Effects of Coronary Blood Flow and Perfusion Pressure on Left Ventricular Contractility in Dogs
Authors: ABEL RONALD M. , REIS ROBERT L.
Published: June 2012

The effects of changes in coronary blood flow and coronary artery pressure on left ventricular (LV) contractility were determined in 18 animals. Dogs on cardiopulmonary bypass provided isovolumetric LV contractions during controlled perfusion of the coronary circulation. Coronary venous efflux, myocardial oxygen consumption, peak LV pressure, LV dp/dt, and the force-velocity relations of the LV were determined at normal and at "supernormal" levels of flow and pressure. Coronary vasodilatation was obtained with nitroglycerine, permitting independent variation of flow and pressure. Augmenting flow by increasing pressure increased LV contractility, as reflected by increases in peak LV pressure, dp/dt max, peak wall tension, and maximal measured contractile element velocity. Increased contractility appeared to be primarily due to increased flow, rather than to pressure, as an increase in flow without an increase in pressure produced similar changes, and decreases in pressure at constant flow did not change maximal measured contractile element velocity or dp/dt max, although some decrease in peak LV pressure and wall tension did occur. These data suggest that coronary flow is an independent determinant of the contractile state of myocardium, and that an increase in flow in excess of that required to supply metabolic demands augments myocardial contractility.
Effect of Sodium Restriction on Renal Hypertension and on Renin Activity in the Rat
Authors: MIKSCHE L. W. , MIKSCHE ULRIKE , Gross F.
Published: June 2012

Control rats and rats with experimental renal hypertension due to unilateral stenosis of one renal artery received a standard diet (0.23% sodium) and a sodium-deficient diet (0.004% sodium), alternately, during which time blood pressure and plasma renin activity were determined. At the end of the experiment, renin content of the kidneys was measured.

In normotensive control rats, the sodium-deficient diet did not affect blood pressure, but plasma renin activity and renin content of the kidneys increased. In rats with renal hypertension, restriction of sodium supply was followed by a fall in blood pressure to normotensive levels, provided that an intact contralateral kidney was present. Similarly, sodium-deficient diet prevented the development of hypertension if given immediately after placing the clip on one renal artery. Restriction of sodium supply provoked a marked increase in plasma renin activity, whereas renin content of the ischemic kidney was only slightly, but significantly, higher than in rats with normal sodium intake. Contrary to this, in unilaterally nephrectomized rats with renal hypertension, neither hypertension nor plasma renin activity or renin content of the kidneys was affected by sodium-deficient diet. In control rats with unilateral nephrectomy, plasma renin activity was only half that of intact rats, and restriction of sodium provoked no more than an increase up to normal values of intact rats. Sodium loss by the contralateral kidney may contribute to both the antihypertensive effect of a sodium-deficient diet and the increase in plasma renin activity.
A Mechanism for Reentry in Canine Ventricular Tissue
Authors: SASYNIUK BETTY I. , MENDEZ CARLOS
Published: June 2012

In isolated canine papillary muscle-false tendon preparations it was possible by selecting the pattern of stimulation to obtain conduction block within the peripheral distribution of the Purkinje network. Action potentials recorded just proximal to the site of block were always extremely brief in duration; refractory periods were abbreviated accordingly. When propagation from specialized fibers to muscle fibers was made very critical, conduction block occurred at some Purkinje-muscle junctions while propagation continued through others. Under these conditions very early reentrant activity could be obtained in terminal Purkinje fibers. With proper timing, the impulse propagated back to the false tendon and emerged as a closely coupled extrasystole. Occasionally, the activity returned again to muscle and resulted in a double reentry. Electrotonic shortening of action potentials of Purkinje fibers at relatively long distances upstream from a site of block facilitated the reentry of proximal elements. Partial reentry of the Purkinje system created conditions favoring fractionation of the reentrant wave front.
Microsphere Measurement of Intrarenal Circulation of the Dog
Authors: SLOTKOFF LAWRENCE M. , LOGAN ALEXANDER , JOSE PEDRO , D'AVELLA JOHN , EISNER GILBERT M.
Published: June 2012

Distribution of cortical blood flow was measured in the dog by a technique based on radionuclide-labeled microspheres. Initially it was necessary to test possible pitfalls of this technique. Completeness of trapping in the kidney, the effect on renal function, and the notion that microsphere distribution reflects blood flow distribution in the kidney cortex were studied. Renal vein blood contained less than 0.2% of the microspheres (16.8µ diameter) found in the renal artery after an aortic injection. No impairment of C

PAH

(control 167±4; postinjection 179±31 ml/min), C
In
(control 39.3%6; postinjection 37.6±2 ml/min), and T
m
glucose (control 90.8±13; postinjection 102±24) was found using doses adequate to measure renal blood flow (5 mg/injection x 4 injections). After 4 injections of 50 mg each significant impairment of renal function was observed. Intrarenal blood flow distribution was determined during hemorrhagic hypotension.
169
Yb-labeled microspheres were injected into the root of the aorta before, and
85
Sr-labeled microspheres after, acute hemorrhage. Radioactivity was measured in the outer two thirds and inner one third of kidney slices. Tissue blood flow was calculated and expressed as the ratio of outer cortex to inner cortex counts. Renal blood flow was redistributed to the inner cortex after hemorrhage (ratio before, 3.00; after 1.30,
P
< 0.01). Finally, the results of this technique were compared to a widely used method of measuring intrarenal blood flow distribution,
133
Xe washout. The first component of the washout technique correlated fairly well with total cortical flow but it was not possible to match the second component with any single anatomical area of the kidney. Limitations of the
133
Xe washout are discussed.
Adrenergic Neurohumoral Influences on Circulation and Lipolysis in Canine Omental Adipose Tissue
Authors: BALLARD KATHRYN , ROSELL SUNE
Published: June 2012

Vascular resistance, capillary filtration coefficient (CFC) and changes in blood volume were determined in canine omental adipose tissue. Release of glycerol and free fatty acids (FFA) were measured. Basal values in acutely denervated tissue for blood flow and CFC were 11 ml/min/100 g (range 4 to 26, N = 36) and 0.05 ml/min/100 g/mm Hg (range 0.018 to 0.090, N = 38), respectively. Stimulation of the sympathetic nerves (1 to 9 Hz) caused initial vasoconstriction, maintained for 1 to 3 minutes. At lower frequencies (1 to 3Hz), the blood flow increased gradually after the initial decrease. At higher frequencies, the constriction often reverted to vasodilatation. The CFC was not changed or increased initially. The clearance rate of locally injected
125
I decreased in spite of a constant blood flow and blood volume was reduced initially. After α-receptor blockade, nerve stimulation caused vasodilatation, which in turn was inhibited by β-receptor blockade. Infusion of norepinephrine produced a pattern of vascular and lipolytic responses similar to those evoked by nerve stimulation. The release of glycerol and FFA was increased by nerve stimulation and by norepinephrine. The lipolytic response was inhibited by β-receptor blockade. It is concluded that sympathetic nerves are physiologically important for the regulation of vascular reactions and control of lipid metabolism in omental adipose tissue. Whether this is also the case for circulating catecholamines remains to be established.
Artificial Atrial Fibrillation in the Dog
Authors: STRACKEE JAN , HOELEN ADRIAAN J. , ZIMMERMAN ARIAEN N. , MEIJLER FRITS L.
Published: June 2012

R-R interval sequences during artificial atrial fibrillation in dogs were studied in the same way as in patients in a previous study and compared with results obtained in dogs with spontaneous atrial fibrillation. Artificial atrial fibrillation was effected by right atrial stimulation in three closed-chest and one open-chest dog. The ventricular rhythm was studied by histograms and autocorrelograms. The ventricular dysrhythmia during artificial atrial fibrillation generally differed from that during true atrial fibrillation. Therefore the findings during artificial atrial fibrillation cannot be used without reservation to explain electrophysiological (or hemodynamic) phenomena in true atrial fibrillation.
Effects of a Digitalis Glycoside on Coronary and Systemic Dynamics in Conscious Dogs
Authors: VATNER STEPHEN F. , HIGGINS CHARLES B. , FRANKLIN DEAN , BRAUNWALD EUGENE
Published: June 2012

The effects of ouabain (G-strophanthin), 20 µg/kg were compared in 12 conscious dogs with Doppler flow transducers on the ascending aorta and left circumflex coronary artery and pressure gauges in the aorta, and in 9 of these dogs after general anesthesia with Na pentobarbital. In conscious dogs ouabain caused an initial bradycardia, but heart rate returned almost to control at 15 to 30 minutes, while arterial pressure rose and remained elevated. Cardiac output and coronary blood flow decreased initially, returned to control by 5 minutes and then remained constant. Systemic, mean, and late diastolic coronary resistances were elevated within 1 minute and remained elevated for 30 minutes. After anesthesia, ouabain caused similar increases in arterial pressure and slightly greater increases in systemic resistance, but the bradycardia and reduction of cardiac output were more profound and sustained. In the anesthetized state, coronary resistance rose when heart rate was allowed to slow after ouabain but was not elevated when heart rate was returned to control. Thus, in the conscious state, ouabain caused a distinct elevation in coronary and systemic resistances with no change in cardiac output, while in the anesthetized state ouabain reduced cardiac output and when heart rate was controlled, did not alter coronary resistance.
Participation of Central Noradrenergic Neurons in Arterial Baroreceptor Reflexes in the Rabbit
Authors: CHALMERS J. P. , WURTMAN R. J.
Published: June 2012

Disappearance rates of intracisternally administered
3
H-norepinephrine and activities of tyrosine hydroxylase were examined in the rabbit in five brain regions (telencephalon, hypothalamus, midbrain, medulla-pons, and cerebellum) and in three cord regions (cervical, thoracolumbar, and lumbosacral) 2 weeks after section of the carotid sinus and aortic nerves. Mean blood pressure rose by 29% and heart rate by 17% in the animals with neurogenic hypertension. Endogenous catecholamine concentrations in the eight regions examined were not altered by denervation. In the thoracolumbar region of the spinal cord,
3
H-norepinephrine turnover and tyrosine hydroxylase activity were increased approximately twofold in hypertensive rabbits. We suggest that these changes reflect increased physiological activity of bulbospinal noradrenergic neurons and that this increase may mediate the rise in arterial pressure or heart rate that follows sinoaortic denervation. The turnover of
3
H-norepinephrine increased in the hypothalamus of denervated animals; tyrosine hydroxylase activity remained unchanged in this region.
Hereditary Patent Ductus Arteriosus and Its Sequelae in the Dog
Authors: Patterson D. F. , Pyle R. L. , Buchanan J. W. , Trautvetter E. , Abt D. A.
Published: June 2012

Further studies of hereditary patent ductus arteriosus (PDA) in the dog show the defect to have a graded phenotypic expression. A high proportion of offspring of test matings had a fully patent ductus arteriosus, while a smaller proportion had a blind diverticulum of the ductus arteriosus which communicated with the aorta. This is considered to be a forme fruste of PDA, representing incomplete closure. Approximately 50% of pups with fully patent ductus arteriosus developed signs of left heart failure, and about 15% developed severe pulmonary hypertension with right-to-left or bidirectional shunts. Genetic analysis indicated that hereditary PDA in the dog is not a simple mendelian trait, Rather, it resembles a quasi-continuous or threshold trait with a high degree of heritability. Results were analyzed using a polygenic model with two developmental thresholds. Liability to defective closure of the ductus arteriosus increased with the proportion of the genome received from dogs with PDA. Moreover, in pups which had PDA, the incidence of serious sequelae (left heart failure and severe pulmonary hypertension) increased in a parallel fashion, suggesting that an increased liability to PDA was accompanied by an increase in the severity of the lesion.