bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentiation of Myocardial Contractility by Continual Premature Extra-activations
Authors: Koch-Weser Jan 
Published: June 2012

Introduction of a premature activation into each interval between regular contractions of isolated kitten papillary muscles greatly increases isometric tension development. This premature extra-activation potentiation is a manifestation of the interval-strength relationship of ventricular myocardium and results both from the increase in the overall frequency of activation (frequency potentiation) and from the prematurity of the extra-activations (prematurity potentiation).
A premature electrical stimulus which elicits a propagated action potential is always followed by a mechanically apparent activation of the contractile element. Potentiation of the regular contractions follows from the occurrence of premature, propagated action potentials, and/or the resulting activation processes. It does not depend on the extent to which the contractile element can respond to the premature activation.
Prematurity potentiation results solely from an increase in the degree of activation of the contractile element. It increases over a wide range with the prematurity of the extra-activation but always decreases when the prematurity interval approaches the refractory period closely. The extent of prematurity potentiation varies with the basal frequency of contraction; it tends to raise tension development to the same high level whatever the basal frequency. Although nonpotentiated strength of contraction increases greatly with frequency, potentiated contractions at low frequencies are stronger than nonpotentiated contractions at high frequencies.

At normal temperature summation of contractions plays no role in prematurity potentiation. Similarly, release of endogenous norepinephrine is not involved, but such release does occur and interferes with the study of potentiation when high-intensity stimuli are used. Premature activations may transiently alter the concentration of available Ca
++
in an intracellular site critical for activation of the contractile element.
Applications of the Lagged Normal Density Curve as a Model for Arterial Dilution Curves
Authors: Bassingthwaighte James B. , Ackerman Francis H. , Wood Earl H. 
Published: June 2012

1. Indicator dilution curves (concentration versus time) were recorded from the femoral and dorsalis pedis arteries of normal men after injections of indocyanine green into the superior vena cava or thoracic aorta. A four-parameter mathematical model, the lagged normal density curve, adequately described the form of the portion of these curves representing indicator passing by the sampling site for the first time.
2. The curves were observed to be of constant shape, the spread of the curve being approximately linearly related to the mean transit time t. The spread was dependent on the injection site; dispersion was shown to be greatest in the central circulation, less in the aorta, and still less in the arteries of the leg. For the latter segment, the mean transit time t. The spread was dependent 0.3 t, the square root of the variance was 0.18 t, and the parameters of the lagged normal density curve, σ and τ, were 0.09 t and 0.16 t, respectively.
3. The linear relationships between parameters of the recorded curves and the mean transit times indicate that the effect of rate of flow, over a range from resting values to four to six times above resting values, has almost no influence on the dispersion. This suggests that the flow characteristics are essentially unchanged over this range. Such linear relationships always occur with laminar flow but cannot prove its existence because turbulent flow can also produce this result. The similarity of the linear relationships at low flow rates to those at high flow rates, where turbulence almost certainly is present, suggests that arterial flow is usually turbulent. Turbulence may be expected at relatively low flow rates in nonhomogeneous fluids driven by a pulsatile head of pressure through elastic, branched, tapering, curved tubes.
Effect of Afterload on Force-Velocity Relations and Contractile Element Work in the Intact Dog Heart
Authors: Levine Herbert J. , Forwand Stanley A. , Mclntyre Kevin M. , Schechter Eliot 
Published: June 2012

The effects of heightened afterload on force-velocity relations and on contractile element work of single systoles were examined in the intact dog heart. The force-velocity curve described during the course of a normal systole represents a composite of curves, each with its own projected isometric force determined by instantaneous changes in fiber length. During the first systole following an afterload intervention, reciprocal changes in force and velocity were observed together with an extension of the projected isometric-force.
The effect of afterload on contractile element work was determined by: (1) the direction and magnitude of the afterload, and (2) the afterload of the control beat itself. When the control beat was lightly loaded, an increase in afterload increased contractile element work by two additive mechanisms: (1) an increase in mean isometric force, and (2) a shift of force-velocity relations to positions of greater power and work production. In normally loaded control beats, an increase in afterload resulted in a decrease in contractile element work, despite the fact that mean isometric force was increased. In this instance, force-velocity relations were shifted to positions where less power and work could be achieved. Thus, the normal systole appears to function at the apex of the contractile element work-load curve (near 60% of the isometric load).
Evidence is presented which suggests that the apparent maximum active state of the entire left ventricle is generally achieved within 30 to 50 msec after the onset of pressure rise, and that its decay is accompanied by abrupt divergence of the force-velocity relations from the inverse curve of that beat. A sudden increase in afterload does not appear to influence the duration of the maximum active state, although the duration of positive contractile element work is shortened and that of negative contractile element work prolonged.
Effect of Cycle-Length Alteration upon the Configuration of the Canine Ventricular Action Potential
Authors: EDMONDS ROBERT E. , GREENSPAN KALMAN , FISCH CHARLES 
Published: June 2012

Action potentials recorded from canine ventricular fibers displayed characteristic alterations in configuration upon abrupt change in the cycle length. After a relative prolongation of the diastolic interval, abbreviation of phase 2 and slowing of phase 3 were consistently observed, while a relative shortening of diastole was terminated by an action potential displaying prolongation of phase 2 and a steeper phase 3. Neither circumstance was attended by a consistent alteration in action potential duration. The more conventional view, directly relating duration of phase 2 to the length of the preceding diastole, clearly does not obtain immediately following an abrupt alteration of cycle length.
This cycle-length-dependent phenomenon may account, in part, for the post-extrasystolic T-wave alterations observed in the human electrocardiogram. It is also consistent with the clinical observation that such T-wave changes may occur without premature contractions, requiring only a relative prolongation of the R-R interval. Evidence is also presented which relates electrical alter-nans of the T wave to this interval-dependent phenomenon.
This characteristic change in action potential configuration occurs under the same temporal circumstances that others have associated with potentiation of contractility. It is therefore suggested that these inotropic phenomena and changes in action potential configuration may relate to alterations in membrane permeability.
Effect of Angiotensin on the Pressor Response to Tyramine in Normotensive Subjects and Hypertensive Patients
Authors: KANEKO YOSHIHIRO , TAKEDA TADANAO , NAKAJIMA KOUJI , UEDA HIDEO 
Published: June 2012

Arterial blood pressure was recorded directly in 11 normotensive subjects, in 11 patients with essential hypertension and in 10 patients with renovascular hypertension. The pressor response to intravenous injections of norepinephrine, tyramine, angiotensin and ephedrine was compared in these three groups. An infusion of angiotensin was then given and the pressor response to injections of norepinephrine, tyramine, and ephedrine was again measured; in some cases, a comparison of the effects of the cold pressor test was made.
In normotensive subjects, angiotensin infusion caused a significant increase in the responses to tyramine and ephedrine but not to norepinephrine; this occurred with subpressor doses and was unrelated to the level of blood pressure. In patients with renovascular hypertension, the mean pressor responses to injections of tyramine and ephedrine and the ratio of response to tyramine to that to norepinephrine were significantly increased, and the infusion of angiotensin failed to cause any further increase in these responses. In contrast, in patients with essential hypertension, the average response to injections of tyramine was not significantly increased, but during angiotensin infusion the response to tyramine increased as in normotensive subjects. It is proposed that increased response to tyramine, and lack of the potentiating effect of angiotensin demonstrated in renovascular hypertension, may be caused by increased formation of endogenous angiotensin due to renin secretion in this disease.
Alterations in Resting Length-Tension Relations of Cardiac Muscle Induced by Changes In Contractile Force
Authors: SONNENBLICK EDMUND H. , ROSS JOHN , COVELL JAMES W. , BRAUNWALD EUGENE 
Published: June 2012

Effects of sustained postextrasystolic potentiation (P.S.), norepinephrine (NE), and calcium on resting length-tension relations of heart muscle were studied in the cat papillary muscle and isovolumic dog ventricle. In papillary muscles, P.S., calcium or NE produced no change in diastolic compliance when the muscles were freely isotonic, or afterloaded, and force remained constant. However, under isometric conditions, P.S. induced a small fall in diastolic tension while systolic force rose. Similar decrements in diastolic tension were observed when force of contraction was augmented by simply increasing afterload from a constant initial muscle length.
In the isovolumic ventricle, P.S., NE, and calcium each induced substantial increments in developed pressure, accompanied by small decreases in end-diastolic pressure. The latter was reduced or abolished by augmenting the initial contractile state with calcium or NE, so that the super-imposition of P.S. induced only trivial increments in developed pressure.
It is concluded that P.S., calcium, or NE do not induce changes in the resting length-tension relations of heart muscle per se. However, resting length at any given resting tension does increase slightly upon the augmentation of systolic force alone. It is postulated that these findings may be explained by the existence of a series viscous component.
Disturbances in the A-V Conduction System in Chagas' Myocarditis in the Dog
Authors: ANSELMI ALFONSO , GURDIEL ORLANDO , SUAREZ JOSé ANGEL , ANSELMI GERARDO 
Published: June 2012

Atrioventricular (A-V) conduction and the functional refractory period (FRP) of the A-V system were studied in 13 dogs chronically infected by T. cruzi that had ECG disturbances indicative of myocarditis. Histopathologic findings at the A-V node and the bundle of His were correlated with the FRP and with conduction times of the A-V propagation system. Retarded conduction was related to inflammatory and fibrotic processes localized at the bundle of His. At relatively slow rates of stimulation, conduction time was prolonged, but the ventricle was capable of following high atrial rates. With augmented FRP, mononuclear cell infiltrates were observed in the A-V node or in the septal muscle around the node. This suggests that the node was included in the inflammatory process. No correlation was found between inflammatory infiltrates of the bundle of His and changes in the FRP. At relatively slow rates of stimulation, normal A-V conduction time corresponded to prolonged FRP. A-V conduction became slow as the atrial rate increased. A point was reached when the ventricle could not follow the moderately increased atrial rates.
Excitability of cardiac tissues was so markedly altered in 5 dogs with severe inflammatory infiltrates that a similar study of the A-V system could not be made.
Cardiac Failure in the Dog as a Consequence of Exogenous Hyperthyroidism
Authors: PIATNEK-LEUNISSEN DOROTHY , OLSON ROBERT E. 
Published: June 2012

Thirty dogs were made hyperthyroid by feeding them 1 g/kg USP thyroid powder or injecting 1.2 mg/kg of 1-thyroxine/day. Seven of the 30 dogs used had surgically induced mild valvular lesions of the right heart to determine whether preexistent organic disease was a requisite to the induction of failure in hyperthyroidism.
At 2 to 27 months the animals were subjected to cardiac catheterization for measurement of cardiac work and metabolism in vivo. The animals were then killed and the levels of the high energy phosphate compounds creatine phosphate (CP) and the adenine nucleotides (ATP+ADP) in the heart were measured as an index of the net efficiency of the processes of oxidative phosphorylation.
By hemodynamic or histopathologic criteria, 13 dogs showed signs of failure, only 3 of which had preexistent valvular lesions. The failure was not accompanied by a decreased efficiency of oxidative phosphorylation. Net levels of CP and ATP + ADP in the myocardium were normal. Preliminary studies with sarcosomes isolated from 5 animals also revealed normal P/O ratios in 3 dogs with and in 2 without signs of cardiac failure. Liver mitochondria isolated from these same 5 animals all demonstrated decreased P/O ratios. Decreased myocardial extractions of both glucose and pyruvate occurred with failure, suggesting some degree of myocardial hypoxia with increased intracellular glycolysis. Areas of relative hypoxia may exist in a hypertrophied myocardium of the hyperthyroid animal.
Effect of Decreasing the Force of Right Atrial Contraction on Right Ventricular Stroke Volume
Authors: BOYD DANIEL L. , WILLIAMS JOHN W. 
Published: June 2012

The effect of reducing the force of right atrial contraction on right ventricular stroke volume was determined in anesthetized open-chest dogs. Atrial contractile force, measured directly with a strain-gauge arch, was decreased by electrical stimulation of the right vagus nerve; right ventricular stroke volume was measured with an electro-magnetic flowmeter. Heart rate was maintained constant by electrical stimulation of the right atrium.
Vagal stimulation decreased atrial contractile force by an average of 47±2.6 (SEM)% of the control, and stroke volume fell by 4.0±0.9%. During vagal stimulation, no change was observed in right ventricular contractile force. In addition, no consistent change was noted in mean right atrial or right ventricular pressures. The relation between the decrease in atrial force and stroke volume was not altered significantly by the rate of right atrial pacing. In 7 of 10 experiments, increasing the inhibition of atrial force produced a further decrease in stroke volume.
Since neural, mechanical, and humoral factors modify atrial contractile force in the intact animal, the present study provides more definitive evidence that the ability to alter atrial force represents another adaptive mechanism in the regulation of cardiac performance.
Ribonucleic Acid Synthesis in Experimental Cardiac Hypertrophy in Rats
Authors: POSNER BARRY I. , FANBURG BARRY L. 
Published: June 2012

The sequence of events which lead to increased RNA synthesis in the heart following aortic constriction was studied with the use of inhibitors of protein and RNA synthesis. Puromycin given during the first 4 hours after operation inhibited the increase in RNA labeling with [
32
P] H
3
PO
4
that occurred after 4 hours of aortic constriction without inhibiting RNA labeling in sham-operated rats. Puromycin had no effect on the
32
P labeling of the alpha-phosphate of AMP which suggests that the effect on labeling of RNA is not mediated by the lowering of precursor specific activity. The dose of puromycin used inhibited the labeling of heart muscle protein with
3
H leucine. Parafluorophenylalanine had no selective inhibitory effect on the increase of RNA labeling in the hypertrophying heart.

The most likely interpretation of these data is that, following aortic constriction, synthesis of protein is required for subsequent stimulation of RNA synthesis, and this protein may be dependent upon the synthesis of new RNA templates. Any early increased synthesis would be of a minority species of protein since there was no increase in amino acid labeling of total heart protein until 4 to 6 hours after aortic constriction.
The stimulation of RNA labeling by aortic constriction was unaffected by digitalis treatment. The pressure-time index did not correlate with the increased labeling of RNA.
Isolation from a Salivary Gland of Granules Containing Renin and Kallikrein
Authors: CHIANG TZU S. , ERDÖS ERVIN G. , MIWA ISAO , TAGUE LARRY L. , COALSON JACQUELINE J. 
Published: June 2012

Granules of the submaxillary gland of the white mouse contain both kallikrein and renin. The granules were separated and concentrated in sequential centrifugation procedures. They were more stable at room temperature and in hypertonic sucrose solutions than in the cold or in isotonic solution. The amylase, acid phosphatase, renin, kallikrein, and benzoyl-L-arginine ethyl ester esterase contents of the granules were determined. Kallikrein and renin showed a similar distribution pattern after fractionation. Granular renin released the equivalent of 9.6 µg angiotensin II amide/mg enzyme protein/min from swine serum angiotensinogen. Granular kallikrein liberated from human kininogen the equivalent of 8.4 µg bradykinin/mg enzyme protein/min.
Electron micrographs of the isolated granules showed various forms; some were spherical and symmetrical, and others were amorphous.
Structural and Functional Characterization of Dog Heart Microsomes
Authors: Pretorius Petrus J. , Pohl W. Gerhard , Smithen Charles S. , Inesi Giuseppe 
Published: June 2012

Several procedures for the preparation of microsomes from heart tissue were compared. Sucrose was found the most effective addition to preserve the activity of the sarcoplasmic reticulum vesicles.
Electron microscopy of sectioned pellets shows uniform vesicles, but negative staining of microsomal suspensions allows recognition of mitochondrial fragments, which are found in cardiac microsomal fractions in greater amounts than in skeletal muscle preparations. The quantity of mitochondrial contaminations in different fractions was estimated by measuring enzymatic activities.

A comparison of Ca
2+
accumulation, Ca
2+
efflux, and ATPase activity shows identical features in preparations from the heart and from skeletal muscle, although the specific activity is approximately ten times lower in those from the heart. The apparent affinity of sarcoplasmic reticulum for Ca
2+
in vitro justifies the assumption that sarcoplasmic reticulum lowers the intracellular Ca
2+
concentration in the in-vivo heart below the level required for contraction. However, in a weight unit of fresh tissue, the ratio between the maximal Ca
2+
accumulated by SR and the amount of contractile protein is much lower in the heart than in skeletal muscle.

Caffeine and, more markedly, propranolol and tetracaine increase efflux of accumulated Ca
2+
and thereby reduce net uptake by fragmented sarcoplasmic reticulum. Isopropylmethoxamine is not effective at millimolar concentrations.
Flow Estimation by Indicator Dilution (Bolus Injection)
Authors: BASSINGTHWAIGHTE JAMES B. , KNOPP THOMAS J. , ANDERSON DENNIS U. 
Published: June 2012

Indicator dilution techniques used for the estimation of flow (F), mean transit time (t), dispersion (σ), and mean transit time volume (V) in the circulation are subject to error when (1) flow is not steady and (2) concentrations are obtained by sampling at a constant rate (time averaging) rather than at rates proportional to the instantaneous flow past the sampling site (volume averaging).
Using a simple descriptive model for indicator transport, the effects of simulated aortic flow or of sinusoidal flow of widely variable frequency were assessed. Errors in estimates of F, t, σ, and V are greater with bolus injections than with constant-rate injections. Errors are roughly proportional to the amplitude of variation in flow. They are maximal when the period of flow fluctuation is similar to the passage time of the dilution curve, which, for the human central circulation, is about the time for one respiratory cycle. With sinusoidal flow between 50% and 150% of the mean flow, errors were at worst up to 60% in F, 30% in t, 50% in σ, and 70% in V, with a bimodal distribution. Errors are minimal at cardiac frequencies. The troublesome lower frequencies can be avoided. Preliminary tests of a method for converting time- to volume-averaged concentrations gave encouraging results.
Pattern of Cholesterol Ester Fatty Acids in Serum in Normal Subjects and in Patients with Essential Hypercholesterolemia
Authors: BJOÖRNTORP PER , HOOD BERTIL 
Published: June 2012

Sera from 10 patients with essential hypercholesterolemia on ad libitum diet have been analyzed for their content of polyunsaturated fatty acids in the cholesterol esters and the results compared with a matched group of normal subjects. Three cases were analyzed after corn oil substitution for other fats in the diet, and 2 of them were analyzed after addition of pyridoxine to the corn oil regimen. One patient was followed 18 months, and during that time he received a large dosage of corn oil.
Patients with essential hypercholesterolemia had an absolute increase in the amount, but generally a lower percentage content of dienes in their cholesterol esters than normals. After the change to corn oil, the content of polyunsaturated fatty acids increased to levels sometimes considerably above those in the normal subjects, although the total serum cholesterol in one of these cases was by no means normalized. The addition of 100 mg. of pyridoxine to the corn oil regimen did not produce any further decrease in the serum cholesterol level and did not produce any changes in the fatty acid fractions.
The absolute increase in the amount of polyunsaturated fatty acids in the cholesterol esters in essential hypercholesterolemia, particularly after an extremely high intake of unsaturated fat, speaks against factors causing an inhibition in esterification with polyenes as being of central importance.