bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Pressure-Induced Stretch and Convection on Low-Density Lipoprotein and Albumin Uptake in the Rabbit Aortic Wall
Authors: Meyer Guy , Merval Re´gine , Tedgui Alain
Published: June 2012

The effects of pressure-driven convection and vessel wall stretching in the pressure-related changes in low-density lipoprotein (LDL) and albumin transport across the arterial wall were studied in vitro in freshly excised rabbit thoracic aorta held at in vivo length and pressurized at 70, 120, or 160 mm Hg for 30 minutes. External rigid polyester sleeves of various diameters (4, 5, or 6 mm) were passed around half of the arterial segments in order to prevent vessel distension during pressurization. The intraluminal solution contained
131
I-LDL and
125
I-albumin. The transmural distribution of relative concentrations of LDL (C
LDL
) and albumin (C
alb
) across the wall was determined in wrapped and unwrapped segments using a serial frozen-sectioning technique. In the unwrapped segments, C
alb
increased uniformly between 70 and 120 mm Hg (
P
<.0001) but did not change significantly between 120 and 160 mm Hg (0.0063±0.0009 [n=4], 0.0520±0.0055 [n=9], and 0.0620±0.0071 [n=12], respectively). In contrast, C
LDL
increased markedly both between 70 and 120 mm Hg (
P
<.001) and between 120 and 160 mm Hg (
P
<.05) (0.0025±0.0005 [n=4], 0.0234±0.0029 [n=9], and 0.0393±0.0056 [n=12], respectively), with the increase being much more pronounced in the inner than in the outer media. In the segments wrapped with the 4-mm sleeves, both C
LDL
and C
alb
did not vary significantly between 70, 120, and 160 mm Hg. In the segments wrapped with the 5-mm sleeves, C
LDL
increased significantly between 120 and 160 mm Hg, whereas C
alb
did not vary significantly with increasing pressure. Our results demonstrate that (1) pressure-induced stretching of the arterial wall is a major determinant of arterial mass transport, and (2) pressure-driven convection accentuates LDL accumulation in the inner media, which may explain enhanced atherosclerosis in hypertension.
Role of an Electrogenic Na
+
-HCO
3
−
Cotransport in Determining Myocardial pH
i
After an Increase in Heart Rate
Authors: Camilión de Hurtado María C. , Alvarez Bernardo V. , Pérez Néstor G. , Cingolani Horacio E.
Published: June 2012

The contribution of electrogenic Na
+
-HCO
3
−
cotransport to pH
i
regulation during changes in heart rate was explored in cat papillary muscles loaded with BCECF-AM in bicarbonate-free (HEPES) medium and in CO
2
/HCO
3
−
-buffered medium. Stepwise increments in the frequency of contraction from 15 to 100 bpm induced a reversible increase in the pH
i
from 7.13±0.03 to 7.36±0.03 (
P
<.05, n=5) in the presence of CO
2
/HCO
3
−
buffer. The same increase in the frequency of stimulation, however, decreased pH
i
from 7.10±0.02 to 6.91±0.06 (
P
<.05, n=5), in the absence of bicarbonate. Moreover, in CO
2
/HCO
3
−
-superfused muscles pretreated with SITS (0.1 mmol/L), this effect of increasing the contraction frequency was reversed, and a decrease of pH
i
from 7.03±0.04 to 6.88±0.06 (
P
<.05, n=4) was observed when the pacing rate was increased stepwise from 15 to 100 bpm. High [K
+
]
o
–induced depolarization of cell membrane alkalinized myocardial cells in the presence of HCO
3
−
ions, whereas acidification was observed as a consequence of hyperpolarization induced by low external [K
+
]
o
. Myocardial resting membrane potential became hyperpolarized upon exposure to HCO
3
−
-buffered media. This HCO
3
−
-induced hyperpolarization was not blocked by the inhibition of Na
+
,K
+
-ATPase activity by ouabain (0.5 μmol/L) but was prevented by SITS. The results suggested that membrane depolarization during cardiac action potential causes an increase in electrogenic Na
+
-HCO
3
−
cotransport. Such depolarizations occurring as a consequence of increases in heart rate would thus, by means of elevated bicarbonate influxes, substantially increase the myocardial cell's ability to recover from an enhanced proton production.
Modulation of Endothelium-Dependent Hyperpolarization and Relaxation to Acetylcholine in Rat Mesenteric Artery by Cytochrome P450 Enzyme Activity
Authors: Chen Guifa , Cheung Donald W.
Published: June 2012

Acetylcholine (ACh) induced hyperpolarization and relaxation in rat mesenteric arteries contracted with norepinephrine, as indicated from studies with simultaneous microelectrode and tension recordings. We tested whether the hyperpolarization to ACh was modified by induction and depletion of cytochrome P450 enzymes. Enzyme induction by treating the animals with 3-methylcholanthrene and β-naphthoflavone for 3 days resulted in a significant increase in the endothelium-dependent hyperpolarization to a maximum of 22.7±1.0 mV from 13.9±0.4 mV in arteries from untreated animals. Enzyme depletion by treating the animals with CoCl
2
for 2 days resulted in a significant reduction in the maximum hyperpolarization to 9.9±0.7 mV. When NO synthesis was inhibited by
N
ω
-nitro-
l
-arginine, the relaxation was correlated to hyperpolarization. The
N
ω
-nitro-
l
-arginine–resistant responses were significantly inhibited by clotrimazole. The relaxation to ACh was not altered by enzyme induction but was significantly reduced by enzyme depletion. In KCl-contracted arteries, modification of cytochrome P450 enzyme activity had no significant effect on the relaxation to ACh. Similarly, hyperpolarization and relaxation to pinacidil were not significantly affected. These results suggest that the hyperpolarization response to ACh is closely regulated by cytochrome P450–dependent enzymes.
Expression of mRNAs for Neurotrophins and Their Receptors in Developing Rat Heart
Authors: Hiltunen Jukka O. , Aruma¨e Urmas , Moshnyakov Maxim , Saarma Mart
Published: June 2012

Because the neurotrophic system has not been systematically studied in developing heart, we studied the expression of mRNAs for neurotrophins and their high- and low-affinity receptors by radioactive in situ hybridization in the rat heart from embryonic day 9 (E9) to parturition. The neurotrophin-3 (NT-3) transcripts were seen in the group of Leu-7 immunoreactive cells in the ventricular region from E11 to parturition, suggesting that NT-3 is expressed in the part of the developing conduction system. mRNAs for truncated trk receptors, trkC.TK− and trkB.T1, were expressed in the outflow tract at E12 and in the walls of developing aorta and pulmonary trunk from E13 to parturition, whereas the mRNA for catalytic trkC.TK+ was revealed in the walls of aorta and pulmonary trunk from E13 to parturition and in the cardiac ganglion neurons from E14 to adult stage. Transcripts for low-affinity neurotrophin receptor (p75) were transiently seen in the distal outflow tract from E11 to E13, declining by E14. At E18, p75 transcripts were also seen in the cardiac ganglia. Transcripts for nerve growth factor, neurotrophin-4/5, trkA, or trkB.TK+ were not detected. Expression of NT-3 mRNA in the developing conduction system and of trkC.TK+ mRNA in the cardiac neurons suggests a role for NT-3 in the innervation of the conduction system. Expression of trkC.TK+ in the wall of aorta and pulmonary trunk suggests that NT-3 also may affect the development of the smooth muscle cells.
Compensatory Mechanisms Associated With the Hyperdynamic Function of Phospholamban-Deficient Mouse Hearts
Authors: Chu Guoxiang , Luo Wusheng , Slack Jay P. , Tilgmann Carola , Sweet Wendy E. , Spindler Matthias , Saupe Kurt W. , Boivin Gregory P. , Moravec Christine S. , Matlib Mohammed A. , Grupp Ingrid L. , Ingwall Joanne S. , Kranias Evangelia G.
Published: June 2012

Phospholamban ablation is associated with significant increases in the sarcoplasmic reticulum Ca
2+
-ATPase activity and the basal cardiac contractile parameters. To determine whether the observed phenotype is due to loss of phospholamban alone or to accompanying compensatory mechanisms, hearts from phospholamban-deficient and age-matched wild-type mice were characterized in parallel. There were no morphological alterations detected at the light microscope level. Assessment of the protein levels of the cardiac sarcoplasmic reticulum Ca
2+
-ATPase, calsequestrin, myosin, actin, troponin I, and troponin T revealed no significant differences between phospholamban-deficient and wild-type hearts. However, the ryanodine receptor protein levels were significantly decreased (25%) upon ablation of phospholamban, probably in an attempt to regulate the release of Ca
2+
from the sarcoplasmic reticulum, which had a significantly higher diastolic Ca
2+
content in phospholamban-deficient compared with wild-type hearts (16.0±2.2 versus 8.6±1.0 mmol Ca
2+
/kg dry wt, respectively). The increases in Ca
2+
content were specific to junctional sarcoplasmic reticulum stores, as there were no alterations in the Ca
2+
content of the mitochondria or A band. Assessment of ATP levels revealed no alterations, although oxygen consumption increased (1.6-fold) to meet the increased ATP utilization in the hyperdynamic phospholamban-deficient hearts. The increases in oxygen consumption were associated with increases (2.2-fold) in the active fraction of the mitochondrial pyruvate dehydrogenase, suggesting increased tricarboxylic acid cycle turnover and ATP synthesis.
31
P nuclear magnetic resonance studies demonstrated decreases in phosphocreatine levels and increases in ADP and AMP levels in phospholamban-deficient compared with wild-type hearts. However, the creatine kinase activity and the creatine kinase reaction velocity were not different between phospholamban-deficient and wild-type hearts. These findings indicate that ablation of phospholamban is associated with downregulation of the ryanodine receptor to compensate for the increased Ca
2+
content in the sarcoplasmic reticulum store and metabolic adaptations to establish a new energetic steady state to meet the increased ATP demand in the hyperdynamic phospholamban-deficient hearts.
Adhesion of Memory Lymphocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Vascular Endothelial Cells Under Simulated Physiological Flow Conditions In Vitro
Authors: Gerszten Robert E. , Luscinskas Francis W. , Ding Han T. , Dichek David A. , Stoolman Lloyd M. , Gimbrone Michael A. , Rosenzweig Anthony
Published: June 2012

The accumulation of mononuclear leukocytes is an early and persistent finding in atherosclerotic plaques. These mononuclear leukocytes are mostly monocyte-derived, but up to 20% are lymphocytes, predominantly CD4
+
CD45RO
+
(memory) T cells. To evaluate the potential of adenovirus vectors for studies of mononuclear leukocyte recruitment in vitro, we studied the effects of adenovirus vectors per se on human umbilical vein endothelial cells (HUVECs), a well-characterized in vitro model of vascular endothelium. A recombinant adenovirus containing the seven-domain isoform of rabbit vascular cell adhesion molecule-1 (rVCAM-1) was constructed and used to study lymphocyte adhesion under defined laminar flow conditions in transduced HUVEC monolayers. No increase in basal HUVEC surface expression of the inducible endothelial adhesion molecules and markers of activation, E-selectin and VCAM-1, was noted across a broad range of multiplicity of infection. A modest dose-dependent increase in surface intercellular adhesion molecule-1 expression was detectable by flow cytometry at an MOI of >30 plaque-forming units per cell. Under defined laminar flow from 1.5 to 0.5 dyne/cm
2
, the adenovirus vector carrying rVCAM-1 mediated stable adhesion of both a Jurkat T-cell line and primary human CD4
+
CD45RO
+
(memory) T cells. Monoclonal antibodies to α
4
-integrin or rVCAM-1 abolished adhesion, whereas monoclonal antibodies to CD18 or P-selectin had no effect. We conclude that adenoviral gene transfer is useful for studies of VCAM-1–dependent leukocyte adhesion in vitro and that endothelial expression of VCAM-1 alone, in the absence of overt endothelial cell activation, is sufficient under simulated physiological flow conditions to support adhesion of memory T cells, the predominant lymphocyte subset in atherosclerotic plaque.
The Effect of Levarterenol on Polarographic Myocardial Oxygen, the Epicardial Electrocardiogram and Contraction
Authors: SAYEN J. J. , KATCHER A. H. , SHELDON W. F. , GILBERT C. M.
Published: June 2012

In open-chest dogs it was found that levarterenol produced primary RS-T segment depression in epicardial surface electrocardiograms together with increases of ventricular muscle contractility. These effects occurred in nonischemic, regionally ischemic, and hypoxic myocardium and were accompanied by rises of polarographic myocardial oxygen and a reddening of coronary venous blood in all but the lowest dosages. The findings are discussed in the light of the pertinent experimental literature.
Prolonged Δ
4
-Cholestenone Feeding in Birds
Authors: NICHOLS C. W. , LINDSAY S. , CHAPMAN D. D. , CHAIKOFF I. L.
Published: June 2012

The pathologic changes in the aorta, liver, and adrenal glands, and the changes in sterols of plasma and liver induced in birds by the prolonged feeding of a diet containing 0.5 per cent Δ
4
-cholestenone are described. Lesions were found in the media of thoracic aortas and intima of the abdominal aortas of the sterol-fed birds and evidence is presented to show that the crystalline material in the abdominal plaques is not cholesterol. There was enlargement of both liver and adrenal glands with a pronounced deposition of total digitonin-precipitable sterols which could not be accounted for by Liebermann-Burchard reacting sterols (LBRS). In the Δ
4
-cholestenone-fed birds the level of LBRS in plasma, fell to about 50 per cent of that in control birds, whereas the levels of total digitonin-precipitable sterols (TDPS) rose to values of 200 mg. per 100 ml. The fraction of the TDPS present as non-LBRS was quite constant in the plasma of the sterol-fed birds (63-69 per cent). By means of isotope dilution procedures the non-LBRS in the livers of sterol-fed birds was identified as dihydrocholesterol.
The Effect of Digoxin on the Intermediary Metabolism of the Heart as Measured by Glucose-C
14
Utilization in the Intact Dog
Authors: KIEN GERALD ALAN , SHERROD THEODORE R.
Published: June 2012

Administration of a therapeutic dose level of digoxin in the intact dog resulted in an augmentation of the glucose utilization of the myocardium accompanied by a greatly increased rate of glycolytic and oxidative activity. The contribution of glucose to the total metabolism of the heart was increased, and the utilization of noncarbohydrate substrates was decreased. These metabolic changes occurred in the absence of changes in the dynamic functions of the heart, indicating that the metabolic alterations were due to a primary effect of the drug rather than an effect secondary to an altered state of cardiac activity.
A Comparative Analysis of Molar Sodium Lactate and Other Agents in the Treatment of Induced Hyperkalemia in Nephrectomized Dogs
Authors: GREENSTEIN SIDNEY , GOLDBURGH WARREN P. , GUZMAN SANTIAGO V. , BELLET SAMUEL
Published: June 2012

Molar sodium lactate, sodium bicarbonate, sodium chloride, glucose insulin, and calcium chloride were used in the treatment of induced hyperkalemia in nephrectomized dogs. The effect of these agents on the electrocardiogram and on potassium partition was studied. Molar sodium lactate appeared to be the agent of choice in the treatment of the hyperkalemic state under these experimental conditions.
Immediate Effects of Intravenous Endotoxin on Serotonin Concentrations and Blood Platelets
Authors: DAVIS RICHARD B. , MEEKER WILLIAM R. , McQUARRIE DONALD G.
Published: June 2012

Adult mongrel dogs were given a lethal dose of E. Coli endotoxin by rapid intravenous injection. Total serotonin levels in the serum fell rapidly, with the concentration in the portal vein and pulmonary artery significantly exceeding that in the femoral artery within the first minute after injection. Small rises in plasma serotonin were found in some of the animals. These changes were coincident with a sharp fall in the number of circulating platelets, with striking changes in platelet morphology, and with the initial fall in blood pressure.
Quinidine and Unidirectional Cation Fluxes in Atria
Authors: KLEIN RICHARD L. , HOLLAND WILLIAM C. , TINSLEY BETTY
Published: June 2012

The effect of quinidine on unidirectional fluxes of Na and K in isolated rabbit atria has been investigated and correlated with known effects of the drug on the electrical and mechanical properties of the heart. Quinidine caused a rapid inhibition of Na entry, which secondarily depressed K efflux. In addition, the drug depressed membrane permeability to K and caused a marked inhibition of active transport, both of which were relatively slow in onset.
Histochemical Studies in Atherogenesis: Human Aortas
Authors: ZUGIBE FREDERICK T. , BROWN KENNETH D.
Published: June 2012

There have been many conflicting reports concerning the relationships of lipid, acid mucopolysaccharides, and elastic changes in the early pathology of atherosclerosis. Various new histochemical methods have been applied to grossly normal and early lesions of aortas of 50 individuals ranging from fetuses to 40 years of age with a view to illuminating these problems. The following paper presents our results of these studies.
Variability of the Viscoelastic Constants Along the Aortic Axis of the Dog
Authors: LAWTON RICHARD W.
Published: June 2012

The application of elastomeric theory to the study of the viscoelastic properties of the dog's aorta shows that the same value of the elastomeric parameter β may be used to describe the elastic behavior of aorta strips under both static and dynamic conditions. The variations in the parameter β and the damping fraction γ with the strip's location may be distinguished only for the extremes of the central arterial axis because of the wide variability of mechanical properties among dogs. The viscoelastic properties apparently do not correlate with the measured geometric properties of the unstressed aortic strip.
Indirect Induction of Vascular Damage by X-Irradiation
Authors: LEVY CHARLES K.
Published: June 2012

The changes in petechial susceptibility of the vessels of hamster cheek to the moccasin venom test have been compared in shielded and irradiated pouches of the same animal which had received median lethal doses of x-irradiation. There was no statistically significant difference demonstrable between the irradiated and controlled cheek pouches, but both showed a greater hemorrhagic response than was found in the cheek pouches of unirradiated control animals.

Similar results were found when the diffusion of intradermally injected Evans blue was used as an indication of x-irradiation damage. The shielded and the exposed areas both showed enhanced permeability to the dye when compared with the unirradiated control animals.

These results suggest that some indirect factor or factors are involved in the vascular and permeability changes following exposure to ionizing radiation.
Method for Experimental Constriction of Arteries with Polyvinyl Alcohol Sponge
Authors: DAHL ELMER V. , EDWARDS ERIC C. , GRINDLAY JOHN H. , EDWARDS JESSE E.
Published: June 2012

Simple plastic constricting devices for producing experimental arterial stenosis may be prepared from formalinized polyvinyl alcohol (surgical ivalon) sponge. Not a single instance of arterial rupture, a common sequel of stenosis produced by rigid devices, was encountered in 56 experiments.
Electrolytes and Arterial Muscle Contractility
Authors: DODD W. ALAN , DANIEL EDWIN E.
Published: June 2012

Arterial contractility in response to various drugs was studied in media designed to alter ionic gradients of sodium and potassium across the cell membrane. Tissues were analyzed to determine the effects of these procedures on tissue electrolytes and to demonstrate any correlation between tissue electrolytes and response.

It was found that the contractile responses progressively decreased in sodium-free media, disappearing in 2 to 2½ hours. A decrease in external potassium, initially caused a potentiation of response. Thereafter, a decreased response was manifested, yet contractility remained even after 7 to 8 hours in potassium free medium. Increased external potassium caused an increase in response.

There was no correlation between the content of sodium and potassium and response in potassium-free solutions, but in sodium-free solutions a positive correlation between contractility and potassium content existed.

Chloride appeared to exist in 2 fractions, a diffusible fraction, and a more tightly bound fraction. Calculation of the ECFV based on the bound chloride yielded values which otherwise would have been absurd.

Sodium appeared to be distributed in 3 fractions; diffusible and extracellular, not diffusible over the duration of our experiments and slowly diffusible and presumably intracellular, the latter fraction being possibly capable of cation exchange.

Evidence obtained does not suggest that the sodium gradient, per se, is responsible for contractility. The concentration of intracellular potassium does not influence contractility directly. However, the potassium gradient may in part determine vascular muscle contractility.
Effect of Addition and Removal of a Kidney Transplant in Renal and Adrenocortical Hypertensive Rats
Authors: GOMEZ A. H. , HOOBLER S. W. , BLAQUIER P.
Published: June 2012

A method is described for preparing and studying the acute effect of renal transplants on the blood pressure of the rat. In such a preparation, renal blood flow, urine flow, and blood pressure are well maintained over a period of several hours. In hypertension of less than 6 months' duration following renal ligation or desoxycorticosterone administration, the transplant consistently reduced the blood pressure and in 36 out of 44 experiments normotensive levels were achieved in 30 to 40 minutes. Exclusion of the kidney permitted a gradual restoration of the hypertension. When the blood pressure was elevated by infusions of renin or angiotensin, the blood pressure did not fall after the transplantation procedure. Introduction of kidney tissue after the hypertension had lasted for 6 months or more reduced the blood pressure in only 10 of 23 experiments, suggesting that after the passage of time irreversible vascular changes had occurred.

The mechanism by which the transplant lowers the blood pressure is unknown, but such factors as the creation of an area of low vascular resistance, the release of non-specific depressor substances into the circulation, and the external loss of a pressor substance into the urine seem to be excluded. Reasons are given for suspecting that the antihypertensive action of normal kidney tissue is a specific metabolic or incretory effect, rather than an excretory action related to urine formation.
Effect of Prolonged Periods of Anoxia on Atrioventricular Conduction and Cardiac Muscle
Authors: COFFMAN CAPT. JAY D. , LEWIS F. BRUCE , GREGG DONALD E.
Published: June 2012

The return of A-V conduction according to the electrocardiogram, the ability to maintain the blood pressure, the cardiac muscle ATP, the coronary venous pH, lactic acid, and potassium were studied to delineate the effects on the heart of prolonged periods of anoxia in dogs maintained on an extracorporeal circulation. Myocardial anoxia for 100 minutes was the limit for return of A-V conduction in all dogs in these experiments. Only 2 of 5 hearts anoxic for 120 minutes, and 1 of 3 hearts anoxic for 150 minutes regained A-V conduction. One heart subjected to anoxia for 165 minutes did not show A-V conduction on reperfusion of the coronary arteries.

The dogs whose hearts were subjected to periods of anoxia longer than 100 minutes could not maintain the blood pressure on removal from the extracorporeal circulation. This was due to the development of an unusual firmness of the left ventricular muscle, usually appearing after 90 minutes of anoxia and progressing to involve the entire heart. This firmness was not reversible on reperfusion of the heart. Since A-V conduction and speed of conduction returned in some of these firm hearts, it was concluded that there was earlier permanent damage to the myocardial muscle than to the conduction system during anoxia.

Cardiac muscle ATP values were not definitely changed after 30 minutes of anoxia, but were decreased and regenerated on reperfusion of the heart after 60 minutes of anoxia. The low levels of ATP did not return toward normal on reperfusion of the heart after 90 and 120 minutes of myocardial anoxia. Additional experiments on anoxic hearts of nonperfused dogs also demonstrated the marked decrease in ATP levels. In both types of studies, the earliest onsets of firmness showed some correlation with low ATP levels. The high lactic acid levels and low pH values of the coronary venous blood found after long periods of anoxia may be related to the failure of ATP regeneration and to the onset of firmness in these hearts.

Potassium arrest of hearts subjected to anoxia showed no difference in the return of A-V conduction, in the ability to maintain blood pressure on removal from the extracorporeal circulation, in the onset or degree of myocardial firmness, nor in the levels of cardiac muscle ATP, coronary venous pH, and lactic acid, from the anoxic, nonarrested hearts.

The variability of the effect of anoxia on A-V conduction and myocardial muscle of different hearts by the parameters measured in this study is stressed.
Labeled Phosphate Distribution in Working and Nonworking Myocardium
Authors: TSUBOI KENNETH K. , BUCKLEY NANCY M. , ZEIG NORMAN J.
Published: June 2012

Investigation of phosphate metabolism with the aid of labeled phosphorus has been carried out, using isolated heart preparations in which only the left ventricles perform external work. The corresponding right ventricles in such preparations perform no external work with the unique experimental advantage of a single heart, providing simultaneously both working and "resting" (nonworking) metabolic states.

Comparative incorporation of labeled phosphorus into nucleotide phosphate groups, non-nucleotide soluble phosphorylated components, phospholipids and ribose nucleic acid was examined as a function of cardiac work. Incorporation of the label into the rapidly exchanged high-energy phosphate groups was found to be restricted by a prior rate--limiting entry of the externally perfused isotope into the cells, thereby precluding a measure of turnover of these groups by this technic. Differences could not be demonstrated in isotope incorporation in either the phospholipids or RNA of working as compared to nonworking myocardium. It was concluded from these results that RNA is clearly not involved in energy reactions associated with cardiac work function. Phospholipid participation, on the other hand, could be clearly excluded only insofar as the phosphate moiety of these compounds is concerned.

Information relevant to a mechanism of phosphate entry into cardiac cells was obtained in which a phosphorylation of hexose appeared to be involved. The composition of cardiac tissue with respect to nucleotide and non-nucleotide soluble components was examined in working and nonworkiug myocardium. Differences in composition were not found with respect to these constituents. A major component appearing in extracts of cardiac tissue was found and subsequently identified to be α-glycerophosphate. On the basis of isotope incorporation data, it was concluded that its metabolic source was of carbohydrate rather than phospholipid origin.
Histamine Release and Intracellular Potentials During Anaphylaxis in the Isolated Heart
Authors: FEIGEN GEORGE A. , WILLIAMS E. M. VAUGHAN , PETERSON JANICE K. , NIELSEN C. B.
Published: June 2012

The response of the sensitized guinea pig heart to perfusion, with an effective dose of ovalbumin, was found to consist of an acceleration of the rate, an increase in the amplitude of contraction, and a decrease in coronary flow, confirming the earlier observations of Wilcox and Andrus. The characteristic mechanical reaction of the isolated atria was an increase in amplitude and frequency of contraction, the more intense effects resulting in fibrillation. Electrophysiologically, atrial activity was demonstrable by bursts of action potentials, recurring as soon as the membrane had repolarized sufficiently to be re-excited. The resting potential was reduced, and the overshoot and the rate of rise of the action potential were diminished.

All of the mechanical and electrical events noted in the Langendorff heart and the atrial preparations during anaphylaxis could be reproduced precisely by an appropriate dose of histamine. Evidence for the release of histamine by both the perfused heart and the isolated atria was first obtained by pharmacologic methods and then confirmed by paper chromatography of butanolic extracts.
*
Histamine was quantitatively estimated by a bioassay method which is discussed in detail in this report.
Effect of Ethanol on Serum Cholesterol Concentration in Dog and Man
Authors: GRANDE FRANCISCO , HAY LYLE J. , HEUPEL H. WILLIAM , AMATUZIO DONALD S.
Published: June 2012

The effect of ethanol on serum cholesterol concentration has been studied in normal male dogs subsisting on diets of low cholesterol content. Daily administration of 1.65 Gm. ethanol/Kg, of body weight produced significant increases of serum cholesterol in dogs when fed either a low-fat diet (4 per cent of fat calories) or a high-fat (40 per cent) diet. The mean cholesterol increase after 2 weeks of ethanol administration was 52 mg./100 ml. (SE, 8.2) for 8 dogs on the low-fat diet, and 75 (SE, 6.6) for 24 dogs on the high-fat (lard) diet. No significant difference was found between the mean increases of serum cholesterol produced by ethanol administration, using either the high-fat diet of saturated fat (lard) or that of unsaturated fat (sunflower oil). Serum cholesterol concentration decreases rapidly after discontinuing the administration of ethanol, reaching the prealcohol levels in 2 to 3 weeks. The higher levels of serum cholesterol are maintained as long as the administration of ethanol continues. Sodium acetate, when given at the same molar quantity as ethanol, failed to produce any change of serum cholesterol concentration in the dog.

The effect of ethanol administration on serum cholesterol concentration in man was tested in 2 switchback experiments, comparing the effects of alcohol and those of a supplement of syrup of equal calorie value while the men were eating a normal diet containing 38 per cent of fat calories. When 0.45 Gm. ethanol/ Kg./day were given to 59 normal men for 3 weeks, no significant difference of serum cholesterol concentration was observed between the values on syrup and on alcohol. However, the administration of 1.35 Gm./Kg./ day to 14 men produced a mean increase of serum cholesterol concentration of 18 mg./100 ml. (SE, 5.0) within 1 week. The individual increases of serum cholesterol are correlated with the intrinsic cholesterol levels of the subjects (r = + 0.67, p > 0.01). It is concluded that ethanol increases serum cholesterol concentration in the dog and man. The response in the dog is much greater than that observed in the human subjects.
Factors Affecting the Filling of the Frog's Ventricle After Isotonic Contraction
Authors: HENNACY RICHARD A. , OGDEN ERIC
Published: June 2012

A measurable factor determining the filling of the heart is the opposition that the myocardium offers to being stretched. This is expressed as "renitence," which is the ratio of filling pressure to the rate of inflow. Isolated frog ventricle was connected to a vessel containing Ringer's solution at a fixed head of pressure. Change in the volume of the heart was recorded optically. From these time-volume curves, renitence was calculated.

For the frog ventricle filling and emptying against a fixed head of pressure, the renitence during the filling period first decreases, passes through a minimum, and then increases. The minimum and average renitences occurring during a cycle appeared to be increased by cooling, a rise in filling pressure, pentobarbital or a combination of hypoxia and acidity.

The renitence early during the filling cycle is largely determined by the residual tension from the previous systole, and the subsequent increase seems to be determined by the elastic properties of the myocardium.
Effect of Dicumarol on Blood Vascular Integrity in the Rabbit
Authors: NELSON THOMAS E.
Published: June 2012

Results of experiments in rabbits in which the disappearance of Evans Blue labeled plasma proteins was used as a measure of vascular integrity, indicate that Dicumarol does increase the rate of loss of plasma proteins from the blood stream. This action does not occur immediately after the introduction of Dicumarol into the blood stream but requires a latent period of between 90 and 180 minutes. During this time there may actually be a decreased rate of loss from the blood.

The degree of increase in the dye disappearance rate, although not directly correlated with the degree of hypoprothrombinemia, can be roughly correlated with the extent and severity of internal hemorrhage. These results tend to confirm the idea that vascular fragility, usually considered independent of vascular permeability, may in this instance be the preliminary manifestation of Dicumarol hemorrhagic diathesis.

In experiments where the effect of Dicumarol on exchange of protein between plasma and the peritoneal cavity was measured, it has been found that the presence of vitamin K
1
in the blood in sufficient amount to completely block the hypoprothrombinemic action will also block the tendency toward increased protein exchange. Also, if Dicumarol is introduced into the peritoneal cavity rather than directly into the blood stream, the increase in transperitoneal protein exchange rate appears to be fairly proportional to the degree of hypoprothrombinemia.

It is concluded that although the possibility of several independent actions of Dicumarol exists, one effecting vascular permeability and another inhibiting the elaboration of coagulation factors, it is more likely that the changes seen in vascular integrity are related to the effects of the drug on the coagulation mechanism by way of vitamin K inhibition.
Effect of Digitalis Glycosides on the Myocardial Sodium and Potassium Balance
Authors: BLACKMON JOHN R. , HELLERSTEIN HERMAN K. , GILLESPIE LOUIS , BERNE ROBERT M.
Published: June 2012

Nontoxic and toxic doses of digitalis glycoside produced a rapid release of potassium from the myocardium and from extracardiac tissues of the dog. For approximately 25 minutes after the administration of a digitalis glycoside the myocardium was in negative potassium balance and within an hour returned to positive balance. The most serious electrocardiographic changes transpired when the myocardium approached or attained potassium balance. Pretreatment with potassium chloride protected the heart against arrhythmias by increasing Ko
+
. Pretreatment with glucose and insulin enhanced the arrhythmic action of the digitalis glycosides presumably by producing a low serum potassium (Ko
+
) and possibly by modifying the state of intracellular potassium (Ki
+
).
Quantitative Analysis of the Development of Experimental Atherosclerosis in the Dog
Authors: DUNCAN LEROY E. , BUCK KATHERIN , Lynch Almorris
Published: June 2012

Atherosclerosis was produced in dogs by feeding them thiouracil and cholesterol. The increments in cholesterol concentration at sites along the length of the aortas of these dogs Avere determined by subtracting from the value for each site the corresponding value obtained from normal dogs. After about 1 month on the experimental regimen the cholesterol increments along the length of the aorta formed a gradient. The increment was greatest in the proximal aorta and progressively less down the length of the aorta. After about 5 months on the regimen, the gradient no longer existed. Instead, the cholesterol increment in the abdominal aorta exceeded that in the thoracic aorta. Albumin is known to enter aortic wall with a gradient of rates that is similar to the gradient of cholesterol increments early in the course of experimental atherosclerosis.

The foregoing facts are consistent with the following theory: In the development of atherosclerosis, intact low-density lipoproteins containing cholesterol enter the aortic wall with a gradient of rates. They enter fastest in the proximal aorta and progressively less rapidly down the length of the aorta. However, cholesterol is removed from the abdominal aorta much more slowly than from the thoracic aorta. Thus, the increment in cholesterol concentration in the abdominal aorta eventually exceeds that in the thoracic aorta.
Intestinal Perfusion in Hemorrhagic Shock
Authors: BLATTBERG BENJAMIN , MALDONADO CARLOS , LEVY MATTHEW N. , Scott Bosa M.
Published: June 2012

Dogs were bled to a mean arterial pressure of 35 mm. Hg and maintained at this level for 4 to 5 hours, or until 40 per cent of their maximum bleeding volume was taken back spontaneously. When the superior mesenteric artery was autoperfused at normal rates with arterial blood, only 2 of 22 animals survived. On the other hand, when a donor animal was included in the perfusion system, a significantly higher (P=0.03) fraction survived (5 out of 14). If the removed blood was not reinfused as soon as 40 per cent of the maximum bleeding volume was taken back but the hypertensive period was maintained for a full 5 hours, then only 1 dog out of 9 survived as long as 35 hours, despite the fact that all 9 dogs in this group were given additional transfusions equal to the "take-up" volume.
Levels of Phosphate Compounds in Experimental Cardiac Hypertrophy
Authors: MINTON PAUL R. , ZOLL PAUL M. , NORMAN LEONA R.
Published: June 2012

Arterial hypertension was produced in 66 rats by means of constricting latex capsules about the kidneys, by the intramuscular implantation of desoxycorticosterone pellets, and by the subcutaneous injection of desoxycorticosterone. The most satisfactory method was the intramuscular implantation of desoxycorticosterone pellets. Myocardial hypertrophy was produced in 43 rats.

Biochemical analysis of the ventricles of 80 control and 45 hypertrophied rats were performed for creatine phosphate, adenosine triphosphate, and free inorganic phosphate. Cardiac hypertrophy in rats was accompanied by a statistically significant decrease in the ventricular concentration of creatine phosphate, while levels of adenosine triphosphate and free inorganic phosphate were not significantly altered.

It is suggested that congestive heart failure in hypertrophied hearts is related to a defect in the utilization of phosphate-bond energy by the hypertrophied myocardial fiber.
Chronic Constriction of the External and Internal Carotid Arteries in Dogs: Its Effect on the Blood Pressure
Authors: KEZDI PAUL
Published: June 2012

Narrowing of the internal and external carotid arteries by a clamp does not lead to hypertension if the carotid sinus nerves remain intact. Subsequent disruption of the carotid sinus nerves results in hypertension. It is concluded that the cause of the chronic hypertension in dogs with constriction of the carotid sinus is not due to altered cerebral hemodynamics, but rather to disruption of the carotid sinus nerves.
Cardiac Arrhythmias Induced by Minimal Doses of Epinephrine in Cyclopropane-Anesthetized Dogs
Authors: DRESEL PETER B. , MacCANNELL KEITH L. , NICKERSON MARK
Published: June 2012

Very small doses (0.1 to 2.0 µg./Kg.) of epinephrine injected in 1 minute into dogs anesthetized with 20 per cent cyclopropane cause a coupled rhythm which is usually bigeminal and characterized by an exceptionally constant interval between the coupled beats. Phenyiephvine also causes this arrhythmia, methoxamine does so rarely, but isoproterenol does not. An elevation in systolic pressure and possibly a tachycardia are required for the appearance of bigeminy. However, this arrhythmia can be elicited consistently by these factors only in the presence of a sympathomimetic amine with cardiac stimulant actions. A focus of automaticity has been ruled out in the genesis of the abnormal ventricular beat by demonstrating the constancy of the coupling interval despite sudden changes in the atrial rate. Dichloroisoproterenol appears to attenuate the induction of bigeminy by epinephrine to a considerably lesser extent than the major arrhythmias expected on injection of large doses of this sympathomimetic.
Cardiographic Observations on a Fin-Back Whale
Authors: SENFT ALFRED W. , KANWISHER JOHN K.
Published: June 2012

The beaching of a 40-ton fia-back whale on a Provincetown shore provided a fortuitous opportunity for taking the first cardiograms of the largest mammal. A representative 15-lead cardiogram is shown. This does not differ materially from other large mammals, except that the time scale of events is extremely prolonged. Abnormal foci of ventricular beats and compensatory pauses are illustrated.
Angiotensin II and Serum Differentially Regulate Expression of Cyclins, Activity of Cyclin-Dependent Kinases, and Phosphorylation of Retinoblastoma Gene Product in Neonatal Cardiac Myocytes
Authors: Sadoshima Junichi , Aoki Hiroki , Izumo Seigo
Published: June 2012

The hypertrophic response in cardiac myocytes and the mitogenic response in other cell types share various early cellular responses. However, how the subsequent cell growth response, such as cell cycle machinery, is regulated in cardiac hypertrophy is not understood. Using cultured neonatal rat cardiac myocytes, we examined the effect of angiotensin II (Ang II), a hypertrophic stimulus, on mRNA and protein expression of cyclins and cyclin-dependent protein kinases (cdks), activity of cdks, and phosphorylation of retinoblastoma gene product (pRb). The effect of FCS, a stimulus that was previously reported to initiate both protein and DNA synthesis in cardiac myocytes, was also examined for comparison. Ang II activated cdk4 and caused phosphorylation of pRb, peaking at 12 hours, but subsequently downregulated cyclin D
1
, D
3
, and A expression and cdk2 activity. FCS increased the expression of G
1
-S cyclins, caused activation of cdk4, cdk2, and cdc2, and strongly phosphorylated pRb but failed to significantly stimulate DNA synthesis in neonatal cardiac myocytes. These results suggest that Ang II transiently activates but subsequently downregulates cell cycle regulators. Induction of G
1
and G
1
-S cyclins and activation of cdks by FCS are not sufficient to drive cardiac myocytes into S phase. The functional role of pRb phosphorylation by Ang II and serum stimulation and, by inference, the subsequent liberation of E2F in terminally differentiated myocytes remain to be elucidated.
E-Selectin Gene Expression in Vascular Smooth Muscle Cells
Authors: Chen Xi-Lin L. , Tummala Pradyumna E. , Olliff Lyn , Medford Russell M.
Published: June 2012

E-Selectin is an inducible, endothelium-specific, cell surface adhesion molecule that mediates inflammatory responses in the vasculature. Nonendothelial cell types such as cultured human aortic smooth muscle cells (HASMCs) lack the ability to express E-selectin. We tested the hypothesis that HASMCs express a negative regulatory factor that inhibits E-selectin gene expression. E-Selectin mRNA and gene transcription were not detected in HASMCs after treatment with tumor necrosis factor-alpha (TNF-alpha) by Northern and nuclear runoff analyses, respectively. However, both E-selectin mRNA and gene transcription were dramatically induced by TNF-alpha in the same cells pretreated with the protein synthesis inhibitor cycloheximide. Lipopolysaccharide demonstrated similar effects. Furthermore, E-selectin was detected on the cell surface of HASMCs after washing out of cycloheximide. Cycloheximide pretreatment enabled immortalized human dermal microvascular endothelial cells that have lost the ability to express E-selectin to induce both E-selectin mRNA and gene transcription in response to TNF-alpha. Induction of E-selectin mRNA by lipopolysaccharide one an TNF-alpha in cycloheximide-treated HASMCs was inhibited by the antioxidant pyrrolidinedithiocarbamate and the serine protease inhibitor N
alpha
-L-tosyl-L-phenylalanine chloromethyl ketone, suggesting that a nuclear factor-kappa B-like mechanism may play an important role in E-selectin gene expression in HASMCs. These data strongly suggest that a labile repressor protein(s) plays an important role in inhibiting E-selectin gene expression in HASMCs likely at the level of gene transcription. Except for this repressor, HASMCs and endothelial cells may share similar regulatory mechanisms for controlling E-selectin expression.
Embryonic Endothelial Cells Transdifferentiate Into Mesenchymal Cells Expressing Smooth Muscle Actins In Vivo and In Vitro
Authors: DeRuiter M.C. , Poelmann R.E. , VanMunsteren J.C. , Mironov V. , Markwald R.R. , Gittenberger-de Groot A.C.
Published: June 2012

Abstract
All blood vessels are lined by endothelium and, except for the capillaries, surrounded by one or more layers of smooth muscle cells. The origin of the embryonic vascular smooth muscle cell has until now been described from neural crest and locally differentiating mesenchyme. In this study, we have substantial evidence that quail embryonic endothelial cells are competent in the dorsal aorta of the embryo to transdifferentiate into subendothelial mesenchymal cells expressing smooth muscle actins in vivo. At the onset of smooth muscle cell differentiation, QH1-positive endothelial cells were experimentally labeled with a wheat germ agglutinin–colloidal gold marker (WGA-Au). No labeled subendothelial cells were observed at this time. However, 19 hours after the endothelial cells had endocytosed, the WGA-Au–labeled subendothelial mesenchymal cells were observed in the aortic wall. Similarly, during the same time period, subendothelial cells that coexpressed the QH1 endothelial marker and a mesenchymal marker, α-smooth muscle actin, were present. In such cells, QH1 expression was reduced to a cell membrane localization. A similar antigen switch was also observed during endocardial-mesenchymal transformation in vitro. Our results are the first direct in vivo evidence that embryonic endothelial cells may transdifferentiate into candidate vascular smooth muscle cells. These data arouse new interpretations of the origin and differentiation of the cells of the vascular wall in normal and diseased vessels.