bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin Peptide and Receptors in Human Atherosclerotic Coronary Artery and Aorta
Authors: Bacon Caragh R. , Cary Nathaniel R.B. , Davenport Anthony P.
Published: June 2012

The aim of this study was to determine whether there is an alteration in the distribution or quantity of endothelin (ET) peptide or receptor subtypes in human atherosclerotic arteries. Levels of endogenous ET and big ET-1 detectable by radioimmunoassay in human aorta containing raised atherosclerotic plaques were significantly higher than those in histologically normal tissue (Student's
t
test,
P
<.01). Immunohistochemistry revealed ET-like immunoreactivity in endothelial cells lining the vessel lumen, neovascularization, recanalization of organized thrombus, and regions rich in macrophages. Little immunoreactivity was associated with vascular smooth muscle cells (VSMCs). Saturation binding assays with [
125
I]ET-1 indicated comparable affinities and maximal densities of receptors in the media of diseased and normal coronary arteries. Quantitative autoradiography with subtype-selective radioligands revealed similar small proportions of ET
B
receptors in the diseased and normal arterial media. In arteries with early and late disease, ET
A
receptors were localized to medial smooth muscle but were lacking in the VSMCs of the intimal layer, where ET
B
receptors were absent. ET
B
receptors were detected on perivascular nerves and lymphoid aggregates. In atherosclerotic arteries, microautoradiography localized ET
B
receptors to neovascularization and, interestingly, to macrophages. The results of this study indicate that there is an increase in ET and big ET-1 associated with fully developed atherosclerotic plaques. It is likely that this is derived from endothelial cells and macrophages but not VSMCs. ET
A
receptors predominate in the media of both normal and diseased arteries. ET receptors are deficient in intimal smooth muscle, and ET
B
receptors, where present, are found on endothelial cells and macrophages.
Wall Remodeling During Luminal Expansion of Mesenteric Arterial Collaterals in the Rat
Authors: Unthank Joseph L. , Fath Steven W. , Burkhart Harold M. , Miller Scott C. , Dalsing Michael C.
Published: June 2012

Wall remodeling associated with rapid luminal enlargement of collateral mesenteric arteries in rats was investigated 1 and 4 weeks after creation of a collateral pathway by ligating three to four sequential arteries. Paired observations were made of inner diameters of collateral and normal arteries in the same animals. Arterial blood flow was measured at the final observation. Sections of arteries were processed for morphological measurements. After 4 weeks, inner arterial diameter was increased more at the beginning (63±6%) than the end (25±9%) of the collateral pathway. At 1 and 4 weeks, respectively, cross-sectional areas of collateral relative to normal arteries were increased by 46±5% and 59±13% (lumen), 55±8% and 65±14% (media), and 89±18% and 60±31% (intima). The wall expansion during luminal enlargement resulted in a normal medial thickness:luminal radius relationship. At 1 week postligation, wall shear rate remained elevated and endothelial but not smooth muscle hyperplasia had occurred (intimal nuclei: 40±1.7 collateral versus 24±3.0 normal; medial nuclei: 42±6.8 collateral versus 37±2.1 normal). At 4 weeks, wall shear rate in collaterals was similar to normal arteries, and smooth muscle hyperplasia had taken place (medial nuclei: 84±9.4 collateral versus 44±4.7 normal). The data demonstrate that wall expansion associated with rapid luminal enlargement of these collaterals involves hyperplasia of both endothelial and smooth muscle cells; however, smooth muscle proliferation does not occur until after wall shear rate is reduced. The specific cellular adaptations that occur during collateral development may depend on the level of wall shear and shear-dependent modulation of endothelial growth factors.
Vasodilatory Effect of Pulsatile Pressure on Coronary Resistance Vessels
Authors: Goto Masami , VanBavel Ed , Giezeman Maurice J.M.M. , Spaan Jos A.E.
Published: June 2012

Intramyocardial pressure becomes high in systole and decreases in diastole. Therefore, the transmural pressure of the intramyocardial vessels is pulsatile, resulting in the cyclic distension of these vessels. However, the effect of pulsatility on the behavior of the coronary resistance vessels has not been evaluated. To assess the influence of pulsatile pressure on the behavior of the coronary arterioles, we measured the luminal cross-sectional area (CSA) of coronary arterioles under cyclically changing transmural pressure. Isolated porcine coronary arterioles (internal diameter, 100 to 150 μm) were cannulated with two micropipettes and pressurized with square waves (1 Hz) through both pipettes so as not to induce flow-dependent vasodilation. During the presence (active, induced by acetylcholine; n=7) or absence (passive, abolished by bradykinin; n=7) of vascular tone, the CSA was measured under the following conditions: (1) The amplitude of the pressure pulse was changed at a fixed mean pressure. (2) The mean pressure was changed at a fixed pressure pulse. With increasing pulse pressure, the mean CSA at steady state increased under active conditions, whereas it decreased under passive conditions (
P
<.0001). This vasodilatory effect of pulse pressure remained present after endothelial denudation (
P
<.0001; n=6 vessels with basal tone, n=9 vessels with U46619-induced tone). The mean steady state CSA under passive conditions increased with the mean pressure (
P
<.05), whereas under active conditions it remained constant in the range of mean pressures between 50 and 100 mm Hg, reflecting myogenic responsiveness. These results indicate that an increase in amplitude of the pressure pulse dilates coronary arterioles. The vasodilating effect of the pulsation may compensate partly for the extra compressing effect of cardiac contraction on the intramyocardial vessels.
Tenascin-C Is Induced With Progressive Pulmonary Vascular Disease in Rats and Is Functionally Related to Increased Smooth Muscle Cell Proliferation
Authors: Jones Peter Lloyd , Rabinovitch Marlene
Published: June 2012

Tenascin-C, an extracellular matrix glycoprotein prominent during tissue remodeling, has been linked to cell migration, proliferation, and apoptosis. To determine its potential role in the pathobiology of pulmonary hypertension, we compared tenascin expression in adult and infant rat pulmonary arteries (PAs) after injection of the toxin monocrotaline. Immunohistochemistry, in situ hybridization, and Northern blot analysis demonstrated induction of tenascin in adult rat central and peripheral PA. Tenascin was not, however, detected in infant vessels, which show spontaneous regression of vascular lesions. To determine a function for tenascin, we correlated its expression with evidence of apoptosis and cell proliferation using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay and 5-bromo-2′-deoxyuridine labeling, respectively. Apoptosis was observed only in the adult rat PA endothelial cell layer, preceding the induction of tenascin, which colocalized both temporally and spatially with proliferating smooth muscle cells (SMCs). A cause-and-effect relationship was documented in cultured rat PA SMCs, where tenascin promoted growth in response to basic fibroblast growth factor and was a prerequisite for epidermal growth factor–induced proliferation. These data provide novel functional information suggesting that endothelial cell apoptosis precedes progressive pulmonary hypertension and that induction of tenascin may be critical to growth factor–dependent SMC proliferation.
Prostaglandins Maintain Renal Vasodilation and Hyperfiltration During Chronic Nitric Oxide Synthase Blockade in Conscious Pregnant Rats
Authors: Danielson L.A. , Conrad K.P.
Published: June 2012

Rats demonstrate renal vasodilation and hyperfiltration in pregnancy. Because both NO and cGMP biosynthesis are increased in gravid rats and because acute administration of NO synthase inhibitors abrogates renal vasodilation and hyperfiltration, NO most likely mediates the renal circulatory changes of gestation. In the present study, we tested the effect of chronic inhibition of NO synthase on effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in chronically instrumented, conscious, gravid rats. Because gestation is a relatively long-term condition, we postulated that chronic withdrawal of NO would result in sustained inhibition of renal vasodilation and hyperfiltration. Contrary to our hypothesis, the renal circulatory changes of pregnancy were maintained during chronic blockade of NO synthase. That is, subcutaneous administration of 10 μg/min
N
ω-nitro-
l
-arginine methyl ester (NAME) for 48 hours did not significantly reduce GFR in either virgin or pregnant rats; thus, hyperfiltration persisted in the latter despite chronic NO synthase blockade. In contrast, ERPF was reduced and effective renal vascular resistance (ERVR) increased in both groups of rats during NAME administration but in a parallel fashion, such that renal vasodilation persisted in the gravid animals despite chronic inhibition of NO synthase. However, with superimposition of acute prostaglandin synthesis inhibition (meclofenamate, 10 mg/kg IV), renal vasodilation and hyperfiltration were abolished; ie, the combined treatments of chronic NO synthase blockade and acute prostaglandin synthesis inhibition led to the equalization of GFR, ERPF, and ERVR in conscious virgin and pregnant rats. Inhibition of prostaglandin synthesis alone had little affect on the renal circulation, as previously reported. In summary, prostaglandins are recruited to maintain renal vasodilation and hyperfiltration during chronic NO synthase blockade in conscious pregnant rats.
Effect of Hemorrhage on the Cardiac Output and Distribution in the Rat
Authors: SAPIRSTEIN LEO A. , SAPIRSTEIN ELIZABETH H. , BREDEMEYER ANTONIE
Published: June 2012

The effects of moderate and severe hemorrhage on the cardiac output and its distribution have been studied in the rat. In moderate hemorrhage, cerebral and adrenal blood flow are well maintained through localized vasodilatation while most other organs show increased vascular resistance and diminished blood flow. After severe hemorrhage, despite further changes in territorial resistances, the blood flow is not maintained in any area of the body.
Hemodynamic Effects of Extracorporeal Circulation
Authors: KUHN LESLIE A. , GRUBER FRANK L. , FRANKEL ALBERT , KUPFER SHERMAN
Published: June 2012

The hemodynamic effects of closed-chest extracorporeal circulation were investigated in normal dogs and in dogs subjected to coronary embolization. In both groups, despite delivery of large volumes of blood into the abdominal aorta through peripheral routes, a rise in proximal aortic pressure could not be achieved; to accomplish this it was necessary to increase vascular resistance by balloon obstruction of the lower abdominal aorta, the distal aorta being supplied with superior vena cava blood. The resulting rise in proximal aortic pressure was accompanied by a diminution in calculated left ventricular work.
Effect of Efferent Vagal Stimulation on Coronary Sinus Outflow and Cardiac Work in the Anesthetized Dog
Authors: WANG HSUEH-HWA , BLUMENTHAL MARVIN R. , WANG S. C.
Published: June 2012

Efferent vagal stimulation in the anesthetized dog with constant ventricular rate caused either no change in coronary sinus outflow and cardiac work, or a decrease in coronary sinus outflow associated with a greater decrease in cardiac work. When the decreases were observed they could best be explained by a negative inotropic effect of vagal stimulation on ventricular muscle, rather than by a direct vasomotor effect of vagal stimulation on the coronary bed. Critical review of apparent divergent results previously reported regarding the effect of vagal stimulation on coronary flow reveals that they are not inconsistent with the above hypothesis.
Atherosclerosis in Rats Induced by Repeated Breedings, ACTH and Unilateral Nephrectomy
Authors: WEXLER BERNARD C. , BROWN THOMAS E. , MILLER BENJAMIN F.
Published: June 2012

Repeatedly-bred rats of both sexes develop subintimal accumulations of acid mucopolysaccharides and fibroblastic proliferation followed by distortion and destruction of elastic lamellae. Fibrosis, endothelial hyperplasia, lipid deposition, calcification and atheromata are also observed. Changes in the elastic tissue occur independently, and later than the alterations of the ground substance and the fibroblasts. Calcification is found in more advanced lesions, showing an affinity for areas rich in mucopolysaccharides. Exogenous ACTH and unilateral nephrectomy augment early atherosclerotic changes associated with multiple breedings.
The Effect of 19-Norandrostenolone on Experimentally-Induced Atheroma in Cockerels
Authors: CAMPBELL R. S. F. , LAWRIE T. D. V. , MACLAURIN J. C. , PIRRIE R.
Published: June 2012

The anabolic and weakly androgenie compound 19-norandrostenolone has been administered to cholesterol-fed cockerels in 2 dose levels. A marked fall in serum cholesterol occurred with the lower dose level and a significant reduction in the incidence of coronary artery lesion was noted with the higher dose level.
The Influence of Boundary Conditions on the Amplitude of R and Other Accession Potentials in Leads from the Ventricular Wall
Authors: CONRAD LOYAL L. , CUDDY T. EDWARD
Published: June 2012

The effects of altering the conductivities of the boundary media at the endocardial and epicardial surfaces of the ventricle on accession potentials in the ventricular wall and at its surfaces were studied in dogs. The amplitude of R at all points in the wall was decreased by any measure which increased the conductivity of the medium surrounding the heart or which decreased the conductivity of the medium in the ventricular cavity. The progression of R in the ventricular wall observed experimentally results, at least in part, from the differing conductivities of intracavitary blood, myocardium, and the medium surrounding the heart.
Mineralocorticoid Hypertensive Cardiovascular Disease Induced in Hypophysectomized Rats
Authors: HALL C. E. , HALL O. , RENNELS E. G.
Published: June 2012

Reports in the literature to the contrary, hypertensive cardiovascular disease proved to be readily induced by desoxycorticosterone in hypophysectomized rats sensitized to steroid action by partial nephreetomy and high NaCl intake. In the absence of the pituitary, however, hypertension was somewhat slower in onset and progress. Although hypophysectomized animals were able to develop hypertension as severely as did intact animals, they were not, as judged by their better survival and less evident cardiorenal vascular lesions, as severely injured thereby.

Contrasted with their exuberant development in hypertensive intact animals, renal lesions in hypertensive hypophysectomized animals were rare. Necrotizing arteritis in the heart was seen in about half of the hypox animals, and periarteritis nodosa of pancreatic and mesenteric arteries was more widespread and severe than in similarly treated intact animals which had, however, died earlier.

Steroid treated animals bearing pituitary autotransplants beneath the renal capsule, developed more severe and widespread cardio-renal lesions than did similarly treated hypophysectomized animals, but incidence and severity of periarteritis nodosa in splanchnic arteries was about the same in each.

The ingestion of sodium chloride caused "salt hypertension" in some of the pituitary-bearing controls, but not in either hypophysectomized or autotransplant-bearing controls.
Early Stages in the Development of Collateral Circulation to the Lung in the Rat
Authors: WEIBEL EWALD R.
Published: June 2012

The early stages of the development of collateral circulation to the lung following experimental ligation of the pulmonary artery were studied in adult rats. Five different types of vessels were found to be involved:

1. The bronchial arteries enlarge. Quantitative gross and microscopic studies indicated that this is first due to hemodynamic factors leading to dilatation of the vessels. After 5 days, true growth of the vessels occurs, associated with proliferative changes in the vessel wall, including mitoses in endothelial and smooth muscle cells.

2. Pre-existing nutrient arteries of the heart muscle coat of the pulmonary veins enlarge by the same processes.

3. New vessels form in the granulation tissue at the ligature. They can grow through the thick vessel wall into the lumen of the main pulmonary artery to form a considerable portal of entry for blood into this vessel.

4. Vessels form in pleural adhesions and can supply blood to the lung from intercostal arteries.

5. New bronchial arteries form in regions where no granulation tissue formation could stimulate their development. The primary anlage consists of a solid cell cord, soon surrounded by an envelope of spindle-shaped cells, representing the anlage of the media. The cell cord differentiates secondarily to an endothelial tube by forming a lumen.

The enlarged systemic arteries are directly connected to the lung capillaries by means of multiple small branches, which are also newly formed arteries or arterioles. Arterial bronchopulmouary anastomoses are not as commonly found early in the development of collateral circulation in the rat, as late in this process in dogs. It may be concluded that the enlargement of collateral arteries to the lung following ligation of the pulmonary artery may be initiated by hemodynamic conditions, such as changed pressure gradients. After 5 days, however, other, probably humoral, factors must be responsible for further stimulation of the growth of pre-existing vessels and for the initiation and guidance of new vessel formation.
Comparison of Two Types of Mechanical Assistance in Experimental Heart Failure
Authors: SALISBURY PETER F. , CROSS CECIL E. , RIEBEN P. ANDRE , LEWIN RICHARD J.
Published: June 2012

In open-chest dog experiments, 7 different types of cardiac failure were produced. In each type of failure, the effect of veno-arterial pumping and of left ventricular bypass (blood pumped from the left atrium to femoral artery) was investigated. Pressures were recorded in the left ventricle, the left atrium, the right ventricle, and the femoral artery.

Veno-arterial pumping reversed failure of the right ventricle. It also was beneficial when overtransfusion had aggravated failure of the right or left ventricles, except in pre-existing aortic insufficiency. Veno-arterial pumping markedly increased decompensation of the left heart in the majority of observations, even though it occasionally reduced pressures in the left atrium and the right ventricle. The experiments suggest the use of veno-arterial pumping or of partial bypass with a heart-lung machine in acute cor pulmonale and in pulmonary congestion caused by abnormalities of the mitral valve where the left ventricle remains compensated. Veno-arterial pumping appears contraindicated in true failure of the left ventricle.

Left ventricular bypass always restored compensation in all types of heart failure except cor pumonale. The experiments suggest the clinical use of left ventricular bypass in left heart failure.
Pressure Variations in Small Veins in the Hindleg of the Dog
Authors: WIEDEMAN MARY P.
Published: June 2012

Rhythmical changes in small vein pressure were shown to follow the direction of changes in intra-abdominal pressure. Pressure waves in small veins could be diminished considerably during femoral artery occlusion when the venous cannula was directed away from the vena cava. They were only slightly affected when the venous cannula was directed toward the vena cava. Small vein pressure waves were markedly decreased by opening the abdomen and reducing intra-abdominal pressure.

It is concluded that intra-abdominal pressure change is a major factor in varying small vein pressure in the hindleg of an anesthetized dog in a supine position.
Effects of Bladder Distention on Pulmonary Vascular Bed
Authors: AGREST ALBERTO , RONCORONI AQUILES J.
Published: June 2012

Hemodynamic data during bladder distention in 2 patients with cervical cord transaction are presented. Rise in pulmonary artery pressure and pulmonary resistance is shown to occur when pressure is increased.
Influence of Sex Difference and Hormones on Elastine and Collagen in the Aorta of Chickens
Authors: CEMBRANO JOSÉ , LILLO MANUEL , VAL JOSÉ , MARDONES JORGE
Published: June 2012

Collagen and elastine of the aorta were estimated in normal chickens of both sexes in cockerels, gonadectomized or treated with estradiol, and in hens treated with testosterone.

The results showed that collagen and elastine were significantly higher in males than in females. Gonadectomy in males decreased significantly the content of collagen and elastine, so that the values became similar to those observed in females. The treatment of males with estradiol lowered the collagen and elastine content to values similar to those observed in females and in gonadectomized males. The treatment of females with testosterone increased significantly the collagen and elastine content of the aorta to levels similar to those observed in males.
Hemodynamic Effects of Continuous Positive and Negative Pressure Breathing in Normal Man
Authors: KILBURN KAYE H. , SIEKER HERBERT O.
Published: June 2012

Alterations in cardiac output, central blood volume, and arterial and central venous pressures were studied in 36 young men subjected to continuous negative or continuous positive pressure breathing. Negative pressure breathing increased cardiac output, stroke volume, and, to a lesser extent, central blood volume. Positive pressure, without overbreathing, decreased both cardiac output and central blood volume, but hyperventilation reversed these effects. On the basis of these observations, it is concluded that decreased intrathoracic pressure is important in maintaining or increasing the blood available to the heart in man, particularly during circulatory stress.
Significance of Mesenteric Arterial Receptors in the Reflex Regulation of Systemic Blood Pressure
Authors: BOYER GARRY O. , SCHER ALLEN M.
Published: June 2012

The isolated abdominal aorta was perfused in 6 cats and 2 dogs, and perfusion of the isolated superior mesenteric arterial system was performed in another 6 cats. In every experiment, wide variations in perfusion pressure produced no alterations in the systemic pressure, although it was responsive to manipulation of the carotid pressure. A comparison of the systemic pressure responses to mesenteric artery occlusion and to carotid artery occlusion prior to and following (1) high spinal transection in 2 cats or (2) venous perfusion of sodium thiopental in 3 cats showed an obliteration of the responses to carotid occlusion while the systemic response to oclusion of the mesenteric artery persisted. The results indicate that the systemic responses seen during mesenteric artery occlusion are probably caused by mechanical diversion of blood from one vascular bed to another and do not represent true reflex responses. The observations indicate that mesenteric pressure receptors do not contribute significantly to the reflex regulation of the systemic blood pressure.
Cause of Genuine Autoregulation of the Renal Circulation
Authors: WAUGH WILLIAM H. , SHANKS ROBERT G.
Published: June 2012

The mechanism causing renal vascular flow to vary less than proportional to changes in arterial-venous pressure gradient, was studied in isolated dog kidneys perfused with whole blood and with cell-free colloidal solutions. This autoregulation of renal flow rapidly deteriorated along with vascular reactivity to drugs when oxygenated polyvinyl-pyrrolidone-Locke solution was used for perfusion. This deterioration was prevented by the addition of plasma to the colloidal perfusate.

During the first 2 seconds of suddenly raised arterial pressure, renal flow normally increased proportionately or slightly more than proportionately to the increase in arterial pressure; intrarenal venous pressure, needle tissue pressure and kidney weight rose simultaneously. During the next 4 seconds, increasing vascular resistance upstream from the intrarenal veins caused parallel reductions in renal flow, intrarenal venous pressure, needle tissue pressure and at times kidney weight. After brief rhythmical changes in prevenous segmental resistance, flow became steady to show intense autoregulation, while intrarenal venous pressure and needle tissue pressure remained relatively low.

This genuine autoregulation of renal flow was abolished by cooling kidneys to 3 to 10 C, and by treatment with chloral hydrate and with procaine in concentrations rendering the smooth muscle of the renal blood vessels relatively inert to direct drug stimulants. On the other hand, at temperatures of 3 to 10 C., and usually with chloral hydrate treatment, a factitious and passive type of flow autoregulation was observed, caused by the effects of abnormally high tissue pressures.

Renal flow autoregulation was not appreciably impaired by anesthetization of the intrarenal nerves by procaine in concentrations which did not simultaneously depress vascular smooth muscle reactivity. Yohimbine induced sympatholysis did not impair autoregulation, and Dibenzyline treatment to intrarenal sympatholysis depressed only slightly autoregulation of renal flow. It was not inhibited by γ-aminobutyric acid.

Anoxic perfusion which did not appreciably depress the reactivity of intrarenal autonomic ganglia, impaired autoregulation moderately. The loss of autoregulation of renal flow, accompanied by vasoconstriction following severe hemorrhage in the kidney donor dog, was slowly reversible upon perfusion of the subsequently isolated kidney and was related to smooth muscle contracture within the arterial-arteriolar vasculature.

It is concluded, that myogenic vasomotion in the renal arterial-arteriolar tree in response to the level of transmural vascular pressure is the fundamental cause of genuine renal circulatory autoregulation. It is furthermore suggested that the myocytes of the juxtaglomerular apparatus may act as myogenic pacemakers in the vasomotion responsible for the essentially perfect autoregulation of the normal kidney.
Circulation of the Giraffe
Authors: GOETZ ROBERT H. , WARREN JAMES V. , GAUER OTTO H. , PATTERSON JOHN L. , DOYLE JOSEPH T. , KEEN E. N. , McGREGOR MAURICE , TILLER L. M. , SMITH M. , Mance E.
Published: June 2012

Observations on the circulatory functions of 4 giraffes are recorded. Both the right and the left heart were catheterized under local anesthesia with a miniature manometer.

Cardiac output was determined by employing both indicator dilution method and the Fick principle. Other parameters, such as the circulation time, blood volume, velocity, right and left ventricular pressure ascent as well as the changes in blood pressure occurring with changes in the Posture of the head were recorded. The difficulties of the experiments created certain limitations in their interpretation. The arterial blood pressure is high by human standards and adequate to maintain cerebral perfusion without other means of support. The arterial pressure pulse contour suggests a relatively lax vascular bed with considerable reserve distensibility. Values for cardiac output and blood volume were roughly comparable to those recorded in domestic cattle of the same approximate weight.
Influence of Cardiac Sympathetic and Vagal Nerve Stimulation on the Relation Between Left Ventricular Diastolic Pressure and Myocardial Segment Length
Authors: MITCHELL J. H. , LINDEN R. J. , SARNOFF S. J.
Published: June 2012

During the continuous and simultaneous recording of left ventricular diastolic pressures and changes in the length of a segment of left ventricular myocardium it was demonstrated that neither cardiac sympathetic nor vagal efferent nerve stimulation produces a change in ventricular myocardial extensibility. It was further shown that, at the heart rates studied, autonomic nerve stimulation does not modify the end-diastolic pressurelength curve. These data indicate that, during cardiac sympathetic stimulation, the augmented ventricular stroke work from any given end-diastolic Pressure is accomplished without a change in end-diastolic fiber length.

Evidence was obtained, however, which suggests that the abbreviation of diastole at high imposed heart rates or large stroke volumes may leave an inadequate time for ventricular relaxation to take place and for inertial and viscous factors to be dissipated. Under these circumstances, sympathetic stimulation, by shortening systole and thereby lengthening diastole, permits the ventricle to remain on its "normal" pressure-length curve. This component of cardiac sympathetic efferent activity is peculiarly appropriate to the tachycardia that occurs with increased sympathetic outflow to the heart.
Negative Diastolic Pressure in the Isolated Hypothermic Dog Heart
Authors: O'BRIEN LARRY J. , BRUNO P. TOLGE
Published: June 2012

Pressure relationships in the left ventricle of the dog were studied under conditions in which left ventricular inflow was controlled by means of an artificial circuit. Hypothermia was used to slow the dynamics of the heart beat. When all inflow to the left ventricle was suddenly stopped, the succeeding beats showed negative diastolic pressures. The greatest drop in pressure occurred early in diastole; in most instances, end-diastolic pressures remained negative. Early diastolic pressures before occlusion average +2.6 mm. Hg; early diastolic pressures after occlusion of inflow averaged -4.7 mm. Hg. A physical model was proposed which could explain the occurrence and decay of the observed subatmospheric pressure. These experiments indicate that diastolic suction can be a factor that accomplishes ventricular filling during diastole in a heart following systolic discharge against a wide range of aortic pressures.
Viscosity of Blood in Myocardial Infarction
Authors: KELLOGG FREDERICK , GOODMAN JOSEPH R.
Published: June 2012

Following myocardial infarction, the pseudoviscosity of whole blood and the viscosity of plasma increase significantly. The increase in viscosity is correlated with increase in fibrinogen. Both are correlated with the severity of the infarction. The pseudoviseosity of blood adjusted to a hematocrit of 40 shows fair correlation with the viscosity of plasma.
Condensing Enzyme Levels in the Serum After Experimental Myocardial Infarction
Authors: KOSICKI GEORGE W. , SWAIN HENRY H. , SRERE PAUL A.
Published: June 2012

Increased levels of condensing enzyme are shown to occur in the sera of dogs after experimental myocardial infarction. The animals with the elevated levels also showed characteristic changes of the electrical activity of the heart and associated increases in the glutamate-oxal acetate transaminase activity of serum.

Condensing enzyme has been detected in the sera of patients who suffered myocardial infarctions.
Dicumarol Therapy
Authors: MURPHY E. A. , MUSTARD J. F.
Published: June 2012

One of the problems of Dicumarol administration has been determination of the adequacy of therapy. A fundamental stage in thrombus formation in the circulation is platelet clumping. Since platelets are involved in both hemostasis and thrombosis, a study of changes in platelet function may prove useful. The effects of Dicumarol on platelet clumping and adhesiveness have, therefore, been studied and related to changes in other clotting mechanisms.

Comparison of platelet function in control periods and during Dicumarol administration shows that this drug lowers the adhesive index and prolongs the platelet clumping time to a highly significant degree. The accuracy of estimates of these 2 platelet functions given by 3 other tests, prothrombin time, whole blood clotting time and plasma activity in the thromboplastin generation tests have been compared. By any criterion, degree of correlation, consistency of regression slopes, intercepts or scatter about regression lines, clotting time was the most efficient of the 3 tests for evaluting platelet function. The prothrombin time was the least efficient. Furthermore, hemorrhage from excessive dosage was closely related to the platelet clumping time and clotting time. It should be pointed out, however, that in about one-third of the patients the prothrombin time was as good an index of platelet clumping time as clotting time. While prothrombin times done with 2 different sources of thromboplastin may give congruous results in untreated patients, considerable discrepancies may appear during Dicumarol therapy.

If prothrombin time is to be used as a guide to Dicumarol therapy, it is important to establish in each patient separately its reliability as a measure of the behavior of the clotting mechanism as a whole. For those in whom it seems reliable, an individual "therapeutic range" should be determined. For other cases, some other suitable test should be employed. It is emphasized that regulation of Dicumarol dosage is an individual problem and that only those tests shown to be reliable indices of safe effective modifications of clotting mechanism in the individual patient should be used.
Electrical Activity During the P-R Interval
Authors: HOFFMAN BRIAN F. , CRANEFIELD PAUL F. , STUCKEY JACKSON H. , BAGDONAS ALBIN A. , Piera Juan
Published: June 2012

Electrical activity of the specialized conducting system (His bundle, bundle branches, false tendons and peripheral Purkinje fibers) of canine hearts has been recorded in situ through electrodes attached to the endocardium during total cardiopulmonary bypass. Simultaneous records from multiple sites have been correlated with electrocardiograms to indicate the sequence of activation of the specialized conducting system during normal and retrograde activation and during vagal stimulation. The results obtained indicate that the method employed has several advantages among which are an absence of injury at the recording site and an applicability to chronic studies.
Mechanism by Which Serotonin, Norepinephrine and Reserpine Cause Central Vasomotor Inhibition
Authors: KANEKO Y. , McCUBBIN J. W. , PAGE IRVINE H.
Published: June 2012

Several vasoconstrictor drugs and reserpine administered into a cerebral lateral ventricle inhibited the reflex pressor response to occlusion of the common carotid arteries in both anesthetized and unanesthetized dogs. This effect was opposed by central administration of the vasodilator drugs, nitroprusside and histamine. Serotonin, norepinephrine and their precursors, 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, and reserpine caused lowering of arterial pressure and slowing of heart rate as well as inhibition of the carotid occlusion response; angiotensin and vasopressin did not. The central inhibitory effect of norepinephrine was opposed by phentolamine; that of 5-hydroxytryptophan was not affected by lysergic acid diethylamide or its brom derivative.

Cooling of cerebrospinal fluid, which presumably caused local vasoconstriction, also caused inhibition of the carotid occlusion response, hypotension and bradycardia, and these effects were counteracted by central injection of vasodilator drugs. Warming of cerebrospinal fluid, presumably associated with local vasodilation, opposed the central inhibitory effect of vasoconstrictor drugs and of reserpine.

In view of the consistently opposite effects of vasoconstrictor and vasodilator drugs and procedures on central vasomotor sympathetic activity, it is tentatively concluded that these effects depend on change in local blood flow. The acute cardiovascular effects of reserpine of central origin are probably due to local decrease of tissue perfusion caused by serotonin, norepinephrine or other vasoconstrictor agent released from a bound to an active form.
Angiotensin II Stimulates c-Jun NH
2
-Terminal Kinase in Cultured Cardiac Myocytes of Neonatal Rats
Authors: Kudoh Sumiyo , Komuro Issei , Mizuno Takehiko , Yamazaki Tsutomu , Zou Younzeng , Shiojima Ichiro , Takekoshi Noboru , Yazaki Yoshio
Published: June 2012

Many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in cardiac hypertrophy. Ang II not only increases protein synthesis but also induces the reprogramming of gene expression in cultured cardiac myocytes. In the present study, to elucidate the mechanism by which Ang II regulates gene expression in cardiac myocytes, we examined whether Ang II activates c-Jun NH
2
-terminal kinase (JNK), which is a member of the mitogen-activated protein kinase family and activates the transcription factor, activator protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of the Ang II dose-response relation revealed detectable JNK activation at 10
−9
mol/L and maximal activation at 10
−6
mol/L. Ang II activated JNK through the AT
1
receptor, and the activation was attenuated by the downregulation of protein kinase C or the chelation of intracellular Ca
2+
. Although the addition of either Ca
2+
ionophore or phorbol ester resulted in little or no activation of JNK, simultaneous addition of both Ca
2+
ionophore and phorbol ester markedly activated JNK. Slight expressions of the c-
jun
gene were observed in unstimulated cardiac myocytes, and Ang II increased expressions of the c-
jun
gene as well as the c-
fos
gene. Ang II increased transcription of the endothelin-1 gene through the AP-1 binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca
2+
and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II–induced cardiac hypertrophy.
Inhibition of Stimulus-Induced Endothelial Cell Intercellular Adhesion Molecule-1, E-Selectin, and Vascular Cellular Adhesion Molecule-1 Expression by Arachidonic Acid and Its Hydroxy and Hydroperoxy Derivatives
Authors: Huang Z. Hua , Bates Edna J. , Ferrante Judith V. , Hii Charles S.T. , Poulos Alf , Robinson Brenton S. , Ferrante Antonio
Published: June 2012

Localized adhesion of peripheral blood leukocytes to the endothelial lining is essential for their exit from the blood under both physiological and pathological conditions. The establishment, development, and resolution of the inflammatory response is regulated by an array of mediators, many of which remain to be categorized. These include arachidonic acid (20:4
n
-6) and its hydroperoxy (HPETE) and hydroxy (HETE) derivatives, which are released during inflammation. The data show that human umbilical vein endothelial cells, pretreated with these fatty acids, have a reduced ability to be stimulated by tumor necrosis factor-α (TNF-α) for enhanced neutrophil and monocyte adhesion; the order of inhibitory activity being 15-HPETE>15-HETE>20:4 (
n
-6). This fatty acid–induced inhibitory activity was reflected in the ability of the mediators to decrease the TNF-α–induced expression of the following endothelial adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1), measured by both enzyme-linked immunosorbent assay and flow cytometric analysis. TNF-α–induced increased expression of ICAM-1, E-selectin, and VCAM-1 mRNA was significantly depressed by 15-HPETE. Constitutively expressed ICAM-1 and ICAM-1 mRNAs were unchanged by the fatty acids. The saturated fatty acid 20:0 and the methyl ester of 20:4(
n
-6) had no inhibitory activity. The binding of TNF-α to its receptors was not altered by these fatty acids. The fatty acids also inhibited the expression of ICAM-1 and E-selectin induced by phorbol 12-myristate 13-acetate, showing that inhibition occurred at a post–TNF-α receptor binding level. The 15-HPETE was found to inhibit the TNF-α–induced increase in adhesion molecule expression in the early stage of the incubation, but expression returned to normal after 18 hours. An effect of 15-HPETE on the early cell signaling system was demonstrated by the ability of this fatty acid to inhibit agonist-induced protein kinase C translocation.
Differential Desensitization of Thromboxane A
2
Receptor Subtypes
Authors: Yukawa Masao , Yokota Ryoji , Eberhardt Robert T. , von Andrian Laila , Ware J. Anthony
Published: June 2012

Abstract
Two subtypes of the thromboxane A
2
(TxA
2
) receptor (TxA
2
R-E and TxA
2
R-P), which differ in their alternatively spliced cytoplasmic tails, have been identified. The initial concentration of the TxA
2
mimetic IBOP required to reduce peak intracellular Ca
2+
concentration ([Ca
2+
]
i
) induced by a second addition of IBOP (100 nmol/L) was similar (IC
50
for TxA
2
R-E and TxA
2
R-P, 0.46±0.16 and 0.40±0.07 nmol/L) in fibroblasts overexpressing either the TxA
2
R-E or -P subtype. Although the number of TxA
2
binding sites decreased in TxA
2
R-P cells after prolonged stimulation with a TxA
2
mimetic, those in the TxA
2
R-E cells increased markedly. To determine whether the mechanism for desensitization differs between subtypes, the effect of activation of protein kinase C (PKC) or cAMP-dependent kinase on TxA
2
-induced [Ca
2+
]
i
mobilization was measured. Forskolin reduced the IBOP-induced peak [Ca
2+
]
i
in neither TxA
2
R-E nor TxA
2
R-P cells; however, treatment with phorbol esters (IC
50
, 0.57±0.70 nmol/L) strongly prevented IBOP-mediated [Ca
2+
]
i
rise in TxA
2
R-E but not in TxA
2
R-P cells. Desensitization of TxA
2
R-E by phorbol esters was prevented by the PKC inhibitor calphostin C or by downregulation of PKC-α. Thus, the response of TxA
2
R-E to prolonged stimulation differs from that of TxA
2
R-P in both the regulation of the number of binding sites and the mechanism for desensitization; agonists that activate PKC-α might interfere with TxA
2
R-E–mediated signaling.
Lysophosphatidylcholine Increases Expression of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Human T Lymphocytes
Authors: Nishi Eiichiro , Kume Noriaki , Ochi Hiroshi , Moriwaki Hideaki , Wakatsuki Yoshio , Higashiyama Shigeki , Taniguchi Naoyuki , Kita Toru
Published: June 2012

Abstract
Atherosclerotic lesions contain substantial numbers of activated T lymphocytes in addition to monocytes/macrophages. T cell–derived cytokines and growth factors may play a role in atherogenesis; however, stimuli responsible for T-cell activation in atherogenesis have not been fully elucidated. In this study, we provide evidence that lysophosphatidylcholine (lyso-PC), a polar phospholipid component increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate gene expression and secretion of heparin-binding epidermal growth factor–like growth factor (HB-EGF) in cultured T lymphocytes isolated from human peripheral blood. Effects of lyso-PC on T lymphocytes appear to be selective and specific, since lyso-PC also increases interleukin (IL)-2 receptor expression but does not affect mRNA levels for IL-2 or IL-4. Lyso-PC–induced upregulation of HB-EGF and IL-2 receptor mRNA in peripheral T cells is mostly dependent on exogenous IL-2 in conditioned medium. The effect of lyso-PC on HB-EGF induction was more potent in CD4
+
cells than in CD8
+
cells, although lyso-PC increases IL-2 receptor expression dramatically in both CD4
+
cells and CD8
+
cells. Lyso-PC similarly increased HB-EGF expression in Jurkat cells, a cell line for human CD4
+
T lymphocytes. These results in vitro suggest that lyso-PC may be an important stimulus for T cells in atherogenesis in vivo to upregulate HB-EGF and that T cell–derived smooth muscle growth factors may modulate atherosclerotic progression.
Characterization of Gap Junction Channels in Adult Rabbit Atrial and Ventricular Myocardium
Authors: Verheule Sander , van Kempen Marjan J. A. , Welscher Pascal H. J. A. te , Kwak Brenda R. , Jongsma Habo J.
Published: June 2012

Abstract
For effective cardiac output, it is essential that electrical excitation spread rapidly throughout the atria and ventricles. This is effected by electrical coupling through gap junction channels at contact sites between myocytes. These channels form a low-resistance pathway between adjacent myocytes and consist of connexin proteins. The connexin family is a large multigene family, and the channels formed by different members of this family have distinct electrical and regulatory properties. We have studied gap junction channels between adult rabbit atrial and ventricular myocytes using immunocytochemical and electrophysiological methods. Gap junctions of ventricular myocytes were immunoreactive to antibodies directed against connexin43 (Cx43) and Cx45, but not to antibodies against Cx37 or Cx40. Gap junctions between atrial myocytes showed immunostaining with anti-Cx40, -Cx43, and -Cx45 antibodies, but not with anti-Cx37 antibody. Endocardial and endothelial tissue were labeled with both Cx37 and Cx40 antibodies. The conductance of rabbit myocardial gap junctions was measured using the double whole-cell voltage-clamp method. The average macroscopic junctional conductance, corrected for series resistance, of atrial and ventricular cell pairs did not differ significantly (169±146 and 175±147 nS, respectively), and both were at most only slightly sensitive to the applied transjunctional potential difference. The difference in connexin expression between atrial and ventricular myocytes was reflected in the distribution of single gap junction channel conductances. A single population of unitary channel conductances with an average of 100 pS was observed between ventricular myocyte pairs. In addition to this population, a population with an average conductance of 185 pS was present between atrial myocyte pairs. The observed difference in connexin expression between atrial and ventricular myocardium may enable differential regulation of conduction in these tissues.
Differential Effects of the Ca
2+
Sensitizers Caffeine and CGP 48506 on the Relaxation Rate of Rat Skinned Cardiac Trabeculae
Authors: Palmer Sue , Kentish Jonathan C.
Published: June 2012

Abstract
During heart failure, force production by the heart decreases. This may be overcome by Ca
2+
-sensitizing drugs, which increase myofibril Ca
2+
sensitivity without necessarily altering intracellular Ca
2+
concentration. However, Ca
2+
sensitizers slow the relaxation of intact cardiac muscle. We used diazo-2, a caged chelator of Ca
2+
, to study the effects of the Ca
2+
sensitizers caffeine and CGP 48506 on the intrinsic relaxation rate of cardiac myofibrils. Trabeculae from rat right ventricles were skinned by 1% Triton X-100 and were activated in a 10-μL bath. In steady state experiments, CGP 48506 (10 μmol/L) shifted the force-pCa curve leftward by 0.41±0.03 pCa units (mean±SEM, n=6). An identical shift was induced by caffeine (20 mmol/L). Photolysis of diazo-2 by a flash of light (160 mJ, 310 to 400 nm) caused an immediate decrease in Ca
2+
-activated force produced by the trabeculae. Relaxation was fitted by a double-exponential decay, and the rate constants were found to be independent of force and preflash Ca
2+
concentration. The initial fast rate, corresponding to myofibrillar relaxation, was increased from 17.3±2.0 to 30.9±3.7 s
−1
(n=4) by caffeine but was unaffected by CGP 48506 (16.6±1.7 and 14.4±2.3 s
−1
in the absence and presence of drug, respectively; n=5). Thus, myofibril relaxation need not be slowed by Ca
2+
-sensitizing agents but can even be accelerated. Despite similarities in their effects on myofibril Ca
2+
sensitivity, caffeine and CGP 48506 affect the myofibrils at least partly via different mechanisms.