bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental myocardial ischemia: dynamic alterations in ventricular contractility and relaxation with dissociation of speed and force in the isovolumic dog heart.
Authors: Serur J R , Galyean J R , Urschel C W , Sonnenblick E H
Published: June 2012

Although the time course of changes in myocardial function during ischemia has been demonstrated for the papillary muscle, this time course in the intact heart is less well understood. Accordingly, in 24 isolated, isovolumic, perfused dog hearts, coronary perfusion pressure (PP) was lowered to various fixed levels. Left ventricular developed pressure (LVP) rapidly fell and reached 63 +/- 3% of control at 1 minute of ischemia 50 +/- 5% at 6 minutes; this was due primarily to an abbreviation of time to peak tension (TPP). dP/dt was 70 +/- 3% of control at 1 minute and 56 +/- 5% at 6 minutes. The rate of relaxation as reflected by negative dP/dt declined as well to 49 +/- 4% of control at 1 minute of ischemia and to 41 +/- 4% control at 6 minutes. These changes were directly correlated with the decrease in PP. When PP was restored to normal, an overshoot of LVP and dP/dt was noted, peaking at 1 minute, returning to control by 5 minutes, and then gradually declining to 90 +/- 2% of control following 25 minutes of recovery. Depression of the rate of relaxation was reduced, but persisted throughout recovery. Diminution of force development early in ishcemia is due primarily to decreased duration of contraction accompanied by a decrease in relaxation rate. Later, the rate of force development also falls, but some preservation of force development may result from the return toward normal of the duration of contraction.
Effects of hyperthermic stress on myocardial function during experimental coronary ischemia.
Authors: Liedtke A J , Hughes H C
Published: June 2012

We evaluated hyperthermic influences on ischemic hearts by comparing two groups of intact working swine hearts (n = 20) made globally ischemic. Heart muscle temperature was selectively increased from 37.5 +/- 0.3 degrees C to 39.7 +/- 0.3 degrees C in one group (n = 11) by warming the coronary perfusate. Ischemia in normothermic hearts significantly (P less than 0.05) decreased mechanical function (as reflected by increases in left ventricular end-diastolic pressure [LVEDP]), myocardial oxygen consumption (MVO2), glucose uptake, glycolytic flux, free fatty acid (FFA) uptake and oxidation, and tissue stores of high energy phosphates. Hearing in ischemic hearts further depressed mechanical function at similar reductions in coronary flow and MVO2. Glucose uptake was terminally increased over normothermic values (329 vs. 221 mumol/hr per g) as was glycolytic metabolism, FFA uptake (26 vs. 17 mumol/hr per g), and FFA oxidation (21 vs. 11 mumol/hr per g). However, these changes were not translated into increased energy stores of tissue creatine phosphate and ATP. Thus, in ischemic hearts, hyperthermia neither prevented the development of mechanical deterioration nor improved oxidative phosphorylation despite increases in metabolic substrate utilization. These data suggest that in experimental global ischemia heat is an added energy drain in already burdened myocardium.
Angiotensin II and its heptapeptide (2-8), hexapeptide (3-8), and pentapeptide (4-8) metabolites in arterial and venous blood of man.
Authors: Semple P F , Boyd A S , Dawes P M , Morton J J
Published: June 2012

We made separate measurements of angiotensin II (A II) and of its immunoreactive metabolites (2-8 heptapeptide, 3-8 hexapeptide, and 4-8 pentapeptide) in arterial and venous plasma from subjects with widely different plasma levels of the peptides. A II and its three metabolites were extracted from blood, separated by paper chromatography, and measured by radioimmunoassay using an A II antiserum which had a 100% cross-reaction with each metabolite. In contrast to results of previous studies, A II was found to predominate in both arterial (60-100%) and venous (55-100%) blood. The biologically active 2-8 heptapeptide metabolite accounted for only 10% of the activity in arterial plasma. Radioimmunoassay of venous plasma extracts using an A II antiserum which had a low cross-reaction with the 3-8 hexapeptide and the 4-8 pentapeptide confirmed the results obtained using the antiserum which had a 100% cross-reaction with the metabolites. We conclude that radioimmunoassay methods for measuring A II in venous blood may be more accurate and relevant than has previously been recognized. The small difference between A II concentrations in arterial and venous plasma suggests further that there may be significant conversion of angiotensin I (A I) to A II in the limb vasculature.
Acute and chronic dose-response relationships for angiotensin, aldosterone, and arterial pressure at varying levels of sodium intake.
Authors: Cowley A W , McCaa R E
Published: June 2012

We examined the acute and chronic dose-response relationships between intravenously infused angiotensin II (A II) and the resulting changes in arterial pressure and plasma aldosterone concentration at varying levels of sodium intake. Sequential analysis of plasma aldosterone at each A II infusion rate resulted in an acute dose-related increase in plasma aldosterone which was markedly attenuated after the first 24 hours of infusion, the final level being directly related to the dose of A II and inversely related to sodium intake. A II infused at 5,15, and 23 ng/kg per min was associated with an initial increase (2nd to 8th hour) in plasma aldosterone to 2,6, and 9 times control values, respectively, in dogs receiving 40 mEq Na+/day. But, after the 1st day, aldosterone averaged only 1, 1.7, and 3 times control values for the next 2 weeks at the same rates of A II infusion. Dogs receiving 120 mEq Na+/day during A II infusion exhibited only a transient increase in plasma aldosterone during the 1st day. Sustained hypertension developed over a period of a week at all doses of A II at normal and high sodium intake, but did not occur at any dose of A II in sodium-depleted dogs. Increasing sodium intake from 40 to 120 mEq/day resulted in higher levels of hypertension, 125% compared to 140% of ocntrol values for dogs infused with A II, 5.0 ng/kg per min. We conclude that primary angiotensin-induced hypertension need not be associated with increased levels of plasma aldosterone, which appears to remain elevated only with amounts of A II greater than those required to sustain a significant degree of hypertension.
The effect of cardiac contraction on collateral resistance in the canine heart.
Authors: Downey J M , Chagrasulis R W
Published: June 2012

We determined whether the coronary collateral vessels develop an increased resistance to blood flow during systole as does the cognate vascular bed. Collateral resistance was estimated by measuring retrograde flow rate from a distal branch of the left anterior descending coronary artery while the main left coronary artery was perfused at a constant pressure. Retrograde flow rate was measured before and during vagal arrest. We found that in 10 dogs the prolonged diastole experienced when the heart was stopped caused no significant change in the retrograde flow rate, which indicated that systole has little effect on the collateral resistance. However, when left ventricular end-diastolic pressure was altered by changing afterload or contractility, a direct relationship between end-diastolic pressure and collateral resistance was noted.
The evolution of early fibromuscular lesions hemodynamically induced in the dog renal artery. I. Light and transmission electron microscopy.
Authors: Baumann F G , Imparato A M , Kim G E
Published: June 2012

In view of the important roles of arterial intimal fibromuscular lesions as precursors of atherosclerotic plaque and occlusive lesions in arterial reconstructions, a model has been developed for the rapid hemodynamic induction of these lesions by anastomosis of the dog right renal artery to the inferior vena cava. Light and transmission electron microscopic observations were made on the arterial shunt after periods of rapid flow ranging form 10 minutes to 2 hours to identify initial factor(s) and evolutionary mechanisms in the etiology of the lesions. The sequence of events included aberrations in ruthenium red staining of the endothelial luminal membrane at 10 minutes, multilayered thickening of the subendothelial basement membrane (BM) at 15 minutes, and initial reorientation and migration of smooth muscle cells (SMC) into the intima along with the appearance of areas of degeneration of the internal elastic lamina (IEL) at 30 minutes. The endothelial cells were still intact in some areas overlying the SMC migration and IEL degeneration, but they were separating from the surface in other such areas. As subendothelium became exposed, some platelet adherence was noted. By 2 hours, the entire wall reaction was fully developed. Initial observations indicate that in the evolution of this hemodynamically induced lesion visible alteration in the endothelial cells is not prerequisite to degeneration of the underlying IEL and reorientation and migration of medial SMC.
Site of myocardial infarction. A determinant of the cardiovascular changes induced in the cat by coronary occlusion.
Authors: Corr P B , Pearle D L , Hinton J R , Roberts W C , Gillis R A
Published: June 2012

The influence of site of acute myocardial infarction on heart rate, blood pressure, cardiac output, total peripheral resistance (TPR), cardiac rhythm, and mortality was determined in 58 anesthetized cats by occlusion of either the left anterior descending (LAD), left circumflex or right coronary artery. LAD occlusion resulted in immediate decrease in cardiac output, heart rate, and blood pressure, an increase in TPR, and cardiac rhythm changes including premature ventricular beats, ventricular tachycardia, and occasionally ventricular fibrillation. The decrease in cardiac output and increase in TPR persisted in the cats surviving a ventricular arrhythmia. In contrast, right coronary occlusion resulted in a considerably smaller decrease in cardiac output. TPR did not increase, atrioventricular condition disturbances were common, and sinus bradycardia and hypotension persisted in the cats recovering from an arrhythmia. Left circumflex ligation resulted in cardiovascular changes intermediate between those produced by occlusion of the LAD or the right coronary artery. Mortality was similar in each of the three groups. We studied the coronary artery anatomy in 12 cats. In 10, the blood supply to the sinus node was from the right coronary artery and in 2, from the left circumflex coronary artery. The atrioventricular node artery arose from the right in 9 cats, and from the left circumflex in 3. The right coronary artery was dominant in 9 cats and the left in 3. In conclusion, the site of experimental coronary occlusion in cats is a major determinant of the hemodynamic and cardiac rhythm changes occurring after acute myocardial infarction. The cardiovascular responses evoked by ligation are related in part to the anatomical distribution of the occluded artery.
Comparison of Changes in Mesenteric Resistance Following Splanchnic Nerve Stimulation with Responses to Epinephrine and Norepinephrine
Authors: DEAL C. P. , GREEN HAROLD D.
Published: June 2012

This is a study of the characteristics of the splanchnic nerve supply to the mesenteric vascular circuit. The flow and pressure responses in the dog's superior mesenteric artery to splanchnic nerve stimulation and to intraarterial injections of epinephrine and norepinephrine, before and during various levels of adrenergic blockade, are analyzed. The results suggest that the splanchnic nerve contains only vasoconstrictor fibers, the mediator of which is probably norepinephrine, but that it also contains fibers which induce the release of epinephrine from the adrenal gland. No evidence for the presence of cholinergic dilator fibers was found.
Reflex Alterations in Venomotor Tone Produced by Venous Congestion
Authors: ALEXANDER ROBERT S.
Published: June 2012

Changes in venous tone produced by partial occlusion of the thoracic inferior vena cava, or of the mitral orifice, have been studied in acute experiments on anesthetized dogs, employing distensibility diagrams obtained from injections into the veins of a loop of intestine to measure venous tone. The results demonstrate a reflex mechanism producing venous dilation in response to venous congestion which is mediated by vagal afferents and inhibition of sympathetic efferents.
Production of Hyperlipemia and Early Atherosclerosis in Rabbits by a High Vegetable Fat Diet
Authors: STEINER ALFRED , DAYTON SEYMOUR
Published: June 2012

Feeding of a high vegetable fat diet made up of ground peanuts and purina chow to rabbits resulted in an increase in the serum cholesterol, as well as other serum lipids, including β-lipoprotein fraction. Microscopic lipid deposits in the intima and underlying media of the ascending and thoracic aorta were present in 10 of 33 rabbits at the end of 5 to 12 months. Small areas of gross atherosclerosis of the aorta were found in two rabbits.
Evidence of the Atrial Location of Receptors Influencing Urine Flow
Authors: HENRY JAMES P. , GAUER OTTO H. , REEVES J. L.
Published: June 2012

Receptors believed responsible for the diuresis of negative pressure breathing have been located by observing the effect on urine flow of a stepwise engorgement of the intrathoracic vascular bed. Distension of the pulmonary arterial tree (injection of plastic beads) and of the entire pulmonary circulation (snares on the pulmonary veins) were without effect. A diuresis was however elicited by expansion of a balloon in the left atrium. It is concluded that stretch receptors in the left atrium and terminal pulmonary veins are instrumental in a mechanism linking changes in the actively circulating blood volume with homeostatic responses of the kidney.
The Coronary Blood Flow in Pulmonary Emphysema and Cor Pulmonale
Authors: ROSE LEONARD B. , HOFFMAN DAVID L.
Published: June 2012

The coronary blood flow was determined in 9 individuals with pulmonary emphysema alone and emphysema with cor pulmonale. Intracardiac pressures, cardiac output and pulmonary functions were also studied. In 8 of the 9 cases coronary blood flow was within the normal range. In one case with a high cardiac output the coronary blood flow was elevated in proportion. The presence of cor pulmonale did not appear to influence the results.
Dynamics of Complete Right Ventricular Failure in Dogs Maintained with an Extracorporeal Left Ventricle
Authors: ROSE JOHN C. , LAZARO ERIC J. , BROIDA HERBERT P.
Published: June 2012

By replacing the left ventricle of a dog with an extracorporeal pump, complete failure of the right ventricle (e.g., fibrillation) caused marked elevation of central venous pressure, the Degrees of elevation being a linear function of left ventricular output. In addition, expansion of the intravascular volume was required in order to maintain circulation by the left ventricle alone. Edema formation was accentuated by the hypervolemia and venous hypertension.
Serum Transaminase Levels in Experimental Pulmonary Infarction
Authors: AGRESS CLARENCE M. , GLASSNER HARVEY F. , JACOBS HOWARD I.
Published: June 2012

No significant increases in serum transaminase levels were produced in acute experimental pulmonary infarction. Although significant transaminase levels have been observed in both clinical and experimental acute myocardial infarction, it was found that a minimal myocardial infarction (5 per cent) is associated with greater rises than that found with pulmonary infarction of the order of 45 per cent.
Production of Endocarditis with Staphylococcus Aureus and Streptococcus Mitis in Dogs with Aortic Insufficiency
Authors: HIGHMAN BENJAMIN , ROSHE JOSEPH , ALTLAND PAUL D.
Published: June 2012

Following the induction of aortic insufficiency, 15 dogs received intravenous injections of either
Staphylococcus aureus
or
Streptococcus mitis
. The clinical course and pathologic picture resembled those of acute and subacute bacterial endocarditis respectively. The valvular lesions were confined largely to contacting surfaces of aortic and mitral leaflets. The dogs given
S. mitis
often developed an acute diffuse proliferative glomerulonephritis. No such valvular or renal lesions were noted in 10 control dogs, including 2 with sham operations, given similar bacterial injections.
The "After-Drop" in Venous Occlusion Plethysmograms
Authors: ALLWOOD M. J.
Published: June 2012

Venous occlusion plethysmograms from the dependent foot showed an "after-drop" in volume not seen with the foot at heart level. Factors affecting the development of this after-drop were studied. Blood flow was measured during the after-drop and corresponding changes in venous pressure recorded. The evidence obtained does not support the existing explanation that the after-drop is due to a reflex vasoconstriction. It is suggested that this phenomenon is due to a shifting of blood in the underlying vessels by the venous occlusion cuff.
Mechanical vs. Reflex Effects of Diffuse Pulmonary Embolism in Anesthetized Dogs
Authors: WILLIAMS M. HENRY
Published: June 2012

The effects of repeated pulmonary embolisms with glass spheres on systemic and right intracavitary pressures and on arterial oxygen saturation of anesthetized dogs are described. The results of studies of intact dogs and of the isolated perfused left lower lobe indicate that the hemodynamic effects were due to mechanical obstruction to the flow of blood through the lungs eventually followed by right heart failure. Evidence for reflex effects on the blood vessels or heart was lacking. The systemic arterial unsaturation which eventually developed after repeated embolisms was completely overcome by the inspiration of oxygen and was attributed to a reduction of the diffusing capacity of the lung.
The Left Atrial Pressure Pulses in Experimental Mitral Valve Lesions
Authors: HARING O. M. , LIU C. K. , TRACE H. D. , Luisada A.A
Published: June 2012

Comparative studies of left atrial electrokymograms, left atrial pressure tracings, and pulmonary wedge pressure tracings were made in dogs with experimental mitral insufficiency or stenosis. Typical patterns were found in pure insufficiency or stenosis. A remarkable coincidence was found between pressure tracings and electrokymograms of the left atrium.
Contractility and Extractability of Heart Actomyosin After Death
Authors: DETTLI L. , BING R. J.
Published: June 2012

The contractility and extractability of actomyosin and proteins prepared from dogs' heart immediately, and one hour after death were compared. The yield of total and soluble proteins and of actomyosin was found to be identical. In addition, there was no difference between the after-loaded contractions of actomyosin bands of fresh preparation and those obtained one hour after death.
Influence of Anomalous Blood Viscosity on Resistance to Flow in the Dog's Hind Limb
Authors: LEVY MATTHEW N. , Zieske Harrison , Slwobe Marcus L.
Published: June 2012

Observations were made on an isolated hind leg preparation of dogs, perfused with blood and various homogeneous perfusates. A wide range of intravascular pressures were used while a constant arteriovenous pressure gradient was maintained. It was found that parallel increases in arterial and venous pressures result in a reduction in resistance to blood flow. A similar change in resistance is observed when more homogeneous perfusates are employed. Therefore, under the conditions of these experiments, the reduction in resistance with elevation of intravascular pressure must be ascribed principally to passive distention of the vascular bed.
Pressure Events of the Cardiac Cycle in the Dog
Authors: MOSCOVITZ HOWARD L. , WILDER ROBERT J.
Published: June 2012

Simultaneous pressure curves from the cardiac cavities, aorta and pulmonary artery of dogs were recorded by manometers of equal sensitivity. It was found that left ventricular pressure during ejection is practically identical with that of the aorta. In the majority of dogs atrial and ventricular end-diastolic pressures were equal. The temporal relations of events in the right and left heart were similar to those reported in man, but the duration of the cardiac cycle is too dependent on cycle length to permit comparison.
Effect of Sympathomimetic Drugs in Acute Experimental Cardiac Tamponade
Authors: BINION JOHN T. , MORGAN WILLIAM J. , WELCH GEORGE H. , SARNOFF STANLEY J.
Published: June 2012

The effect of Aramine and Wyamine on the depressed circulation in acute cardiac tamponade was studied in six dogs. As a result of tamponade, there was marked depression of the apparent right and left ventricular function curves which were then significantly re-elevated by the administration of these drugs. Evidence of coronary insufficiency was demonstrated in very severe tamponade where there was a low coronary perfusion gradient. The value of these drugs in acute clinical tamponade is suggested as a temporary expedient for maintaining an adequate coronary circulation until more definitive therapy can be initiated.
Influence of Experimental Myocardial Infarction on Free Amino Acids of Dog Heart
Authors: CHANIN MARTIN , ROBERTS EUGENE , GOLDMAN ALFRED
Published: June 2012

Free or easily extractable amino acids were determined by two-dimensional paper chromatography in infarcted and noninfarcted areas of the left ventricles of dog hearts after ligation of the anterior descending coronary artery. Changes in amino acid content in infarcted areas were characterized by decreases in some of the major ninhydrin-reactive constituents and appeared coincidentally with histologic signs of myocardial damage.
The effect of indomethacin blockade of prostaglandin synthesis on blood pressure of normal rabbits and rabbits with renovascular hypertension.
Authors: Romero J C , Strong C G
Published: June 2012

Indomethacin inhibits the synthesis of prostaglandin and the release of renin. These effects were studied in normal rabbits and rabbits with two-kidney Goldblatt hypertension (2KGH) and one-kidney Goldblatt hypertension (1KGH) by giving daily intravenous injections of indomethacin (3mg/kg after two initial doses of 9 mg/kg), and in appropriate control rabbits given diluent phosphate buffer without indomethacin. In normal rabbits, indomethacin significantly decreased immunoreactive plasma prostaglandin E-like substance (IPGE) and plasma renin activity (PRA). Indomethacin did not change plasma creatinine (PCr) or mean blood pressure but it decreased renal blood flow (RBF) and glomerular filtration rate (GFR). In 2KGH rabbits, responses depended on the level of renal function and, to a lesser extent, on the level of PRA. In six of10 2KGH rabbits in which hypertension developed without significant changes in PRA, IPGE, PCr, RBF, and GFR, indomethacin produced changes similar to those seen in normals. In the other four rabbits, development of 2KGH was accompanied by increased PRA, increased IPGE, and decreased RBF and GFR, and indomethacin produced renal failure, oliguria, malignant hypertension, and death within 5 days. In 1KGH rabbits, indomethacin decreased IPGE, PRA, and renal function but increased mean blood pressure. These observations suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
Steady state aldosterone dose-response relationships.
Authors: Young D B , Guyton A C
Published: June 2012

The steady state effects of different infusion rates of aldosterone on plasma concentrations of sodium and potassium, plasma renin activity, sodium space, and mean arterial pressure were determined. Measured amounts of aldosterone were infused continuously into adrenalectomized dogs for 13 weeks. Four rates of aldosterone administration were used: 16 +/- 1 mug/day, 48 +/- 3 mug/day (approximately the normal secretory rate for 22-kg dogs on a daily sodium intake of 27 mEq, potassium intake of 27 mEq), 91 +/- 4 mug/day, and 219 +/- 10 mug/day. Each rate of infusion was continued until the dogs were in sodium and potassium balance and measured variables were steady. Decreasing the rate of aldosterone administration below normal led to sharp decreases in plasma sodium concentration and sodium space, while raising the rate above normal had little effect. Plasma potassium concentration varied inversely and significantly with changes in aldosterone administration over the entire range of rates. Plasma renin activity rose extremely rapidly as the level of aldosterone fell below normal and went to zero at aldosterone infusion rates slightly above normal. Arterial pressure increased as aldosterone rose above normal but did not fall below normal at subnormal aldosterone levels, probably because of the pressor effects of simultaneously generated angiotensin II.
Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.
Authors: Bland R D , Demling R H , Selinger S L , Staub N C
Published: June 2012

To determine whether hypoxia directly affects pulmonary microvascular filtration of fluid or permeability to plasma proteins, we measured steady state lung lymph flow and protein transport in eight unanesthetized sheep breathing 10% O2 in N2 for 4 hours. We also studied three sheep breathing the same gas mixture for 48 hours. We surgically prepared the sheep to isolate and collect lung lymph and to measure average pulmonary arterial (Ppa) and left atrial (Pla) pressures. We placed a balloon catheter in the left atrium to elevate Pla. After recovery, the sheep breathed air through a tracheostomy for 2-4 hours, followed by 4 or 48 hours of hypoxia. In 13 4-hour studies, the average arterial PO2 fell from 97 to 38 torr; Ppa rose from 20 to 33 cm H2O; and lung lymph flow and lymph protein flow were unchanged. We also found that during 48-hour hypoxia, with a sustained elevation in Ppa and a decline in Pla, lymph flow and protein flow did not increase. In four sheep, we also raised Pla for 4 hours, followed by 4 hours of hypoxia with elevated Pla. Again, despite the added stress of elevated Pla, we found that lymph flow and lymph protein flow remained constant during hypoxia. We conclude that severe alveolar hypoxia, for 4 or 48 hours, alone or with increased pulmonary microvascular pressure, produced no change in lung fluid filtration or protein permeability, a finding supported by normal postmortem histology and extravascular lung water content.
Mechanism of renin release during acute ureteral constriction in dogs.
Authors: Eide I , Loyning E , Langård O , Kiil F
Published: June 2012

The relationship between renal arterial pressure and renin release was examined in anesthetized dogs during complete or partial ureteral constriction. During complete ureteral occlusion ureteral pressure rose to 95+/-4 mm Hg and renin release increased from 1.7+/-0.7 to 22.3+/-3.1 mug/min; renal blood flow (RBF) was not significantly changed. Renin release was not further increased during subsequent renal arterial constriction; RBF fell in proportion to perfusion pressure, indicating maximum autoregulated arteriolar dilation. During partial ureteral constriction to a ureteral pressure of 65+/-6 mm Hg, renin release was moderately raised but release mechanisms became fully stimulated when renal arterial pressure was reduced to 104+/-3 mm Hg. By further constricted of the renal artery, RBF fell in proportion to perfusion pressure and renin release remained high and constant. In control experiments without ureteral constriction, renal arterial pressure had to be reduced to below 65+/-8 mm Hg to fully stimulate renin release (22.0+/-3.8 mug/ml which is not different from 22.3+/-3.1 mug/min during ureteral occlusion). During partial ureteral constriction, saline infusion (0.9% NaCl at 40 ml/min) raised urine flow, sodium excretion, renal pelvic pressure, and renin release. Thus, the stimulatory effect on renin release of a rise in ureteral pressure exceeded the inhibitory effect of increased sodium excretion. This observation, together with maximum renin release coinciding with complete arteriolar dilation during various combinations of renal arterial and ureteral constriction, is compatible with the conclusion that arteriolar dilation is predominating stimulus to renin release during ureteral constriction.
Role of the thyroid gland in the development and maintenance of spontaneous hypertension in rats.
Authors: Rioux F , Berkowitz B A
Published: June 2012

We studied the vascular mechanisms involved in the prevention of the development of hypertension following thyroidectomy. Ablation of the thyroid gland of 4-week-old spontaneously hypertensive (SH) rats inhibited the development of hypertension and reduced the sensitivity of aortic strips to the vasoconstrictors phenylephrine, norepinephrine, and potassium chloride and the vasodilator isoproterenol. Daily injections of a replacement dose of L-thyroxine caused a complete recurrence of hypertension in these rats. This was accompanied by complete recovery of the aortic sensitivity to the vasconstrictors and isoproterenol. In 10-week-old SH rats thyroidectomy prevented a further increase of blood pressure but did not reverse the hypertention. Here, the aortic sensitivity to vasoactive substances also was reduced but to a lesser extent than in the SH rats thyroidectomized at 4 weeks of age. Hypertension was not obviously associated with hyperfunction of the thyroid gland. Furthermore, we found that at 4 weeks of age, during the prehypertensive period, SH rats have a significantly lower (42%) serum thyroxine level than age-matched normotensive Kyoto Wistar, American Wistar, and Sprague-Dawley rats. However, at 6 and 9 weeks, the serum thyroxine levels of SH rats are similar to those of the normotensive rats. In conclusion, we propose that the reduced sensitivity to endogenous vasoconstrictors in arteries of SH rats following juvenile ablation of the thyroid gland may prevent the development of hypertension in these rats. Moreover, the low serum thyroxine level in SH rats during the prehypertensive period may explain why young SH rats do not develop hypertension before 6 weeks of age.
Characteristics of left ventricular receptors with nonmedullated vagal afferents in cats.
Authors: Thorén P N
Published: June 2012

Activity from left ventricular receptors with non-medullated afferents was recorded in the right cervical vagus in anesthetized, thoracotomized cats. Probing of the open heart demonstrated that the receptors were distributed throughout the free wall and the interventricular septum. Fibers from posterior receptors pass along the posterior descending coronary artery and the lateral surface of the right atrium to join the right main cardiac nerve; those from the anteriolateral region pass behind the aorta and the pulmonary trunk. The control receptor discharge was 1.4 (range, 0-6) impulses/sec at a mean left ventricular end-diastolic pressure (LVEDP) of 4.5 (range, 2-10) mm Hg. It was observed that receptor discharge increased with progressive increase in LVEDP produced either by transfusion or by aortic occlusion. At a mean LVEDP of 8 mm Hg, the mean discharge rate was 3.2 impulses/sec, and at 16 mm Hg it was 7.0 impulses/sec. It was also found that propranolol reduced and isoproterenol increased the discharge frequency at any given LVEDP. Measurement of total conduction times indicated that during the increase in LVEDP the receptors were activated principally in the systolic portion of the cardiac cycle. Despite this there was no obvious relationship between the discharge frequency and left ventricular systolic pressure.
Effects of the antibiotic ionophore X-537A on contractility and ionic exchange in rabbit ventricular myocardium.
Authors: Wendt I R , Langer G A
Published: June 2012

The effects of the ionophore X-537A on mechanical function and on ionic exchange were studied in the isolated, arterially perfused rabbit interventricular septum. X-537A produced an initial positive inotropic response which was, however, transient in this preparation and appeared to be dependent on an effect of the ionophore on catecholamines. The positive inotropy gave way to a progressive decline in force development which was unrelated to the action of catecholamines and was not accompanied by the development of contracture. Isotope uptake experiments revealed that coincident with this decline in force development there was a continuous net loss of tissue K+ and a net gain of Na+. X-537A (5 micronM) perfused for 20 minutes resulted in a net K+ loss of 50.2 +/- 4.6 mmol/kg dry weight and a net Na+ gain of 74.0 +/- 4.5 mmol/kg dry weight. Isotope washout experiments confirmed that the entire net loss of K+ could be accounted for by increased K+ efflux. X-537A did not alter Na+ efflux nor did it have any detectable effect on 45Ca exchange of the perfused septum in which the ability to detect net movements is at a level of approximately +/- 550 micron mol/kg dry weight. On removal of the ionophore the decline in force development ceased and reversed to near control levels and the progressive ionic changes ceased. However, despite the near total recovery of contractile function the Na+ and K+ levels remained at values little different from those reached at the termination of X-537A perfusion. In addition, after removal of the ionophore, we found that K+ exchange rate remained significantly less than control and, furthermore, a kinetic inhomogeneity of tissue K+ was observed. The results emphasize a dissociation between cellular Na+ and K+ content and function following the ionic perturbations induced by the ionophore.
The canine heart as an electrocardiographic generator. Dependence on cardiac cell orientation.
Authors: Corbin L V , Scher A M
Published: June 2012

Traditionally it is assumed that during cardiac depolarization the macroscopic current generators that produce electrocardiographic voltages can be represented as a uniform double-layer source, coincident with the macroscopic boundary between resting and depolarized cardiac fibers as measured with extracellular electrodes ("uniform" hypothesis). A segment of this boundary is thus considered as a current dipole oriented perpendicular to the boundary. We present evidence that, contrary to the above, the effective dipoles largely parallel the long axes of cardiac fibers ("axial" hypothesis). Calculated potentials in volume conductors differ markedly in the two cases. The magnitudes of rapid local "intrinsic" deflections also differ markedly. In our experiments, potential fields prodlced by stimulation at several cardiac sites and measured magnitudes of intrinsic deflections during normal depolarization and that caused by stimulation support the axial hypothesis and are incompatible with the uniform hypothesis. Our results suggest that axial orientation of sources is sufficiently strong so that predictions assuming the uniform hypothesis would be seriously in error, although the axial theory alone does not exactly describe all the measured potentials. Axial orientation of current generators must be considered in quantitative prediction of electrocardiographic potentials. tfurther study of the geometry of the intracellular depolarization boundary and its relation to fiber direction and to the frequency of lateral intercellular junctions is required to describe the generators exactly.
Vulnerability of the mildly ischemic ventricle to cathodal, anodal, and bipolar stimulation.
Authors: Mehra R , Furman S , Crump J F
Published: June 2012

We studied the difference between myocardial vulnerability to arrhythmias caused by cathodal, anodal, and bipolar stimulation in 29 dogs with partial right coronary artery occlusion. We used 2-msec duration stimuli of up to 8 mA to determine the ventricular vulnerable periods, their relationship to the refractory periods, and the fibrillation or multiple response thresholds for unipolar anodal and cathodal stimulation after two premature ventricular contractions. The vulnerable period for arrhythmias began at the end of the respective refractory periods and terminated at a specific time within the cardiac cycle. Within this period the arrhythmia and excitation thresholds were equal. Because shorter refractory periods were obtained with anodal stimulation than cathodal, the vulnerable periods for anodal stimulation were longer. This indicated that the vulnerable periods for bipolar stimulation also would be longer than for unipolar cathodal stimulation since bipolar and anodal refractory periods are equal when the cathode and anode are of similar surface area. Results from seven of the experiments showed that a dual focus of excitation, which can only occur with bipolar stimulation, did not make the ventricle more vulnerable to arrhythmias than did unifocal stimulation. These results indicate that the difference between the arrhythmia vulnerability to unipolar cathodal, anodal, and bipolar stimulation is dependent on the relationship between their excitability characteristics, i.e., their strength-interval curves.
Electrical activity of sinoatrial node cells of the rabbit surviving a long exposure to cold Tyrode's solution.
Authors: Nishi K , Yoshikawa Y , Takenaka F , Akaike N
Published: June 2012

The right atrium including the sinoatrial node was excised from the rabbit heart, immersed in Tyrode's solution, and kept at 0-3 degrees C for several days. The tissue then was warmed to 36-37 degrees C in well oxygenated Tyrode's solution. Transmembrane potentials from cells in the sinoatrial node region and the right atrium were recorded with microelectrodes. After 3 days of storage, the maximum diastolic potential of cells in the sinoatrial node region decreased, but the configuration of the action potential was identical to that of the pacemaker pacemaker potential in the fresh preparation. After 5-7 days of storage, the sinoatrial node tissues in some preparations showed well preserved membrane potentials and pacemaker activity, while in others, the cells were electrically quiescent, or showed subthreshold oscillatory potentials of low amplitude. Transmembrane potentials could not be recorded from the right atrial tissue after storage for this period. Sinoatrial node action potentials with normal configuration were recorded from preparations stored for longer than 10 days. The sinoatrial cells in these preparations responded well to norepinephrine and acetylcholine, indicating that the reactivity of receptors was well preserved. The results provide electrophysiological evidence that cells in the sinoatrial node region can withstand long exposure to cold and retain their sensitivity to neuromediator action, but atrial myocardial cells cannot.
Effects of prostaglandin inhibition on intrarenal hemodynamics in acutely saline-loaded rats.
Authors: Düsing R , Melder B , Kramer H J
Published: June 2012

We studied the effect of inhibition of the prostaglandin (PG)-synthesizing enzyme system in female Sprague-Dawley rats following acute expansion of the extracellular fluid volume (ECV). In 57 conscious rats expansion of the ECV with isotonic saline corresponding to an increase in body weight of 10% was induced. Prior to ECV expansion 31 rats received indomethacin (10 mg/kg of body wt) by stomach tube. In six non-ECV-expanded rats indomethacin had no effect on glomerular filtration rate (GFR) and renal plasma flow (RPF). In ECV-expanded rats pretreated with indomethacin, GFR was unaltered but 125I-hippuran clearance decreased, and filtration fraction significantly increased. Intrarenal 86Rb distribution was similar in control and ECV-expanded rats. Indomethacin caused a slight increase in relative cortical 86 RB activity in non-ECV-expanded rats, but had no effect on intrarenal 86Rb distribution in ECV-expanded rats. No difference in intracortical glomerular perfusion was noted between control and ECV-expanded rats. In indomethacin-treated ECV-expanded rats an increase in relative inner cortical perfusion was observed. Absolute perfusion remained unaltered. Thus the decrease in total RPF was entirely due to decreased perfusion of outer cortical nephrons. Renal prostaglandins therefore may play a permissive role for physical factors to promote renal sodium excretion in acute ECV expansion via changes in intrarenal hemodynamics.
Circulatory reflexes from carotid and extracarotid baroreceptor areas in man.
Authors: Mancia G , Ferrari A , Gregorini L , Valentini R , Ludbrook J , Zanchetti A
Published: June 2012

The carotid sinus baroreceptor reflex was studied in 11 normotensive subjects, using a variable pressure neck chamber and correcting for imperfect pressure transmission to the carotid sinus. Decreased carotid baroreceptor stimulation caused a sustaineded rise in arterial pressure, and increased carotid baroreceptor stimulation caused a sustain fall. The responses were in linear relation to the stimulus, and, after reaching the steady state, greater for the reduced than for the increased baroreceptor stimulation. Thus the carotid sinus baroreceptor reflex of the normotensive man is an effective antihypotensive and antihypertensive feedback system, though the former function may have more sensitivity. The increased and decreased baroreceptor stimulation by the neck chamber also caused bradycardia and tachycardia which were modest in magnitude and often transient. In eight subjects the reflex changes in heart rate induced by the neck chamber were compared with those induced by altering transmural pressure not merely at the carotid sinus but throughout the arterial tree (injection of phenylephrine and trinitroglycerin). The slopes of these relations were 3 times as great in the latter circumstance. Thus the carotid baroreceptors play a lesser role in heart rate control than do extracarotid baroreceptors.
Effect of hyaluronidase and methylprednisolone on myocardial function, glucose metabolism, and coronary flow in the isolated ischemic rat heart.
Authors: Rovetto M J
Published: June 2012

Ischemia in the isolated perfused rat heart resulted in an increase in coronary vascular resistance. Studies were undertaken to determine the effect of hyaluronidase and methylprednisolone on this increase in resistance as well as on glycolytic rate and mechanical function of ischemic hearts. Neither hyaluronidase nor methylprednisolone affected the rate of glucose utilization in working perfused control or ischemic rat hearts. However, both agents prevented a reduction in coronary flow during a 2-hour ischemic period. Associated with the higher coronary flows were higher tissue concentrations of creatine phosphate and lower concentrations of lactate. These agents also prevented accumulation of tissue water in the ischemic hearts. Such changes would appear to be beneficial to the ischemic heart, although mechanical function of post-ischemic hearts was not enhanced by the presence of either hyaluronidase or methylprednisolone. The results, however, suggest that the reduction in myocardial infarct size noted with hyaluronidase and methylprednisolone may be due to their prevention of further reduction of coronary flow in marginally eschemic tissue.
Wall shear stress distribution in a model canine artery during steady flow.
Authors: Lutz R J , Cannon J N , Bischoff K B , Dedrick R L , Stiles R K , Fry D L
Published: June 2012

The wall shear stress pattern was measured in a rigid plastic cast of a canine artery during steady flow by means of an electrochemical technique. The topographic distribution of shear stress is very nonuniform, with regions of high and low shear in close proximity. The steady shear stresses are highest at the leading edge of flow dividers and at the entrance regions to branch vessels. The shapes of the shear stress curves in the celiac branch are primarily a function of the ratio of branch flow to total aortic flow. However, the shapes of the shear stress curves in the adjacent anterior mesenteric branch remain the same for different anterior mesenteric branch flow ratios, although the shear increases with the branch flow ratio. An unstable pattern of flow separation and reattachment is found at the anterior mesenteric flow divider lip and remains localized to that region. A correlation is suggested between sites of high shear stress, extremes in the range of stress, and unstable stress patterns and sites at which atherosclerosis has been shown to develop.
Differential effects of digoxin at comparable concentrations in tissues of fetal and adult sheep.
Authors: Berman W , Ravenscroft P J , Sheiner L B , Heymann M A , Melmon K L , Rudolph A M
Published: June 2012

Electrocardiogram (ECG) electrodes and carotid arterial and superior vena caval (SVC) catheters were placed in eight nonpregnant ewes and 11 fetuses (109-129 days gestation) to measure heart rate, arterial presssure, P-R interval, left ventricular pre-ejection period (PEP), and left ventricular ejection time (LVET), before and after digoxin infusion into the SVC. After the ewes were killed, the steady state concentration of digoxin in plasma was related to the concentration in midbrain and left ventricular free wall. Although concentrations of digoxin in tissue differed between fetuses and ewes, tissue-plasma ratios were similar; the myocardial-plasma ratio was 87 for fetuses and 90 for ewes and the midbrain-plasma ratios were 6.4 and 5.3, respectively. In spite of these similarities, physiological and toxic effects differed at comparable plasma concentrations. Reduction in PEP/LVET ratio was greater in ewes than fetuses, and P-R interval prolongation was linearly related to digoxin concentration in fetuses but uncommon at plasma concentrations below 2 ng/ml in ewes. Arrhythmias occurred in six ewes, but in only one fetus, even though the mean steady state concentration of digoxin in plasma was 4.5 ng/ml in the fetuses and 2.3 ng/ml in the ewes. Atropine had little effect on digoxin-induced P-R interrval prolongation, and isoproterenol produced no tachyarrhythmias in the fetuses. Age-related differences in inotropic and arrhythmogenic effects of digoxin exist exist and are related to differences in drug response rather than drug kinetics; this provides experimental support for the different dosage responses.
Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta.
Authors: Hoff H F , Heideman C L , Gotto A M , Gaubatz J W
Published: June 2012

Apoliporotein B (apoB) was measured in buffer-extracted homogenates of grossly normal and artherosclerotic human aortic intima by means of an electroimmunoassay procedure. The apoB values which were expressed as microgram per mg tissue dry weight, varied widely, ranging from 0.34 to 18.45 in normal intima and from 0.8 to 12.5 in fatty fibrous plaques. No consistent differences in apoB content were found between normal intimas from thoracic and abdominal aortic regions. There was a statistically significant positive correlation between the quantity of buffer-extractable apoB in normal regions and the plasma cholesterol and triglyceride concentration. Buffer-extractable apoB values were significantly higher in fatty fibrous plaques than in ulcerated lesions from the same vessel. However, fatty fibrous plaque apoB values were significantly lower than those from grossly normal regions from the same aorta, although the topographical distribution of apoB was more widespread in plaques than in normal regions, as shown by immunofluorescence studies. This apparent discrepancy reflected the incomplete extraction of apoB from plaques as contrasted to normal regions. The relatively loosely bound apoB, extractable by standard buffers, may represent intact low density lipoprotein (LDL) and/or very low density lipoprotein (VLDL), while the tightly bound fraction may represent insoluble complexes of intact lipoproteins within the plaque or delipidated apoB.