bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological observations on the digitalis-potassium interaction in canine Purkinje fibers.
Authors: Anderson G J , Bailey J C , Reiser J , Freeman A
Published: June 2012

We studied the effects of elevating potassium concentration on the membrane potential of Purkinje cells exposed to toxic concentrations of acetylstrophanthidin or ouabain. Conventional intracellular microelectrode techniques were employed. Rapid elevation of [K+]o from 2.7 to 5.4 mEq/liter resulted in an initial increase (more negative) in membrane potential of cells demonstrating ouabain-induced phase 4 depolarization. The increase in maximal diastolic potential occurred initially without suppression of phase 4 depolarization. In cells rendered inexcitable by ouabain or acetylstrophanthidin, elevation of [K+]o consistently increased membrane potential and restored excitability. In four experiments automaticity was initiated within 2 minutes after the increase in [K]o. Although automaticity reappeared, as maximal diastolic potential increased, the automatic rate slowed and then pacemaker activity was suppressed. Studies with 3H-ouabain showed that the increase in membrane potential paralleled K+-induced release of 3H-ouabain from Purkinje cells. These studies suggest that elevation of [K+]o reverses digitalis toxic manifestations in canine Purkinje fibers by causing release of cardiac glycosides bound to the membrane. The observed increase in membrane potential of ouabain-treated Purkinje fibers that occurred after [K+]o elevation was considered to be mediated in part by restoration of the Na pump and by electrogenic pumping.
Depression and enhancement of baroreceptor pressor response in cats after intracerebroventricular injection of noradrenergic blocking agents: dependence on supracollicular areas of the brain.
Authors: Tadepalli A S , Mills E , Schanberg S M
Published: June 2012

The alpha-adrenergic blocking drugs, phentolamine and Hydergine, both act centrally at different sites to depress and enhance the pressor and sympathetic nerve response to decreased baroreceptor afferent input in anesthetized cats. Depression of the rise in blood pressure and sympathetic nerve discharge during bilateral carotid occlusion (BCO) followed injection of the agents into the 4th cerebral ventricle when the brain was intact but not when connections were interrupted at the midcollicular level by transection or lesion. Enhancement of responses occurred when drug distribution was confined to the brain rostral to the midcollicular level via injection into the 3rd cerebral ventricle with the cerebral aqueduct cannulated. Both agents decreased resting blood pressure and Hydergine decreased heart rate in intact and decerebrate preparations but not in 3rd ventricle-cerebral aqueduct experiments. We found that pretreatment with the noradrenergic precursor. L-dopa consistently prevented depression by phentolamine but was less effective against Hydergine. The results indicate that mechanisms which enhance and suppress the baroreceptor pressor response are normally operative in anesthetized cats and, furthermore, that neural pathways mediating the effects are ones connecting the caudal brainstem with supracollicular levels of the brain. It is further suggested that the pathways may be noradrenergic.
Effect of quinidine and temperature on sodium uptake and contraction frequency of cultured rat myocardial cells.
Authors: McCall D
Published: June 2012

The effects of quinidine and temperature on Na influx and contraction frequency of synchronously contracting rat myocardial cells in monolayer cultures were studied. Quinidine (10(-6) M to 10(-1) M) produced a prompt reduction in Na influx, maximum after 30 seconds of exposure, and dose-dependent along a sigmoid log dose-response curve. At 37 degrees C, Na influx (mumol/10(11) cells per sec) decreased from 30.19 to 24.70 (P less than 0.001) and 10.49 (P less than 0.001) on exposure to quinidine, 10(-6) and 10(-2) M, respectively. Simultaneously the contraction frequency decreased from a control of 120/min to 105/min and 48/min with 10(-6) M and 5 X 10(-4) M quinidine. At higher concentrations spontaneous contractions ceased. The effects on Na influx and contraction were reversible by washing the cells free of the drug (30 seconds). A temperature-dependent decrease in the Na influx between 37 degrees C and 22 degrees C also induced a decrease in contraction frequency. Between 25 degrees C and 35 degrees C the Q10 values for Na influx and contraction frequency were 2.41 and 2.44 respectively. Under all conditions tested there was a constant linear relationship (r = 0.98) between Na influx and contraction frequency for all values of Na influx greater than 11.82 mumol/10(11) cells per sec. Na influx and contraction frequency were insensitive to tetrodotoxin (10(-5) g/ml) but very sensitive to verapamil and to changes in extracellular Na. Quinidine affected only the verapamil-sensitive Na influx. The results indicate a close relationship between verapamil-sensitive inward Na movement and automaticity in these cells and demonstrate that the quinidine-induced changes in automaticity are closely linked to the effect on Na influx.
Automatic activity in depolarized guinea pig ventricular myocardium. Characteristics and mechanisms.
Authors: Imanishi S , Surawicz B
Published: June 2012

Membrane potential was changed uniformly in segments, 0.7-1.0 mm long, of guinea pig papillary muscles excised from the right ventricle by using extracellular polarizing current pulses applied across two electrically insulated cf preparations superfused with Tyrode's solution at maximum diastolic membrane potentials ranging from-35.2+/-7.5 (threshold) to +4.0+/-9.2 mV. The average maximum dV/dt of RAD ranged from 17.1 to 18.0 V/sec within a membrane potential range of -40 to +20 mV. Raising extracellular Ca2+ concentration [Ca2+]0 from 1.8 to 6.8 mM, or application of isoproterenol (10(-6)g/ml) enhanced the rate of RAD, but lowering [Ca2+]0 to 0.4 mM or exposure to MnCl2 (6 mM) abolished RAD. RAD were enhanced by lowering extracellular K+ concentration [K+]0 from 5.4 to 1.5 mM. RAD were suppressed in 40% of fibers by raising [K+]0 to 15.4 mM, and in all fibers by raising [K+]0 to 40.4 mM. This suppression was due to increased [K+]0 and not to K-induced depolarization because it persisted when membrane potential was held by means of a conditioning hyperpolarizing puled gradually after maximum repolarization. These observations suggest that the development of RAD in depolarized myocardium is associated with a time-dependent decrease in outward current (probably K current) and with increase in the background inward current, presumably flowing through the slow cha-nel carrying Ca or Na ions, or both.
Reduction in baroreflex cardiovascular responses due to venous infusion in the rabbit.
Authors: Stinnett H O , Bishop V S , Peterson D F
Published: June 2012

We studied reflex bradycardia and depression of mean arterial blood pressure (MAP) during left aortic nerve (LAN) stimulation before and after volume infusion in the anesthetized rabbit. Step increases in mean right atrial pressure (MRAP) to 10 mm Hg did not result in a significant change in heart rate or MAP. After volume loading, responses to LAN stimulation were not as great and the degree of attenuation was propoetional to the level of increased MRAP. A change in responsiveness was observed after elevation of MRAP by only 1 mm Hg, corresponding to less than a 10% increase in average calculated blood volume. after an increase in MRAP of 10 mm Hg, peak responses were attenuated by 44% (heart rate) and 52% (MAP), and the initial slopes (rate of change) were reduced by 46% (heart rate) and 66% (MAP). Comparison of the responses after infusion with blood and dextran solutions indicated that hemodilution was an unlikely explanation for the attenuation of the reflex responses. Total arterial baroreceptor denervation (ABD) abolished the volume-related attenuation was still present following bilateral aortic nerve section or vagotomy. It thus appears that the carotid sinus responds to changes inblood volume and influences the reflex cardiovascular responses to afferent stimulation of the LAN. On the other hand, cardiopulmonary receptors subserved by vagal afferents do not appear to be involved.
Ventricular pressure-volume curve indices change with end-diastolic pressure.
Authors: Glantz S A
Published: June 2012

Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed indices has been shown convincingly to discriminate one group of patients from another. While this situation in part arises from the relatively large amount of noise introduced by the technical difficulties of measuring synchronous pressures and volumes during diastole in man, ther is a more fundamental difficulty. In practice, one can measure only a short segment of the entire pressure-volume curve, and the values of all diastolic pressure-volume curve parameters investigated change significantly when one uses different segments of the same pressure-volume curve to compute them. These results were derived from relatively noise-free pressure-volume curves obtained by filling nine excised dog left ventricles at a known rate and monitoring pressure-volume curve used to compute the parameter. Merely increasing measurement fidelity will not resolve this problem, because none of these parameters accurately characterizes the entire diastolic pressure-volume curbe from a segment like that which one can reasonably expect to obtain from humans.
Facial vein in the rabbit. Neurogenic vasodilation mediated by beta-adrenergic receptors.
Authors: Pegram B L , Bevan R D , Bevan J A
Published: June 2012

A segment of the facial vein of the rabbit, that opposite the buccal cavity, responds to norepinephrine (NE) and opposite the buccal cavity, responds to norepinephrine (NE) and transmural nerve stimulation (TNS) by a brisk biphasic dilation. The dilation in response to both procedures is reveresed by prior exposure to propranolol (10(-6)M). Pretreatment with phenoxybenzamine (10(-5)M) increases the size of the neurogenic response and displaces the NE dose-relaxation curve to the left. Histamine causes a constrictor response exclusively. Sympathetic stimulation of a segment of the facial vein proximal to this buccal segment, and also of the external jugular vein, results in constriction. Light microscopy showed no fequtres which can account for the dilation, and fluorescence histochemistry using a modified Flack technique showed a dense adrenergic nerve plexus extending throughout the thickness of the media. We found that frequency-response characteristics and neuronal uptake of 3H-NE were consistent with findings for a blood vessel with a heavy medial innervation. Also, monoamine oxidase and catechol O-methyltransferase activities were similar to those found in other rabbit veins. Furthermore, these results are consistent with an adrenergic neuroeffector organization in which there is a predominance of beta- over alpha-adrenergic receptors. In conclusion, the presence of a dilator response in this buccal segment of the facial vein may be related to its location in the wall of the cheek, where it may be subjected to considerable stretch.
The Initiation of Ventricular Tachycardia and Fibrillation by Procaine in the Isolated-Perfused Rabbit Heart
Authors: GRUMBACH LEONARD , Merrill V. I.
Published: June 2012

An accelerating ventricular tachycardia ending in fibrillation can be initiated in isolated hearts by procaine injections after the administration of epinephrine, but not in untreated hearts. The run of tachycardia consists of a supraventricular or idioventricular impulse followed by an accelerating train of premature systoles coupled to it. Fibrillation results when the train reaches a frequency of 10 to 12 per second. In hearts with their bundles of His cut, epinephrine injections alone cause only a ventricular tachycardia of constant frequency. Therefore, the initiation of ventricular arrhythmias by procaine must entail the production of A-V blockade and some process which causes the tachycardia to accelerate.
The Hypocholesterolizing Effects of Drugs
Authors: KING J. STANTON , CLARKSON THOMAS B. , WARNOCK NELTA HYDER
Published: June 2012

The hypocholesterolizing effect on serum and tissue cholesterol of α-phenylbutyramide (PB) is evident in the cholesterol-fed fowl. PB and Gallogen (the diethanolamine salt of the mono-(+)-camphoric acid ester of α,4-dimethylbenzyl alcohol) are mutually antagonistic with respect to this effect, while PB and soybean sterols are additive. The latter combination is approximately as effective as a Gallogen-soybean sterol combination, but has distinct toxic effects that are not observed with the Gallogen-soybean sterol combination.
Cardiac Dilatation Without Hypertrophy from Reduced Ambient Pressure in Rats
Authors: STICKNEY J. CLIFFORD , NORTHRUP DAVID W. , VAN LIERE EDWARD J.
Published: June 2012

Short exposures of rats to greatly reduced ambient pressure after explosive decompression was found to result in cardiac dilatation. The dilatation, determined roentgenographically, was seen to persist for two or three days. Some rats were submitted to one long exposure, while others were repeatedly subjected to short exposures. Sacrifice of the rats sufficiently long after exposure to permit cardiac hypertrophy to develop revealed no evidence of it as determined from heart weightbody weight ratios.
Histochemical Evaluation of Canine Coronary Artery and Aortic Lesions Induced by Intravenous Allylamine
Authors: CONRAD L. L. , GONZALEZ I. E. , JOEL W. , FURMAN R. H.
Published: June 2012

The early lesions of the coronary arteries and aorta in animals given intravenous allylamine are described and are noted to be characterized by glycogen accumulation and by ground substance change indicated by increased PAS-positive material present after incubation with diastase. It is suggested that heterogeneous polysaccharides and/or substances containing 1-2 glycol linkages, other than sulphated acid polysaccharides, may be of importance in the early lesion.
The Effect of Dicumarol on the Transvascular Exchange of T-1824-Labeled Protein in Rabbits
Authors: NELSON THOMAS E. , CASTRONOVA ELIA , HYMAN CHESTER
Published: June 2012

The effect of Dicumarol on the peritoneal transvascular transfer of T-1824-labeled plasma protein was investigated in the intact rabbit by a specially designed method. A significantly increased transfer rate was found in animals given two injections of Dicumarol 48 and 24 hours prior to testing; but determinations made 3 hours after a single injection demonstrated variable susceptibility to the drug. Prothrombin levels were depressed in every case.
The Electric Heart Center for the QRS Complex in Cardiac Patients
Authors: SEIDEN GEORGE E.
Published: June 2012

A modification of Frank's cancellation data-matching method for location of the QRS electric heart center in the human was applied to 40 patients, most of whom had advanced cardiac disease. The equivalent dipole locations for the QRS complex were found to cluster in a 5 cm. by 5 cm. square area forward and to the left in the transverse plane. Correlation of electric heart center location with orthodiagraphic estimate of the center of ventricular mass was poor in many of the cases.
Hemodynamic Effects of Anemia with and without Plasma Volume Expansion
Authors: FOWLER NOBLE O. , FRANCH ROBERT H. , BLOOM WALTER L. , Ward John A.
Published: June 2012

Hypervolemic anemia and normovolemic anemia were produced in dogs. Cardiac outputs increased comparably with similar degrees of anemia in the hypervolemic and normovolemic animals. No significant association between right atrial mean pressure and cardiac output was found. Right atrial and pulmonary arterial pressures increased in a degree comparable to blood volume increase. Systemic mean pressures did not change significantly; there was a significant decrease in total peripheral resistance. The results are consistent with the concept that the increase in cardiac output occurring with hypervolemic anemia is related primarily to the anemia and not to the increase in blood volume.
Movements of the Mitral Valve
Authors: RUSHMER ROBERT F. , FINLAYSON BLISS L. , NASH ALDEN A.
Published: June 2012

Cinefluorographic analysis of mitral valve motion in intact dogs provided evidence that the motility of the valve cusps is restrained by tension exerted through the chordae tendineae throughout the cardiac cycle, except for the rapid filling phase. At the onset of ventricular systole, early contraction of the papillary muscles may play an important role in approximating the mitral valve cusps. During ventricular ejection, the mitral cusps and valve ring move toward the apex of the heart. During diastole, separation of the valve cusps is remarkably slight. The valves were observed to fling wide during rapid ventricular filling when the heart was much smaller than normal, immediately after surgery.
Coronary Vasodilator Properties of Purine and Pyrimidine Derivatives
Authors: WOLF MARY M. , BERNE ROBERT M.
Published: June 2012

The vasodilator potency of the adenine nucleotides has been quantitated. Adenosine and AMP were found to be of equal potency and approximately one fourth as effective as ADP and ATP in increasing coronary blood flow. With the exception of UTP, which was also one fourth as potent as ATP, the derivatives of the hypoxanthine, guanine, cytosine and uracil bases lacked vasodilator properties. An increase in myocardial oxygen consumption was observed during infusion of ATP and UTP. However, the elevation in coronary blood flow was greater than that necessary to meet the increased oxygen requirements of the myocardium.
Measurement of Pulmonary Blood Flow Using the Indicator-Dilution Technic in Patients with a Central Arteriovenous Shunt
Authors: RAMIREZ DE ARELLANO ALFREDO A. , HETZEL PETER S. , WOOD EARL H.
Published: June 2012

The possibility of measuring pulmonary blood flow in patients with central arteriovenous shunts utilizing the initial portion of indicator-dilution curves was explored in 16 patients by comparing these values for pulmonary blood flow with determinations by the direct Fick method. A good correlation between Fick and indicator-dilution values was obtained, and no systematic differences were demonstrated. The standard deviation of the differences between Fick and dye values was in the order of 20 to 25 per cent.
Demonstration of Preferential Flow of Blood From Inferior Vena Cava and From Right Pulmonary Veins Through Experimental Atrial Septal Defects in Dogs
Authors: SILVER ARTHUR W. , KIRKLIN JOHN W. , WOOD EARL H.
Published: June 2012

Preferential right-to-left shunting of inferior vena caval blood and left-to-right shunting of right-lung blood has been demonstrated to occur in experimental atrial septal defects in dogs as in the congenital defects in human beings. Existence of these preferential shunts proves that uniform mixing of blood does not occur in either atrium.
Hypotension (Shock) in Dogs Produced by
Escherichia coli
Endotoxin
Authors: MACLEAN LLOYD D. , WEIL MAX H.
Published: June 2012

Intravenous injection of endotoxin from
Escherichia coli
in dogs is characterized by an immediate and precipitous decline in blood pressure with a simultaneous elevation of portal vein pressure. This reaction is abolished by hepatectomy or exclusion of the liver from the circulation and is believed due to trapping of blood in the liver. The reactions observed suggest that the profound biological effects of endotoxin are at least partially the result of anaphylaxis. The lethal effects of endotoxin are enhanced by removal of the liver.
Absence of Vasomotor Responses to Epinephrine and Arterenol in an Isolated Intracranial Circulation
Authors: GREEN HAROLD D. , DENISON ADAM B. , Hill Arthur T. , Kelly Ronald C. , Lewis N. Maxwell , McLain Bill R. , Myers William S. , Smitherman F. Byron , Watts Lester E. , White Arthur F.
Published: June 2012

Four experimental procedures were tried with the dog before one was found which enabled us to record vasomotor changes in an intracranial vascular bed, uncomplicated by alteration in vasomotor tone in the extracranial beds. This required extensive dissection and cannulation technics. In experiments in which this was accomplished by complete elimination, on one side, of the communications between the internal carotid artery and the various extracranial arteries, it was demonstrated that doses of epinephrine and arterenol, which have marked vasomotor activity on all other vascular beds, are without effect on the intracranial bed supplied by the internal carotid artery.
Plasma Hypertensinase in Experimental Renal Hypertension
Authors: HARAKAL CONCETTA D. , COLLINS DEAN A.
Published: June 2012

A lowered plasma hypertensinase cannot be implicated as an essential factor in either acute or chronic renal hypertension in the dog. No uniform or persistent change occurs in the enzyme. However, marked fluctuations out of the normal range do occur in many, but not all, animals. Prolonged decreases are most frequent in acute hypertension and elevations in chronic hypertension. A modification of Dexter's method for the determination of plasma hypertensinase is described.
Effect of Elevation of Intraluminal Pressure on Renal Vascular Resistance
Authors: HADDY FRANCIS J. , Scott Jerry , Armstrong Edwin
Published: June 2012

Elevation of renal venous pressure in pentobarbitalized laparotomized dogs elicits renal vascular constriction. Part of the vasoconstriction appears to be dependent upon a venous-arteriolar reflex. The reflex pathway is not distributed locally. A portion of the vasoconstriction is dependent upon still unrecognized local factors.
Reactive Hyperemia in the Human Finger
Authors: PATEL DALI J. , BURTON ALAN C.
Published: June 2012

Reactive hyperemia in the finger was investigated in 16 experiments on 5 normal subjects, using venous occlusion plethysmography. Since the flow is so variable from moment to moment, the simultaneous "corrected" flow in a control finger, not occluded, was subtracted from the flow in the test finger, so the difference gave the effect of occlusion free from fluctuations of central origin. The absolute amount and the duration of extra blood flow increased with the period of occlusion. The percentage of the calculated "blood flow debt" repaid was variable, with a mean of 51 percent ± 36. S.D. (σM ± 6 per cent). This is greatly in excess of nutritional debt of the skin.
The mechanical characteristics of hypertrophied rabbit cardiac muscle in the absence of congestive heart failure: the contractile and series elastic elements.
Authors: Hamrell B B , Alpert N R
Published: June 2012

Right ventricular papillary muscles from normal rabbits and rabbits with sustained pulmonary artery constriction (67% decrease in external diameter) were studied at several resting muscle lengths and at an early instant in the isometric twitch. Instantaneous force-velocity data were obtained at 30-38% of time to peak tension (TPT) and at 96%, 98%, and 100% of the resting muscle length at which active twitch tension was maximal. Unloaded shortening velocity (Vmax) was estimated with a linearized form of the Hill hyperbolic formula, and was depressed in hypertrophy to 36% less than normal. We found that Vmax did not change with muscle length in the normal or hypertrophied muscles; therefore there was a length- and time-independent depression of contractile element shortening capacity that was consistent with previous work from this laboratory which demonstrated a depression of myosin and actomyosin ATPase activity in hypertrophy.
Reflex changes in hindlimb and renal vascular resistance in response to distention of the isolated pulmonary arteries of the dog.
Authors: Ledsome J R , Kan W O
Published: June 2012

We describe a preparation that uses a constant flow, right heart bypass for perfusion of an isolated pouch of the main pulmonary arteries at controlled pressures, and show that increments in pressure in the pulmonary arterial pouch are accompanied by increases in systemic vascular resistance and in hindlimb vascular resistance. These changes are demonstrated over the whole range of 5-120 cm H2O pressure in the pulmonary arterial pouch. In contrast there are no significant changes in renal vascular resistance or heart rate. We find that changing the temperature of the perfusate in the pulmonary arterial pouch from 37 degrees C to 30 degress C is associated with a decrease in systemic vascular resistance. Furthermore, the effects of raising the pulmonary arterial pouch pressure and of cooling are abolished by cervical vagotomy. These findings suggest that there is a tonic reflex vasoconstrictor tone generated by the activity of receptors lying in or close to the walls of the pulmonary artery. These findings also suggest that the differential effects on systemic vascular resistance and renal resistance may provide one mechanism by which changes in blood volume may lead to appropriate changes in renal solute excretion.
A possible molecular mechanism of the action of digitalis: ouabain action on calcium binding to sites associated with a purified sodium-potassium-activated adenosine triphosphatase from kidney.
Authors: Gervais A , Lane L K , Anner B M , Lindenmayer G E , Schwartz A
Published: June 2012

Calcium binding at 0 degrees C to a purified sheep kidney Na+,K+-ATPase was described by linear Scatchard plots. Binding at saturating free calcium was 65-80 nmol/mg of protein, or 30-40 mol of calcium/mol of enzyme. Aqueous emulsions of lipids extracted from Na+,K+-ATPase yielded dissociation constants and maximum calcium-binding values that were similar to those for native Na+,K+-ATPase. Phospholipase A treatment markedly reduced calcium binding. Pretreatment of native Na+,K+-ATPase with ouabain increased the dissociation constant for calcium binding from 131 +/- 7 to 192 +/- 7 muM without altering maximum calcium binding. Ouabain pretreatment did not affect calcium binding to extracted phospholipids, ouabain-insensitive ATPases, or heat denatured Na+,K+-ATPase, Na+ and K+ (5-20 mM) increased the dissociation constants for calcium, which suggests competition between the monovalent cations and calcium for the binding sites. At higher concentrations of monovalent cations, ouabain increased the apparent affinity of binding sites for calcium. Extrapolation to physiological cation concentrations revealed that the ouabain-induced increase in apparent affinity for calcium may be as much as 2- to 3-fold. These results suggest: (1) calcium binds to phospholipids associated with Na+,K+-ATPase; (2) ouabain interaction with Na+,K+-ATPase induces a perturbation that is transmitted to adjacent phospholipids, altering their affinity for calcium; and (3) at physiological concentrations of Na+ or K+, or both, ouabain interaction with Na+,K+-ATPase may lead to an increased pool of membrane-bound calcium.
Pressor response to 1-sar-8-ala-angiotensin II (saralasin) in hypertensive subjects.
Authors: Anderson G H , Streeten D H , Dalakos T G
Published: June 2012

An angiotensin II (A II) analogue (1-Sar-8-Ala-angiotensin II) (saralasin) was infused into 418 untreated hypertensive subjects during a 1-day evaluation while blood pressure was recorded every 2 minutes by Arteriosonade. At 5 mug/kg per min, saralasin produced a change in mean blood pressure which correlated significantly (r=-0.54, P less than 0.001) with the stimulated plasma renin activity (PRA) (after intravenous furosemide and ambulation for 2 hours. Saralasin caused a rise inmean blood pressure of at least 7.0 mm Hg in 97 hypertensive subjects, who also had a low stimulated PRA (1.3+/-SEM, 0.1 ng/ml per hour; normal range, 1.7-8.5). On a low sodium diet, the pressor response of hypertensive subjects to saralasin continued and was an even better indicator of a low stimulated PRA. Infusion of saralasin at 10 mug/kg per min into normal subjects on an unrestricted diet, a low sodium diet, and a high sodium diet produced, respectively, no change, a fall (P less than 0.05), and a rise (P less than 0.005) in blood pressure. The same saralasin dose in six hypertensive subjects who showed a pressor response to the analogue in the 1-day study also produced a rise in blood pressure when given on a low sodium diet, and this rise was more than twice that seen in normal subjects on a high sodium diet. Hypertensive subjects who showed the pressor response had a significantly greater (P less than 0.01) pressor sensitivity to A II than did hypertensive nonresponders to saralasin and noraml subjects on an uncontrolled diet. The affinity of the vascular receptors for the analogue was greater in the hypertensive group that showed the pressor response to saralasin. In summary, the pressor response to saralasin, as defined above, occurred in 23% of a large unselected group of hypertensive subjects and was associated with salt loading, a low stimulated PRA, and increased pressor sensitivity to A II.
Balloon-induced right ventricular outflow obstruction: a new approach to control of acute interventricular shunting after myocardial infarction in canines and swine.
Authors: Babb J D , Waldhausen J A , Zelis R
Published: June 2012

Current management of ventricular septal defect (VSD) after myocardial infarction (MI) is aimed at improving left ventricular (LV) performance by afterload reduction as a means of hemodynamic stabilization or shunt control. The current investigation was undertaken to determine whether primary manipulation of right venticular (RV) performance by afterload enhancement was an effective means of reducing MI-VSD shunting. In five open-chest dogs an external LV-RV shunt was created with pulmonary-systemic flow ratios (Qp/Qs) averaging 2.26:1. Inflation of a balloon-tipped catheter in the main pulmonary artery (PA) reduced average QP/Qs to 1.28:1 and shunt flow from 783 to 343 ml/min. However, this increase in RV afterload caused further significant increases in RV systolic and end-diastolic pressure and suggested that deterioration of RV function might be limiting the usefulness of this technique. To investigate whether inotropic support for the RV would overcome this limitation, a similar shunt was created in 11 open-chest swine. We then investigated the effects of dopamine, infused at 24, 60, and 120 mug/min, on QP/QS and other hemodynamic variables both with and without PA balloon inflation. Optimal shunt control was obtained when effects of dopamine were added to those of PA balloon inflation. Shunt flow that had been 1,633 ml/min was reduced to 892 ml/min with the PA balloon and reduced further to 757 ml/min with dopamine, which also lowered RV and LV end-diastolic pressure and reduced total systemic vascular resistance. In four other swine with left anterior descending ligations, PA balloon inflation and dopamine infusion again favorably affected hemodynamics. Epicardial mapping in these swine showed an increase in S-T segment displacement, suggesting that the cumulative effect of these interventions allowed hemodynamic improvement at the expense of enhanced ischemic injury. These data indicate that acute RV outflow obstruction with a balloon catheter is an effective means of temporarily reducing acute ventricular shunting and that dopamine may be a useful pharmacological agent to use with RV afterload manipulation to stabilize a patient prior to transfer to a medical center for more definitive therapy.
Role of prostaglandins in the control of renin secretion in the dog.
Authors: Yun J , Kelly G , Bartter F C , Smith H
Published: June 2012

Infusion of indomethacin into anesthetized, salt-depleted dogs cuased an increase in mean arterial blood pressure (MABP), and decreases in heart rate (HR), urine flow rate (V), renal plasma flow (RPF), and renin secretion rate. MABP was 112.1 +/-5.4 mm Hg during control periods and was 147.7 +/- 5.6 mm Hg (P less than 0.005) 80 minutes after the infusion of indomethacin. V was 0.38 +/- 0.06 ml/min during control periods and was 0.08 +/- 0.01 ml/min (P less than 0.005) 80 minutes after the infusion of indomethacin. RPF was 126.3 +/- 13.3 ml/min and 41.5 +/- 7.5 ml/min, respectively (P less than 0.005), before and after 80 minutes of infusion. Renin secretion rate decreased from 1,194.1 +/- 353.9 U/min during control periods to reach 384.0 +/- 125.8 U/min (P less than 0.025) by 80 minutes of infusion of indomethacin. Subsequent infusion of prostaglandin E2 (PGE2) into the renal artery for 80 minutes caused increases of V to 0.53 +/- 0.13 ml/min (P less than 0.01), of RPF to 102.4 +/- 23.1 ml/min (P less than 0.01), and of renin secretion rate to 2,582.6 +/- 786.4 U/min (P less than 0.005). The decrease in renin secretion rate during the infusion of indomethacin persisted when renal perfusion pressure (RPP) was maintained relatively constant before and during the infusion of indomethacin. Furthermore, we found that infusion of prostaglandin E1 (PGE1) into the kidney gave the same pattern of response as PGE2. The data suggest that PGE1 and PGE2 play a role in the control of renin secretion.
Differences between proximal left and right bundle branch block action potential durations and refractoriness in the dog heart.
Authors: Bailey J C , Lathrop D A , Pippenger D L
Published: June 2012

To date the electrophysiological mechanism responsible for aberrant intraventricular conduction of critically timed premature supraventricular impulses has not been documented. Microelectrode techniques were used to measure in vitro action potential and refractory period durations of the canine proximal right and left bundle branches equidistant from the distal bundle of His. Both measurements in the right bundle branch were statistically significantly longer than these parameters of the left bundle branch. Transection of the bundle branches immediately distal to the distalmost recording sites effected no change in the proximal right bundle action potential but caused marked prolongation of proximal left bundle branch action potential and refractory period durations. We conclude that functional right bundle branch aberrancy is most likely due to the longer proximal right bundle action potential duration and refractoriness. Our data also suggest that the shorter proximal left bundle branch action potential durations and refractory periods may be due to the proximity of the low ohmic resistance Purkinje fiber-muscle junctions on the left septal surface, effecting electrotonic foreshortening of these proximal left bundle branch parameters.
Isolation and characterization of myosin from subjects with asymmetric septal hypertrophy.
Authors: Maron B J , Ferrans V J , Adelstein R S
Published: June 2012

Human cardiac myosin isolated from operatively obtained samples of ventricular septum and left ventricular free wall of subjects with asymmetric septal hypertrophy (ASH) was compared, with respect to structural and enzymatic properties, to myosin isolated from hearts of subjects without heart disease. The following parameters were studied: (1) activation of myosin ATPase activity by K+-EDTA and Ca2+, (2) molecular weight of the heavy and light chains of myosin as determined by electrophoretic migration in polyacrylamide-sodium dodecyl sulfate (SDS) gels and (3) ability to form bipolar aggregates at low ionic strength, as examined by electron microscopy. No difference was present in any of these parameters between human cardiac myosin from subjects with ASH and from subjects without heart disease. Thus, the genetic defect present in subjects with ASH is not expressed in the particular structural and functional characteristics of myosin evaluated in this study.
alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.
Authors: Watanabe A M , Hathaway D R , Besch H R , Farmer B B , Harris R A
Published: June 2012

We determined the effect of alpha-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of alpha-adrenergic receptors with either phenylephrine (10(-8) M to 10(-6) M) or epinephrine (10(-8) M to 10(-6) M) plus propranolol (10(-6) M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10(-6) M). Phenylephrine (10(-5)M attenuated cyclic AMP generation in response to isoproterenol (10(-8) M and 10(-5) M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10(-6) M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by beta-adrenergic receptors, whereas decreases appear to by mediated by alpha-adrenergic receptors.
Intercapillary distance and capillary reserve in hypertrophied rat hearts beating in situ.
Authors: Henquell L , Odoroff C L , Honig C R
Published: June 2012

Functional intercapillary distance (ICD) was measured in stop-motion photomicrographs of hypertrophied, normally compensated, well oxygenated rat hearts beating in situ. Left ventricular hypertrophy was produced by salt loading and unilateral nephrectomy. Minimum ICD (when all capillaries are open) also was measured. Ventricular weight increased by 30-40% within 8-9 weeks after nephrectomy. To compare the effect of normal and pathological growth, ICD was also measured in normal rats. In normal animals, minimum ICD and functional ICD increased linearly and proportionately with left ventricular weight. Consequently, the extent to which capillary recruitment could decrease ICD was the same in large and small normal hearts (about 2 micrometer). In the hypertrophied hearts, capillary recruitment could have maintained ICD within normal limits at rest for several weeks. After 8-9 weeks, however, the capillary reserve in hypertrophy was fully utilized at rest, and mean functional ICD was 1.5-2.0 micrometer greater than normal for the age of the animal. An analysis of O2 transport indicates that anoxic foci would exist throughout the hypertrophied heart and particularly in subendocardium when the capillary reserve is exhausted. The calculated amount of anoxic tissue appears sufficient to account for the focal necrosis and fibrosis observed in hypertrophy and for the development of circulatory failure.
Purification of high molecular weight forms of renin from hog kidney.
Authors: Inagami T , Murakami K
Published: June 2012

To elucidate the possible regulatory function of high molecular weight renins in blood pressure control, studies were initiated to purify and characterize the high molecular weight enzyme. To avoid the destructive effect of acidification during affinity chromatographic elution, pepstatin-aminobutyl-agarose gel was used from which renin could be eluted at a neutral pH in 2 M urea. Three additional steps of conventional chromatography after the affinity technique produced two types of high molecular weight renins in electrophoretically homogeneous forms. Big renin with a molecular weight of 61,000 has a specific activity approximately 20% of the fully active small molecular weight renin (mol wt 40,000). Big big renins with molecular weights of 140,000 were discovered and purified in two homogeneous forms with specific activities less than 1% of the fully active renin. The possibility of zymogen-enzyme relationship involving the big big, the big, and the fully small molecular weight renins is discussed.
Heterogeneity of the hypoxic state in perfused rat heart.
Authors: Steenbergen C , Deleeuw G , Barlow C , Chance B , Williamson J R
Published: June 2012

Tissue oxygen gradients were examined in the saline-perfused rat heart by NADH fluorescence photography. In high flow hypoxia, where the coronary flow was maintained and the arterial oxygen tension was gradually reduced, oxygen extraction was virtually complete before oxygen consumption was significantly diminished. Inadequate oxygen delivery resulted in a well defined pattern of anoxic zones. The anoxic zones were several hundred microns in width, an order of magnitude greater than intercapillary distances. In low flow hypoxia (ischemia), where the arterial oxygen tension remained at its control value and the coronary flow was diminished, anoxic zones also developed, following the same pattern as in high flow hypoxia. However, in ischemia, the anoxic areas developed while the effluent oxygen tesion was significantly greater than zero. Whereas respiratory acidosis between pH 7.3 and 6.9 resulted in vasodilation, below PH 6.8 there was a marked increase in vascular resistance. Anoxic zones appeared despite only a slight change in effluent oxygen tension from the control. In high flow hypoxia, ischemia, and acidosis-induced ischemia, the anoxic zones disappeared when control perfusion conditions were restored. The data demonstrate that tissue oxygen gradients are very steep in the hypoxic state, so that ischemia and hypoxia result in discrete heterogeneous areas of anoxic tissue bounded by sharp areas where the oxygen supply is sufficient to maintain normal mitochondrial oxidative function. In these states in which oxygen delivery is less than oxygen demand, coronary perfusion appears to be regulated at the level of the arterioles rather than the capillaries.
Effects of muscle contraction and of adenosine on capillary transport and microvascular flow in dog skeletal muscle.
Authors: Durán W N
Published: June 2012

The postarteriolar response of capillary transport and microvascular flow distribution to muscle contraction and to adenosine was measured by the indicator dilution technique in isolated dog gracilis muscles perfused with blood at controlled flows. A model of dual circulation was used to analyze the partition of microvascular flow. The extraction (E) of 125I-iodoantipyrine (IAp) served as an indicator of capillary flow whereas the capillary transport capacity coefficient (PSc) of 22Na was used to assess the changes in capillary surface area available for exchange. Muslce contraction produced by electrical stimulation of the motor nerve increased mean E-IAp from 0.94 +/- 0.03 (sd) to 0.95 +/- 0.01 and produced a 2.0- to 2.9-fold increase in PSc-Na. Intra-arterial adenosine produced results similar to those caused by muscle contraction. We conclude that (1) in resting muscle, most of the flow circulates through exchanging blood vessels and (2) in addition to the primary mechanisms of arteriolar vasodilatation, a substantial increase in the number of capillaries available for exchange of materials plays an important role in the adaptive response to increased metabolic demand.
Electrophysiological responses of cardiac muscle to isoproterenol covalently linked to glass beads.
Authors: Becker E , Ingebretsen W R , Mayer S E
Published: June 2012

We investigated the effects of isoproterenol aryl glass beads on the electrical properties of cardiac muscle and related these to our previous results concerning biochemical and contractile effects (Ingebretsen et al., Circ, Rs., 40: 474-484, 1977). Beads (10-15) were placed near one end to guinea pig papillary muscles mounted horizontally in a bath perfused with Krebs-Henseleit solution at 30 degrees C and stimulated at 0.2 Hz. The beads produced increased tension and elevation and slight lengthening of the plateau potential when [k+]o = 3.8 mM. After depolarization to a resting potential of -49 mV with [K+]o = 22 mM, isoproterenol beads restored contraction to a comparable extent as occurred with 10(-8) M soluble drug. During field stimulation, action potentials were initiated at the site of bead application and spread decrementally. When beads were placed distal to the site of point stimulation, virtually no excitation could be obtained from cells in the vicinity of the beads. When they were placed close to the stimulating electrode, the beads increased excitability and typical slow action potentials spread to the other end of the muscle. These potentials had the characteristics associated with the slow inward Ca2+ current. The slow channel blocker, D-600, blocked responses to isoproterenol beads. Tetrodotoxin caused responses similar to those obtained with K+ depolarization. The beads probably act by stimulating only a small fraction of the papillary muscle catecholamine receptors. Spread of action potentials from these sites and propagated tension depend on Ca2+ influx, but the nature of an intermediate messenger involved in the propagation of contractions is unknown.
Altered performance of rat cardiac muscle follows changes in mechanical stress during relaxation.
Authors: Wiegner A W , Bing O H
Published: June 2012

We compared two sets of loading conditions for their effect on the mechanical performance of isolated rat trabecular muscle: (1) loading which approximated that of the intact ventricle; (2) nonphysiological afterloaded isotonic contractions. Improved performance, manifested by increased shortening and rate of shortening at constant load, was seen when lengthening occurred at light loads, as in the intact heart. In contrast, lengthening occurring at the same load against with shortening had taken place was followed by diminished performance. Viscous elements in series with the muscle could not account for this phenomenon. The results suggest the presence of an autoregulatory response of myocardium to mechanical stress during relaxation.
A theoretical model of regionally ischemic myocardium.
Authors: Elings V B , Jahn G E , Vogel J H
Published: June 2012

The isometric tension development of a one-dimensional regionally ischemic muscle was analyzed theoretically. The model consist of a one-dimensional normal segment in series with a one-dimensional ischemic segment. Each segment is modeled as a three-element muscle. The inputs to the various elements, except the contractile element in ischemic segment, were obtained from published data for cat papillary muscles. To be consistent with segment length measurements on ischemic canine hearts, it was assumed that the ischemic contractile element contracted normally at the beginning of contraction and then at some tension, TM, fell behind in its rate of tension development compared to the contractile element in the normal segment. Rate of tension development of various lengths of the ischemic segment and strengths of the ischemic contractile element. At the tension, TM, the ischemic segment begins undergoing paradoxical expansion and, simultaneously, as a result of the expansion. the time derivative of the tension produced by the regionally ischemic muscle exhibits a sudden decrease.