bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial purification of a high molecular weight renin from hog kidney.
Authors: Levine M , Lentz K E , Kahn J R , Dorer F E , Skeggs L T
Published: June 2012

Previous investigators have reported finding a high molecular weight (HMW) renin in various species which is activated by acidification. Two laboratories have reported that a decrease in molecular weight of the renin accompanies the acidification step. This report describes the partial purification of an HMW renin from hog kidney extracts which had previously been acidified to pH 2.5. The HMW renin, with a molecular weight of 57,000-59,000, constitutes only a small, relatively constant fraction of the total renin isolated. Omission of the acidification step or initial acidification to pH 1.6 does not change the amount of HMW renin significantly. The HMW renin attacks the protein substrate to produce angiotensin at about one-fourth the rate expected, based upon the rate at which it cleaves the tetradecapeptide substrate or a model nonapeptide substrate. It is inactivated by antiserum to hog kidney renin prepared in dogs. It is less stable than hog renin when stored at 0 degrees C. The HMW renin has a pH optimum between 6.5 and 7.0. It is not activated by acidification to pH 3, nor by tryptic or peptic digestion. We have been unable to activate HMW renin or to change its molecular weight by procedures reported by other investigators and therefore conclude that the HMW renin differs from material previously reported and may be an isoenzyme of renin.
Limitations of the double sucrose gap voltage clamp technique in tension-voltage determinations on frog atrial muscle.
Authors: Tarr M , Trank J W
Published: June 2012

The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inward current associated with an apparent step depolarization (step-clamp) as a function of the magnitude of the step depolarization. In the second case, an action potential was elicited, the voltage clamp was applied early during the plateau phase of the action potential, and the tension response was determined as a function of the clamp potential (action potential-clamp). Under both step-clamp and action potential-clamp conditions, the waveform of the tension response rose to a peak value (Tp) and then decayed with time to a tension that was maintained for the duration of the depolarization. The Tp-clamp potential relationships obtained under step-clamp and action potential-clamp conditions were similar. Microelectrode measurements of transmembrane potential of cells in the "voltage-clamped" region of the preparation demonstrated the lack of temporal and spatial voltage control under both step-clamp and action potential-clamp conditions, and also demonstrated that acquisition of spatial voltage control occurred at about the same time that the tension response reached its peak value. These data indicate that this voltage clamp technique does not allow an accurate determination of the so-called phasic tension-voltage relationship in frog atrial muscle because of a lack of temporal and spatial control of voltage during the rising phase of the tension response.
Calcium accumulation and enzymatic activities of subcellular fractions from aortas and ventricles of genetically hypertensive rats.
Authors: Wei J W , Janis R A , Daniel E E
Published: June 2012

Subcellular fractions were obtained from aortas and ventricles of 6-month-old spontaneously hypertensive and normotensive Wistar rats by the use of differential and sucrose density gradient centrifugation. These preparations were studied to determine what alterations in calcium accumulation and enzymatic activities might be associated with hypertension. The total amount of calcium accumulation (in the presence of ATP and 17 muM free calcium) by the plasma membrane-enriched fraction from hypertensive rat aortas significantly less than that from normotensive rats (11.3 +/- 0.4 vs 16.2 +/- 1.6 mumol of calcium/g of protein, n = 8). In contrast the specific activities of the plasma membrane marker enzymes, 5'-nucleotidase and phosphodiesterase I, were 80% and 40% greater, respectively, in the hypertensive than in the normotensive fractions. On the other hand, various fractions from ventricles of the two types of rats were generally similar in enzyme activities and calcium accumulation. The decreased rate of relaxation of aortas from spontaneously hypertensive rats may be caused by the decreased rate of calcium transport demonstrated in this study.
Evidence for an adenosine receptor on the surface of dog coronary myocytes.
Authors: Olsson R A , Davis C J , Khouri E M , Patterson R E
Published: June 2012

Adenosine and theophylline were linked covalently to oxidized stachyose to produce compounds too large to penetrate cell membranes. These compounds were used in two conscious and six open-chest anesthetized dogs to test the hypothesis that there is an adenosine receptor on the surface of the coronary myocyte. Intracoronary infusions of the adenosine derivative produced dose-dependent coronary vasodilation which was antagonized by theophylline; two types of theophylline derivative antagonized the coronary vasodilatory action of adenosine. Although these results show that both adenosine and theophylline exert their coronary effects at the surface of the smooth muscle cells, this evidence does not establish that they are competing for a common receptor.
Mechanism for the postive inotropic effect of angiotensin II on isolated cardiac muscle.
Authors: Freer R J , Pappano A J , Peach M J , Bing K T , McLean M J , Vogel S , Sperelakis N
Published: June 2012

Angiotensin II (A II) and analogues were tested for their ability to restore electrical and mechanical activity to cardiac muscle preparations in which the fast Na+ channels had been inactivated by partial depolarization (22-27 mM K+) or by tetrodotoxin (TTX). The partially depolarized or TTX-blocked preparations were chosen because under these conditions electrical and mechanical responses are primarily Ca2+ -dependent. In depolarized rabbit right atria, A II restored spontaneous mechanical and electrical activity (measured by both intracellular and extracellular recording techniques). The frequency of action potential discharge was concentration-dependent; the threshold concentration of A II was 10(-10) M, the ED50 was 8 X 10(-9) M, and the maximum effect was observed at 5 X 10(-8) M. In contrast, depolarized guinea pig atria were insensitive to A II, Sar1-angiotensin II, and des-Asp1-angiotensin II, even at concentrations as high as 10(-5) M. Rabbit papillary muscle (TTX-blocked), embryonic (18-day) chick heart (partially depolarized) and chick heart reaggregates (TTX-blocked) responded similarly to rabbit atria in that A II (9.6 X 10(-7) M) restored both electrical and mechanical activity. We found that in these preparations the action of A II was unaffected by propranolol (5.0 X 10(-6) M to 5.0 X 10(-5) M) but was blocked by Mn2+ (10(-3) M), D-600 (1 X 10(-7) g/ml) and the specific A II antagonists Sar1-Ala8-angiotensin II (P-113) (5.0 X 10(-5) M) and Sar1-Ile8-angiotensin II (5.28 X 10(-5) M). We conclude that the positive inotropic effect of A II on the myocardium is due to its ability to increase transmembrane ion movements in or through the cell membrane. The ability of Mn2+ and D-600 to block this effect suggests that this ion movement is via the so-called "slow channels."
Enzymatic properties of native and N-ethylmaleimide-modified cardiac myosin from normal and thyrotoxic rabbits.
Authors: Banerjee S K , Flink I L , Morkin E
Published: June 2012

Cardiac myosin from thyrotoxic animals (myosin-T) exhibits elevated Ca2+ -ATPase activity which is resistant to further stimulation by sulfhydryl modification. In the present study, we have compared the enzymatic properties of myosin-T with those of myosin from euthyroid rabbits (myosin-N) and the derivatives of myosin-T and myosin-N formed by blocking the most rapidly reacting class of thiols (SH1) with N-ethylmaleimide (NEM). Vmax for Ca2+ -ATPase of myosin-T was about 250% greater than myosin-N and was nearly the same as NEM-modified myosin-N. Values for the apparent Km of myosin-T and NEM-modified myosin-N were 200% greater than the value for unmodified myosin-N. Vmax and Km for K+ (EDTA)-ATPase activity of NEM-modified myosin-T and myosin-N were identical. The Ca2+ saturation, pH, and salt-dependency curves for the ATPase activity of myosin-T were parallel to the curves for myosin-N and differed from those for the NEM-modified myosins. Myosin-T exhibited an increased rate of hydrolysis of ATP, CTP, and UTP in both low (0.05m) and high (0.5m) KCl medium. NEM-modified myosin-N showed increased hydrolysis of ATP and CTP in low KCl medium and increased hydrolysis of ATP, CTP, and UTP in high KCl medium. These results support the hypothesis that the enzymatic behavior of myosin-T may be caused by an alteration in the active site near the SH, thiols. The unique enzymatic properties of myosin-T did not seem to be the result of a major change in structure. The electrophoretic pattern of light chains from myosin-T and myosin-N was the same in polyacrylamide gels containing either 8 M urea at pH 8.6 or sodium dodecyl sulfate. Also, myosin-T had a normal amino acid composition and lacked 3-methyl-histidine and hot acid-stable phosphate.
Swine aortic smooth muscle in tissue culture. Some effects of purified swine lipoproteins on cell growth and morphology.
Authors: Brown B G , Mahley R , Assmann G
Published: June 2012

Smooth muscle cells (SMC) were grown from inner media explants of swine aorta and used as a model for studying the role of lipoproteins in atherogenesis. These cultured cells retain the characteristics of SMC through multiple passages. Cell growth curves, in time, were obtained by using standard counting techniques, SMC grew slowly (0.019 cycle/day) in modified Dulbecco-Vogt medium supplemented with 1.5% swine serum. Purified lipoproteins were prepared from three normolipidemic and two hyperlipidemic (cholesterol-fed) swine. When the medium of 84 growth experiments was supplemented with these lipoproteins, SMC growth rate increased linearly with lipoprotein cholesterol concentration up to 10 mg/dl. At 10 mg/dl of lipoprotein cholesterol, very low density lipoproteins (VLDL) increased growth rate 7.2-fold (P less than 0.01); low density lipoproteins (LDL) 5.7-fold (P less than 0.01); high density lipoproteins (HDL2) 3,4-fold (P less than 0.02); and HDLc, and lipoprotein appearing in the hyperlipidemic swine, 3.0-fold (P less than 0.01). Addition of 10% lipoprotein-free serum stimulated growth rate 6.0-fold (P less than 0.01). There was no difference between normo- and hyperlipidemic lipoproteins with respect to cell growth rate. Factors present in the ultracentrifugal bottom, and factors appearing during the platelet release reaction, were shown to contribute to the SMC growth response. Morphological alterations characteristic of intimal foam cells occurred in SMC grown in VLDL at triglyceride levels in excess of 15 mg per 100 ml. Thus there are distinct parallels between SMC response in this model in vitro and atherogenesis in vivo.
Cell permeability, sodium transport, and the hypertensive process in the rat.
Authors: Friedman S M , Friedman C L
Published: June 2012

The tail artery of the spontaneously hypertensive rat (SHR) (Carworth Farms), excised rapidly and immersed immediately in cold (2 degrees C) Li-substituted physiologic salt solution (LiPSS), continues to exchange cell Na+ and K+ for Li+, this exchange is negligible to the control (Carworth Farms normotensive) CFN). In the incubated artery at 37 degrees C, when the vascular smooth muscle cell is slack, the leakiness of the cell membrane in the SHR is more than offset by increased Na+ pumping activity, so that cell Na+ is subnormal. A high precision technique with ion-specific electrodes was developed to follow the passive downhill and active uphill phases of Na+-K+ exchange in the perfused artery exposed to K+-free physiologic salt solution (K+-free PSS) followed by physiological salt solution (PSS). The exchange was found to be fully reversible and sufficiently equimolar to be definable in terms of movements of K+ alone. The rates of ionic movement across the vascular smooth muscle cell were found to be about 6 times faster for the vessel perfused at low pressure (less than 3 mm Hg) than for the slack incubated artery. The rate of passive downhill movement was significantly accelerated in the mature SHR compared with CFN, and the net active transport activity much enhanced. Similar changes were seen as early as 3 weeks after treatment with DOCA and were pronounced at 8 weeks. It is proposed that conditions favoring a sustained accumulation of Na+ in the vascular smooth muscle cell are countered by an enhanced synthesis of transport protein, of contractile protein, and of paracellular matrix protein which progressively restructure the wall.
Gestational changes in pulmonary vascular responses in fetal lambs in utero.
Authors: Lewis A B , Heymann M A , Rudolph A M
Published: June 2012

Pulmonary arterial (PA) blood flow patterns, changes in pulmonary blood flow, and pulmonary vascular responses to graded hypoxemia and intravenous acetylcholine (ACh) were studied in 15 fetal lambs in utero 3-12 days after surgical implantation of an electromagnetic flow transducer and PA catheter. Phasic PA flow in the fetus was forward only during the first third of systole, almost zero during midsystole, and backward during late systole and early diastole. In contrast, neonatal lambs showed forward PA flow throughout systole. The constriction of the fetal pulmonary vasculature in response to progressive hypoxemia varied with gestational age. At 103 days there was no significant drop in PA flow and only a small increase in pulmonary vascular resistance (Rp) with hypoxemia. The greatest increase in Rp was seen in fetuses after 121 days of gestation. This response was unaffected by alpha- and beta-sympathetic and parasympathetic blockade. Similarly, the pulmonary vascular response to ACh injected into the fetal jugular vein depended on gestational age. Little or no increase in pulmonary flow was noted in the youngest fetus, whereas ACh produced a marked increase in pulmonary flow in festuses over 120 days of gestation. These data suggest that the mechanisms by which hypoxemia constricts and ACh relaxes the pulmonary vascular smooth muscle are not fully developed in fetal lambs at 100 days of gestation and furthermore, that these mechanisms progressively develop during the last third of gestation.
Myocardial contractile function and myofibrillar adenosine triphosphatase activity in chemically sympathectomized rats.
Authors: Dowell R T
Published: June 2012

The contractile properties and contractile protein enzymatic activity of skeletal muscle can be altered by neural influences. To determine whether similar influences apply to cardiac muscle, adult rats were chemically sympathectomized by intravenous injection of 6-hydroxydopamine (6-OHDA). After 2 weeks of treatment, rats were anesthetized and an index of myocardial contractility (max dP/dt) was measured in situ. Max dP/dt was depressed in 6-OHDA-treated rats [4560 +/- 420 (mean +/- SE) mm Hg/sec] when compared to controls (6710 +/- 580 mm Hg/sec). Sympathectomy was verified by reduced hemodynamic responsiveness to tyramine injections. After functional measurements had been completed, the heart was excised. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar protein yield averaged 38 +/- 2 mg/g in controls and was not significantly different in 6-OHDA rats. Myofibrillar ATPase activity was 0.314 +/- 0.014 mumol P1/mg per min in controls. Enzyme activity was significantly reduced to 0.230 +/- 0.020 mumol P1/mg per min in 6-OHDA rats. The results demonstrate that a chronic reduction in sympathetic stimulation to the heart results in a depression of an index of myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. Acute (16-18 hours) chemical sympathectomy depressed the contractile function index without altering ATPase activity. Bilateral adrenalectomy produced no further decrement in myofibrillar ATPase activity in chronically (2 weeks) sympathectomized rats. Therefore, it appears that the changes in contractile protein enzymatic properties are mediated by sympathetic neural influences and may involve the synthesis of new contractile protein(s) with altered enzymatic properties.
The effect of an acute increase in renal perfusion pressure on sodium transport in the rat kidney.
Authors: Kunau R T , Lameire N H
Published: June 2012

We used micropuncture techniques to examine the intrarenal response to an acute elevation of the renal perfusion pressure. In one series of studies (epinephrine, group I) the renal perfusion pressure was acutely increased by intravenous epinephrine infusion; in another series, by bilateral carotid occlusion and vagotomy. A third series of studies (epinephrine, group II) was performed identically to the epinephrine, group I, studies except that the renal perfusion pressure was held constant during the epinephrine infusion by suprarenal aortic constriction. After epinephrine infusion (group I) and following bilateral carotid occlusion and vagotomy the renal perfusion pressure increased, from 119 +/- 1.0 (SEM) to 166 +/- 1.85 mm Hg and from 122 +/- 5.9 to 168 +/- 3.1 mm Hg, respectively. Fractional sodium excretion rose from 2.31 +/- 0.34% to 5.09 +/- 0.58% (P less than 0.001) after epinephrine and from 1.80 +/- 0.71 to 6.40 +/- 1.0% (P less than 0.01) following carotid occlusion and vagotomy. In neither study, however, did we find that the increase in renal perfusion pressure changed the glomerular filtration rate (GFR) (both kidneys) or fractional sodium delivery from the superficial cortical late distal tubule. Furthermore, we found that epinephrine infusion at a constant renal perfusion pressure (epinephrine, group II) did not affect fractional sodium excretion, although a small, but significant, decrease in the GFR and sodium delivery from the superficial late distal tubule occurred. These data suggest that the natriuresis which follows an acute elevation of the renal perfusion pressure cannot be attributed to enhanced sodium delivery from superficial nephrons but must result from (1) inhibition of sodium reabsorption in inner cortical nephrons or (2) an effect on sodium transport in the collecting system.
Evaluation of the force-frequency relationship as a descriptor of the inotropic state of canine left ventricular myocardium.
Authors: Anderson P A , Rankin J S , Arentzen C E , Anderson R W , Johnson E A
Published: June 2012

The short-term force-frequency characteristics of canine left ventricular myocardium were examined in both isolated and intact preparations by briefly pertubing the frequency of contraction with early extrasystoles. The maximum rate of rise of isometric tension (Fmas) of the isolated trabeculae carneae was potentiated by the introduction of extrasystoles. The ratio of Fmas of potentiated to control beats (force-frequency ratio) was not altered significantly by a change in muscle length. However, exposure of the trabeculae to isoproterenol (10(-7)M) significantly changed the force-frequency ratio obtained in response to a constant frequency perturbation. Similar experiments were performed on chronically instrumented conscious dogs. Left ventricular minor axis diameter was measured with implanted pulse-transit ultrasonic dimension transducers, and intracavitary pressure was measured with a high fidelity micromanometer. Atrial pacing was performed so that the end-diastolic diameters of the beats preceding and following the extrasystole could be made identical. Large increases in the maximum rate of rise of pressure (Pmas) were seen in the contraction after the extrasystole. The ratio of Pmax of the potentiated beat to that of the control beat was not changed by a 9% increase in the end-diastolic diameter, produced by saline infusion. Conversely, isoproterenol significantly altered this relationship in the same manner as in the isolated muscle. Thus, either in vitro or in situ, left ventricular myocardium exhibits large functional changes in response to brief perturbations in rate. The isoproterenol and length data indicate that the force-frequency ratio reflects frequency-dependent changes in the inotropic state, independent of changes in length.
Production of Atrial Fibrillation in Dogs by Thyroid Administration and Acetylcholine Injection
Authors: LEVEQUE PHILLIP E.
Published: June 2012

The observation of susceptibility to atrial fibrillation in the thyrotoxic patient suggests a method by which a similar condition may be produced in dogs. This has been accomplished by long-term thyroid extract feeding. Administration of acetylcholine to these dogs by intravenous injection has resulted in a high percentage (81 per cent) of atrial fibrillation.
The Histology of the Common Carotid Baroceptor Areas of the Cat
Authors: Boss J. , GREEN J. H.
Published: June 2012

The areas of the cat's common carotid arteries, where baroceptor activity, similar to that in the carotid sinus, has recently been discovered, have been examined histologically; the nervous structures observed were similar to those in the carotid sinus and Nonidez' area. Additional information regarding the characteristic histology of these structures is presented.
Circulatory and Renal Effects Following Transfusion of Human Blood and its Components to Dogs
Authors: CONN HADLEY L. , WOOD JOHN C. , ROSE JOHN C.
Published: June 2012

The cardiovascular effects of the transfusion of human blood and of some of its components were studied in dogs. Human blood, hemoglobin, globin and red cell stroma produced significant circulatory depression. The reaction to stromal materials was considered to represent a combination of peripheral pooling and myocardial depression. The reactions to human hemoglobin and globin indicated primary vasoconstriction as the initial abnormality. The reaction to human blood, apparently, was a combination of the reactions to stroma and hemoglobin, with an anaphylactoid response after second blood transfusions.
Studies on Mitral Valve Function. Effect of Acute Hypervolemia, Premature Beats and Other Arrhythmias
Authors: FRIEDMAN BEN , DAILY WILLIAM M. , WILSON RUSSELL H.
Published: June 2012

A direct method for studying valvular competence is described based on changes in impedance in the blood induced by injections of concentrated saline. It does not require withdrawal of blood samples and may be repeated at frequent intervals in the same animal. It detected mitral insufficiency in the absence of significant changes in atrial pressure tracings. Mitral insufficiency was observed frequently in association with ventricular arrhythmias, occasionally with atrial arrhythmias and in half of the dogs made acutely hypervolemic.
Cardiac Resuscitation and Neurologic Tolerance to Anoxia
Authors: READ RAYMOND C. , LILLEHEI C. WALTON , VARCO RICHARD L.
Published: June 2012

Complete inflow stasis of the heart was associated with less central nervous system damage, if the heart was resuscitated with massage. Ventricular fibrillation did not occur during the period of circulatory arrest, but it was seen occasionally after the heart filled. Its incidence was increased by the use of Adrenalin and by allowing the heart to recover without massage. The administration of various doses of heparin had no effect on the Degrees of brain damage resulting from interruption of the circulation.
The Hypocholesterolizing Effect of Gallogen and its Potentiation by Soybean Sterols
Authors: CLARKSON THOMAS B. , KING J. STANTON , WARNOCK NELTA HYDBR
Published: June 2012

Gallogen (the diethanolamine salt of the mono-(+)-camphoric acid ester of α,4-dimethylbenzyl alcohol) and soybean sterols have been tested for their effect, singly and in combination, on hypercholesterolemia and aortic cholesterol in cholesterol-fed cockerels. Gallogen alone was found to impede the rise of serum and aortic cholesterol, and also to potentiate these effects of soybean sterols.
Cortisone Hypertension in Potassium-Deficient Rats with a Renal Ligature
Authors: ROSENMAN RAY H. , FREED S. CHARLES , GEORGE SHIRLEY ST.
Published: June 2012

The pressor effects of cortisone were explored in potassium-deficient and control diet rats. It was found that marked hypertension was induced by cortisone only when there was the combined background of a renal-ligature, potassium depletion, and adrenalectomy.
An Analysis of Normal and Abnormal Left Atrial Pressure Pulse in Man
Authors: ANKENEY JAY L. , FISHMAN ALFRED P. , FRITTS HARRY W.
Published: June 2012

Pressure pulses were obtained under direct vision, in the left atrium of subjects without clinical evidence of cardiac disease and in patients with mitral valvular disease, after exposure of their hearts during the course of surgical intervention. It was found that the c wave is produced by valvular closure and the subsequent fall of pressure during early ventricular systole (x wave) is related to atrial relaxation. Evidence is presented that mitral incompetence cannot be determined from direct atrial recordings, unless the Degrees of insufficiency is of great magnitude.
Current Trends in Atherosclerosis Research
Authors: KATZ LOUIS N.
Published: June 2012

Obviously, crystallization of information concerning atherosclerosis will come only by the proper free interplay and adequate fusion of the three major approaches to the problem, epidemiologic, clinical and experimental. We are getting to our goal--but we have not reached it yet. We have a motif, the life span unbalanced luxus diet, rich in calories, fats and cholesterol. We must look into other aspects, as for example: (1) the causes for localization of lesions in particular sites, (2) the causes for intimal ulceration, (3) the influence of hemorrhage and thrombosis, (4) the influence of physical and psychic stresses. These are, as it were, decorations to beautify the motif, they must not be mistaken for the motif itself.

We have come a long way along the road to the solution of the problem of atherosclerosis in the last two decades. The goal is dimly glimpsed through the haze ahead. But we are not there yet, considerable labor on the part of many, carried out in a truly scientific atmosphere still lies ahead. But the reward will more than repay the effort still to be employed.
Factors Altering the Filling of the Isolated Left Ventricle of the Dog Heart
Authors: BUCKLEY N. M. , SIDKY M. , OGDEN E.
Published: June 2012

Ventricular filling was studied in an isolated left ventricle preparation, and mechanical impedance of the ventricular wall was computed throughout the filling period. Changes in work load or heart rate were accompanied by changes in intraventricular pressure curve contours and in the timecourse of the mechanical impedance throughout filling. The filling pattern is characteristically altered as work load or heart rate increases, and after the administration of epinephrine or norepinephrine.
The Effect of Beta-Sitosterol Upon Intestinal Absorption of Cholesterol in the Rat
Authors: FRIEDMAN MEYER , ROSENMAN RAY H. , BYERS SANFORD O.
Published: June 2012

Thoracic duct lymph was collected from groups of rats fed varying doses of β-sitosterol concomitantly with cholesterol. The results indicated that β-sitosterol exerts only a slightly inhibiting effect upon intestinal absorption of cholesterol in the rat.
Planar Dipole Loops
Authors: FRANK ERNEST
Published: June 2012

This is a theoretic discussion of characteristics of body surface potentials produced when the equivalent heart dipole is confined to a plane. Various experimental findings are unified by a single theory, and broad comprehension of the potential behavior is possible.
Studies with the Ganglionic Blocking Agent, Chlorisondamine Chloride in Unanesthetized and Anesthetized Dogs
Authors: MAXWELL R. A. , PLUMMER A. J. , OSBORNE M. W.
Published: June 2012

The normotensive unanesthetized dog receiving chlorisondamine chloride, pentapyrrolidinium, or hexamethonium exhibits a drop in systolic blood pressure, narrowing of pulse pressure, tachycardia and relaxation of nictitating membranes. The relative potencies of these compounds are in the ratio 8:3:1 respectively. While these compounds are apparently equally well absorbed, the activity of chlorisondamine chloride is markedly prolonged. This prolonged activity of chlorisondamine chloride after oral administration is probably due, in large part, to its persistence in the tissues. Chlorisondamine chloride and hexamethonium can suppress the pressor response induced in neurogenic hypertensive dogs by application of annoying stimuli.
In Vivo Fibrinolytic Activity and Pharmacology of Various Plasmin (Fibrinolysin) Preparations
Authors: BACK N. , AMBRUS J. L. , GOLDSTEIN S. , HARRISSON J. W. E.
Published: June 2012

A quantitative method based on the disappearance of I
131
labeled fibrin has been used to study the in vivo effect of fibrinolytic agents. Various preparations of human and bovine plasmin were found to lyse clots effectively. The minimal effective dose of human plasmin prepared by the method of Kline was 15 Loomis units/Kg. Plasmin preparations given intravenously produced hypotension and leukopenia followed by leukocytosis. Doses above 30 Loomis units/Kg. caused decrease in fibrinogen level and clotting index.
Measurement of Circulation Times with NaI
131
Authors: SHIPLEY REGINALD A. , CLARK RICHARD E.
Published: June 2012

Circulation time from an arm vein to the femoral artery as determined with I
131
averaged 11.2 seconds in normal male adults. In the presence of heart failure the time of initial arrival was prolonged, and the slope of ensuing rise flattened. Decholin time, determined simultaneously, averaged 25 per cent longer than I
131
time in both normal subjects and patients with congestive failure. Theoretical considerations indicate that arrival time measured with a radioactive tracer is less affected by cardiac dilatation than is arm to tongue time obtained with Decholin. Arm to heart time measured with I
131
was prolonged in the presence of failure but marked overlap with normal subjects was evident.
A Muscle Column Preparation from the Rat's Left Ventricle
Authors: ULLRICK WILLIAM C. , WHITEHORN WILLIAM V.
Published: June 2012

A muscle preparation from the left ventricle of the rat heart suitable for in vitro studies is described. It consists of one of the trabeculae carneae of the posterior ventricular wall extending from the apex of the ventricle to the auriculoventricular junction. Studies on the excitability, extensibility, tension development, and oxygen consumption of the preparation are reported. The preparation offers economic and technical advantages over other types of isolated heart muscle preparations currently in use.
Experimental Evidence of Ventricular Diastolic Suction
Authors: BRECHER GERHARD A.
Published: June 2012

Intraventricular pressures were measured during brief periods of mitral orifice occlusion to determine whether or not the ventricle can exert a sucking force during diastole. This procedure was based on the premise that with a wide open mitral orifice negative diastolic transmural pressures cannot be detected in the ventricle because the adjoining atrium has collapsible walls. During mitral orifice closure, negative intraventricular pressures were recorded, and Ringer's solution was sucked against the force of gravity into the ventricle. It is concluded that the mammalian ventricle is capable of sucking blood from the atrium into its cavity.
Effect of Hypothermia on Oxygen Consumption and Energy Utilization of Heart
Authors: BADEER HENRY , Khachadurian Avedis
Published: June 2012

The oxygen uptake of the denervated dog's heart doing constant work in a modified HLP appears to vary logarithmically with temperature between 36 and 26 C. Under these conditions hypothermia increases the mechanical efficiency of the heart. It is concluded that cold does not interfere with the conversion of aerobic energy into useful work done by the myocardium.
Complete Prevention of Cerebral Accidents in Malignant Hypertension
Authors: ROBERT ANDRÉ
Published: June 2012

Ligation of the common carotid arteries was found to prevent the development of cerebral lesions (edema, hemorrhage, softening) in animals rendered hypertensive by daily injections of desoxycorticosterone acetate. The protection was complete when both carotids were ligated, and limited to the homolateral side in the case of unilateral ligation.
Effect of Hypothermia in Irreversible Hemorrhagic Shock
Authors: POSTEL ALLEN H. , REID L. CORSAN , HINTON J. WILLIAM
Published: June 2012

Irreversible hemorrhagic shock was studied in normothermic dogs and in dogs subjected to hypothermia at three different periods following the onset of the hemorrhage. A significant prolongation of life was observed in the hypothermia dogs, the increase in survival time being greatest in those dogs cooled early in the shock sequence. The temperature, pulse, respiration, blood pressure, electrocardiogram, rate of uptake of blood from a blood reservoir and autopsy findings in the two groups were noted.
Specific Resistance of Body Tissues
Authors: SCHWAN HERMAN P. , KAY CALVIN F.
Published: June 2012

The resistive properties of various tissues surrounding the heart were investigated in a number of living dogs. Alternating currents of a frequency varying between 10 and 10,000 c.p.s. have been used for this purpose. Technical problems associated with such measurements are analyzed. The results show that the resistive properties of most tissues are comparable and that the resistivity decreases slowly as the frequency increases.
Role of Abdominal Aortic Branches in Pulse Wave Contour Genesis
Authors: RYAN JOSEPH M. , STACY RALPH W. , WATMAN ROBERT N.
Published: June 2012

Central and peripheral pulse wave contours were recorded in dogs before and after occlusion of the major visceral arteries. Comparison of the pulse wave contours indicates that occlusion of the visceral branches produces very little effect upon the wave form of the central and peripheral pulse. The major changes noted were slight shifts in the timing of reflected components, and it would appear that the timing changes can be explained on the basis of the increase in pulse wave velocity attendant with a rise in the arterial blood pressure. Both the importance of these findings in the understanding of pulse wave contour genesis and the basic assumptions of the standing wave hypothesis are discussed.
Paradoxical dynamic interaction of heart period and vagal activity on atrioventricular conduction in the dog.
Authors: Martin P
Published: June 2012

The dynamic interaction of simultaneously changing heart period and single vagal stimuli on atrioventricular conduction (AV interval) was quantified by subtracting the vagally induced responses of the paced heart preparation from those of the unpaced heart preparation. This difference was significantly greater (P less than 0.05) than the AV responses to changes in heart period (delta A) alone without vagal stimulation (using the identical delta AA recorded from the unpaced heart in the same preparation, but with a crushed sinoatrial node). That is, for a given increase in AA interval, the AV conduction time was considerably less when the change in AA was associated with increased vagal activity than in the absence of any vagal activity. Data from some dogs in which a complete AV block was produced for both paced and unpaced hearts suggested that one mechanism of the paradoxical response was located in AV nodal tissue. Data from other dogs, in which two surface atrial recording sites were used, indicated that shifts of pacemaker site and atrial activation patterns also are an important mechanism of the paradoxical response. The relative contribution of these two mechanisms is not fixed, but can vary considerably from animal to animal.
Alterations in canine myocardial excitability during ischemia.
Authors: Elharrar V , Foster P R , Jirak T L , Gaum W E , Zipes D P
Published: June 2012

Changes in the ventricular diastolic excitability threshold following occlusion of the left anterior descending coronary artery (LAD) were studied in open-chest anesthetized dogs by using a new automatic threshold-following pacemaker (ATFP). The ATFP measures the diastolic excitability threshold by successively decreasing the duration of regularly occurring pacing stimuli until the ventricle fails to respond. Under control conditions, the threshold stimulus duration was 60 +/- 4 (mean +/- SEM) musec. In the first 1-3 minutes following occlusion of the LAD, the diastolic excitability threshold in the ischemic zone (IZ) decreased to 51 +/- 5 musec and then rapidly increased to 600 musec at 5 minutes. The initial decrease in excitability threshold at IZ could be abolished by elevating the serum K+ concentration prior to the LAD occlusion. These changes in excitability threshold at IZ could be prevented by infusing nonoxygenated solutions into the LAD at a site distal to the occlusion. As the excitability threshold increased in IZ during ischemia, the earliest time at which IZ could be reactivated by a stimulus with a voltage equal to twice the preligation diastolic voltage threshold was increased. In nine of 16 dogs, after 5 minutes of LAD ligation, the IZ to normal zone (NZ( activation time (when stimulating at IZ) exceeded the NZ to IZ activation time (when stimulating at NZ) by an average of 9 msec. We also found that in four dogs the NZ to IZ activation time exceeded the IZ to NZ activation time by an average of 10 msec. We conclude from these findings that a gradient of increasing excitability threshold exists as one moves from normally perfused toward more ischemic tissue, passing through a heterogenous border zone that manifests some areas which have a decreased excitability threshold and other areas which have an increased excitability threshold, and that these changes in excitability importantly influence the determination of refractory period durations and conduction times.
Chronic one-kidney hypertension in rabbits. III. Renopressin, a new hypertensive substance.
Authors: Skeggs L T , Kahn J R , Levine M , Dorer F E , Lentz K E
Published: June 2012

The blood pressure of rabbits with chronic one-kidney hypertension can be lowered to normal by immunization with hog kidney cortex preparations that do not contain renin, thus providing evidence for a new factor essential for the maintenance of an elevated blood pressure. A search for the new factor has led to the discovery of a hypertensive substance which we have named renopressin. Subcutaneous injection of the new substance into normal rabbits produces a delayed, slow increase in blood pressure, and after a few days the development of a moderate hypertension which persists indefinitely. The response of the blood pressure to renopressin is totally unlike that to renin. While the pressor action of renin can be blocked by an angiotensin II antagonist, the hypertension caused by renopressin cannot. Renin can increase the blood pressure of hypertensive rabbits; renopressin has no effect. The blood pressure of hypertensive rabbits and of normal rabbits made hypertensive by injection of renopressin can be lowered to normal by passive immunization with the same antibody preparation. The evidence is consistent with the possibility that renopressin and the agent causing the elevation of blood pressure in hypertensive rabbits are similar or identical.
Change in liver blood flow and blood content in dogs during direct and reflex alteration of hepatic sympathetic nerve activity.
Authors: Carneiro J J , Donald D E
Published: June 2012

A mean decrease of 60% in liver blood volume was recorded by a plethysmographic technique during electrical stimulation of the hepatic nerves in anesthetized, vagotomized dogs. A decrease in pressure in the vascularly isolated carotid sinus to 40 mm Hg, from a mean control of 144 mm Hg, decreased liver blood volume by a mean of 16%; arterial blood pressure increased by a mean of 77 mm Hg. Carotid sinus hypotension was accompanied by respective mean increases of 16% and 1.4% in hepatic arterial and portal venous blood flows, and of 45% and 22% in arterial and portal resistances. Increase in sinus pressure to 240 mm Hg increased liver blood volume by a mean of 20%; arterial blood pressure decreased by 90 mm Hg. Sinus hypertension was accompanied by respective mean decreased of 10% and 1.5% in hepatic arterial and portal venous blood flows, and of 44% and 18% in arterial and portal resistances. Interruption of afferent vagal traffic from cardiopulmonary receptors was maximally effective in decreasing liver blood volume at a carotid sinus pressure of 40 mm Hg and was ineffective at carotid sinus pressures greater than 160 mm Hg. Combined withdrawal of carotid and cardiopulmonary vasomotor inhibition decreased liver blood volume by 42%; of this 37% was due to the cardiopulmonary and 63% to the carotid baroreflex. The study showed the canine liver to function as a blood reservoir by active mobilization of a portion of its blood volume.
The amino acid composition of actin and myosin and Ca2+-activated myosin adenosine triphosphatase in chronic canine congestive heart failure.
Authors: Raszkowski R R , Welty J D , Peterson M B
Published: June 2012

The Ca2+-activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, shamoperated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum and left ventricle and each sample was individually analyzed. Calcium-activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+-activated myosin ATPase. This study suggests that protein metabolism is abnormal and that altered proteins are produced in hypertrophy and congestive heart failure. It appears that these changes do not affect all proteins, since actin was normal by the parameters studied. It is clear that the stressed ventricle is the most severely involved, but the entire heart is altered to some degree. Thus, we conclude that altered protein metabolism may be an important primary factor in the genesis of heart failure.
Intrarenal renin-angiotensin-sodium interdependent mechanism controlling postclamp renal artery pressure and renin release in the conscious dog with chronic one-kidney Goldblatt hypertension.
Authors: Ayers C R , Katholi R E , Vaughan E D , Carey R M , Kimbrough H M , Yancey M R , Morton C L
Published: June 2012

We studied postclamp renal artery pressure and renin release in eight conscious dogs with one-kidney Goldblatt hypertension. On normal sodium intake, intrarenal blockade of angiotensin II with Sar1-Ala8-angiotension II (P-113, saralasin acetate) markedly decreased postclamp renal artery pressure and increased renin release during the first 5 days after renal artery constriction. We found that 10-14 days after renal artery constriction, the maintenance of postclamp renal artery pressure and negative feedback on renin release became markedly less dependent on angiotensin II, as shown by almost no change in postclamp renal pressure or renin release with intrarenal blockade of angiotensin II. At this stage of our study the dogs were given a sodium diet of less than 5 mEq/day and we found that within 5-10 days intrarenal blockade of angiotensin II once again markedly decreased postclamp renal artery pressure and increased renin release. These observations support the concept of an angiotensin II-sodium interdependent negative feedback mechanism for renin release.
Length-dependent activation: its effect on the length-tension relation in cat ventricular muscle.
Authors: Lakatta E G , Jewell B R
Published: June 2012

In cat papillary muscles at 30 degrees C, bathed with Tyrode's solution containing 2.25 mM Ca2+, the effect of various inotropic interventions (varying the stimulus frequency and continual paired stimulation) on the shape of the steady state length-tension relation was examined at lengths from Lmax, where tension production is maximal, to 0.87 Lmax. The relative steepness of the length-tension curves for peak tension developed (DT) and for maximum rate of tension development (dT/dT) varied inversely with the degree of potentiation. Thus, during paired pulse stimulation the relative decline in DT and dT/dT for a given change in muscle length was significantly less than the decline observed during stimulation at 5 min-1. When a muscle was stretched DT did not reach its final steady level for several minutes, and this slow increase in DT contributed significantly to the steepness of the steady state length-tension relation. The half-time of the slow increase in DT exhibited beat-dependency, and conditions that reduce the transsarcolemmal influx of calcium (reduction in bathing [Ca2+] or the presence of verapamil) significantly prolonged the time course of the slow increase and reduced its magnitude. These results support the hypothesis (1) that there is length-dependence of the excitation-contraction coupling process, such that an increase in muscle length is accompanied by greater activation of the contractile system; and (2) that this is due at least in part to an increased influx of calcium into the muscle cells. The implication of this hypothesis is that the influence of muscle length on myocardial performance (the Frank-Starling relation) should not be regarded as fundamentally different in character from other inotropic interventions.
Relationship between blood pressure of spontaneously hypertensive rats and alterations in membrane properties of mesenteric arteries.
Authors: Wei J W , Janis R A , Daniel E E
Published: June 2012

Spontaneously hypertensive rats (SHR) and two strains of normotensive rats were compared with respect to enzymatic activities and calcium accumulation of plasma membrane and endoplasmic reticulum enriched fractions from their mesenteric arteries. Increased specific activities of alkaline phosphatase, 5'-nucleotidase and Mg2+-ATPase, and increased ATP-dependent calcium accumulation were found in 5- to 6-month-old SHR as compared to both strains fo age-matched normotensive rats. Alkaline phosphatase was increased in 33-day-old "early hypertensive" and 3- to 4-month-old SHR, but 5'-nucleotidase, Mg2+-ATPase, and calcium accumulation were not. Hydralazine treatment of young SHR partially prevented the increase of both alkaline phosphatase activity and blood pressure that develops with age. The relationship between alkaline phosphatase activity and the alterations in vascular reactivity associated with hypertension remains to be determined.