bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoregulation of the Total Systemic Circulation Following Destruction of the Central Nervous System in the Dog
Authors: Granger Harris J. , Guyton Arthur C.
Published: June 2012

The quantitative importance of total systemic autoregulation in the whole body was studied in dogs in which the cardiovascular control loops of the central nervous system were eliminated by decapitation and alcohol destruction of the spinal cord. Transient changes in cardiac output, right atrial pressure, oxygen consumption, arteriovenous oxygen difference, and hematocrit that occurred immediately after single-step changes of 25 to 50 mm Hg in arterial pressure were followed by gradual return of the variables toward control values. The time required to reach a new steady state ranged from 13 to 75 minutes with an average of 35 minutes. The calculated open-loop gain of the autoregulation control system ranged from 0.93 to 9.5 with an average gain of 3.32±0.7 (SE) indicating more than 75% compensation. In a second group of animals the arterial pressure was increased from 50 mm Hg to as high as 150 mm Hg in small steps of 10 to 15 mm Hg allowing 5 to 20 minutes on each step for the autoregulation response to occur. The pressure-flow curves showed significant total systemic autoregulation. The return of arteriovenous oxygen difference and oxygen consumption toward control values is consistent with a metabolic mechanism of autoregulation. The absence of significant transcapillary fluid flux in autoregulating preparations indicates (a) that the locus of autoregulatory resistance changes is completely or almost completely in the precapillary vessels of the circulatory system and (b) that autoregulation is important in maintaining capillary pressure at a normal level as well as in maintaining blood flow at the level required by the tissues.
Release of Adenosine by the Normal Myocardium in Dogs and Its Relationship to the Regulation of Coronary Resistance
Authors: Rubio Rafael , Berne Robert M.
Published: June 2012

The evidence supporting the hypothesis that adenosine is the mediator of metabolic regulation of coronary blood flow was obtained from experiments characterized by myocardial hypoxia. If adenosine serves the role of physiological regulator of coronary blood flow, it must also be released by the normal heart. Experiments designed to study this question were performed on 15 open-chest dogs in which adenosine was sought in perfusates of the epicardial surface of the well-oxygenated heart. The pericardial space was perfused with warm (37°C) Tyrode's or Krebs-Henseleit solutions (400 to 1200 ml over 1 to 3 hours), and the perfusates were analyzed for adenosine. With a normal myocardial oxygen supply, adenosine was present in the perfusates in a concentration of 3.1 ± 0.5 x 10>
-8
M. Partial asphyxia, induced by reducing pulmonary ventilation, significantly (
P
≤ 0.02) increased the adenosine concentration of the perfusates to 5.4 ± 0.8 x 10
-8
M. In four dogs the normal pericardial fluid was found to contain adenosine in a concentration of 10.9 ± 2.9 x 10
-7
M, which probably represents the basal extracellular adenosine concentration in the myocardium. The results indicate that the normal myocardial cells release adenosine continuously into the surrounding interstitial fluid, and it is suggested that the level of the interstitial fluid concentration of adenosine probably regulates coronary blood flow to maintain the oxygen balance of the myocardium.
Pseudorenin: A NEW ANGIOTENSIN-FORMING ENZYME
Authors: Skeggs Leonard T. , Lentz Kenneth E. , Kahn Joseph R. , Dorer Frederic E. , Levine Melvin
Published: June 2012

A new enzyme, pseudorenin, has been discovered which resembles renin in its ability to form angiotensin I from the synthetic tetradecapeptide renin substrate and from purified hog renin substrate A. Its maximal activity occurs at a much lower pH value than does that of renin. The two enzymes may be easily separated by DEAE-cellulose chromatography. Unlike renin, pseudorenin does not attack substrate A in the presence of serum, nor does it produce angiotensin I from renin substrate as it exists in serum. In contrast to renin, which occurs primarily in the kidney, pseudorenin has been found in every one of the 13 different tissues which have been tested, and also in the plasma. The natural substrate for the new enzyme as well as its physiological function are not known.
Positive Inotropic Effects of Dibutyryl Cyclic Adenosine 3',5'-Monophosphate
Authors: SKELTON C. LYNN , LEVEY GERALD S. , EPSTEIN STEPHEN E.
Published: June 2012

The positive inotropic effects of catecholamines have been postulated to result from an increase in the intracellular level of cyclic AMP (adenosine 3',5'-monophosphate) produced by activation of adenyl cyclase. Although lack of an inotropic effect by exogenously administered cyclic AMP has cast doubt on this hypothesis, cardiac cells are not readily permeable to cyclic AMP. The N
6
-2'-O-dibutyryl derivative of cyclic AMP is thought to enter cells more readily and is resistant to enzymatic degradation by phosphodiesterase. We examined the effects of cyclic AMP and its dibutyryl derivative on the contractile performance of isolated cat right ventricular papillary muscles. Cyclic AMP (1 x 10
-4
to 5 x 10
-3
M) had no effect on papillary muscle function. However, dibutyryl cyclic AMP caused a concentration-dependent increase in isometric tension and rate of tension development, the threshold concentration being 5 x 10
-4
M. The increments in tension (4.5 ± 0.4 g/mm
2
) and rate of tension development (58.4 ± 5.4 g/mm
2
/sec) at peak concentration (3 x 10
-3
M) were similar to those found at peak norepinephrine concentration (10
-5
M). Dibutyryl cyclic AMP (10
-3
M) also caused a marked shift of the force-velocity curve upward and to the right. Although 10
-6
M propranolol depressed the inotropic effects of norepinephrine, it did not alter the contractile response to dibutyryl cyclic AMP. These findings are consistent with the hypothesis that the positive inotropic effects of catecholamines are mediated by cyclic AMP.
Propagation of Impulses across the Purkinje Fiber-Muscle Junctions in the Dog Heart
Authors: MENDEZ CARLOS , MUELLER WILLIAM J. , URGUIAGA XAVIER
Published: June 2012

In canine Purkinje fiber-papillary muscle preparations it was shown directly that electrotonic spread can take place across the junctions between Purkinje fibers and ordinary muscle fibers (P-M junctions). The P-M delay recorded during orthodromic propagation varied considerably within any given preparation. Moderate increases in the external concentration of K
+
(up to 6 m
M
) consistently decreased the P-M delay; when the concentration of external K
+
was increased to 8 m
M
the P-M delay increased. With larger concentrations of K
+
(10 to 11 m
M
), total conduction block from the terminal Purkinje fibers to the muscle occurred; under the same conditions antidromic propagation from muscle to Purkinje fiber was still possible. The results can be explained satisfactorily by assuming that propagation across the P-M junction is electrical and that the geometry of the functional syncytium changes progressively from a cable-like system at the level of the terminal Purkinje fibers to a two- or three-dimensional irregular syncytium at the bulk of the myocardial mass.
Similarity of Blood Flow in the Normal and the Sympathectomized Dog Hind Limb during Graded Exercise
Authors: DONALD DAVID E. , ROWLANDS DEREK J. , FERGUSON DAVID A.
Published: June 2012

The possibility of sympathetic vasoconstrictor control of blood flow to active muscles was studied in dogs during graded exercise by comparing the blood flow in the normal with that in the Sympathectomized hind limb. Blood flow was measured by electromagnetic flow transducers around each external iliac artery, or inferred from the oxygen saturation of blood samples from the common iliac veins. The dogs either ran for successive periods of 3 minutes at 5.5 km/hr and grades of 0, 7, 14, 21, and 28% or ran each level of exercise separately. Unilateral lumbar sympathectomy (L-2 through L-7) was performed when the flow transducers were implanted or later by a snare technique. The latter allowed observations during exercise as early as 4 hours after sympathectomy. The magnitude of limb blood flow during exercise and the decline of exercise hyperemia were similar in the normal and the sympathectomized limb, as were the changes in the oxygen saturation of limb venous blood. However, electric stimulation of the lumbar sympathetic chain at the L-5 level in the conscious dog by a chronically implanted electrode reduced limb blood flow at all levels of exercise, the maximal flow of 1,000 ml/min was almost halved.
Effect of Glucagon on Cyclic 3',5'-AMP, Phosphorylase Activity and Contractility of Heart Muscle of the Rat
Authors: MAYER STEVEN E. , NAMM DONALD H. , RICE LUCIAN
Published: June 2012

The purpose of this investigation was to contrast the effect of glucagon and that of epinephrine on the concentration of cyclic adenosine 3',5'-monophosphate (cyclic AMP), the activity of phosphorylase
a
and the contractile amplitude of isolated perfused rat hearts. The two drugs were about equally effective except that the maximal augmentation of contractility by epinephrine (5 x 10
-9
moles) was twice that produced by an equivalent dose of glucagon with a fourfold greater increase in cyclic AMP concentration. Combination of large doses of the two drugs caused increases in the cyclic nucleotide considerably greater than those required for maximal phosphorylase activation or associated with a maximal inotropic response. The effects of glucagon also developed more slowly than those of epinephrine. An increase in cyclic AMP was not detectable until after phosphorylase
a
and contractile amplitude had increased.

The beta-receptor-blocking agents dichloroisoproterenol and pronethalol did not block the biochemical responses to glucagon in doses which abolished the epinephrine-induced increases in cyclic AMP and phosphorylase
a
. These results, along with those obtained by other investigators, indicate that glucagon can elicit the same biochemical responses in intact heart as have been obtained with epinephrine, but by action at a different receptor site.
Circulatory Changes during Growth in the Fetal Lamb
Authors: RUDOLPH ABRAHAM M. , HEYMANN MICHAEL A.
Published: June 2012

The changes in circulation with advancing gestation were investigated in 44 fetal lambs in utero; gestational ages ranged from about 60 days to 150 days. Spinal analgesia was administered to the ewe, polyvinyl catheters were inserted into fetal vessels, and umbilical blood flow was measured by the steady-state diffusion Fick method during antipyrine infusion. Cardiac output, distribution of cardiac output, and actual organ blood flows were calculated from injections of nuclide-labeled microspheres (50µ diam) into a forelimb and into an umbilical or hindlimb vein.

Umbilical Po
2
, Pco
2
and pH did not change significantly during gestation. Umbilical blood flow and total cardiac output increased in proportion to fetal weight. The proportion of the combined ventricular output distributed to the placenta decreased from about 50% in the youngest fetuses to about 40% just before term. The proportion of the cardiac output distributed to the lungs, as well as the actual flow in relation to lung weight, increased throughout gestation, with a more rapid rise after about 120 days. There was also a late increase in intestinal flow. Cerebral blood flow increased gradually throughout gestation, both as a proportion of cardiac output and in relation to brain weight. There were no significant changes in percent of cardiac output, or flow related to weight in the kidney, heart, or skin and muscular tissues. The studies suggest that, since lung blood flow is a relatively small proportion of total cardiac output, it is not important in regulating distribution of blood flow, but that the peripheral circulation in skin and muscle, which receives a large percent of fetal cardiac output, is the site where vasomotor responses may effect major redistribution of the fetal circulation.
Shifts in Pacemaker Dominance within the Sinoatrial Region of Cat and Rabbit Hearts Resulting from Increase of Extracellular Potassium
Authors: LU HSIN HSIANG
Published: June 2012

Simultaneous recording of action potentials from cells in different parts of sinoatrial preparations from cat and rabbit hearts confirms the suggestion by Meek and Eyster that the dominant pacemaker site shifts during treatment with high [K
+
]. The direction of the shift can be either upward or downward depending upon the location of the original dominant pacemaker site. In the majority of cases, the original dominant site is located in the upper part of the preparation, consequently the shift is from above downward. In environments with high [K
+
], both true and latent pacemaker cell action potentials show a decrease in both maximal diastolic potential and the slope of the prepotential but these changes seem to be more marked in the true pacemaker cell. It is suggested that the shift of dominant pacemaker site in response to high [K
+
] is due to the difference in sensitivity to K
+
between these two types of pacemaker cells.
Cardiac Impairment in Adrenal Insufficiency in the Cat
Authors: ROVETTO MICHAEL J. , MURPHY RICHARD A. , LEFER ALLAN M.
Published: June 2012

Cardiac contractile protein ATPase activity was studied in cats 10 days after adrenalectomy at a time when the mean arterial blood pressure was 27% lower than that of control cats. The Ca
2+
-dependent, azide-insensitive ATPase activity of myofibrils isolated from the ventricles of adrenalectomized cats was 63% of the activity of control preparations (
P
<0.025). Similarly, the specific activities of cardiac actomyosin (myosin B) and myosin from adrenalectomized cats had decreased to 54 and 75% of control values, respectively (
P
<0.005). The percent reductions in ATPase activities in the three protein preparations from adrenalectomized animals were not significantly different, suggesting that the depression was associated with myosin per se. The reduction in the myosin ATPase activity in adrenal insufficiency was prevented by dexamethasone treatment adequate to prevent the decline in mean arterial blood pressure of the adrenalectomized cats. The reduction in cardiac performance in frank adrenal insufficiency may reflect a decrease in the rate of conversion of chemical to mechanical energy by the myocardial contractile proteins.
Measurement of Arterial Geometry and Wall Composition in the Carotid Sinus Baroreceptor Area
Authors: REES PETER M. , JEPSON PETER
Published: June 2012

The overall dimensions of the carotid sinus, the thicknesses of the individual layers within its wall, and the tissue composition of the tunica media were measured on histological sections of the carotid bifurcation fixed in vivo in anesthetized dogs, cats, and rabbits. The outstanding dimensional features of the carotid sinus as compared to the adjoining carotid segments are its thinned media-intima layer and increased ratio of internal radius to media-intima thickness. These differences carry a high level of significance statistically. There appears to be no marked increase in the ratio of radius to whole-wall thickness in the sinus portion of the carotid tree. The tunica media in the carotid sinus wall contains more than twice as much elastic tissue per unit volume (mean value 62.3% elastin) as the media in the carotid vessels adjoining the sinus; reciprocally, smooth muscle constitutes 16.4% of the tunica media in the sinus wall but approximately 50% or more of the media in the common, internal, and external carotid arteries caudal and cranial to the sinus (mean values in percent of total volume). Results are discussed in relation to the position of the baroreceptors within the sinus wall and mechanisms of stimulating them.
Mechanism of Function of the Mitral Valve Leaflets, Chordae Tendineae and Left Ventricular Papillary Muscles in Dogs
Authors: KARAS STEPHEN , ELKINS RONALD C.
Published: June 2012

In five dogs (18 to 28 kg) under pentobarbital anesthesia metal clips were placed on the free margin of the anterior and posterior mitral valve leaflets, and on the epicardial surface of the left ventricle at the apex and at the base. After full recovery cineangiograms were taken in the right anterior oblique and right lateral position and the length from the apex of the left ventricle to the free margins of the mitral valve leaflet was measured. The average distance between the apex and the free margin of the anterior leaflet in two dogs and on a clip placed on the chordae tendineae above the anterior leaflet in two dogs was the same during slow ventricular filling, atrial systole, and during ventricular ejection. The average distance between the apex and the free margin of the posterior leaflet in three dogs was also the same during the same time periods in the cardiac cycle. The maintenance of the same distance between the free margin of the mitral valve leaflet and the apex during diastole when the papillary muscle is relaxed and during systole when it is contracted suggests that the papillary muscle contracts isometrically.
Effects of Hepatic Venous Pressure on Transsinusoidal Fluid Transfer in the Liver of the Anesthetized Cat
Authors: GREENWAY CLIVE V. , LAUTT W. WAYNE
Published: June 2012

Arterial pressure, portal pressure, hepatic venous pressure, and hepatic volume were measured simultaneously in anesthetized cats. When hepatic venous pressure was raised, hepatic volume increased at first rapidly then slowly. After 20 minutes, the volume increased at a steady rate which continued for at least 4 hours. During this period, the hepatic blood volume (
51
Cr-tagged red blood cells) was constant, and fluid with a high protein content accumulated in the plethysmograph. When the hepatic lymphatics were tied, the rate of filtration (0.060 ± 0.003 ml · min
-1
· mm Hg
-1
· 100 g
-1
) was directly proportional to the hepatic venous pressure. When hepatic venous pressure was restored to zero, the filtered fluid was not reabsorbed by the liver. The data are discussed in relation to Starling's hypothesis and the formation of ascites. It is concluded that transsinusoidal fluid filtration in the liver is dependent on the sinusoidal hydrostatic pressure and that no protective mechanisms are available to prevent filtration when hepatic venous pressure is raised for long periods.
Inhibition of Coronary Vasodilating Action of Dipyridamole and Adenosine by Aminophylline in the Dog
Authors: AFONSO SKODA
Published: June 2012

Experiments were performed to determine (1) whether intravenously administered aminophylline inhibits the coronary vasodilating effects of intravenous or intracoronary administration of dipyridamole or adenosine and (2) whether aminophylline locally administered in the coronary artery inhibits the vasodilating action of adenosine given intravenously or injected into the coronary artery. Coronary vasodilator responses to dipyridamole or adenosine were determined before and after administration of aminophylline. Intravenous aminophylline was found to inhibit coronary vasodilatation induced by intravenous or intracoronary dipyridamole or adenosine. After intravenous aminophylline, adenosine administered intravenously or into the coronary artery was 2.5 to 4 times less effective in inducing coronary vasodilatation. Aminophylline injected locally into the coronary artery was also effective in inhibiting coronary vasodilatation induced by intravenous and intracoronary adenosine. The mechanism of this inhibitory phenomenon has not been elucidated.
Effects of Carotid Sinus Nerve Stimulation on the Coronary Circulation of the Conscious Dog
Authors: VATNER STEPHEN F. , FRANKLIN DEAN , VAN CITTERS ROBERT L. , BRAUNWALD EUGENE
Published: June 2012

Control of the coronary circulation by the carotid sinus was studied in intact, unanesthetized dogs instrumented with Doppler ultrasonic flow probes on the left circumflex coronary artery, miniature pressure gauges in the aorta, and stimulating electrodes on the carotid sinus nerves. A radiofrequency pacemaker was used to stimulate the nerves in dogs at rest, during sleep, exercise, and after autonomic blockade. Thirty-second periods of stimulation in the resting conscious dog resulted in an average decrease in aortic pressure of 28%, an average decrease in mean coronary flow of 7%, while heart rate decreased by 13% at the beginning of stimulation and then returned to control levels. Mean and late diastolic coronary resistances decreased by an average of 22% from control. Similar results occurred with carotid sinus nerve stimulation during sleep and during treadmill exercise. Combined beta-receptor blockade with propranolol and atropine prevented the changes in heart rate with carotid sinus nerve stimulation but not the decrease in arterial pressure or the coronary dilatation. After alpha-receptor blockade with phenoxybenzamine or sympathetic blockade with guanethidine, coronary dilatation was not observed with carotid sinus nerve stimulation. Thus sympathetic constrictor tone is present in the resting conscious dog and the coronary dilatation observed with electrical stimulation of the carotid sinus nerves is due to a reduction in resting sympathetic constrictor tone.
Renal-Clip Hypertension in Rabbits Immunized Against Angiotensin II
Authors: MACDONALD GRAHAM J. , LOUIS WILLIAM J. , RENZINI VINCENZO , BOYD GRAHAM W. , PEART W. STANLEY
Published: June 2012

The rabbit immunized against angiotensin II was shown to be a valid model for the study of renal-clip hypertension. In particular, there was a specific and complete blockade of the pressor effect of high doses of intravenous renin and angiotensin in vivo, even at angiotensin II production rates which far exceeded those associated with renal-clip hypertension. Despite this, four immunized rabbits developed hypertension after renal-artery clipping with contralateral nephrectomy, and in three of these the hypertension was severe. In four other rabbits, there was no evidence of modification of an established hypertension after immunization against angiotensin II. In both groups, the specific absence of pressor response to high doses of renin and angiotensin II after immunization was confirmed. These studies provide strong evidence that angiotensin is not the sole or even the major factor in either the initiation or maintenance of this form of hypertension.
Myocardial Amino Acid Transport in the Isolated Rabbit Right Ventricular Papillary Muscle
Authors: LESCH MICHAEL , GORLIN RICHARD , SONNENBLICK EDMUND H.
Published: June 2012

The amino acid analog, alpha-aminoisobutyric acid (AIB) has been used to study myocardial amino acid transport in the isolated rabbit right ventricular papillary muscle. Intracellular AIB accumulation is linear for 2 hours and reaches a plateau at 3 hours at an intracellular/extracellular concentration gradient of 3.4. Anoxia does not inhibit this process whereas simultaneous inhibition of aerobic and anaerobic metabolism inhibits AIB accumulation. Intracellular AIB accumulation follows Michealis-Menten kinetics with a Km of 6.8 x 10
-3
M and a V
max
of 6.6 µmoles. ml intracellular fluid
-1
. hour
-1
. Sodium ion is obligatory for the transport process whereas no absolute potassium or calcium requirement exists. Ouabain, 10
-5
M, inhibits AIB uptake. Myograph techniques were utilized to determine the effect on AIB accumulation of subjecting unstimulated papillary muscles to various degrees of passive stretch. Muscles incubated at any tension above zero developed a greater intracellular/extracellular fluid AIB concentration ratio than muscles incubated at zero tension. These data suggest that increased myocardial wall tension may be a mechanical stimulus capable of inducing adaptive changes in myocardial metabolism.
Determination of Fetal, Placental and Neonatal Blood Volumes in the Sheep
Authors: Creasy Robert K. , Drost Maarten , Green Michael V. , Morris John A.
Published: June 2012

A sheep preparation was developed for studying fetoplacental and neonatal blood volumes using isotope dilution techniques. Fetoplacental blood volume was measured in 46 fetal lambs (gestational age 112 to 146 days) using radioactive iodinated human serum albumin (
125
I-RISA). In 28 of the 46 animals, blood volume was also computed using
125
I-RISA and maternal red cells labeled with radiochromium (
51
Cr). Blood volume averaged 156.1 ml/kg of fetal weight with the single-label method and 134.7 ml/kg with the double-label method. Blood volumes measured in 17 neonatal lambs with the single-label technique averaged 110.0 ml/kg, and with the double-label technique in 10 animals averaged 104.0 ml/kg. Placental blood volume, determined by subtracting the neonatal blood volume from the fetoplacental blood volume, although varying from animal to animal, was independent of fetal weight and remained relatively constant during the last fourth of gestation.
Effects of Carotid Sinus Nerve Stimulation on Blood-Flow Distribution in Conscious Dogs at Rest and during Exercise
Authors: Vatner Stephen F. , Franklin Dean , Van Citters Robert L. , Braunwald Eugene
Published: June 2012

The effects of stimulating the carotid sinus nerves on the distribution of cardiac output and peripheral vasoactivity was studied in intact, unanesthetized dogs instrumented with ultrasonic or electromagnetic flow probes on the ascending aorta, mesenteric, renal, and iliac arteries, and miniature pressure gauges in the aorta. A radiofrequency pacemaker was used to stimulate the nerves in dogs at rest, during treadmill exercise, and after autonomic blockade. Thirty-second periods of stimulation in the resting dog resulted in an average decrease in aortic pressure of 28%, cardiac output remained unchanged, total peripheral resistance fell 29%, mesenteric flow 12%, mesenteric vascular resistance 18%, renal flow 8%, and renal vascular resistance 22%. In the iliac bed flow increased by 90% while resistance declined by 62%. Heart rate decreased initially by 13%, and returned to control during stimulation. The bradycardia was determined to be predominantly due to vagal stimulation. During treadmill exercise carotid sinus nerve stimulation resulted in similar decreases in arterial pressure, mesenteric and renal resistance, and a further decrease in iliac resistance from exercise control values. Thus, electrical stimulation of the carotid sinus nerves in the conscious dog produced a differential pattern of peripheral vasodilatation, the most profound dilatation being observed in the hind-limb circulation. This release of sympathetic tone also occurred during stimulation in exercising animals when the muscular bed was already dilated on a metabolic basis.
Phenomenon of the Gap in Atrioventricular Conduction in the Human Heart
Authors: WIT ANDREW L. , DAMATO ANTHONY N. , WEISS MELVIN B. , STEINER CHARLES
Published: June 2012

The phenomenon of the "gap in atrioventricular conduction" was studied in eight human subjects, using a catheter technique for recording electrical activity of the His bundle. Premature atrial stimuli were applied throughout the basic atrial cycle, either during sinus rhythm or atrial pacing. As the coupling interval between the basic (A
1
) and premature (A
2
) atrial depolarizations was decreased, a point was reached where A
2
was no longer conducted to the ventricles. The region of conduction block was localized distal to the His bundle. The interval between basic and premature His bundle depolarizations at which block occurred provided a value for the effective refractory period of the His-Purkinje system. If A
2
was then made to occur earlier in the basic cycle, a point was reached where conduction of the premature response to the ventricles resumed. When this occurred, conduction delay of A
2
in the atrioventricular node had increased sufficiently to allow for recovery of excitability of the His-Purkinje system (the interval between successive His bundle depolarizations was greater than the effective refractory period of the His-Purkinje system). The gap phenomenon could be abolished by decreasing the basic cycle length or by beta-receptor blockade, both of which prevented conduction block of A
2
in the His-Purkinje system.
Mechanism of Antihypertensive Action of Prolonged Administration of Hydrochlorothiazide in Rabbit and Dog
Authors: ZSOTÉR Thomas T. , HART FRED , RADDE I. C.
Published: June 2012

The effect of hydrochlorothiazide on vascular reactivity to various drugs was studied in rabbit and dog. In rabbit, dose response in the mesenteric artery and vein was examined in vitro following a treatment with hydrochlorothiazide for 6 to 10 weeks. Norepinephrine produced significantly less contraction in the vein of treated than of control animals (P < 0.005), but the effect of aeetylcholine, barium chloride, angiotensin, papaverine, and adenosine triphosphate (ATP) was not altered. In the hindlimb of dogs treated with hydrochlorothiazide for 6 to 8 weeks, intra-arterial norepinephrine caused substantially less pressure increment in the resistance vessels, perfused at constant flow rate, of treated than of control animals. Stimulation of lumbar sympathetic nerves also augmented pressure in the femoral artery less in treated than in control dogs. No such difference in the effect of intra-arterial ATP or angiotensin was observed between the two groups of animals. Preliminary results both in the rabbit and in the dog failed to demonstrate a significant alteration in water, sodium, potassium, and calcium content of the iliap artery or vein after hydrochlorothiazide treatment. Diminished response to norepinephrine in the vessels after hydrochlorothiazide treatment may be responsible for the antihypertensive effect after the prolonged administration of this drug.
Velocity Profiles in the Main Pulmonary Artery of Dogs and Man, Measured with a Thin-Film Resistance Anemometer
Authors: REUBEN S. R. , SWADLING J. P. , LEE G. DE J.
Published: June 2012

Instantaneous velocity of pulmonary artery blood was measured using a thin-film resistance anemometer mounted on a hypodermic needle. Studies were performed, at thoracotomy, in five dogs and five patients. Instantaneous blood velocity was recorded at several sites across the transverse axis of the main pulmonary artery to determine the shape of the velocity profile.

We found the velocity profile, in both man and dog, to be approximately flat. In dog, the mean velocity, normalized to that at the center line, ranged from 1.18 (SD ± 0.03) to 0.81 (SD ± 0.27). In man, mean velocity of pulmonary artery blood, normalized in a similar fashion, ranged from 1.08 (SD ± 0.03) to 0.84 (SD ±0.07), while the normalized peak systolic velocity ranged from 1.04 (SD ± 0.07) to 0.95 (SD ± 0.16). The results, in dogs, suggest that there is little asymmetry of the velocity profile and therefore these have been taken as evidence that the use of cuff electromagnetic flowmeters on the pulmonary artery of dogs is not subject to significant inaccuracies associated with a nonsymmetrical flow profile. The finding of a relatively flat velocity profile in patients, moreover, will make it easier for catheter-tip flowmeters to measure bulk velocity in the pulmonary artery.
Mechanism of Synchronization in Isorhythmic A-V Dissociation
Authors: LEVY MATTHEW N. , ZIESKE HARRISON
Published: June 2012

An analog computer model has been developed to study the mechanism of the atrioventricular synchronization in one type of isorhythmic A-V dissociation (pattern I). The computer model simulates the following biological feedback control system: (1) the ventricular pacemaker frequency is independent of arterial blood pressure (analogous to artificial ventricular pacing); (2) the frequency of the atrial pacemaker (usually the S-A node) varies inversely as the arterial blood pressure; (3) the phase difference (P-R interval) between these pacemakers is a determinant of the stroke volume; (4) for a given systemic arterial impedance and heart rate, the stroke volume determines the arterial blood pressure; and (5) after a finite delay, the arterial blood pressure exerts an inverse effect on the atrial frequency, to close the loop. Stroke volume increases progressively as the P-R interval increases from 0 to some optimum value. Stable synchronization can exist only when the mean P-R interval falls within this range of values, because only within this range does negative feedback prevail. Over the range of ventricular pacing frequencies within which synchronization can persist, the mean cardiac output and arterial blood pressure will vary inversely as the ventricular pacing frequency. Synchronization will persist only when there is an adequate closed-loop gain (consisting of the change in arterial blood pressure per unit change in P-R interval and change in heart rate per unit change in blood pressure).
Action of Diazoxide on Skeletal Muscle Vascular Resistance
Authors: POWELL WM. JOHN , GREEN RICHARD M. , WHITING RICHARD B. , SANDERS CHARLES A.
Published: June 2012

Controversy exists as to whether arteriolar dilation after diazoxide (DZ) administration is due to a prolonged vascular effect that outlasts the presence of circulating levels of DZ or to equilibrium of arteriolar sites with circulating DZ. To resolve this question, the direct effects of DZ on the vascular resistance (VR) of the isolated blood-perfused (constant-flow) gracilis muscle were evaluated in 44 anesthetized dogs. Intra-arterial infusions of DZ resulted in falls in vascular resistance (-35.9±5.5
SEM
%) which returned to control levels after the infusions, thus indicating that irreversible binding to arterioles or a prolonged arteriolar effect independent of plasma levels of the drug did not obtain. Decreases (- 16% to -35%) in VR could also be achieved by premixing DZ in the blood perfusion reservoir at concentrations between 40 and 100 mg/L (which may be achieved clinically); thus albumin binding does not abolish the activity of DZ. Decreases in VR by DZ were not related to stimulation of beta-adrenergic receptors, alteration in Na
+
or K
+
balance, or changes in venous levels of glucose, lactate, pO
2
, pCO
2
, or pH. When norepinephrine and angiotensin II were infused during diazoxide infusions their vasoconstrictor response was attenuated. Thus DZ has a direct effect in lowering VR which is independent of measurable changes in gracilis muscle metabolism. Moreover, the VR effect of DZ is not dependent on a prolonged arteriolar effect independent of plasma concentrations of the drug.
Distribution Theory of Resistance of Neurogenic Vasoconstriction to Alpha-Receptor Blockade in the Rabbit
Authors: BEVAN JOHN A. , SU CHE
Published: June 2012

The effects of α-receptor-blocking agents on the contractile responses of isolated rabbit arteries to sympathetic nerve stimulation and exogenous
l
-norepinephrine (
l
-NE) were compared. In the pulmonary artery and aorta, yohimbine, phentolamine, and phenoxybenzamine blocked the response to nerve stimulation less than that to an equipotent dose of
l
-NE. This resistance of neurogenic response was independent of the frequency and number of stimuli and persisted after inhibition of the nerve
l
-NE uptake by cocaine. The neurogenically released transmitter
l
-NE probably forms a high concentration near the adventitia-media junction, whereas the exogenous NE is distributed evenly throughout the thickness of media. Thus higher concentrations of α-receptor-blocking agents would be needed to block the effect of neurogenic
l
-NE than to block that of exogenous
l
-NE. This explanation of the resistance was thought to be more appropriate to the large vessels tested than that based on neuroeffector proximity.
Effects of 6-Hydroxydopamine on the Canine Sinus Node
Authors: ELHARRAR VICTOR , DE CHAMPLAIN JACQUES , NADEAU RÉGINALD A.
Published: June 2012

The acute effects of 6-hydroxydopamine (6-OH-DA) injected directly into the sinus node artery were studied in 57 dogs. The positive chronotropic effect of 6-OH-DA was intermediate between that of norepinephrine and that of tyramine, when these substances were compared on the basis of their
ED
50
. The increase in heart rate produced by 6-OH-DA was inhibited by prior intranodal injection of propranolol and desmethylimipramine. At high doses, injection of 6-OH-DA was often associated with arrhythmias such as periodic slowing of the sinus rate, atrial premature beats, atrial fibrillation, and ventricular extrasystoles. In the 72 hours following injection of 1.5 mg 6-OH-DA, the norepinephrine content of the sinus node region decreased progressively. In agreement with the norepinephrine depletion, response to intranodally injected tyramine was significantly diminished. The number of fluorescent adrenergic nerve fibers was also reduced. Impaired norepinephrine uptake and enhanced release were also demonstrated by using tritiated norepinephrine. After 6-OH-DA treatment, response to right stellate stimulation was diminished, and the response to vagal stimulation was not altered. It was concluded that the local perfusion of the sinus node with 6-OH-DA produces a marked norepinephrine depletion of the perfused region compatible with a localized degeneration of the sympathetic nerve terminals.
Converting Enzyme Activity in Human Plasma
Authors: FITZ ANNETTE , BOYD GRAHAM W. , PEART W. STANLEY
Published: June 2012

Human plasma converting enzyme activity was investigated by comparing biological with immunological activity of added or generated angiotensin after plasma incubation. Sodium citrate (2 x 10
-2
M
), 2:2'-dipyridyl (1 x 10
-4
and 1 x 10
-2
M
), chromotropic acid (3 x 10
-2
and 3 x 10
-3
M
) and desferrioxamine (10 and 100 mg/100 ml) did not interfere with converting enzyme. By contrast, EDTA (3 x 10
-3
M
and 3 x 10
-2
M
), EGTA (3 x 10
-2
M
), 8-quinolinol (1 x 10
-2
M
), and oxalic acid (3 x 10
-2
M
) were shown to interfere with plasma converting enzyme activity. The EDTA inhibition of converting enzyme activity could be partially reversed by molar excess amounts of calcium, zinc and cobalt. The ability of these ions to restore converting enzyme activity to the plasma was quantitatively variable. Inhibition of converting enzyme activity by EDTA could not be reversed by the addition of iron, copper or manganese to the samples.
Synergistic Effect of Propranolol and Nicotinic Acid on the Inhibition of Plasma Free Fatty Acid Release in the Dog
Authors: LIPSON MANUEL J. , NAIMI SHAPUR , PROGER SAMUEL
Published: June 2012

Fatty acid mobilization was effected in 24 anesthetized dogs by infusion of norepinephrine over a four-hour period. Infusions of propranolol and nicotinic acid at various doses, individually and in combination, were added and free fatty acid levels were serially determined. Synergistic action of the two agents was apparent in that minimally effective concentrations of the two agents when used in combination suppressed the release of free fatty acids to 29 percent of levels achieved with norepinephrine (1,186 µEq/L). and 70 percent of levels in saline control animals (501 µEq/L). Large individual doses were no more effective than low doses used in combination. The synergistic action of propranolol and nicotinic acid in the suppression of free fatty acid mobilization may be explained by the action of these two agents on the inhibition of the adenyl cyclase system of the adipose tissue cell. This synergistic action in reducing plasma free fatty acids and their effect on lipid synthesis would allow the use of smaller doses that could reduce the risk of side effects.
Autonomic Control of Cardiac C-AMP
Authors: LARAIA PAUL J. , SONNENBLICK EDMUND H.
Published: June 2012

Although catecholamines are known to increase cyclic adenosine 3'5'-monophosphate (C-AMP) in heart muscle, the relations of adrenergic and cholinergic mechanisms to inotropy and myocardial C-AMP levels and adenyl cyclase have not been defined. Accordingly, atrial and ventricular muscle preparations were studied in a myograph with a tension recorder. Adenyl cyclase, phosphodiesterase, and C-AMP were measured by chromatographic and isotopic methods. In atrial preparations, norepinephrine (10
-5
M
) increased tension by 80±10% (mean±
SE
), adenyl cyclase by 40±10% and C-AMP by 75±12%, while carbamylcholine chloride (10
-4
M
) reduced tension by 65±10%, adenyl cyclase by 30±12% and C-AMP by 50±14%. The effects of carbamylcholine chloride on tension, adenyl cyclase, and C-AMP were blocked by atropine 10
-5
M
. In paced ventricular (papillary) muscles, norepinephrine (10
-5
M
) increased tension by 70±10%, adenyl cyclase by 50±11% and CAMP by 90±17%. In contrast, carbamylcholine chloride (10
-5
M
) reduced tension by only 7±5%, adenyl cyclase by 12±8%, and C-AMP by 10±7%. These results demonstrate parallel changes in tension, adenyl cyclase, and C-AMP in atrium and ventricle. The failure of ventricular muscle to respond to carbamylcholine is mirrored by the adenyl cyclase system and C-AMP. Furthermore, the cholinergically mediated tension and adenyl cyclase changes in atria were specifically blocked by atropine. Thus these results relate the different effects of cholinergic agents on atrium and ventricle to adenyl cyclase and C-AMP, and suggest specific receptor localization in these two types of myocardia.
Absence of a Direct Effect of Phosphate or 5'-AMP on the Contractile Proteins of Hog Carotid Arteries
Authors: HERLIHY JEREMIAH T. , MURPHY RICHARD A.
Published: June 2012

Two to 4 m
M
5'-adenosine monophosphate (AMP) caused a 28% inhibition of the ATPase activity of a crude "fibrillar" contractile protein preparation isolated from porcine vascular smooth muscle. This effect was absent in highly purified Ca
2+
-insensitive actomyosin extracted from carotid arteries as well as a Ca
2+
-dependent actomyosin preparation. Inorganic phosphate (P
1
) caused no inhibition of ATPase activity in either actomyosin preparation, but 4 m
M
P
1
produced a slight depression in ATP hydrolysis of the crude fibrillar proteins. Superprecipitation of actomyosin remains unaffected by additions of either 4 m
M
P
1
or 4 m
M
AMP to the purified protein solutions. The effects of P
1
and AMP in combination were additive in the fibrillar system. However, the combination of the two agents had no effect on the ATPase activity of the two actomyosin preparations. These results indicate that concentrations of P
1
and AMP which might be produced under physiological conditions have no direct inhibitory action on the vascular smooth muscle actin-myosin interaction.
Pressor Reflexes Produced by Stimulation of Afferent Fibers in the Cardiac Sympathetic Nerves of the Cat
Authors: PETERSON D. FRED , BROWN ARTHUR M.
Published: June 2012

Afferent fibers in cardiac sympathetic nerves were stimulated electrically in an attempt to evoke circulatory reflexes. A pressor response was always elicited during stimulation of the central end of the cut left inferior cardiac or pericoronary nerve in vagotomized intact-brain or spinal cats. The maximum blood pressure rise was 21.5 mm Hg during inferior cardiac nerve stimulation and 14.1 mm Hg during pericoronary nerve stimulation. Heart rate and respiration were unaffected by stimulation. The alpha-receptor-blocking agent phenoxybenzamine hydrochloride abolished the pressor response. Sequential sectioning of cardiac nerves arising from either the stellate ganglion or the thoracic sympathetic trunk, or of white rami 1 through 4, indicated that each branch carried afferents contributing to the pressor response. Evoked potentials revealed that excitation of Aδ fibers in the inferior cardiac nerve elicited a weak pressor response, and excitation of C fibers provoked a much stronger response. C fiber continuity between the pericoronary nerve and the inferior cardiac nerve was demonstrated.
Effects of Variations in the Strength of Left Ventricular Contraction on Aortic Valve Closure in the Dog
Authors: VON BERNUTH GÖTZ , TSAKIRIS ANASTASIOS G. , WOOD EARL H.
Published: June 2012

The efficiency of aortic valve closure was studied in five experiments on three normal dogs by simultaneous roentgen videodensitometry, upstream sampling of dye dilution and recording of flow velocity and direction in the ascending aorta using a chronically implanted electromagnetic flowmeter. The aortic valve closed effectively during regular ventricular contractions. However, aortic reflux was observed whenever a weak ventricular contraction produced an opening of the aortic valve that was barely detectable, as evidenced by a minimal aortic pressure pulse and stroke volume. This type of aortic regurgitation was mild and invariably occurred at the end of ventricular ejection, coincident with the aortic incisura. Such regurgitation may be clinically significant in some instances of bigeminal rhythm or rapid atrial fibrillation, and is especially important for the evaluation of aortic angiograms. It further supports the concept that competent aortic valve closure depends on vortex formation in the sinus of Valsalva of sufficient degree to keep the aortic valve leaflets in partial apposition during ejection of blood from the ventricle across the aortic valve.
Studies of the Equivalent Cardiac Generator Behavior of Isolated Turtle Hearts
Authors: Brody Daniel A. , Warr Otis S. , Wennemark James R. , Cox John W. , Keller Francis W. , Terry Fred H.
Published: June 2012

Equivalent cardiac generator components were determined for a series of excised turtle hearts immersed in Ringer's solution. Relatively large preparations were contained within a specially designed spherical chamber, and electric field potentials were derived from 20 evenly spaced electrodes on the chamber wall. A laboratory computer was used to acquire and store the 20 leads of signal data in digitized form in real time. An eccentric dipole was optimally fitted to the surface potentials for each 2 msec sample; the remaining voltages were used to determine a centric multipolar series through octapolar content. In addition to the purely quantitative parameters which were thus determined, sequential mapping of isopotential distribution over the spherical boundary gave valuable qualitative insights into the behavior of the equivalent generator throughout ventricular depolarization. This activity varied in complexity from predominantly dipolar to strongly nondipolar among different preparations. Peak quadripolar activity ranged from a low of 10 to a high of 60%; the corresponding figures for octapole content were 5-61%. The overall technique permits experimental exploration of several theoretical principles which have been advanced since 1954. Pilot studies on rabbit hearts indicate that the method will also be applicable to mammalian hearts.
Effect of Interaction of the Hypothalamus and the Carotid Sinus Mechanoreceptor System on Renal Hemodynamics in the Anesthetized Dog
Authors: Bagshow Roger J. , lizuko Masahiko , Peterson Lysle H.
Published: June 2012

The purpose of this investigation was to show how the operating characteristics of the reflex having carotid sinus pressure as an input and renal pressure and flow as an output are modified by graded stimulation of the posterior hypothalamus. Consequently, the effects of graded stimulation of the posterior hypothalamus on renal hemodynamics were investigated in the anesthetized dog. The carotid sinuses were isolated and subjected to controlled pulsatile pressures. In general, discrete stimulation of the hypothalamus caused a frequency-dependent increase in renal impedance, and stimulation of the carotid sinus caused a decrease. Concomitant stimulation of the hypothalamus and the carotid sinuses had a significant, nonalgebraic effect on the d-c impedance (renal resistance) but no effect on renal impedance at high frequencies. Hypothalamic stimulation modified the sensitivity of renal resistance to carotid sinus pressure. This reflex sensitivity to hypothalamic stimulation passed through a single maximum. The estimated characteristic renal impedance varied inversely with carotid sinus pressure due to active vasomotor changes in renal vascular mechanical properties, rather than to passive effects of concomitant blood pressure changes.