bluuebunny/crossref_metadata_2025 huggingface dataset:
Dlastolic Pressure-Volume Relationship in the Canine Left Ventricle
Authors: Diamond George , Forrester James S. , Hargis James , Parmley William W. , Danzig Ronald , Swan H. J. C.
Published: June 2012

Analysis of the passive pressure-volume filling curve of the left ventricle demonstrates that heart size and ventricular geometry exert major effects on the pressure-volume curve in the absence of changes in intrinsic muscle stiffness. Because the pressure-volume relationship is curvilinear, both quantitative and qualitative comparison of pressure-volume curves from different hearts is difficult. In the fresh isolated canine left ventricle, the pressure-volume relation was found to be almost perfectly exponential throughout a range of filling pressures from 5 to 30 mm Hg. Therefore, a precise linear and quantitative expression of the pressure-volume relation (dP/dV=aP+b) was developed (r=0.995). The effect of isolated changes in either initial ventricular volume (mean δa=3.1%) or ventricular geometry (mean δa=27.1%) upon the slope, or
a
constant of this function was small in comparison to changes induced by rigor mortis (mean δa =45%). It was concluded that the
a
constant was primarily affected by changes in left ventricular wall stiffness. In this manner, comparison of the pressure-volume relationship from different hearts is possible, and the contribution of changes in wall stiffness may be quantified.
Role of Adenine Nucleotides, Adenosine, and Inorganic Phosphate in the Regulation of Skeletal Muscle Blood Flow
Authors: Dobson James G. , Rubio Rafael , Berne Robert M.
Published: June 2012

Experiments were performed on isolated frog sartorius muscle and in situ dog skeletal muscle to determine whether adenine nucleotides and their degradation products are released during contraction in concentrations capable of producing arteriolar dilation ATP was not detectable (>10
-8
M) in the bathing solution of the resting or contracting frog sartorius muscle. Inorganic phosphate (P
1
) in the muscle bath increased from 9 x 10
-5
M to 28 x 10
-5
M with 30 minutes of contraction (2 Hz) or with rest. With the dog hindlirnb preparation, ATP, ADP, and AMP were not detectable (>5 x 10
⊟8
M in the venous blood collected after 5 minutes of ischemic contraction whereas P
1
was present at a concentration of 3.7 x 10
x8
M. Arterial blood levels required to elicit detectable vasodilation for ATP, ADP, AMP, and P
1
were 28.7 x 10
-8
M, 27.1 x 10
-8
M 31.4 x 10
-8
M and 7.2 ⊠ 10
-4
M respectively. The adenosine concentration in dog muscle increased from 0.7 to 1.5 nmole/g with ischemic contraction, and hypoxanthine and inosine increased from 4.5 to 8.5 nmole/g and 2.0 to 5.5 nmole/g, respectively. The adenosine concentration in venous plasma collected from the hiodlimb immediately after termination of the irchemic contraction period was 2.2 x 10
-7
MM as compared to 0.4 x 10
-7
M in control venous and arterial blood samples. Hypoxanthine and inosine concentrations in venous blood increased 22- and 270-fold, respectively, foflowing ischemic contraction. The calculated interstitial fluid adenosine concentration was twice the arterial concentration of adenosine required to elicit maximal arteriolar dilation. These findings suggest that adenosine may play a role in the metabolic regulation of skeletal muscle blood flow, whereas ATP, ADP, AMP, and P
1
may not.
Ventricular Function
Authors: BERGLUND ERIK , SARNOFF STANLEY J. , ISAACS JAMES P.
Published: June 2012

The influence of the pericardium on cardiovascular phenomena has been examined and evaluated in the light of both ventricular function (modified Starling) curves and pressure-volume relationship of the pericardium. When the left ventricle is stressed, as by an increased aortic resistance, it dilates. The resulting pericardial tension limits right ventricular diastolic expansion and right ventricular work. By this mechanism pulmonary blood volume and pressures are kept at lower levels than would otherwise be present. The pericardium also protects against ventriculo-atrial regurgitation which may account for the observed descending limb of the classically conceived Starling curve.
Effect of Changes in Limb Posture on Peripheral Blood Flow
Authors: BEACONSFIELD PETER , GINSBURG JEAN
Published: June 2012

Venous occlusion plethysmography was used to measure the effect of changes in limb position on the peripheral blood flow. The validity of the method with the limb dependent was investigated, and found to be reliable in the conditions of the experiment. The blood flow in the limb was found to be decreased when it was raised or lowered 45 degrees. At 15 degrees of elevation, the flow was increased. Similar changes were found in recently sympathectomized limbs. The reactions may therefore be regarded as local vascular responses to postural change.
Cardiac Output of Men and Dogs Measured by in vivo Analysis of Iodinated (I
131
) Human Serum Albumin
Authors: HUFF REX L. , FELLER DAVID D. , JUDD OLIVER J. , BOGARDUS GEORGE M.
Published: June 2012

A time-intensity analysis of I
131
was carried out with a highly shielded well-collimated scintillation detector placed over the chest of normal men and women, patients and dogs. I
131
human serum albumin solution was injected intravenously. The curves thus obtained when analyzed for cardiac output gave values not significantly different from simultaneously obtained direct Fick values.
Registration of Left Ventricular Volume Curves in the Dog with the Systemic Circulation Intact
Authors: KATZ ARNOLD M. , KATZ LOUIS N. , WILLIAMS FRANCIS L. , Eugene Boyd
Published: June 2012

A method is described whereby it is possible to obtain volume curves from the
left
ventricle of an open-chested dog with an essentially intact systemic circulation. Several applications of such univentricular records to the study of the heart's performance are suggested and examples of analyses from recorded curves are presented. Changes in the physicochemical properties of the myocardium are seen to accompany alterations in the chemical environment of the heart.
Endothelial Nuclear Patterns in the Canine Arterial Tree with Particular Reference to Hemodynamic Events
Authors: FLAHERTY JOHN T. , PIERCE JOSEPH E. , FERRANS VICTOR J. , PATEL DALI J. , TUCKER W. Kirk , FRY DONALD L.
Published: June 2012

The objective of the study was (1) to measure systematically the orientation, morphology, and population density of endothelial nuclei of the canine thoracic aorta and its major branches and (2) to obtain evidence in a chronic in vivo preparation that altered flow patterns do indeed change patterns of nuclear orientation. For this purpose, a segment of the descending thoracic aorta was removed, opened longitudinally, and reclosed to form a tube with a new longitudinal axis 90° from the original vessel axis. The new segment was then sutured back in place. The animals were killed at suitable postoperative periods. Endothelial nuclear patterns were studied from
en face
photomicrographs of preparations stained with Evans blue dye. Results indicated: (1) In uniform vessel segments, e.g., middle and lower descending thoracic aorta, the nuclei were oriented parallel to the axis of the blood vessel, and the ratio of major to minor axes of the nucleus was large. The flow in these regions is known to be stable. (2) Nonaxial, less-ordered nuclear orientation with smaller ratios of major to minor axes were found in entrance regions of many major arteries and in the ascending aorta. (3) In chronic studies in which the flow pattern was altered, the nuclear pattern realigned in the direction of flow within 10 days after surgery.
Excitation-Contraction Coupling in Rabbit Aorta Studied by the Lanthanum Method for Measuring Cellular Calcium Influx
Authors: VAN Breemen CORNELIS , FARINAS BLANCA R. , GERBA PEGGY , MCNAUGHTON ELIZABETH D.
Published: June 2012

Lanthanum inhibits
45
Ca efflux from internally injected squid axons. Evidence for La
3+
blockade of Ca
2+
fluxes across the cell membrane was also obtained for aortic smooth muscle: 1mM La
3+
completely inhibited contractions which otherwise resulted from adding Ca
2+
to calcium-free depolarizing solutions, and 2 mM La
3+
caused a 50% inhibition of the late
45
Ca efflux. Ca
2+
bound extracellularly could be displaced by La
3+
, and the binding sites preferred La
3+
over Ca
2+
. We could thus use La
3+
to eliminate extracellular bound Ca
2+
from our calcium-influx measurements as follows: after exposure of the aortic strips to experimental solutions labeled with
45
Ca, the extracellular Ca
2+
label was displaced by putting the strips in a calcium-free solution containing 2 mM La
3+
for 60 minutes. The loss of intracellular Ca
2+
was minimized during this hour by the La
3+
blockade of Ca
2+
membrane fluxes. Tissue weight,
45
Ca, and total Ca
2+
were then measured using standard techniques. Studies employing this new method showed that depolarization by high K
+
, Na
+
replacement, and high pH activate smooth muscle contraction by stimulating Ca
2+
influx. Low pH and La
3+
block Ca
2+
influx. Norepinephrine initiates aortic contractions by release of intracellularly sequestered Ca
2+
. Angiotensin and histamine appear to release Ca
2+
from this same fraction.
Renovascular Hypertension in Rats Immunized with Angiotensin II
Authors: EIDE IVAR
Published: June 2012

The experimental design which most closely reproduces clinical renovascular hypertension is constriction of one renal artery, with the other renal artery and kidney left intact. To test the role of renin and angiotensin in the pathogenesis of renovascular hypertension, attempts were made to induce such hypertension in rats previously immunized with angiotensin. In 29 highly immunized and 33 control rats, one renal artery was partially constricted and the other kidney and renal artery left intact. Preoperative blood pressures were equal in all rats (means: immunized, 118 ± SE 0.95; controls, 117 ± 0.70 mm Hg). Both groups developed hypertension during the 13 days following operation (means: immunized, 173 ± 3.42; controls, 169 ± 4.65 mm Hg). The high blood pressures persisted throughout the observation period (56 days). Immune sera completely inactivated large amounts of angiotensin (mean, 1130 ± SD 887 ng/ml antiserum; range 200-4000), and high intravenous doses of renin and angiotensin had no effect on the blood pressure of immunized rats. These data provide strong evidence that the direct pressor effect of circulating angiotensin is not essential for the development of hypertension evoked by constricting one renal artery in the rat.
Effects of Autonomic Blockade on the Baroreflex in Man at Rest and During Exercise
Authors: PICKERING T. G. , GRIBBIN B. , PETERSEN E. Strange , CUNNINGHAM D. J.C. , SLEIGHT P.
Published: June 2012

The reflex bradycardia produced by a transient phenylephrine-induced rise of arterial pressure was investigated in man during rest and supine exercise, before and after autonomic blockade of the heart. Reflex bradycardia diminished proportionally to the tachycardia of exercise. Propranolol slowed the heart at rest and during exercise, but increased the reflex response only at rest, having no effect during exercise. Atropine, or atropine with propranolol, blocked the reflex during rest and exercise. The tachycardia following hypotension induced by amyl nitrite was similarly affected by the two drugs. Tachycardia induced by standing up and by isoprenaline also diminished the reflex bradycardia. It is concluded that reflex heart rate changes following sudden changes of arterial pressure are predominantly parasympathetic, and diminish during exercise in parallel with the decrease of parasympathetic tone. The reflex response is determined partly by the interaction of parasympathetic and sympathetic impulses at the sinoatrial node, shown by the effects of peripheral sympathetic stimulation and blockade at rest. During exercise central depression of the reflex may also occur.
Finite-Element Model for the Mechanical Behavior of the Left Ventricle
Authors: JANZ RONALD F. , GRIMM ARTHUR F.
Published: June 2012

A finite-element model is used to analyze the mechanical behavior of the left ventricle. The ventricle is treated as a heterogeneous, linearly elastic, thickwalled solid of revolution. The inner third of the ventricular wall is assumed to be transversely isotropic with a longitudinal Young's modulus, transverse modulus, and shear modulus of 60 g/cm
2
, 30 g/cm
2
, and 15.5 g/cm
2
, respectively. In the outer two-thirds of the ventricular wall the myocardium is assumed to be isotropic with a Young's modulus of 60 g/cm
2
. Polsson's ratio is assumed to be equal to 0.45 throughout the ventricular wall. The valvular ring at the base of the ventricle is simulated by a homogeneous layer cf collagen. The model appears to predict gross free-wall deformation in the left ventricle of the potassium-arrested rat heart fixed in situ. The presence of a relatively compliant transversely isotropic region near the endocardial surface results in significantly lower axial and circumferential stresses in this region than are present in a homogeneous, isotropic model. The presence of a simulated valvular ring results in a concentration ofrelatively large stresses near the base of the ventricle.
Effects of Estrogen and Progestogen Treatment on the Response of the Aorta of Male Rats to Hypertension: MORPHOLOGICAL AND CHEMICAL STUDIES
Authors: WOLINSKY HARVEY
Published: June 2012

The effects of estrogen and progestogen treatment on the response of the thoracic aortic wall of male rats to hypertension were studied. Hypertension levels induced by clipping the renal artery were similar in untreated (H), estrogen-treated (E), and progestogen-treated (P) hypertensive groups. Hypertension of 8 weeks' duration caused increased wall thickness, increased calculated tangential tension, and increased medial area in groups H and P compared to normotensive controls (C), but wall thickness and medial area in groups E and C were similar despite the striking elevation in calculated tension and wall stress in group E. Chemical studies also showed that the absolute amounts of aortic collagen and elastin in groups H and P were similarly increased over group C values, but absolute amounts of both these fibrous proteins in vessels from group E were no different from those of group C. Noncollagenous alkali-soluble proteins in these vessels were present in absolute and relative amounts corresponding to the following rank: P > H > E > C. Thus, it appears that estrogen-treatment has a distinctly inhibitory effect and progestogen-treatment a slightly stimulatory effect on the aortic wall response to hypertension. Since hypertension-induced morphological and chemical changes have many similarities to features of arteriosclerotic plaque growth, recognition of these differences in hormonal effects on the response of the vessel wall to hypertension may have implications beyond their physiological role as sex hormones.
Nature of Enhanced Performance of the Dilated Left Ventricle in the Dog during Chronic Volume Overloading
Authors: ROSS JOHN , MCCULLAGH WILLIAM H.
Published: June 2012

The size and the performance of the left ventricle were examined in six conscious dogs early (within 1 week) and late (average 7 weeks) after the production of a large infrarenal arteriovenous fistula. Radiopaque beads were implanted near the endocardium of the left ventricle, and in each study the end-diastolic pressure was adjusted to 22 mm Hg by transfusion or bleeding. The shortening of the minor equator of the left ventricle and its mean velocity of shortening were compared in each dog before and after chronic left ventricular dilatation (ventricular end-diastolic volumes of 71 ml early and 101 ml late,
P
< 0.05). In five dogs the stroke volume increased by an average of 42% (
P
< 0.05) between early and late studies, but the percent change in circumference and the mean velocity of shortening remained unchanged (24.2 ± 2% (SE) and 23.6 ± 2%, 1.43 ± 0.12 circumferences/sec and 1.44 ± 0.09 circumferences/sec, respectively) at comparable heart rates. In one animal with congestive heart failure, the percent change in circumference and the mean velocity of shortening fell progressively to 19% and 0.74 circumferences/sec. It is concluded that in the absence of myocardial failure the enhanced performances of the chronically dilated left ventricle is mediated by normal performance of each unit of circumference of the enlarged chamber. The nature of this adaptation supports the application of several measures of contractility used for the assessment of chronic variations of inotropic state. Previously, diastolic sarcomere lengths were shown to be maximal and essentially the same after acute over-transfusion as they were during chronic volume overloading, and the present studies provide physiological support for the view that the chronic adaptation to volume overload need not involve the Frank-Starling mechanism at the sarcomere level. The observed adaptation provides a reserve mechanism, in addition to the usual factors regulating cardiac performance, by which chronic alterations in ventricular geometry allow the delivery of more external work.
Effects of Blood Perfusion on Electrophysiological Properties of Isolated Canine Purkinje Fibers
Authors: ROSEN MICHAEL R. , GELBAND HENRY , HOFFMAN BRIAN F.
Published: June 2012

Microelectrode techniques were used to study isolated canine Purkinje fibers perfused alternately with Tyrode's solution and extracorporeally circulated arterial blood from heparinized donor dogs. Action potential amplitude and resting membrane potential were similar in both perfusates and varied with the potassium concentration of the perfusate. Action potential duration also varied with the potassium concentration of the perfusate, being shorter when potassium concentration was higher. Conduction in free-running Purkinje fibers usually was more rapid in blood than in Tyrode's solution; this difference often was not related to changes in potassium concentration, maximal slope of phase 0, and action potential amplitude. Automaticity was comparable in both perfusates. Because conduction time in isolated tissues differs during perfusion with blood and Tyrode's solution, it would seem that experiments on conduction performed during blood perfusion might reflect in vivo events more closely than results obtained using Tyrode's solution.
Pulmonary Extraction of 5-Hydroxytryptamine and Norepinephrine before and after Cardiopulmonary Bypass in Man
Authors: GILLIS C. N. , GREENE N. M. , CRONAU L. H. , HAMMOND G. L.
Published: June 2012

Pulmonary extraction of
14
C-5-hydroxytryptamine and
3
H-norepinephrine was estimated in patients undergoing aortocoronary saphenous vein grafting. Identical mixtures of both amines were administered intravenously before Cardiopulmonary bypass and again just after bypass. Immediately after each injection, 6 ml of blood was withdrawn into tubing, at a constant rate, simultaneously from both the pulmonary artery and the left atrium. Each set of tubing was then divided into six segments, and the
3
H and
14
C content of each segment was measured. In this manner, total isotope collected and blood isotope concentration as a function of time at the two sampling sites were compared directly. Before bypass in every patient studied, less 5-hydroxytryptamine and norepinephrine were withdrawn on the left than on the right of the lungs, implying pulmonary extraction of both amines. In nine patients, the mean percent extraction was 65 ± 4% for 5-hydroxytryptamine and 23 ± 5% for norepinephrine (
P
< 0.005). After bypass, the percent extraction of both norepinephrine and 5-hydroxytryptamine was increased in all but one patient; values for norepinephrine were increased to a realtively greater extent. These data represent a direct demonstration of 5-hydroxytryptamine and norepinephrine extraction by human lungs and also suggest that total Cardiopulmonary bypass may alter the process.
Lipid Depletion in Atheromatous Coronary Arteries in Rhesus Monkeys after Regression Diets
Authors: ARMSTRONG MARK L. , MEGAN MARJORIE B.
Published: June 2012

Lipids were measured in the coronary arteries of monkeys on an atherogenic diet and in the arteries of matched monkeys on the atherogenic diet followed by regression diets. Cholesterol content was 51 mg/g dry weight in the arteries of monkeys with atheromatosis; after 40 months on the regression diets it was 18 mg/g. Cholesteryl ester was 69% lower and free cholesterol 53% lower after the regression diets. Decreases in triglycerides and phospholipids were not significant. The cholesterol content of the arteries of two monkeys autopsied after 20 months on the regression diets was close to the mean value after 40 months. The data show that cholesterol in both its free form and its ester form is depleted from experimentally induced coronary atheromatosis by dietary regression regimens. The data also suggest that most of the cholesterol depletion occurs during the first half of regression; the susceptibility of the residual excess arterial cholesterol to mobilization from the vessel wall by dietary means is questionable.
Alterations in Preload and Myocardial Mechanics in the Dog and in Man
Authors: Grossman William , Haynes Florence , Paraskos John A. , Saltz Stephen , Dalen James E. , Dexter Lewis
Published: June 2012

Based on a myocardial mechanics approach to the analysis of left ventricular contraction, several indexes have been advanced as specific measures of myocardial contractility. Although two of these indexes, Vmax and [(d
P
/d
t
)/
P
]max, have been shown to be appropriately responsive to interventions known to alter the inotropic state, controversy has arisen as to whether they are unaffected by alterations in preload or initial cardiac muscle fiber length. This study was undertaken to determine which, if any, of the indexes obtained from myocardial mechanics analysis of left ventricular systole is independent of preload in the intact heart. Increases in left ventricular enddiastolic pressure were produced in seven dogs by infusion of dextran or whole blood and in eight patients by sudden elevation of the legs during cardiac catheterization. In dogs, elevation of left ventricular end-diastolic pressure was accompanied by a progressive decline in both Vmax and [(d
P
/d
t
)/
P
]max measured using total pressure (
P
< 0.01). In contrast, Vmax measured using developed pressure was unaffected over a wide range of left ventricular end-diastolic pressures. Similarly, in the eight patients, increases in left ventricular end-diastolic pressure induced by sudden elevation of the legs were consistently associated with reductions in [(d
P
/d
t
)/
P
]max measured using total pressure (
P
< 0.01), but these changes in pressure had no effect on developed pressure Vmax. In the intact heart, measurements of myocardial mechanics using developed pressure appear to be independent of preload, but similar measurements using total pressure are inversely dependent on preload. This finding raises doubt as to the validity of total pressure measurements as indexes of myocardial contractility.
Effect of I-Norepinephrine on the Diameter of Pial Arterioles and Arteries in the Cat
Authors: Wahl M. , Kuschinsky W. , Bosse O. , Olesen J. , Lassen N. A. , Ingvar D. H. , Michaelis J. , Thurau K.
Published: June 2012

The influence of norepinephrine on the diameter of single pial arteries and arterioles was investigated by adding the drug to the perivascular space with micropipettes. The mock spinal fluid solution in which the norepinephrine was dissolved contained 0, 11, or 22 mEq/liter of bicarbonate. These concentrations of bicarbonate were by themselves found to dilate, cause no change, and constrict the pial vessels, respectively. Concentration-response curves with 11 mEq/liter of bicarbonate over the concentration range of 5 x 10
-4
to 5 mmoles/liter of norepinephrine showed significant constriction at 5 x 10
-2
mmoles/liter and maximal constriction (40% of diameter) at 2.5 mmoles/liter. In bicarbonate-free solution, the slope of the concentration-response curves was less, and at 22 mEq/liter of bicarbonate norepinephrine had no effect. The pial arteries seemed to be less sensitive than the mesenteric and the cremasteric arteries to norepinephrine. The present data demonstrate the existence of norepinephrine receptors on the pial arterial smooth muscle cells, which satisfies the major requirement for the possible existence of a sympathetic control of cerebral blood flow.
Sympathetic Control of Cerebral Blood Flow in Dogs
Authors: D'Alecy Louis G. , Feigl Eric O.
Published: June 2012

The effect of sympathetic stimulation on cerebral blood flow was investigated in dogs anesthetized with chloralose. A preparation has been developed for the moment-to-moment measurement of cerebral venous outflow with an electromagnetic flow transducer. The brain's arterial supply was left undisturbed. The sympathetic innervation of the cerebral vessels was stimulated at the stellate ganglion (3-9 v, 3 msec, and 1, 3, 6, 10, and 15 Hz for 60 or 90 seconds). Stimulation at 15 Hz resulted in an average decrease in cerebral blood flow of 79.7%. During stimulation the arterial oxygen tension decreased from 93.2 to 84.9 mm Hg, the arterial carbon dioxide tension increased from 32.9 to 34.6 mm Hg, and arterial pH fell from 7.392 to 7.378. These changes in blood gas variables all opposed the observed vasoconstriction. Interactions between intracranial pressure and sympathetic cerebral vasoconstriction were evaluated by measuring cerebrospinal fluid pressure and cerebral venous outflow pressure. Stimulation of the left sympathetic stellate ganglion produced a 64% decrease in cerebral blood flow and an 8 mm Hg increase in intracranial pressure. Infusion of saline into the cisterna magna, raising intracranial pressure to 47 mm Hg, produced a 3% decrease in cerebral blood flow. Opening the cerebrospinal fluid space and thus fixing intracranial pressure at zero (atmospheric pressure) did not alter the cerebral blood flow response to sympathetic stimulation. It was concluded that stimulation of the sympathetic stellate ganglion resulted in cerebral vasoconstriction which was independent of changes in arterial P
CO
2
, Po
2
, and pH and was also independent of changes in cerebrospinal fluid pressure.
Excitation-Contraction Coupling of Isolated Cardiac Fibers with Disrupted or Closed Sarcolemmas: CALCIUM-DEPENDENT CYCLIC AND TONIC CONTRACTIONS
Authors: Fabiato Alexandre , Fabiato Françoise
Published: June 2012

Single cells of adult rat ventricle were separated with 0.1% trypsin and 0.05-0.1% collagenase. Ten percent of these cells were tubular and striated, contracted spontaneously in the presence of 0.05 mM CaCl
2
or after addition of 0.1-0.5 mM CaCl
2
, and developed contracture in 1 mM CaCl
2
. A resting potential of -30 to -50 mv and an action potential more than 100 msec in duration were recorded in some of the cells. These relatively intact cells were contrasted with myocardial fibers (10-100
µ
) obtained by homogenization. In the presence of 0.025 mM ethyleneglycol bis(β-aminoethylether)-N, N'-tetraacetic acid (EGTA), localized cyclic contractions with intracellular asynchrony were observed under the phase microscope in obviously disrupted areas of these mechanically separated fibers. These contractions were insensitive to the ratio of Na
+
to K
+
, and neither resting potentials nor action potentials were observed. Thus, these disrupted fibers were considered skinned fibers of cardiac muscle; this assumption was further supported by the absence of modification of fiber sensitivity to Ca
2+
by simultaneous skinning with EDTA. Effects of Ca
2+
were studied with control of pCa in the medium by EGTA-Ca buffers, either directly on the homogenate or after depletion of Ca
2+
content of the tissue. At 22°C, pH 7.0, and in the presence of 4 mM MgCl
2
, 5 mM adenosine triphosphate, and 2 mM EGTA, cyclic contractions were inhibited and a tonic contraction was induced at a pCa of 6.25-6.5, which represented the threshold for activation of myofilaments. With the same medium but with low EGTA (less than 0.2 mM), cyclic contractions were obtained if pCa was equal to or lower than 7.4-7.6. Therefore, these contractions corresponded to a cyclic release of Ca
2+
from cellular stores, yielding a transient activation of myofilaments. This large release of Ca
2+
within the fiber was induced by a small addition of Ca
2+
to the medium. It was concluded that a regenerative release of Ca
2+
could be demonstrated in heart muscle under these conditions. Localized cyclic contractions were not observed in disrupted fibers of frog heart, in which spontaneously beating cells could be separated with enzymes.
Radioimmunoassay and Clearance of Circulating Dopamine-β-Hydroxylase
Authors: Rush Robert A. , Geffen Laurence B.
Published: June 2012

Release of the enzyme dopamine-β-hydroxylase (DBH) into the circulation by activity of the sympathetic nervous system was demonstrated by enzymatic assay of serum DBH. The development of a sensitive and specific solid-phase radioimmunoassay suitable for routine assay of serum DBH is described. It is sensitive to 1 ng of purified sheep DBH and is reproducible with a coefficient of variation of 4%. The mean of serum values for five normal sheep was 0.59 ± 0.02 (SE) µg/ml. The assay was sufficiently sensitive to measure DBH in 10 µliters of human serum even though cross-reactivity with antibodies against sheep DBH was incomplete. Clearance of circulating DBH was measured by the decay of radioactivity due to
125
I-DBH after steady state intravenous infusion in lambs. The estimated half-life of circulating DBH after correction for labeled metabolites was approximately 3 hours, and it was cleared from blood at 250 ml/hour. Under resting conditions, the rate of release of DBH into the circulation was about 10 µg DBH/hour kg
-1
body weight. The distribution of radioactivity in various organs 7 to 48 hours after infusion showed that only the kidneys, lungs, and liver were significantly labeled. Since circulating DBH does not appear to be selectively taken up by sympathetic nerves nor rapidly metabolized, radioimmunoassay of serum DBH may be useful in measuring sympathetic activity in a wide range of physiological and disease states.
Development of Baroreflex Activity in Unanesthetized Fetal and Neonatal Lambs
Authors: SHINEBOURNE ELLIOT A. , VAPAAVUORI EERO K. , WILLIAMS ROBERT L. , HEYMANN MICHAEL A. , RUDOLPH ABRAHAM M.
Published: June 2012

Baroreflex activity was assessed in 10 fetal lambs at 85-145 days of gestation. ECG leads sewn to the fetal chest wall, vinyl catheters in brachial artery and femoral vein, and a balloon catheter in the descending aorta were exteriorized through the ewe's flank. After at least 36 hours, the reflex bradycardia, in response to increased blood pressure by balloon inflation, was measured. Baroreflex sensitivity was expressed as the slope of the beat-to-beat relationship between systolic (S.P.) or pulse (P.P.) pressure and the subsequent R-R interval or instantaneous heart rate (H.R.). Baroreflex activity was considered absent if the slope did not differ significantly from zero or if the correlation coefficient was less than 0.7. Throughout gestation baroreceptors could respond to pressure elevation, but the proportion of positive responses increased with age. Baroreflex sensitivity increased up to term when either S.P. or P.P. were plotted against the next R-R interval. Regression analysis of S.P. or P.P. vs. R-R interval, or of P.P. vs. H.R showed increasing baroreflex sensitivity with maturation Analysis of S.P. vs. H.R. showed no significant increase in response with advancing gestation; however, this type of analysis does not take into account the slower resting heart rates of older animals.
Effects of Angiotensin II and Some Analogues on Vascular Permeability in the Rabbit
Authors: ROBERTSON ABEL Lazzarini , KHAIRALLAH PHILIP A.
Published: June 2012

Recent investigations in the rat have shown that endothelial cell contraction should be included among the multiple actions of angiotensin II (AII) in large arteries. In the current study, after intravenous injections (60 mg/kg) of the azo dye Evans blue, a segment of the rabbit abdominal aorta was isolated between temporary ligatures and injected with 1 x 10
-10
g of AII diluted in Ringer's solution. Diffuse increased permeability of the aortic endothelium occurred within 60 seconds only in areas exposed to AII. Although injections of Ringer's solution alone produced no blueing, surface staining and scanning electron microscopy of the aortic endothelium after AII administration showed endothelial cell contraction, widening of the interendothelial junctions, and surface sudanophilia. Similar studies were carried out to determine changes in dermal vascular permeability. Of all the substances tested, AII, prostaglandin E
1
(1 x 10
-10
-1 x 10
-8
g), and serum triglycerides (1 x 10
-6
g) produced the most marked vascular response characterized by the appearance, within 15 minutes, of a bluish wheal or papule. Injections of angiotensin I or norepinephrine at concentrations of 10-100 x 10
-9
g or of Ringer's solution alone did not induce skin changes. Synthetic peptides, competitive antagonists to the myotropic and vasopressor activities of AII, blocked extravasation of Evans blue dye injected simultaneously with the octapeptide, but antihistaminics did not inhibit its effects. We concluded that the multiple actions of AII in blood vessels are related not only to the control of blood pressure but also to the regulation of the permeability and the function of the vascular wall as a whole.
A Weighted Least-Squares Technique for the Analysis of Kinetic Data and Its Application to the Study of Renal
133
Xenon Washout in Dogs and Man
Authors: DELL RALPH B. , SCIACCA ROBERT , LIEBERMAN KENNETH , CASE DAVID B. , CANNON PAUL J.
Published: June 2012

A computer program was written in PL/1 to successively fit the sum of two, three, and four exponential terms to data by an iterative least-squares technique, using a combination of the steepest-descent and the Newton-Raphson methods for convergence. Each data point was weighted by the reciprocal of its variance, assuming that the errors followed a Poisson distribution. A compartment, i.e., an exponential term, was declared nonsignificant if it did not significantly reduce the least-squares error about the fitted line as judged by an
F
test. Validity of the data was assessed by a "runs" test and by the frequency with which data points fell outside the 95% confidence range. Results of the analysis showed that (1) 9 of 12 normal human kidney
133
Xe washout curves were best described by a four-compartment model, (2) 18 of 38 studies in patients with essential hypertension yielded a four-compartment curve with significant reduction in compartment-1 flow, (3) nine patients with congestive heart failure all had three-compartment washout curves, (4) two patients with oliguric renal failure had washout curves described best by a two-exponential equation (one of these patients responded to an injection of furosemide with the appearance of a third, more rapid compartment). Obviously, this form of analysis can be easily applied to other sets of data which are described by nonlinear equations.
A Cardiocardiac Sympathovagal Reflex in the Cat
Authors: SCHWARTZ PETER J. , PAGANI MASSIMO , LOMBARDI FEDERICO , MALLIANI ALBERTO , BROWN ARTHUR M.
Published: June 2012

The reflex changes in single cardiac vagal efferent fibers elicited by excitation of afferent cardiac sympathetic fibers were studied in cats anesthetized with chloralose and urethane. Efferent vagal and sympathetic units were dissected from the end of a cardiac nerve cut at its junction with the right atrium. In some cases, efferent vagal units were dissected from the cervical vagus. Excitation always evoked a clear reduction in the discharge of cardiac vagal units and a clear increase in the discharge of cardiac sympathetic fibers. The effects on cervical vagal efferents were variable. Hence, excitation of afferent cardiac sympathetic fibers could simultaneously elicit inhibition of the vagal outflow to the heart and excitation of the sympathetic outflow. By contrast, stimulation of the cut central end of the contralateral vagus produced the opposite effects. Convergence of afferent fibers in the vagi and the cardiac sympathetic nerves on the same cardiac vagal and cardiac sympathetic postganglionic neurons was demonstrated. Convergence from carotid sinus baroreceptors was also observed.
Active State in the Smooth Muscle of the Rat Portal Vein in Relation to Electrical Activity and Isometric Force
Authors: JOHANSSON BÖRJE
Published: June 2012

Contractile activity in smooth muscle is usually too variable to permit a meaningful analysis of the time course of the active state. A regular activity of uniform contractions was obtained in the present experiments on isolated rat portal veins by simultaneous increases in the external potassium and calcium concentrations. The contractions were associated with electrical discharges which lasted between 0.8 and 1.5 seconds. The active state during these uniform contractions was determined from the shortening velocities after isotonic releases and from the redevelopment of tension after controlled releases. Results obtained with the two methods agreed satisfactorily. The active state increased over the first 0.4-0.6 seconds. Suggestive evidence of a plateau phase was found in some experiments. The active state clearly began to fall about 1 second after the start of the contraction, and this fall coincided with the fall in the first time derivative of isometric force (dP/dt). The maximal intensity of the active state was, on the average, 173% of the maximal isometric force. During isometric contractions, the series elastic element was stretched by as much as 15% of the total muscle length. Active-state values were therefore corrected for changes in contractile element length. The curve then obtained might represent the time course of the level of activation, reflect variations in internal calcium concentration, and relate to the electrical response. Concepts developed for the mechanics of striated muscle can apparently be applied to propagating vascular smooth muscle, and this applicability might help to clarify electromechanical relations and the actions of vasoactive substances in blood vessels.
Diffusion Bypass of Xenon in Brain Circulation
Authors: BRODERSEN POUL , SEJRSEN PER , LASSEN NIELS A.
Published: June 2012

The diffusion bypass of
133
Xe between arteries and veins was studied in the brains of anesthetized dogs. A mixture of
51
Cr-labeled red cells and
133
Xe was injected as a bolus into the internal carotid artery. Gas-tight venous samples were taken every 0.4-0.8 seconds from the superior sagittal sinus. An excess of
133
Xe in the early venous blood samples over that expected from blood-tissue equilibration considerations was demonstrated in all the experiments. The excess was most marked in the first samples, and it was enhanced by lowering cerebral blood flow by decreasing the cerebral perfusion pressure to 20-30 mm Hg. We concluded that diffusion bypass of the tissue by
133
Xe is the most likely explanation for these experimental findings. The fraction of the bolus which appeared to bypass the tissue amounted to about 2-3% at the normal perfusion pressure (i.e., normal blood flow) and about 10% at a reduced cerebral perfusion pressure of 20-30 mm Hg (i.e., about half of normal blood flow). We concluded that measurement of cerebral blood flow by a bolus injection of
133
Xe in the internal carotid artery and external detection of the washout is not influenced significantly by the diffusion bypass of
133
Xe in the normal flow range.
Pitfalls in Digital Computation of the Impulse Response of Vascular Beds from Indicator-Dilution Curves
Authors: GAMEL JOHN , ROUSSEAU WILLIAM F. , KATHOLI CHARLES R. , MESEL EMMANUEL
Published: June 2012

Many methods are available for digital computation of the impulse response from indicator-dilution measurements representing input and output signals. In all instances, the only criterion for validity of the computation is comparison of the reconvolution of the computed impulse response and the input with the actual output. In this paper, a model mathematical system was constructed with a known impulse response; noise and time variation could be introduced independently or simultaneously in the input and the output data. Six methods for digital computation of the impulse response were applied to data from this system and to actual dye-dilution data. Precision of reconvolution did not assure that the computed response would resemble the actual response of the system. Some numerical considerations also significantly affected the digital computation of a valid response.
Role of the Baroreceptor Reflex in Daily Control of Arterial Blood Pressure and Other Variables in Dogs
Authors: COWLEY ALLEN W. , LIARD JEAN FRANCOIS , GUYTON ARTHUR C.
Published: June 2012

Normal and sinoaortic baroreceptor-denervated dogs were monitored continuously (24 hours a day) to quantify the role of the baroreceptors in determining the average level and the variability of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance. The frequency of occurrence over 24-hour periods was obtained for each variable using a fiber optic curve-scanning system to read the variables from continuously recorded charts and a digital computer system to plot curves. The results indicate that the degree of hypertension previously reported for this preparation has been highly exaggerated, presumably due to the methods of study. The average 24-hour mean arterial blood pressure was 101.6 mm Hg in normal dogs and only 112.7 mm Hg in baroreceptor-denervated dogs. The normal dogs exhibited narrowly distributed 24-hour frequency distribution curves for blood pressure; in contrast the denervated dogs exhibited curves with twice the 24-hour standard deviation. Similar analysis indicated that the baroreceptors exerted less influence on the daily stabilization of heart rate than they did on arterial blood pressure and that they had very little if any influence on the daily stabilization of cardiac output and total peripheral resistance. Hemodynamic variables during postural changes were studied along with diurnal rhythms. We concluded that the primary function of the baroreceptor reflex is not to set the chronic level of arterial blood pressure but, instead, to minimize variations in systemic arterial blood pressure, whether these variations are caused by postural changes of the animal, excitement, diurnal rhythm, or even spontaneous fluctuations of unknown origin.
A Cellular Mechanism for the Generation of Ventricular Arrhythmias by Acetylstrophanthidin
Authors: FERRIER GREGORY R. , SOUNDERS JAMES H. , MENDEZ CARLOS
Published: June 2012

Transmembrane activity was recorded from canine false tendons bathed with Tyrode's solution at 37°C. Stimulus patterns provided a 3-second pause after every ten beats. Acetylstrophanthidin was infused at concentrations up to 2x10
-7
g/ml. One or two transient depolarizations (TDs) followed the last driven response of each series. The appearance of TDs was associated with depression of normal phase-4 depolarization. The peak of the earliest TD (TD-1) occurred at an interval approximately equal to the basic cycle length. The later TD (TD-2) occurred at about twice the basic cycle length. Coupling intervals were determined primarily by the last cycle length. The amplitude of TD-1 was maximal when the basic cycle length was 600 msec, but TD-2 continued to increase as the basic cycle length diminished further. The amplitude of both TDs increased with the number of beats in the train. Either or both could reach threshold and induce single extrasystoles or trains of extrasystoles. TDs could be induced to reach threshold after each driven response, resulting in sustained bigeminal rhythms with fixed coupling. Possibly TDs provide a mechanism for various clinically observed arrhythmias induced by cardiac glycosides.
Comparison of Sympathetic Nerve Activity in Normotensive and Hypertensive Subjects
Authors: WALLIN B. GUNNAR , DELIUS WOLFRAM , HAGBARTH KARL-ERIK
Published: June 2012

A microneurographic technique was used to record multiunit sympathetic activity in skin and muscle nerves of 24 healthy subjects and 21 hypertensive subjects. In both groups, the sympathetic activity recorded during rest appeared in bursts following one of two highly different temporal patterns--one characteristic for muscle nerves and the other characteristic for skin nerves. Muscle nerve sympathetic activity probably consisting of vasoconstrictor impulses, occurred in bursts that followed the pulse rhythm and waxed and waned in inverse relation to spontaneous blood pressure fluctuations. Transient random elevations of blood pressure above a certain level caused total suppression of the sympathetic bursts. This inhibitory blood pressure level was higher in hypertensive subjects than it was in normotensive subjects, suggesting an elevated baroreflex working range in hypertension. No other important differences in muscle nerve sympathetic activity were noted between the two groups. Skin nerve sympathetic activity, probably consisting of both vasoconstrictor and sudomotor impulses, had a similar temporal pattern in normotensive and hypertensive subjects at rest: bursts of variable duration occurred randomly or were loosely related to the respiratory rhythm. In both groups of subjects, the strength of this activity increased in response to arousal stimuli, mental stress, and body cooling. These findings emphasize the necessity of having highly standardized experimental conditions in future studies aimed at a quantitative comparison of the absolute strength of sympathetic activity in normotensive and hypertensive subjects.
Differential Response of Large and Small Coronary Arteries to Nitroglycerin and Angiotensin
Authors: COHEN MICHAEL V. , KIRK EDWARD S.
Published: June 2012

Large proximal and smaller distal coronary arteries respond differently to pharmacologic agents, but the role of autoregulation is not known. We examined this role in dogs by cannulating the main left coronary artery and a distal left anterior descending artery branch. With coronary flow held constant, the distal coronary artery pressure and the gradient from proximal to distal artery were proportional to the small and the large vessel resistance, respectively. At normal perfusion pressure, nitroglycerin injected directly into the coronary artery caused a transient fall in small vessel resistance and a prolonged decrease in large vessel resistance. During ischemia, when small vessels autoregulated and small vessel resistance was minimal, nitroglycerin lowered only large vessel resistance. Angiotensin injected directly into the coronary artery increased small and large vessel resistance; the slower response of large vessel resistance followed a passive dilation caused by increased perfusion pressure. Continuous infusions of nitroglycerin and angiotensin maintained dilation and constriction of large vessels, respectively, but small vessels demonstrated tachyphylaxis. Only adenosine infusion maintained dilation in both large and small vessels. In response to varying perfusion, small vessels autoregulated and large vessels responded passively to changes in perfusion pressure. We concluded that small coronary arteries respond to cardiac metabolism and demonstrate escape from prolonged dilation and constriction. Conversely, large vessels respond continuously to sustained mechanical and pharmacologic stimuli independently of the nutritional state of the myocardium.