bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential Velocity Development in the Ascending and Descending Aorta of the Dog
Authors: Falsetti Herman L. , Kiser Kenneth M. , Francis Gerald P. , Belmore Edward R.
Published: June 2012

A conical hot-film probe was used to measure instantaneous velocities in the ascending and descending aorta of anesthetized open-chest dogs. From these point measurements, the radial distributions of velocity were obtained over one cardiac cycle. In general, the hot-film measurements confirmed the observation that the velocity profiles tend to be flat with the highest rates of shear confined to the region of the wall. There were, however, significant variations in the detail from one dog to another. These variations in the shape of the profiles probably are a consequence of many geometrical factors, which include valve inlet geometry, configuration and orientation of the valve plane, and aortic curvature and branching in the descending aorta.
Aldosterone Excretion: PHYSIOLOGICAL VARIATIONS IN MAN MEASURED BY RADIOIMMUNOASSAY OR DOUBLE-ISOTOPE DILUTION
Authors: Sealey J. E. , Bühler F. R. , Laragh J. H. , Manning E. L. , Brunner H. R.
Published: June 2012

A reliable, simple radioimmunoassay for measurement of the urinary excretion rate of the acid-labile conjugate of aldosterone is described, in which aldosterone, reconstituted by acid hydrolysis of a urinary metabolite, is quantified. The results were compared with those obtained by double-isotope dilution. Using both methods, aldosterone excretion rates were characterized in normal subjects over a wide range of dietary sodium intakes. Identity of results from the two methods was demonstrated. Aldosterone excretion ranged from 18 to 85 µg/day at sodium excretion rates of less than 25 mEq/day, from 5 to 26 µg/day at sodium excretion rates between 75 and 125 mEq/day, and from 1.5 to 12.5 µg/day at excretion rates above 200 mEq/day. However, a more precise index was derived with limits inscribed by the whole curve used as a nomogram. During sodium depletion of normal subjects, aldosterone excretion reacted slowly and inadequately until a critical level of sodium or volume depletion was reached. During maintained sodium loading for up to 11 days, initial sodium retention was followed by natriuresis and then by slight sodium retention. Mean urinary aldosterone during these three periods was 23.4, 3.6, and 4.5 µg/day, respectively. Urinary sodium excretion exhibited a more consistent relationship to aldosterone activity than did either sodium intake or cumulative sodium balance, even when constant dietary regimens were used. These data suggest a dynamic role for aldosterone in governing renal sodium excretion, even at very high levels of sodium excretion.
Increased Plasma Aldosterone Concentration In Response to Hemodialysis In Nephrectomized Man
Authors: McCaa Robert E. , McCaa Connie S. , Read Dale G. , Bower John D. , Guyton Arthur C.
Published: June 2012

The nephrectomized patient maintained on intermittent hemodialysis while awaiting renal transplantation provides an excellent model for studying the influence of factors other than the renal renin-angiotensin system that play a role in the regulation of plasma aldosterone concentration. Peripheral plasma aldosterone concentrations were determined using a sensitive radioimmunoassay method in nine anephric patients in the recumbent position immediately before and after hemodialysis. Average patient weight fell 1.5 kg following 12 hours of dialysis on the Kiil dialyzer. Plasma sodium concentration decreased from 137 ± 1 (SE) to 132 ± 1 mEq/liter, plasma potassium concentration decreased from 4.8 ± 0.3 to 3.2 ± 0.1 mEq/liter, and the ratio of sodium to potassium increased from 31.3 ± 1.9 to 41.7 ± 0.9. Plasma aldosterone concentration increased from 9.7 ± 1.6 ng/100 ml plasma before dialysis to 17.9 ± 2.1 ng/100 ml plasma after dialysis despite the lack of kidneys to produce renin. Plasma cortisol concentration did not change significantly (17.5 ± 2.0 µg/100 ml plasma to 14.8 ± 1.9 µg/100 ml plasma). These results show that plasma aldosterone concentration increased in anephric patients in response to hemodialysis. This increase occurred without a concomitant increase in plasma cortisol levels, suggesting absence of an adrenocorticotropic hormone response, and was independent of the renal reninangiotensin system.
Restoration of Electrical Activity of Guinea Pig Atria during Hypothermia: EFFECTS OF NOREPINEPHRINE AND ELECTRICAL STIMULATION ON MEMBRANE POTENTIALS
Authors: Carpentier Robert , Vassalle Mario
Published: June 2012

Guinea pig right atria were perfused in vitro at 30°C. When the temperature was lowered to about 20°C, atrial activity ceased and the resting potential of atrial fibers decreased significantly. When activity was restored during hypothermia by electrical stimulation, both the resting and the action potentials were similar to those recorded at 30°C. Blockade of receptors by atropine or propranolol reduced the effects of electrical stimulation on the membrane potentials, and the reduction was greatest when both drugs were present. In particular, propranolol reduced the amplitude of the action potential. Strophanthidin also reduced the increment in resting potential induced by electrical stimulation at low temperature. Norepinephrine restored atrial activity, but the action potential and its rate of rise were small and the resting potential remained low. We concluded that (1) electrical stimulation restored atrial activity by simultaneously depolarizing the membrane to threshold, liberating autonomic mediators, and stimulating the sodium-potassium pump and (2) norepinephrine removed the sinoatrial block induced by low temperature by increasing the slow calcium and sodium currents.
Reexamination of the Applicability of the HIII Model of Muscle to Cat Myocardium
Authors: Noble Mark I. M. , Else Wendy
Published: June 2012

In cat papillary muscles, which were perfused with oxygenated physiologic saline at 26°C and contracting isometrically at 15 beats/min, shortening steps were imposed 330 msec after stimulation-near the peak of isometric twitch force-and 170 msec or 250 msec after stimulation-during force development. The force immediately following the shortening step was measured. From the results at 330 msec, we predicted the results at the earlier times assuming that the sudden drop in force was due to recoil of a series elastic component (SEC) alone; however, the actual results differed from the predicted results. The shortening step required to drop the force to zero at the earlier times was greater than was predicted; in other words, the force immediately following a shortening step predicted to drop the force to zero was finite. The results are not compatible with the hypothesis that the sudden drop in force accompanying the shortening step (the quick-release phenomenon) is due to the sudden recoil of the SEC, which is stretched to different lengths at the two times. They are compatible with the hypotheses that (1) the quick-release phenomenon is a property of the contractile component or (2) the SEC compliance is a function of the degree of activation. Therefore, we concluded that nonseries elasticity contributes to the quick-release phenomenon and should be considered when the Hill model is applied to heart muscle. In particular, isometric contraction cannot be modeled by a contractile component stretching an SEC of constant physical characteristics.
Central Nervous System Control of Baroreceptor Reflexes in the Rabbit
Authors: KORNER P. I. , SHAW J. , WEST M. J. , OLIVER J. R.
Published: June 2012

Aortic and inferior vena caval balloons were used to alter mean arterial blood pressure, pulse pressure (
PP
), and right atrial pressure (
RAP
) in unanesthetized rabbits and to reflexly evoke changes in heart period (pulse interval). Curves relating mean arterial blood pressure to heart period were compared in different groups of rabbits at similar Δ
PP
and Δ
RAP
. Median blood pressure (
BP
50
), average gain (G), and heart period range (maximum to minimum heart period) were calculated from the S-shaped curves. The reflex was evoked from arterial baroreceptors and probably from cardiac and pulmonary baroreceptors. Curves relating mean arterial blood pressure and heart period differed with regard to
BP
50
and G in sham-operated, thalamic, and pontine rabbits, indicating that suprabulbar centers normally play a role in the reflex. Curves from sham-operated and pontine rabbits treated with atropine also differed, suggesting suprabulbar control of sympathetic effectors. In intact rabbits, forebrain and diencephalic centers caused vagal and sympathetic effectors to respond over the same arterial blood pressure range, but, in pontine rabbits, the effectors responded over dissimilar ranges. In intact rabbits, changes in mean arterial blood pressure evoked reciprocal and nearly equal changes in vagal and sympathetic effectors, but, in pontine rabbits, a given pressure change altered heart period predominantly through one effector. In sham-operated rabbits, vagal effects on heart period were lower by a constant amount at every level of mean arterial blood pressure than they were in pontine rabbits, suggesting that suprabulbar centers exerted a tonic inhibitory effect on vagal motoneurons not involved in the reflex.
Simultaneously Measured Isometric Tension and ATP Hydrolysis in Glycerinated Fibers from Normal and Hypertrophied Rabbit Heart
Authors: HENRY PHILIP D. , AHUMADA Gail G. , FRIEDMAN WILLIAM F. , SOBEL BURTON E.
Published: June 2012

Adenosinetriphosphatase (ATPase) activity, isometric tension, and sarcomere length of glycerinated fibers from 14 hypertrophied and 18 normal rabbit hearts were measured simultaneously to characterize the altered performance of hypertrophied myocardium. ATPase activity was assessed radiochromatographically, and contributions from mitochondria, sarcolemma, and sarcoplasmic reticulum were excluded. The active length-tension and the active tension-pCa relationships in fibers from hypertrophied myocardium were normal in sharp contrast to the depressed active length-tension curves in corresponding intact papillary muscles. Total ATPase activity associated with contraction at a given developed tension was decreased significantly in fibers from hypertrophied hearts (
P
<0.001). ATPase activity was diminished in glycerinated myofibrils, actomyosin, and homogenates from hypertrophied hearts as well. On the other hand, the increase in ATPase activity associated with a given increase in developed tension was virtually identical in fibers from hypertrophied and normal hearts. Thus, depressed total ATPase activity in glycerinated fibers from hypertrophied hearts does not appear to impair maintenance of isometric tension.
Pharmacology of Antagonists of Angiotensin I and II
Authors: NEEDLEMAN PHILIP , JOHNSON EUGENE M. , VINE WILLIAM , FLANIGAN EVERETT , MARSHALL GARLAND R.
Published: June 2012

The octapeptide analogues 8-Cys-AII, 8-Ile-AII, 4-Phe-8-Tyr-AII, and
p
-fluoro-4-Phe-AII were potent competitive antagonists of angiotensin I and II (AI and AII) in rat uterus strips, whereas the decapeptide analogues 4-Phe-8-Tyr-AI and 8-Ile-AI were weak antagonists, 8-Cys-AII and 8-Ile-AII were potent antagonists of the rise in blood pressure induced by angiotensin, although 4-Phe-8-Tyr-AII and
p
-fluoro-4-Phe-AII were less potent antagonists. AI was rapidly converted and was equipotent to AII in vivo, but 8-Ile-AI was a hundred times less potent than 8-Ile-AII. However, some conversion of 8-Ile-AI did occur, since SQ 20881 (an inhibitor of angiotensin-converting enzyme) markedly diminished the All antagonistic action of 8-Ile-AI. The decapeptides AI, 8-Ile-AI, and 4-Phe-8-Tyr-AI were potent competitive antagonists of the hydrolysis of hippurylhistidylleucine by converting enzyme in vitro. Infusion of the octapeptide and the decapeptide angiotensin analogues resulted in a significant lowering of the blood pressure in anesthetized rats treated with phenoxybenzamine and propranolol and made acutely hypertensive by unclamping a renal pedicle that had been temporarily occluded. The decapeptide analogues, therefore, can function as inhibitors of angiotensin-converting enzyme and simultaneously generate octapeptide antagonists in vivo.
Multibolus Technique for Measuring the Distribution of Cerebral Blood Flow over Short Intervals in Man
Authors: RISBERG JARL , INGVAR DAVID H.
Published: June 2012

Repeated measurements of cerebral blood flow distribution were made in man at 1-minute intervals: a
133
xenon solution was injected into the internal carotid artery, and gamma radiation was recorded extracranially in multiple hemispheric regions. In each study, a full-length
133
xenon clearance curve was recorded for 15 minutes and a series of about 15 equal isotope injections separated by 1-minute intervals was given. Following each injection in this multibolus series, a sudden increase in activity was recorded from each brain region. The complete series yielded a slowly rising sawtooth curve for each region; the perpendicular heights of these curves are a measure of the amount of isotope arriving at each region of the brain following each injection and this amount of isotope is proportional to the flow in the region, according to the bolus-fractionation principle. The reproducibility of the method during steady-state conditions was tested in four subjects, and the standard error of measurement was found to be 4%. In four other subjects a visual memory test was given during five of the determinations, and it caused transient flow changes in the occipital regions.
Use of Potassium Canrenoate to Suppress Ouabain-Induced Ventricular Arrhythmias in Dogs
Authors: YEH BILLY K. , SUNG PEI-KUN , SAHA ASIS K.
Published: June 2012

Potassium canrenoate, a steroidal compound and a specific antagonist of aldosterone, had (1) a potent protective effect against ouabain-induced ventricular tachycardia in intact closed-chest dogs and (2) a potent antiarrhythmic effect in abolishing ventricular bigeminy and ventricular tachycardia due to ouabain intoxication in dogs. Conversion of ouabain-induced arrhythmias was usually associated with an improvement in atrioventricular conduction, but no significant alterations in blood pressure or myocardial contractility occurred. Equivalent doses of potassium chloride failed to delay the occurrence of or to abolish the ouabain-induced ventricular tachycardia. Therefore, the antiarrhythmic activity of potassium canrenoate does not seem to be related to the potassium ion in the molecule. Since the compound combines both antiarrhythmic and diuretic activity, potassium canrenoate may be a valuable clinical agent for patients on digitalis therapy.
Chronic Partial Occlusion of the Pulmonary Artery in Cats
Authors: BASSETT ARTHUR L. , GELBAND HENRY
Published: June 2012

The relation of single cell electrical activity to generation of force was determined for myocardium during the development of hypertrophy induced by pressure loading. Transmembrane potentials and isometric active force at optimal length (P
o
) were monitored in isolated right ventricular papillary muscles and trabeculae carneae after inducing chronic right ventricular outflow tract obstruction. Cats subjected to partial pulmonary artery occlusion or to sham operation were studied 1, 3, 7, 10, 21, and > 90 days after surgery. Right ventricular muscles were stimulated at 30/min at optimal length in Tyrode's solution (36°C). Muscles from sham-operated and 1 day pressure-loaded hearts had electrical and mechanical properties similar to normal muscles. Right ventricular peak systolic and end-diastolic pressures were increased for 1 and 3 day pressure-loaded hearts; the percent of right ventricular water was increased for 3, 7, and 10 day pressure-loaded hearts. Muscles from 3 day pressure-loaded ventricles had significantly decreased P
o
, maximum rate of force development, time to peak force, and duration of contraction compared with normal muscles, and their action potential plateaus originated at more negative potentials (mean 24.7 mv for 11 muscles). The alteration in action potential configuration was less obvious in muscles studied 7 and 10 days after partial pulmonary artery occlusion and did not occur 21 and > 90 days after pressure loading; however, P
o
and maximum rate of force development remained decreased, although time to peak force and duration of contraction returned to normal for preparations from 7, 10, 21, and > 90 day pressure-loaded ventricles.
Aortic Valve Leaflet Motion during Systole
Authors: SWANSON W. MILTON , CLARK RICHARD E.
Published: June 2012

An approximate numerical-graphical solution was made for the motion of a human aortic valve leaflet in a meridional plane through the center of the sinus of Valsalva. The observed buckling, whipping action of the leaflet was obtained. Of primary significance in the results was the location and the determination of the maximum curvature of the leaflet in this plane, since this point corresponds to the point of maximum fatigue bending stress. The approximate dimensionless curvature was on the order of 3.5 (referred to the aortic diameter) at a dimensionless radial location of 0.55-0.6. The most important feature determining leaflet curvature and motion was the initial contour shape. The initial shape of a normal human leaflet produces smaller curvatures than the curved shapes usually illustrated for aortic valves.
Evidence for Summation and Voltage Dependency in Rabbit Atrioventricular Nodal Fibers
Authors: ZIPES DOUGLAS P. , MENDEZ CARLOS , MOE GORDON K.
Published: June 2012

This study demonstrated summation in the rabbit AV node and suggested that the action potential rise time (dV/dt) of nodal cells was voltage dependent. Summation was produced in two ways. (1) The atrium and the floor of the coronary sinus were divided to establish two noncontiguous, anatomically separate atrial inputs to the AV node. Conduction to the His bundle occurred when both sides of the atrium were stimulated simultaneously at premature cycle lengths which produced local responses in the N region when either side was stimulated individually. (2) With the atrium intact, the atrium and the His bundle were stimulated together at intervals which allowed the simultaneous arrival of the advancing wave fronts at the impaled N cell. This collision resulted in an N action potential which occurred slightly earlier and had an increased dV/dt and amplitude, suggesting that the nodal cells tested, as well as other cardiac cells, were voltage dependent. Further evidence was provided by the influence of the N region on nodal action potential contours according to the direction of propagation. During orthograde conduction, cells close to N in the AN region had a larger dV/dt and cells in the NH region had a smaller dV/dt than these respective cells had during retrograde conduction. Since dV/dt is a major determinant of conduction velocity, during orthograde conduction rapid conduction within the AN region but relatively slow conduction where N cells supply excitatory current to NH cells occurred. In the retrograde direction, conduction from the His bundle to the midnodal region was prompt, but deceleration occurred where the N region feeds the upper nodal cells.
Transport of
14
C-4-Cholesterol between Serum and Wall in the Perfused Dog Common Carotid Artery
Authors: CARO COLIN G. , NEREM ROBERT M.
Published: June 2012

The transport of certain materials between the blood and the wall in arteries appears to be dependent on wall shear rate with shear rate-enhancing flux; however, the mechanism is unclear. If the transport is diffusional, it must involve three steps: diffusion across a boundary layer, uptake at the blood-wall interface, and transport within the wall. If the first step is rate controlling, if wall shear rate is spatially uniform, and if a diffusion boundary layer commences upstream at the junction between the vessel and an impermeable tube, then flux will be proportional to the cube root of wall shear rate divided by distance and will depend on the species diffusion coefficient. A dog's common carotid artery was perfused with serum containing
14
C-4-cholesterol linked with lipoprotein; the fluid mechanics resembled those described above. In 20 experiments, there was no spatial dependence of uptake of the label, flux was lower by a factor of about a hundred than that predicted, and there was a suggestion (statistically nonsignificant) of shear dependence. The first two findings are inconsistent with transport controlled by the diffusion boundary layer. An uptake-controlled transport could be shear dependent.
Substrate Requirements for Angiotensin I Conversion In Vivo and In Vitro
Authors: OPARIL SUZANNE , KOERNER TERRY , TREGEAR GEOFFREY W. , BARNES BENJAMIN A. , HABER EDGAR
Published: June 2012

The substrate requirements for angiotensin I-converting enzyme were studied in vivo in the dog lung and in vitro in plasma, using angiotensin I (AI), 5-
D
-Ile-AI, 7-
D
-Pro-AI, and 8-D-Phe-AI which had been synthesized by the solid-phase technique. All peptides were inactive in the rabbit aortic strip preparation. None of the D-amino acid-substituted peptides gave a pressor response in the anesthetized dog; none showed significant immunologic cross-reactivity with anti-AI serum or antiangiotensin II serum. Each peptide was labeled with
125
I, and the monoiodinated species was isolated. The iodinated peptides were incubated with diluted dog plasma or injected into the right ventricle of intact anesthetized dogs. In vitro,
125
I-AI,
125
I-5-D-IIe-AI, and
125
I-7-D-Pro-AI were converted to angiotensin II (AII). 8-D-Phe-AI was not converted. In vivo, 15 seconds after injecting
125
I-AI,
125
I-5-D-IIe-AI, or
125
I-7-D-Pro-AI into the right ventricle,
125
I-AJI accounted for 70, 60, and 45%, respectively, of the radioactive material in aortic blood. These results and our previous observations on the importance of the C-terminal sequence of AI for conversion indicate that the enzymatic binding sites for AI-converting enzyme in vivo and in vitro extend from position 10 to position 8 but not to position 7. D-amino acid substitution at positions 7 and 5 abolishes biologic and immunologic activity without interfering with conversion.
Arterial Baroreceptor Fibers from the Aortic Region of the Dog in the Cervical Vagus Nerve
Authors: ITO CYRIL S. , SCHER ALLEN M.
Published: June 2012

The neural pathways followed by sensory fibers from arterial baroreceptors in the aortic region of the dog were investigated with neurophysiological recording. Systemic arterial baroreceptor fibers separate from the depressor nerve were found in the left cervical vagus in each of five dogs investigated; at most two fibers were isolated from each dog due to the difficulty of the dissection. These fibers originated from or above the aortic arch region. One baroreceptor fiber had its arterial sensory ending below the fifth rib. In the right cervical vagus in six dogs, visual evidence of fiber activity from systemic arterial baroreceptors could not be produced; only subjective (auditory) evidence for the presence of systemic arterial baroreceptor fibers was obtained. The number of these arterial baroreceptor fibers, which run in the vagus nerve but are not part of the depressor nerve, appeared to be smaller than the number of arterial baroreceptor fibers in the depressor nerve.
Effects of Atrial Premature Systoles on Sinus Rhythm in the Rabbit
Authors: KLEIN HERMAN O. , SINGER DONALD H. , HOFFMAN BRIAN F.
Published: June 2012

Although it is well known that atrial premature depolarizations (APD
s
) frequently lead to lengthening of the next cycle (returning cycle), it is usually not appreciated that shortening of the returning cycle (RC) can also occur. Moreover, the mechanism for these alterations is not clearly understood. APD
s
were therefore electrically induced in rabbit sinoatrial (SA) preparations, and four basic patterns of alteration in the SA nodal rhythm were observed. The type of change depended very much on the timing of the APD in the cycle. The atrial events, more often than not, failed to reflect the underlying SA nodal events. Thus, lengthened atrial RC
s
occurred in spite of shortened SA nodal RC
s
. This and other discrepancies indicate that the extracellular records of atrial activity do not faithfully reflect the events within the SA node and that information gathered from them should be interpreted with caution. Timing of the APD in the cycle, antegrade and retrograde SA conduction time, SA nodal action potential characteristics, and shifts in pacemaker sites are important in the determination of the altered SA nodal and atrial responses to APD
s
.
Acute Fulminating Neurogenic Hypertension Produced by Brainstem Lesions in the Rat
Authors: DOBA NOBUTAKA , REIS DONALD J.
Published: June 2012

Bilateral electrolytic lesions of the nucleus tractus solitarii in the rat at the level of the obex abolished baroreceptor reflexes and resulted in an immediate, marked elevation in systemic blood pressure without a change in heart rate. In unanesthetized rats the hypertension was associated with a marked increase in total peripheral resistance, a reduction in blood flow in the abdominal aorta, and an increase in central venous pressure. The cardiac output was reduced to 62% of control as a consequence of reduced stroke volume, which was reflected, in turn, by increased end-diastolic pressure. The hypertension was abolished and the end-diastolic pressure lowered by blockade of alpha receptors with phentolamine. The hypertension was not due to changes in blood gases or to release of agents from the kidneys or the adrenal glands; it was very sensitive to anesthetics and was abolished or aborted by midcollicular decerebration. Within hours after lesioning, the rats developed progressive congestive heart failure and died in shock, often in association with pulmonary edema. We concluded that the fulminating hypertension evoked by lesions of the nucleus tractus solitarii was due to the increased vasoconstriction caused by the augmented discharge of sympathetic nerves in response to central deafferentation of baroreceptor reflexes; the hypertension was mediated by alpha receptors and depended on the integrity of structures lying above the midbrain.
Human Serum Dopamine-β-Hydroxylase: Relationship to Hypertension and Sympathetic Activity
Authors: HORWITX DAVID , ALEXANDER R. WAYNE , LOVENBERG WALTER , KEISER HARRY R.
Published: June 2012

Serum dopamine-β-hydroxylase activity varied from 3 to 581 units/ml in a group of 168 untreated adults (90 normals, 78 with borderline or overt hypertension). Levels did not correlate with blood pressure or age, but mean values were significantly lower in blacks than they were in whites. Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine. Pronounced blood pressure reduction by antihypertensive drugs did not change serum dopamine-β-hydroxylase activity, and intensive bicycle exercise produced only small and variable increases. Two subjects with severe sympathetic dysfunction, i.e., orthostatic hypotension, showed normal levels of dopamine-β-hydroxylase activity (89-123 units/ml). Serum dopamine-β-hydroxylase activity varied from 450 to 950 units/ml in five subjects with pheochromocytomas and decreased to one-tenth the preoperative level in one subject who underwent curative surgery. Therefore, serum dopamine-β-hydroxylase activity is not a satisfactory index of sympathetic function; moreover, activity levels do not correlate with prevailing blood pressure. Subjects with pheochromocytomas, however, may show increased serum levels of the enzyme, which demonstrates that such tumors can release dopamine-β-hydroxylase.
Intrarenal Role of Angiotensin II
Authors: FREEMAN RONALD H. , DAVIS JAMES O. , VITALE STEPHEN J. , JOHNSON J. Alan
Published: June 2012

The analogue, l-sarcosine-8-alanine-angiotensin II, a specific competitive antagonist of the vascular action of angiotensin II in the rat, blocked the decrease in renal blood flow after a single intrarenal injection of angiotensin II but not after an injection of norepinephrine in normal dogs, in a sodium-depleted dog, and in a dog with thoracic vena caval constriction. Infusion of the analogue at 0.2 µg/kg min
-1
into the renal artery consistently increased renal blood flow and decreased renal resistance in both sodium-depleted dogs and dogs with vena caval constriction but did not alter these functions in normal dogs. In five sodium-depleted dogs, renal blood flow increased from an average control value of 196 ± 5 ml/min to 222 ± 11 and 246 ± 12 ml/min after 20 and 40 minutes of antagonist infusion (P < 0.01 and P < 0.005, respectively); renal resistance fell from 0.71 ± 0.03 mm Hg/ml min
-1
to 0.62 ± 0.06 and 0.54 ± 0.03 mm Hg/ml min
-1
(P < 0.005 for the 40-minute value). In five dogs with vena caval constriction, renal blood flow increased from 143 ± 16 ml/min to 178 ± 23 and 190 ± 19 ml/min after 20 and 40 minutes of analogue infusion (P < 0.02 and P < 0.005, respectively); renal resistance fell from 0.90 ± 0.14 mm Hg/ml min
-1
to 0.73 ± 0.14 and 0.64 ± 0.10 mm Hg/ml min
-1
(P < 0.01 and P > 0.02, respectively). Mean arterial blood pressure was not altered significantly by the analogue when it was infused at 0.2 µg/kg min
-1
. Infusion of the analogue at 2.0µ/kg min
-1
decreased arterial blood pressure and renal resistance and increased renal blood flow in five sodium-depleted dogs and in three dogs with vena caval constriction. These observations suggest an important intrarenal role for angiotensin II in the homeostatic regulation of renal blood flow in sodium-depleted dogs and in dogs with vena caval constriction.
The Radiolabeled Frog Red Blood Cell
Authors: BAEHLER RICHARD W. , CATANZARO ANDREW J. , STEIN JAY H. , HUNTER WILLIAM
Published: June 2012

The red cell of the bullfrog
Bufo vulgaris
was used to measure the intrarenal distribution of blood flow in the kidney of the dog. These cells were fixed in 1% glutaraldehyde and labeled with sodium pertechnetate (
99M
Tc); they were 18 x 10µ in size and had a specific gravity of 1.076--a value close to that of the dog red blood cell. These cells had no discernible effect on systemic or renal hemodynamics after injection, did not agglutinate, were well mixed and evenly distributed throughout different areas of the renal cortex, and were completely extracted in one circulation through the kidney. When the renal cortex was divided into four equal zones, the fractional distribution of the frog red blood cells was 39, 33, 20, and 8% going from the outer to the inner cortex. These values were not significantly different from those obtained in the same dogs with radioactive microspheres--particles much denser than the frog red cells. In two other models involving intrarenal acetylcholine administration and hemorrhagic hypotension, there was no difference between the regional blood flow distribution measured with the frog red cell method and that measured with the microsphere method. However, with both acetylcholine infusion and hemorrhage, there was a redistribution of renal cortical blood flow to the inner cortex compared with the distribution determined by either method during hydropenia. Thus, a similar intrarenal distribution of blood flow was found with two indicators of different size, shape, and density. We suggest that the primary rheologic factor affecting a particle such as a frog red blood cell or a microsphere markedly diluted among circulating red cells is its interaction with these normal cells.
Relationship between Epicardial S-T Segment Changes and Myocardial Metabolism during Acute Coronary Insufficiency
Authors: KARLSSON JAN , TEMPLETON GORDON H. , WILLERSON JAMES T.
Published: June 2012

Canine left ventricular wall metabolites (ATP, creatine phosphate, glycogen, glucose, glucose-6-phosphate, and lactate) were assessed in the ischemic region of the wall after 17 minutes of ligation of the left anterior descending coronary artery at its midlevel. Variations in the degree of lactate accumulation were found between different sites in the same ischemic region and between the outer and the inner left ventricular wall at the same site. High levels of lactate were associated with S-T segment elevation in the epicardial electrocardiogram, but no lactate accumulation or only mild lactate accumulation was found at isoelectric sites. Lactate accumulation at isoelectric sites was higher in the outer wall than it was in the inner wall; the opposite tendency was observed at sites of S-T segment elevation. In addition to high lactate levels, sites of S-T segment elevation demonstrated a more pronounced depletion of ATP and creatine phosphate, indicating not only a marked anaerobic glycolysis but also a more pronounced overall anaerobic stress. No relationship was found, however, between the absolute magnitude of S-T segment elevation and the degree of lactate accumulation or ATP depletion at sites of S-T segment elevation within the ischemic region. The data obtained in this study demonstrate that during myocardial ischemia epicardial sites of S-T segment elevation are sites of pronounced subendocardial and epicardial ischemia and of anaerobic metabolism.
Circus Movement in Rabbit Atrial Muscle as a Mechanism of Tachycardia
Authors: ALLESSIE MAURITS A. , BONKE FELIX I. M. , SCHOPMAN FRANCIEN J. G.
Published: June 2012

The isolated left atrium of the rabbit, which showed no spontaneous activity, was electrically driven for 20 beats with a cycle length of 500 msec. Tachycardia could be repeatedly initiated by the application of a single adequately timed stimulus shortly after the refractory period of the last basic beat. After the termination of the tachycardia, either spontaneously or artificially by a properly timed stimulus, this procedure was repeated. The number of beats of these tachycardias varied from just one (coupled extrasystole) to many hundreds. Surface electrograms were recorded at about 300 different sites. From the moments of activation of these sites, the spread of activation during regular driving and during the premature beat and the subsequent tachycardia could be determined. In contrast to the radial spread of the activation during basic rhythm, the impulse of the premature beat was propagated in a circular pathway. This circus movement was maintained during tachycardia. These results show that even in a small area of atrial muscle containing no anatomical obstacle the impulse can be entrapped in a circus movement. This circus movement was the underlying mechanism of the arrhythmia.
Integrative Reflex Control of Heart Rate in the Rabbit during Hypoxia and Hyperventilation
Authors: KORNER PAUL I. , SHOW JOHN , WEST MALCOLM J. , OLIVER JUDITH R. , HILDER ROLAND G.
Published: June 2012

Baroreceptor mean arterial blood pressure-heart period curves were obtained for unanesthetized sham-operated, thalamic, or pontine rabbits at an arterial Po
2
of 100 or 30 mm Hg. Each curve was S-shaped: it had a lower heart period plateau below threshold pressure, a part where heart period increased monotonically with rising mean arterial blood pressure, and an upper heart period plateau above upper saturation pressure. In spontaneously breathing rabbits, the pressure-dependent parameters of the curves were altered during hypoxia; in addition, there were baroreflex-independent shifts in heart period plateau levels. Suprapontine centers participated in both of these changes. An afferent analysis performed in rabbits treated with atropine and subjected to controlled ventilation showed that the changes in curve parameters were due to afferent interactions in cardiac sympathetic motoneurons between (1) arterial baroreceptor and chemoreceptor inputs which increased threshold, (2) arterial baroreceptor and cardiopulmonary baroreceptor inputs which lowered threshold and increased gain, and (3) cardiopulmonary baroreceptor and chemoreceptor inputs which increased gain and heart period range. Baroreflex-independent shifts in plateau levels were due to increased chemoreceptor and lung inflation receptor activity. The baroreflex-dependent and the baroreflex-independent components of the heart period response were mediated (as in spontaneously breathing rabbits) through both suprapontine centers and pontine centers.
Effects of Norepinephrine and Sympathetic Stimulation on Extraction of Oxygen and
86
Rb in Perfused Canine Small Bowel
Authors: SHEPHERD A. PITT , MAILMAN DAVID , BURKS THOMAS F. , GRANGER HARRIS J.
Published: June 2012

Previous studies have shown that sympathetic stimulation can cause a redistribution of intestinal capillary blood flow. Our computer model of the intestinal circulation predicted that the diffusion parameters (e.g., capillary surface area and mean capillaryto-cell diffusion distance) altered by precapillary sphincter closure would be sufficient to affect intestinal oxygen extraction. To test this prediction in an animal model, we made continuous measurements of arteriovenous oxygen difference (ΔO
2
) and perfusion pressure during constant-flow perfusion of isolated loops of canine small bowel. Intraarterial infusion of norepinephrine or stimulation of sympathetic nerves for 7 minutes produced sustained increases in vascular resistance and sustained reductions in arteriovenous ΔO
2
. Maximal changes in resistance and arteriovenous ΔO
2
occurred by the second minute of norepinephrine or sympathetic nerve stimulation, and subsequently both parameters escaped somewhat. The maximal and steady-state values of these parameters were dose-dependent or frequency-dependent. In other experiments, sympathetic nerve stimulation caused synchronous decreases in arteriovenous ΔO
2
and
86
Rb extraction. These results support the hypothesis that the infusion of norepinephrine and the stimulation of sympathetic nerves cause sustained reductions in the density of the perfused capillary bed which are sufficient to reduce intestinal extraction of Rb and oxygen despite constant-flow perfusion.
Comparative Effects of Castration and Antiandrogen Treatment on the Aortas of Hypertensive and Normotensive Male Rats
Authors: WOLINSKY HARVEY
Published: June 2012

Lowering androgen levels by gonadectomy or inhibiting circulating androgen by administration of the antiandrogen, BOMT, did not affect morphological or compositional changes induced by hypertension in the thoracic aorta of male rats. However, treatment with cyproterone acetate, another antiandrogenic drug, did result in the maintenance of total elastin and collagen at levels the same as those for the normotensive group and significantly lower than those for other treated and untreated hypertensive groups. In rapidly growing normotensive rats, neither castration nor administration of an antiandrogenic drug had any detectable effect on aortic wall morphology or composition regardless of whether the latter was expressed in absolute or relative terms. These findings suggest that growth and hypertension result in the accumulation of connective tissue proteins, elastin, and collagen in the blood vessel wall by different, independent mechanisms.
Mechanism for the Abnormal Energetics of Pressure-Induced Hypertrophy of Cat Myocardium
Authors: COOPER GEORGE , SATAVA RICHARD M. , HARRISON CARLOS E. , COLEMAN HENRY Neal
Published: June 2012

Depressed myocardial contractility with paradoxically increased oxygen consumption has been demonstrated in previous studies of pressure overload hypertrophy. To determine whether altered mitochondrial respiration participates in the abnormal energetics of this muscle, right ventricular hypertrophy (RVH) was produced in 12 cats by pulmonary artery banding. A polarographic muscle bath was used to study eight control and eight RVH papillary muscles, and the respiration of mitochondria isolated from these right ventricles was characterized. RVH muscles demonstrated depressed force-velocity and length-tension curves. The myocardial oxygen consumption per gram of peak active tension was increased from 0.65 ± 0.05 nliters/mg beat
-1
(control) to 1.10±0.07 nliters/mg beat
-1
(RVH) (
P
<0.001). Abnormal mitochondrial respiration was shown by an increase in the rate of state 4 oxygen consumption from 12.5±0.8 natoms/mg min
-1
(control) to 19.9±0.8 natoms/mg min
-1
(RVH) (
P
< 0.001). The altered oxygen cost of active isometric tension in the RVH muscles was linearly correlated with the altered rate of mitochondrial state 4 oxygen consumption (
r
= 0.91). Ruthenium red, a compound that blocks mitochondrial calcium uptake, reduced the rate of RVH state 4 oxygen consumption to the control level. The present study suggests a mechanism for the abnormal myocardial oxygen consumption in pressure overload hypertrophy and relates it to nonphosphorylating mitochondrial respiration linked to calcium transport.
Myocardial Reactive Hyperemia and Coronary Vascular Reactivity in the Dog
Authors: EIKENS EDUARDS , WILCKEN DAVID E. L.
Published: June 2012

Using electromagnetic flow transducers on the circumflex branch of the left coronary artery in anesthetized dogs and in conscious dogs, we examined the effects of repeated brief coronary artery occlusions on reactive hyperemic responses and those of injected vasodilators given before the occlusions and in the immediate postreactive hyperemic period on coronary blood flow responses. Three successive occlusions (4 or 8 seconds) at 1-minute intervals were accompanied by decreasing reactive hyperemia; the full response was restored after 5 minutes. Beta-receptor blockade reduced resting coronary blood flow, blood pressure, and heart rate, but it did not change this response pattern. When injections of adenosine, glyceryl trinitrate, or papaverine were given before and after a sequence of a 4-second and an 8-second occlusion performed 1 minute apart, the postocclusion vasodilator responses were reduced for up to 3 minutes. We concluded that the coronary vascular reactivity in the immediate postreactive hyperemic period was temporarily reduced. The mechanisms are not understood, but the results suggest that the reduced reactivity was not due to the depletion of a vasodilator metabolite produced during ischemia or to the development of tachyphylaxis to the coronary vasodilating action of adenosine. Also, the reduction in reactivity was not mediated through beta action of catecholamines.
Role of the Atrium in Determining the Functional and Effective Refractory Periods and the Conductivity of the Atrioventricular Transmission System
Authors: FERRIER GREGORY R. , DRESEL PETER E.
Published: June 2012

Relative contributions of the atria and the atrioventricular (AV) node to AV conduction were studied in isolated, blood-perfused dog hearts. The functional refractory period of the atria, although shorter than that of the AV node, determined the functional refractory period of the entire transmission system in 50% of the hearts. Slow atrial conduction of early beats greatly influenced the shape of the curve used to determine the functional refractory period of the transmission system. The atrial effective refractory period was also shorter than the effective refractory period of the AV node. However, the effective refractory period of the entire transmission system was equal to that of the atrium when the driving interval was longer than 320 msec, and it decreased as the driving interval was shortened. At driving intervals of 320 msec or less, the effective refractory period of the AV transmission system abruptly increased and became equal to the effective refractory period of the node. Conduction of early premature responses from near the sinoatrial node to the AV node was supernormal in 50% of the hearts. Supernormal conduction of premature atrial responses in the ventricles was also observed. The period of supernormal conduction in both tissues shifted toward greater prematurity as heart rate increased. The importance of the atrium in determining the functional properties of the AV transmission system has been previously underestimated.
Effect of Sodium Balance on Arterial Blood Pressure and Renal Responses to Prostaglandin A
1
in Man
Authors: KRAKOFF LAWRENCE R. , GUIA DAISY DE , VLACHAKIS NICHOLAS , STRICKER JENNIE , GOLDSTEIN MARVIN
Published: June 2012

The effect of sodium balance on systemic arterial blood pressure and the renal response to intravenous infusion of prostaglandin A
1
(PGA
1
) was studied in hypertensive subjects. PGA
1
(0.4 µg/kg min
-1
) was infused for 1 hour in ten hypertensive subjects who were receiving a constant diet containing 40 mEq of sodium and 80 mEq of potassium. During PGA
1
infusion a significant fall in both systolic and diastolic arterial blood pressure occurred. There was a significant rise in urine flow rate, renal plasma flow, and urine sodium excretion; plasma renin activity (PRA) rose slightly but not significantly. Eight of the ten subjects and one additional subject were then placed on furosemide (80 mg/day) for 1 week. In all subjects, a significant weight loss and a rise in midday PRA occurred with the administration of the diuretic. Systolic blood pressure fell, but diastolic pressure was unchanged. Following salt depletion with furosemide, PGA
1
infusion studies were repeated. PGA
1
then produced no significant change in systolic or diastolic blood pressure. Urine flow, renal plasma flow, and urine sodium excretion rose, but the degree of increase was markedly less than that observed prior to furosemide administration. In the salt-depleted subjects, a significant rise in PRA occurred during PGA
1
infusion. The results indicate that volume depletion diminishes the systemic and renal hemodynamic response to infused PGA
1
but enhances the PRA response. The increased PRA response during PGA
1
infusion observed in saltdepleted subjects might in part account for the blunted hemodynamic changes. Alternatively, recent evidence indicates that the enhanced production of endogenous vasodilating prostaglandins which occurs in the salt-depleted state might account for the diminished hemodynamic responses to exogenous PGA
1
.
Altered Ion Transport in Vascular Smooth Muscle from Spontaneously Hypertensive Rats
Authors: JONES ALLAN W.
Published: June 2012

The interaction of vascular electrolytes and early spontaneous hypertension was studied in the rat aorta. Chemical composition (H
2
O, Na, K, Ca, Mg, Cl, collagen, and elastin), extracellular space, and cell water content were little changed. Only uronic acid and hexosamine contents were significantly elevated in the spontaneously hypertensive rat. Approximately 37% of the aortic weight was cellular. Functional changes in ion transport were observed in smooth muscle from hypertensive rats; the muscle exhibited decreased ability to accumulate K and extrude Na and increased turnover of
42
K (0.0165 ± 0.0009 vs. 0.0086 ± 0.0002 min
-1
) and
36
C1 (0.162 ± 0.011 vs. 0.118 ± 0.003 min
-1
). Spontaneously hypertensive rats maintained increased
42
K exchange after adrenalectomy and reserpinization. The bioregulants, aldosterone, norepinephrine, and angiotensin had important actions on ion exchange. After adrenalectomy, aldosterone therapy reduced
42
K exchange toward intact levels. Norepinephrine increased the rate of
42
K exchange with the dose-response relation having a lower median effective dose (ED
50
) for spontaneously hypertensive rats (10
-9
g/ml) than it did for normal Wistar rats (2 x 10
-9
g/ml). Angiotensin also increased
42
K exchange with similar dose-response relations for both groups. I concluded that functional alterations observed in spontaneously hypertensive rats probably resulted from primary changes in ion transport by vascular smooth muscle rather than from secondary effects of altered regulatory systems. The decreased selectivity to K over Na and the increased turnover of ions could lead to increased reactivity to norepinephrine through effects on membrane potentials.