bluuebunny/crossref_metadata_2025 huggingface dataset:
Biphasic Vasoconstriction of the Rabbit Ear Artery
Authors: STEINSLAND ODD S. , FURCHGOTT ROBERT F. , KIRPEKAR SADASHIV M.
Published: June 2012

Sympathetic nerve stimulation and intraluminal norepinephrine infusion for more than 15 seconds produced a biphasic response in the isolated rabbit ear artery perfused with Krebs solution. This response consisted of an initial rapid constriction (phase A), which was followed by partial relaxation, and a final slowly developing constriction (phase B), which lasted for the duration of nerve stimulation or norepinephrine administration. Raising the potassium concentration of the Krebs solution to 12mM decreased the relaxation time between the two constrictor phases in response to norepinephrine; lowering the potassium concentration to 1.2 mM increased the relaxation time and decreased the degree of constriction of both phases. Biphasic vasoconstrictor responses were also elicited by the intraluminal infusion of phenylephrine, histamine, serotonin, or 35 m
M
potassium. When calcium was absent from the perfusing solution or when manganous sulfate (1m
M
) was present, norepinephrine produced only a fast phase A constriction, with no subsequent slow phase B constriction. However, after treatment of the artery with ryanodine, the phase A constriction in response to norepinephrine was markedly inhibited, but the phase B constriction was not. We concluded that the fast phase A constriction depends on the release of calcium from an intracellular pool and that the slow phase B constriction depends on the influx of extracellular calcium.
Photoelastic Stress Analysis of Silastic Poppets in Prosthetic Heart Valves
Authors: GREENFIELD HARVEY , HAMPTON THOMAS , GASCOIGNE HAROLD , KOLFF WILLEM
Published: June 2012

Some prosthetic heart valves with Silastic ball poppets undergo degeneration and variance. The problem is avoided with metal poppets; however, their impact can damage the cloth coverings on the struts, resulting in distorted blood flow paths. Consequently, renewed interest in mild-cured Silastic poppets and inserts is developing. With photostress equipment, we analyzed two spherical poppet models to study poppet degeneration. The first analysis simulated the ring type of loading transmitted from the valve seat to the poppet, and the second analysis involved hydrostatic pressure loading and a detailed stress analysis to simulate cage confrontation. Results showed that regions of the poppet were susceptible to stress cycling with relatively large tensions below the upper surface but above the ring support. This same location could experience large compressive stress, depending on how the poppet was positioned during a seating stroke. Shear stresses near the valve support ring were at least four times the hydrostatic pressure load. Such subsurface stress cycling should play a role in the formation of internal fissures that surface and fracture the poppet.
Effects of Angiotensin I and Angiotensin II on Canine Hepatic Vascular Resistance
Authors: DI SALVO JOSEPH , BRITTON STEVEN , GALVAS PATRICK , SANDERS THOMAS W.
Published: June 2012

The effects of angiotensin I (0.2-3.2 µg) and angiotensin II (0.1-1.6 µg) injections into the pump-perfused arterial supply of the liver were studied in dogs anesthetized with sodium pentobarbital. Marked increases in hepatic artery perfusion pressure (10-50%), reflecting directionally similar changes in resistance to blood flow, were caused by either angiotensin I or angiotensin II. Resistance increases produced by angiotensin I were significantly attenuated by the synthetic nonapeptide SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, 50 µg/kg, iv) that inhibits enzymatic conversion of angiotensin I to angiotensin II. In contrast, responses caused by angiotensin II were unaltered by SQ 20881. However, resistance increases caused by either angiotensin I or angiotensin II were blocked by 1-Sar-8-Ala-angiotensin II (100 µg/kg min
-1
, ia), a specific angiotensin II antagonist. These findings parallel the finding that responses to angiotensin I in the vasculature supplied by the hepatic artery are largely caused by local enzymatic conversion of angiotensin I to angiotensin II. Such conversion appears to occur to the extent of about 46%.
Dynamic Anisotropic Viscoelastic Properties of the Aorta in Living Dogs
Authors: PATEL DOLI J. , JANICKI JOSEPH S. , VAISHNAV RAMESH N. , YOUNG JOHN T.
Published: June 2012

The purpose of this paper is to describe the incremental dynamic anisotropic viscoelastic properties of the middle descending thoracic aorta in ten living dogs. A segment of the middle descending thoracic aorta was isolated in situ and connected to a reservoir filled with oxygenated blood. The height of the reservoir could be adjusted to impress a known pressure on the segment. In addition, a sinusoidal fluid displacement pump was connected to this assembly to superimpose small sinusoidal pressures at various frequencies (0-5 Hz); in another phase of the experiment small sinusoidal changes in length were also imposed on the segment. The pressure, the longitudinal force, and the length of the segment were monitored continuously with specially designed transducers. From these data, the incremental elastic (
E
') and the viscous (
E
'') moduli in the circumferential (θ), longitudinal (
z
), and radial (γ) directions were calculated around a given state of strain in the physiological range. In general, the viscoelastic moduli were functions of the initial stretches, indicating the nonlinear nature of the arterial wall. Within the physiological range of pressure,
E
z
' >
E
θ
' >
E
γ
' (
P
< 0.01) and
E
z
'' >
E
γ
'' >
E
θ
'' (P < 0.01). These results indicated that the vessel wall was anisotropic, having its largest values of elastic and viscous moduli in the longitudinal direction. The ratio of
E
' /
E
' < 0.123 at 2 Hz, indicating a small viscous component relative to its elastic counterpart. The elastic moduli increased markedly from 0-2 Hz and then settled down to a relatively constant value; this finding was consistent with previously published data. The values of
E
z
' and
E
z
'' from the in vivo experiments were higher than those from the in vitro experiments, and the difference was attributed to the vascular tethering present in the in vivo state.
Effect of Changes in Cycle Length on Diastolic Depolarization Produced by Ouabain in Canine Purkinje Fibers
Authors: DAVIS LARRY D.
Published: June 2012

Isolated canine papillary muscle-false tendon tissue preparations stimulated at a cycle length of 630 msec were treated with ouabain (2.1 x 10
-7
M
) until an increase in the slope of diastolic depolarization of Purkinje fibers was produced. Then the effects of changes in cycle length on the slope were tested. Sustained shortening of the cycle length increased the slope, and sustained lengthening had the opposite effect. An abrupt decrease in cycle length caused by a stimulus during phase 3 of a driven beat induced an increase in the slope of diastolic depolarization for one or more subsequent cycles. This procedure occasionally led to the spontaneous generation of an action potential which propagated into surrounding tissue. Suspension of stimulation often was followed by spontaneous beats. Shortening of the cycle length decreased the time of onset and increased the number and frequency of spontaneous beats. These effects were correlated with increases in the slope of diastolic depolarization. The diastolic depolarization of Purkinje fibers in false tendons was increased earlier and to a greater degree by ouabain than was the depolarization of Purkinje fibers on the muscle surface. These findings suggest that enhancement of diastolic depolarization of Purkinje fibers to the point of spontaneous discharge of action potentials may be a common means by which digitalis produces a variety of ventricular arrhythmias observed in intact animals.
Evidence for Hemodynamic Autoregulation of Renin Release
Authors: EIDE IVAR , LOslash;YNING EINAR , KIIL FREDRIK
Published: June 2012

To examine the relationship between renal arteriolar dilatation and renin release, arterial perfusion pressure in anesthetized dogs was lowered in steps within and below the range of autoregulation of renal blood flow. Renin release, determined by both bioassay and radioimmunoassay, averaged 2.7 ± 0.9 (
SE
) µg/min at control pressure and increased to 20.0 ± 4.1 (
SE
) µg/min at the lowest autoregulating pressure, which averaged 66.4 ± 2.9 (
SD
) mm Hg. However, renin release then remained constant during further lowering of arterial perfusion pressure despite reductions in renal blood flow. This response was not significantly changed when sodium excretion was increased by intravenous infusion of mannitol. In another series of experiments, renin release was raised by reducing arterial perfusion pressure below the range of autoregulation, and control sodium excretion was reestablished by mannitol or saline infusion; renin release remained high. Therefore, renin release appears to be related to autoregulated dilatation of the renal arterioles, and it becomes maximal when the arterioles are completely dilated at the lowest pressure of autoregulation of renal blood flow. This mechanism is different from release mechanisms dependent on sodium delivery to the distal nephron.
Adrenergic Stimulation of Renin Secretion in the Isolated Perfused Rat Kidney
Authors: VANDONGEN ROBERT , PEART W. STANLEY , BOYD GRAHAME W.
Published: June 2012

To avoid complicating systemic effects, the influence of adrenergic hormones on renin secretion was examined in the isolated rat kidney perfused with Krebs-dextran solution at a constant mean pressure and flow rate. Isoproterenol and glucagon produced a consistent increase in renin secretion without a change in perfusion pressure and flow. Similarly the increase in renin secretion with norepinephrine, which was associated with intense vasoconstriction and raised perfusion pressure, was still observed after the vasoconstrictive effect was abolished with phenoxybenzamine. Isoproterenol- stimulated renin secretion, unaffected by phenoxybenzamine, was markedly suppressed by
dl
-propranolol but not by
d
-propranolol. The failure of
dl
-propranolol to suppress the renin response to glucagon confirms observations in other tissues and suggests involvement of other receptors or alternative mechanisms. These findings support a direct intrarenal effect of adrenergic hormones on renin secretion, and this effect may be mediated specifically by beta receptors in the case of catecholamines.
Adrenergic Influences on the Distal Purkinje System of the Canine Heart
Authors: HARRISON LURA ANN , WITTIG JOHN , WALLACE ANDREW G.
Published: June 2012

The purpose of these experiments was to examine the effects of norepinephrine and propranolol on distal Purkinje fibers of the canine heart. Previous studies have indicated that action potential duration is normally greatest in distal Purkinje fibers 3-4 mm from the Purkinje-muscle junction. In such preparations, premature beats initiated either proximal or distal to the area of maximal action potential duration may propagate with delay or block. Our experiments were performed on the right bundle branch and the distal Purkinje fibers of dog hearts and used standard microelectrode techniques. Premature beats with a coupling interval comparable to the duration of action potentials at the area of maximal duration were conducted with delay. Earlier beats were confined to fibers proximal to the area of maximal action potential duration. Norepinephrine (1 x 10
-5
M
) increased action potential duration in some fibers, consistently prolonged the functional refractory period of distal Purkinje fibers, and produced a marked delay in the propagation of early premature beats. Propranolol (0.25-1.0 mg/liter) shortened action potential duration, shortened the functional refractory period of distal fibers, and reduced or abolished conduction delay and block of early premature beats. These observations suggest that the unique properties of the Purkinje-muscle junction may contribute to the genesis of arrhythmias and that this region is an important site of action of propranolol. The action of propranolol on the Purkinje-muscle junction was dose dependent.
Reflex Diuresis during Tachycardia in the Dog
Authors: GOETZ KENNETH L. , BOND GARY C.
Published: June 2012

Renal function and systemic hemodynamics were studied during rapid atrial pacing in dogs with complete heart block and in control dogs with normal atrioventricular conduction. Rapid atrial pacing in dogs with complete heart block produced no significant change in urine flow, sodium excretion, or systemic hemodynamics. In contrast, rapid cardiac pacing in control dogs produced progressive increases in urine flow and sodium excretion and a decrease in arterial pulse pressure. Plasma antidiuretic hormone levels were not changed significantly by pacing in either group of dogs; likewise, mean atrial type B (volume) receptor discharge rate was not increased by pacing in either group. Rapid sequential atrioventricular pacing in three dogs with complete heart block did produce an increase in urine flow and sodium excretion, but rapid pacing of the atria alone in the same dogs did not cause a diuresis or a natriuresis. In other experiments on dogs with chronic sinoaortic denervation, rapid cardiac pacing caused no significant changes in urine flow or sodium excretion. Hence, the study provided no evidence to support the hypothesis that diuresis during tachycardia is elicited reflexly from atrial receptors. The data from dogs with sinoaortic denervation did suggest that receptors in the carotid sinus and the aortic arch participate in reflexly eliciting a diuresis during tachycardia.
Sinus Node Reentry
Authors: PAULAY KARLEN L. , VARGHESE P. JACOB , DAMATO ANTHONY N.
Published: June 2012

The phenomenon of sinus node reentry was investigated in 20 dogs by programed atrial stimulation during sinus rhythm and atrial pacing. Recordings were made simultaneously at multiple atrial sites. In 18 dogs, a closely coupled premature atrial beat (A
2
) introduced into the region of the coronary sinus, the right or the left atrial appendage, or the Bachmann bundle was followed 100-300 msec later by an accelerated beat (A
3
) consistent with sinus node reentry. The atrial activation sequence and the P-wave morphology of A
3
and of the spontaneous sinus beats were similar. The occurrence of A
3
during sinus rhythm and atrial pacing was dependent on the coupling interval of A
2
and the arrival time of excitation in the region of the sinus node but was independent of the atrial site at which A
2
was introduced; A
3
could be clearly distinguished from local or atrioventricular node reentry and sinus node entrance block. Moreover, crushing of the sinus node (10 dogs) or vagal stimulation (7 dogs) prevented the appearance of A
3
in all dogs, presumably by blocking the sinus node reentry pathway. During graded vagal stimulation a progressive increase in the A
2
-A
3
interval occurred. Sinus node reentry was sustained for three cycles in 1 dog. Sinus node reentry may be one mechanism for interpolated atrial premature depolarization and some atrial tachyarrhythmias seen clinically.
Biochemical Alterations Caused by Hypoxia in the Isolated Rabbit Aorta: CORRELATION WITH CHANGES IN ARTERIAL CONTRACTILITY
Authors: NOMM DONALD H. , ZUCKER JOAN L.
Published: June 2012

A graded reduction in the oxygen tension of the medium bathing aortic strips resulted in a decrease in creatine phosphate and adenosine triphosphate levels in the tissue, but only the fall in creatine phosphate could be correlated with the contractile changes observed during hypoxia. The tissue glycogen concentration was not altered at any oxygen tension, indicating that under the conditions of the experiment glycogenolysis did not contribute substrate in significant amounts. Although lactate concentrations rose as the oxygen tension was progressively lowered, changes in the concentration of this metabolite did not correlate with the contractile response to hypoxia. The reduction in contractile tone induced by lowering oxygen tension of the medium was less when the tissue was exposed to 25 mM glucose than it was with 5 mM glucose. Addition of pyruvate did not mimic this sparing effect of glucose. These results indicate that the loss of contractile tone in arterial muscle exposed to low oxygen tensions is not directly attributable to a deficit in the availability of adenosine triphosphate within the tissue but, rather, is a consequence of more subtle alterations in the energy metabolism of the muscle.
Reflex Tachycardia Due to Temporary Coronary Occlusion in the Conscious Dog
Authors: PETERSON D. FRED , KASPAR ROBERT L. , BISHOP VERNON S.
Published: June 2012

Reflex increases in heart rate which occurred during 1-minute occlusions of the left circumflex coronary artery were studied in conscious dogs. The results indicated that occlusion produced tachycardia (latency to onset 8.5 seconds) preceded by a rise in left atrial pressure (7.2 seconds) and followed by a small fall in arterial pressure (19.5 seconds). Bilateral baroreceptor denervation indicated that the onset of the changes in heart rate could not be accounted for by subtle baroreceptor sensitivity, although the peak response was much reduced (from 34.0 beats/min to 17.5 beats/min), indicating that the magnitude of the response did depend on intact baroreceptors. Beta-receptor blockade with propranolol or cardiac sympathectomy reduced the peak response from 34.0 beats/min to 16.1 beats/min or 12.2 beats/min, respectively. Vagal blockade with atropine reduced the response to 5.3 beats/min, indicating that the remainder of the response was carried in the vagus. Responses were much reduced after baroreceptor denervation plus β-receptor blockade (5.2 beats/min), indicating that the efferent vagal branch of the reflex originated primarily in the arterial baroreceptors. Tachycardia during coronary occlusion, then, is initiated by receptors in or near the heart, and the magnitude of the response is a combination response from these receptors and the arterial baroreceptors.
Total Systemic Autoregulation in the Dog and Its Inhibition by Baroreceptor Reflexes
Authors: LIEDTKE A. James , URSCHEL CHARLES W. , KIRK EDWARD S.
Published: June 2012

Although many organs maintain constant blood flow despite changes in perfusion pressure, autoregulation in the total systemic circulation has only been reported in animals after destruction of the central nervous system. The present study examined the role of the baroreceptors in this autoregulatory response in open-chest dogs anesthetized with chloralose-urethane. Cardiac output was varied over nearly a twofold range by altering myocardial contractility with either inotropic agents or controlled myocardial ischemia. Cardiac output, determined by dye dilution, and mean aortic pressure stabilized within 3 minutes after the start of infusions of calcium (15-62 mg/min) into the cannulated left coronary artery or the reduction of coronary flow. With bilateral vagotomy and carotid sinus denervation, autoregulation of total peripheral flow was observed. Thus, changes in cardiac output evoked parallel changes in total peripheral resistance and wide variations in aortic pressure. However, with the baroreceptors intact, changes in cardiac output evoked inverse changes in total peripheral resistance which resulted in regulation of aortic pressure. We concluded that autoregulation in peripheral vascular beds could result in autoregulation of total peripheral flow after simple baroreceptor denervation. However, the baroreceptor reflexes normally achieved regulation of aortic pressure by inhibiting autoregulation in much of the peripheral circulation.
Variations in Adrenergic Innervation and Contractile Responses of the Rabbit Saphenous Artery
Authors: BEVAN JOHN A. , PURDY RALPH E.
Published: June 2012

The Falck fluorescence histochemical method was used to compare the adrenergic innervation in segments from the proximal saphenous artery, the distal saphenous artery and the popliteal artery. Adrenergic neurons penetrated the media of the proximal saphenous artery but not that of the distal saphenous artery or the popliteal artery. Responses of these vessel segments to exogenous
l
-norepinephrine and to electrical stimulation of their intramural innervation were measured. The median effective dose (ED
50
) of
l
-norepinephrine was ten times greater in the proximal saphenous artery than it was in the distal saphenous artery and the popliteal artery. The response of the proximal saphenous artery to neural stimulation was nearly double that of the distal vessel and required one-fifth of the time to achieve maximum tension; the response of the popliteal artery was negligible due to its low density of innervation. The three-dimensional medial distribution of the adrenergic neuronal plexus in the proximal saphenous artery should (1) increase the efficiency of neuronal uptake of
l
-norepinephrine and thereby account for the increased ED
50
of
l
-norepinephrine, and (2) decrease the mean distance between adrenergic nerves and medial smooth muscle cells. Therefore, transmitter would accumulate more rapidly and reach a higher level in the media during neural activity.
Influence of Acute Stimuli on Plasma Aldosterone Concentration in Anephric Man and Kidney Allograft Recipients
Authors: McCAA ROBERT E. , READ VIRGINIA H. , COWLEY ALLEN W. , BOWER JOHN D. , SMITH GEORGE V. , McCAA CONNIE S.
Published: June 2012

The response of plasma aldosterone concentration to postural variation, adrenocorticotropic hormone (ACTH), and angiotensin II was studied in five kidney allograft recipients and compared with the response observed in the same five subjects during the anephric period. Normal subjects acted as intact controls. After 2 hours of normal ambulation, plasma aldosterone levels increased in normal subjects (6.7 ± 1.6 to 22.9 ± 2.7 ng/100 ml plasma), remained unchanged in anephric patients (4.5 ± 1.0 to 5.2 ± 1.1 ng/100 ml plasma), and increased in kidney allograft recipients (6.8 ± 1.5. to 25.6 ± 1.9 ng/100 ml plasma). After ACTH administration, plasma aldosterone levels increased in normal subjects (7.5 ± 1.8 to 24.3 ± 2.5 ng/100 ml plasma), anephric subjects studied immediately after hemodialysis (16.6 ± 1.6 to 30.0 ± 2.6 ng/100 ml plasma), and kidney allograft recipients (5.0 ± 1.6 to 22.3 ± 1.4 ng/100 ml plasma). After angiotensin II infusion, plasma aldosterone levels increased in normal subjects (7.2 ± 1.8 to 42.5 ± 3.6 ng/100 ml plasma), remained unchanged in anephric subjects (8.6 ± 2.1 to 7.4 ± 1.6 ng/100 ml plasma), and increased in kidney allograft recipients (6.3 ± 1.5 to 40.2 ± 3.1 ng/100 ml plasma). In anephric man after prolonged absence of the renal renin-angiotensin system ACTH increased the rate of aldosterone secretion but angiotensin II had little effect. An intact renal renin-angiotensin system was necessary for increased aldosterone secretion in response to postural variation.
Resistance and Venous Oxygen Dynamics during Sinusoidal Exercise of Dog Skeletal Muscle
Authors: MOHRMAN DAVID E. , SPARKS HARVEY V.
Published: June 2012

We observed the response of vascular resistance and venous oxygen (O
2
) saturation to sinusoidally modulated continuous exercise of the isolated dog calf. Stimulus frequency was varied sinusoidally between 0.5 Hz and 1 Hz with modulation frequencies ranging from 0.005 Hz to 0.05 Hz. Venous O
2
responses were corrected for dispersion due to vascular and catheter transit. As modulation frequency was increased, the amplitude of the response of both resistance and venous O
2
to changing stimulation frequency decreased. The dynamics of the resistance response depended on flow rate. At high constant flow (56 ±8 ml/100 g min
-1
) the resistance response followed higher modulation frequencies without loss of amplitude (Bode corner frequency = 0.016 ± 0.003 Hz) than it did at low constant flow (25 ± 7 ml/100 g min
-1
) (Bode corner frequency = 0.0049 ± 0.0006 Hz). The dynamics of the venous Osaturation response were not significantly altered by flow. In the low constant-flow range, vascular resistance and venous O
2
saturation had similar dynamics in response to sinusoidal modulation of exercise rate. This finding indicates that oxidative metabolism may be linked to the resistance changes at low flow. At high constant flow, however, the vascular resistance response followed higher modulation frequencies without loss of amplitude than did venous O
2
saturation in three of four dogs. Given certain assumptions, it is doubtful that changes in oxidative metabolism are linked to changes in vascular resistance at high constant flow. Vascular resistance, under the conditions of this experiment, appeared to be controlled by at least two mechanisms, the slower of which may be related to oxidative metabolism.
Cardiovascular and Metabolic Effects of Whole or Fractionated Gram-Negative Bacterial Endotoxin in the Unanesthetized Rhesus Monkey
Authors: REICHGOTT MICHAEL J. , MELMON KENNETH L. , FORSYTH RALPH P. , GREINEDER DIRK
Published: June 2012

Rhesus monkeys were infused with endotoxin lipopolysaccharide (LPS) (10 mg/kg [LPS
10
] or 2.5 mg/kg [LPS
2.5
]) or with fractions of LPS containing 6.3% lipid (PS
1
) or 0.5% lipid (PS
2
) (2.5 mg/kg). Systemic and regional hemodynamics, leukocyte counts, blood gases, pH, and plasma bradykinin concentration were measured. Monkeys receiving LPS
10
, LPS
2.5
, or PS
1
became hypotensive (mean blood pressure -37 ± 10 mm Hg) and had decreased peripheral vascular resistance (-10% to -24% of the base line), compensated metabolic acidosis, and elevated plasma bradykinin concentrations (14 ± 6 ng/ml) 2 hours after infusion. Vasodilation occurred in coronary, hepatic, and splanchnic vasculature; vasoconstriction occurred in the spleen. Cardiac output was diverted from muscle to viscera. Monkeys receiving PS
2
were normotensive with elevated peripheral vascular resistance (+46%) and no measurable plasma bradykinin concentration. By 6 hours, marked elevation of peripheral vascular resistance developed in monkeys given LPS
10
(+113%) and LPS
2.5
(+57%). Monkeys receiving PS
1
returned to base-line values, but monkeys receiving PS
2
remained unchanged. Leukopenia (-50% to -65%) was persistent only in monkeys receiving LPS or PS
1
. Toxicity of LPS apparently depends on the lipid portions of the molecule. Vasodilation and bradykinin generation are correlated with persistent granulocytopenia. Late toxicity may be independent of early cardiovascular events.
Reduction by Propranolol of Myocardial Necrosis following Temporary Coronary Artery Occlusion in Dogs
Authors: REIMER KEITH A. , RASMUSSEN MARGARET M. , JENNINGS ROBERT B.
Published: June 2012

The effect of propranolol on the severity of myocardial necrosis following 40 minutes of temporary coronary artery occlusion was assessed in dogs. The circumflex coronary artery was occluded 1-2 cm from the aorta in open-chest dogs anesthetized with sodium pentobarbital. One group of dogs was untreated and a second group received propranolol (5.0 mg/kg, iv) 10 minutes prior to the occlusion. After 40 minutes the clamp was removed and arterial perfusion was restored. Dogs which survived this procedure were killed 2-5 days later for gross and histologic assessment of the necrosis. The relative area of necrosis (percent of fibers involved) in the posterior papillary muscle of each heart was quantified from stained histologic sections prepared from serial longitudinal slices of each posterior papillary muscle. Dogs treated with propranolol showed significantly less necrosis than did untreated controls, but the mechanism of the drug's action remains unknown. During coronary artery occlusion, propranolol-treated dogs exhibited somewhat lower heart rates, systolic blood pressures, and S-T segment elevations than did untreated dogs. However, none of these latter differences between groups was significant.
Effect of Neomycin and Other Antibiotics on Serum Cholesterol Levels and on 7α-Dehydroxylation of Bile Acids by the Fecal Bacterial Flora in Man
Authors: SAMUEL PAUL , HOLTZMAN CHARLES M. , MEILMAN EDWARD , SEKOWSKI IGNACY
Published: June 2012

Fresh feces from 25 patients were homogenized and incubated with labeled cholic or chenodeoxycholic acid. After 24 hours of incubation, the percent change to the 7α-dehydroxylated form was measured. In 11 patients, the oral administration of 2g of neomycin daily significantly reduced the levels of serum cholesterol (from an average of 316 mg/100 ml plasma to 237 mg/100 ml plasma) and markedly inhibited the extent of 7α-dehydroxylation of cholic acid (from 89% to 9%); in 2 patients whose serum cholesterol levels were not lowered, the degradation of cholic acid remained unchanged (control 93%, neomycin 91%). In 5 patients the administration of kanamycin reduced serum cholesterol levels (from 280 mg/100 ml plasma to 252 mg/100 ml plasma) and also inhibited 7α-dehydroxylation of cholic acid (from 92% to 21%); in 3 additional patients this drug failed to lower serum cholesterol concentrations and had no effect on bile acid degradation (control 91%, kanamycin 92%). Similar results were obtained with chloramphenicol in 3 patients, and equivocal results were obtained with chlortetracycline in 3 patients. The correlation coefficient between undegraded cholic acid and percent decrease in serum cholesterol concentrations (
r
= 0.732) was statistically significant (
P
< 0.001). It is proposed that serum cholesterol levels might be controlled in part by the prevalence of bile acid-degrading bacteria within the gastrointestinal tract.
Further Observations on the Activation and Inhibition of Lipoprotein Lipase by Apolipoproteins
Authors: KRAUSS RONALD M. , HERBERT PETER N. , LEVY ROBERT I. , FREDRICKSON DONALD S.
Published: June 2012

ApoC-II was the only apolipoprotein from human very low density lipoprotein that activated rat adipose tissue lipoprotein lipase. Activation was blocked by antiserum against apoC-II. Addition of increasing amounts of activator did not alter the apparent K
m
of lipoprotein lipase (0.32 mM triolein), but it did produce a progressive increase in the apparent V
max
from 0.8 to 2.2 µmoles free fatty acid/mg hour
-1
. Substrate concentrations above 1.27 mM triolein diminished activation by 0.25-5.0 µg/ml of apoC-II as much as 20%. Reversal of this apparent substrate inhibition was achieved by increasing the activator concentration to 50.0 µg/ml. Each of five nonactivating apolipoproteins-apoC-I, C-III-1, C-III-2, A-I, and A-II-inhibited lipoprotein lipase up to 85-100%. ApoC-II also produced less inhibition under appropriate conditions. Inhibition was dependent on apoprotein concentration, inversely related to substrate triglyceride concentration, and unobserved with nonlipoprotein proteins. The inhibitory capacity of the nonactivating apolipoproteins was about the same, was independent of apoC-II concentration, and occurred when the ratio of nonactivator apoprotein to triglyceride exceeded 3% (w/w). It is possible that these apoproteins function partly to modulate the hydrolysis of very low density lipoprotein triglyceride by lipoprotein lipase.
Mechanisms of Activation of Cardiac Glycogen Phosphorylase in Ischemia and Anoxia
Authors: DOBSON JAMES G. , MAYER STEVEN E.
Published: June 2012

The effects of ischemia and anoxia on cardiac adenosine 3', 5'-monophosphate (cyclic AMP) concentration, glycogen phosphorylase activity ratio (-5'-AMP: +5'-AMP), phosphorylase kinase activity ratio (pH 6.8:8.2), and myocardial contractility (left ventricular dP/dt) were studied in an open-chest rat heart preparation. Ischemia produced by termination of coronary blood flow increased cyclic AMP from 0.55 to 0.77 µmoles/kg in 5 seconds and phosphorylase from 0.14 to 0.57 in 20 seconds. Anoxia induced by breathing N
2
increased cyclic AMP from 0.50 to 0.62 µmoles/kg in 10 seconds and phosphorylase from 0.14 to 0.65 in 30 seconds. Phosphorylase kinase increased with ischemia but did not change with anoxia. Beta-receptor blockade with practolol prevented the rise in cyclic AMP and phosphorylase kinase but blocked the increase in phosphorylase only in ischemia. Myocardial contractility declined precipitously during the first 20 seconds of anoxia. Epinephrine (0.1 µg/kg) caused an increase in cyclic AMP comparable to that elicited by anoxia, and it produced an increase in dP/dt during N
2
breathing. These results suggest that in the intact working heart ischemia induces phosphorylase
a
formation through a cyclic AMP-dependent transformation of phosphorylase kinase; however, in anoxia phosphorylase
a
formation depends only on the regulation of the catalytic activity of phosphorylase kinase without conversion of this enzyme to its activated form. An increase in cyclic AMP during anoxia is not associated with a positive inotropic response even though such a response is obtained with epinephrine. Factors other than the elevation of myocardial cyclic AMP may be limiting in the control of both cardiac glycogenolysis and inotropic state.
Effect of Calcium on Acetylstrophanthidin-Induced Transient Depolarizations in Canine Purkinje Tissue
Authors: FERRIER GREGORY R. , MOE GORDON K.
Published: June 2012

The role of calcium ions (Ca
2+
) in the generation of transient depolarizations (TDs) by acetylstrophanthidin was examined. Transmembrane activity was recorded from isolated canine false tendons exposed to acetylstrophanthidin; concentrations from 7.5 x 10
-8
to 2 x 10
-7
g/ml caused TDs coupled to driven action potentials and depressed slow diastolic depolarization. TDs could reach threshold and induce extrasystoles. Elevation of the Ca
2+
concentration increased the amplitude of TDs induced by acetylstrophanthidin. High Ca
2+
concentration (12.5 mM) caused TDs and depression of slow diastolic depolarization in the absence of acetylstrophanthidin. Elevation of potassium (K
+
) concentration depressed and reduction of K
+
concentration potentiated TDs caused by either acetylstrophanthidin or high Ca
2+
concentration. The production of TDs and the depression of slow diastolic depolarization by acetylstrophanthidin were reversed by reduction of the Ca
2+
concentration or addition of manganese (2 mM) to the superfusing Tyrode's solution. The results suggest that TDs and arrhythmias produced by acetylstrophanthidin may be caused by a transient Ca
2+
influx.
Left Atrial Receptor Discharge during Atrial Arrhythmias in the Dog
Authors: ZUCKER IRVING H. , GILMORE JOSEPH P.
Published: June 2012

Afferent receptor discharge originating in the atria was recorded from slips of the cervical vagus in the open-chest dog. The activity of two types of atrial receptor endings was identified. Type A receptors exhibited a discharge pattern that was synchronous with the
a
wave of the atrial pressure pulse in the control recordings, and type B receptors discharged only during the v wave of the atrial pressure pulse in the control recordings. Atrial arrhythmias (flutter or fibrillation) were induced by mechanical stimulation of the area around the sinoatrial node. During atrial arrhythmias, there was a moderate rise in mean left atrial pressure (7.5 ± 0.7 cm H
2
O to 8.6 ± 0.6 cm H
2
O during arrhythmias in which type B receptors were studied, 6.1 ± 0.1 cm H
2
O to 7.8 ± 0.4 cm H
2
O during arrhythmias in which type A receptors were studied), a fall in aortic blood pressure, and a decrease in right atrial force. Atrial contractions were asynchronous and rapid. Type A atrial receptors showed a relatively greater increase in discharge (184.1%) during fibrillation than did type B atrial receptors (27.5%). These experiments demonstrated that both types of atrial receptors increased their discharge rate during atrial arrhythmias, indicating that they might be involved in a reflex diuresis which occurs during these arrhythmias in humans.
Effect of Arterial Hypoxia on Myocardial Oxygen Consumption
Authors: POWERS ERIC R. , POWELL WILLIAM John
Published: June 2012

To evaluate the effect of arterial hypoxia on myocardial oxygen consumption (MVO
2
) under controlled conditions of stable or decreased contractility and tension, 18 anesthetized, adrenergically blocked dogs on right heart bypass were studied. Heart rate, cardiac output, pH, and Pco
2
were constant. In 9 dogs, progressive decreases in arterial oxygen content were associated with progressive significant increases in MVO
2
to a peak of 1.5 ± 0.5 ml/min 100 g
-1
left ventricle (
P
<0.005) above the control level at an arterial oxygen content of 7-9 ml/100 ml blood (Po
2
=30 mm Hg). This value represents a 19% increase from a control MVO
2
of 7.9 ml/min 100 g
-1
left ventricle (arterial oxygen content 15-18 ml/100 ml blood, Po
2
> 200 mm Hg). Progressive decreases occurred in mean aortic pressure (
P
< 0.001) and tension-time index (
P
< 0.001) with no significant change in mean ejection rate, left ventricular dP/dt, or left ventricular end-diastolic pressure. Quantitatively similar increases in MVO
2
with controlled hemodynamics were found when coronary flow was held constant (5 dogs), after catecholamine depletion with reserpine (2 dogs), and in the beating, empty ventricle (2 dogs). Thus, arterial hypoxia results in (1) an increase in MVO
2
despite no change or a decrease in the magnitude of the hemodynamic parameters correlated with MV
2
and (2) a decrease in myocardial efficiency.
Structural Requirements for Substrates and Inhibitors of Angiotensin I-Converting Enzyme In Vivo and In Vitro
Authors: OPARIL SUZANNE , KOERNER TERRY , O'DONOGHUE J. KEVIN
Published: June 2012

The mechanism of action of peptide inhibitors on angiotensin I-converting enzyme (Al-converting enzyme) was studied in relation to the substrate requirements of the enzyme in vivo in the dog lung and in vitro in plasma. 1-
d
-Asp-8-Ile-AI prepared by the solid-phase technique was compared with the known peptide inhibitors of Al-converting enzyme. BPP
5a
(Pyr-Lys-Trp-Ala-Pro) and SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro)
125
I-1-
d
-Asp-8-Ile-AI was evaluated for susceptibility to cleavage by the Al-converting enzyme. In vitro and in vivo,
125
I-1-
d
-Asp-8-Ile-AI or BPP
5a
in 50,000-fold molar excess produced only a slight delay in conversion of
125
1-AI to
125
I-angiotension II (AII); SQ 20881 blocked conversion completely. In vivo, l-
d
-Asp-8-Ile-AI or BPP
5a
injected into the pulmonary circulation in 250-fold molar excess (250 nmole/kg) did not cause a diminution in the pressor response to AI administered 30 seconds later; SQ 20881 blocked the pressor response to Al for 60-90 minutes. 1-
d
-Asp-8-Ile-AI was a poor substrate for converting enzyme, since
125
I-1-
d
-Asp-8-Ile-AI was not converted to
125
I-1-
d
-Asp-8-Ile-AII, and unlabeled 1-
d
-Asp-8-Ile-AI did not block the pressor response to exogenous AII.
125
I-1-
d
-Asp-8-lle-AI was stable in plasma and in the pulmonary circulation The results suggest that since 1-
d
-Asp-8-Ile-AI is neither a substrate nor a blocker, substitution of the aliphatic residue Ile in the 8 position of AI may prevent binding to an active site in the AI-converting enzyme.
Lithium Substitution and the Distribution of Sodium in the Rat Tail Artery
Authors: FRIEDMAN SYDNEY M.
Published: June 2012

The exchange of lithium (Li) with sodium (Na) was explored in an effort to quantify cellular Na in the rat tail artery. Two phases of cellular Na were demonstrated by the kinetics of exchange at 37°C. Cellular Na, was rapidly lost following cell disruption and increased in proportion to potassium (K) loss during conventional Na enrichment in a K-free medium. Cooling to 2°C almost abolished the transmembrane movement of Li; therefore, a simple 30-minute incubation in cold Li medium removed extracellular but not cellular Na. To prove that the residual Na after such a wash in cold Li was cellular, we demonstrated that Na exchanges readily with Li even at 2°C after cells are disrupted, increases slowly in proportion to K loss during prolonged cooling, and increases rapidly in a precise one-to-one ratio with K loss when active Na transport is stopped by incubation in a K-free medium. Cellular Na in the normal artery was about 20-25 mmoles/kg dry weight when cellular K was about 225 mmoles/kg dry weight. In arteries from rats with deoxycorticosterone acetate-induced hypertension of 8 weeks duration, a 13% fall in cellular K was balanced one to one by an increase in cellular Na.
Inhibition by Acetylcholine of Adrenergic Neurotransmission in Vascular Smooth Muscle
Authors: VANHOUTTE PAUL M.
Published: June 2012

Changes in the isometric tension of isolated strips of cutaneous, femoral, mesenteric, pulmonary, and muscle arteries and veins were recorded at 37°C in an organ bath. Acetylcholine (5 x 10
-8
and 10
-7
g/ml) caused relaxation of strips from the saphenous veins, the femoral veins, and all of the arteries after contraction by norepinephrine released from nerve terminals by electrical stimulation (2-5 Hz); in the pulmonary and mesenteric veins, acetylcholine caused a further increase in tension. Pulmonary artery and mesenteric vein strips were incubated with [
3
H] norepinephrine and mounted for superfusion (3 ml/min) and isometric tension recording. Electrical stimulation increased the tension and the total radioactivity released in both preparations. Acetylcholine (2 x 10
-7
g/ml) depressed the contractions of the pulmonary artery strips but augmented those of the mesenteric vein strips; it diminished the efflux of radioactivity in both, indicating that acetylcholine inhibits adrenergic neurotransmission. In the absence of sympathetic stimulation, acetylcholine (5 x 10
-10
-10
-5
g/ml) caused all vein strips to contract; the most common reaction in artery strips was a slight relaxation (at 10
-9
-10
-8
g/ml) followed by a contraction (at 5 x 10
-8
-10
-5
g/ml). During contractions caused by norepinephrine, acetylcholine caused a further increase in tension in vein strips but a relaxation in artery strips. Atropine abolished the effects of acetylcholine. The results of this study suggest the presence in vascular smooth muscle of both excitatory and inhibitory cholinergic receptors.
Effect of Dopamine and Calcium on Lipolysis and Myocardial Ischemic Injury following Acute Coronary Occlusion in the Dog
Authors: LEKVEN JON , SEMB GUDMUND
Published: June 2012

Ischemic myocardial injury was quantified as the sum of S-T segment elevations in epicardial electrocardiogram recordings (ΣS-T) following acute coronary artery occlusions in 17 dogs. ΣS-T rose from 3 ± 1 mv to 26 ± 4 mv (
P
< 0.001) following occlusion. Myocardial contractility was similarly stimulated by intravenous infusions of dopamine or calcium. At reocclusions of the coronary artery, ΣS-T increased to 73 ± 12 mv (
P
< 0.001) with dopamine and to 41 ± 7 mv (
P
< 0.001) with calcium; the difference was statistically significant (
P
< 0.005). Arterial concentrations of free fattv acids (FFA
a
) were raised from 248 ± 33 µEq/liter to 888 ± 161 µEq/liter (
P
< 0.005) with dopamine, but administration of calcium did not influence FFA
a
. After inhibition of lipolysis with β-pyridyl carbinol, no difference in ΣS-T or FFA
a
was observed; the mean values were 31 ± 4 mv for ΣS-T and 144 ± 13 µEq/liter for FFA
a
. Myocardial lipolysis was suggested in three experiments in which β-pyridyl carbinol reduced ΣS-T with dopamine, although FFA
a
remained unchanged. These measurements suggest that dopamine-induced lipolysis contributes significantly to the enlargement of ischemic injury in the myocardium following acute coronary artery occlusion, probably due to the metabolic stimulation of myocardial oxygen requirements. Test doses of dopamine given to seven patients raised FFA
a
by 225 ± 87 µEq/liter (
P
< 0.03).
Evidence for Different Angiotensin II Receptors in Rat Adrenal Glomerulosa and Rabbit Vascular Smooth Muscle Cells
Authors: WILLIAMS GORDON H. , McDONNELL LYNNE M. , RAUX MARIE C. , HOLLENBERG NORMAN K.
Published: June 2012

Angiotensin II (AII) acts as both an endogenous vasoconstrictor agent and a specific trophic hormone that controls aldosterone secretion. The characteristics of vascular and adrenal receptors for AII were examined in vitro by comparing stimulation and blockade induced by two structural analogues of AII. The adrenal response was assessed on the basis of corticosterone and aldosterone production by isolated rat glomerulosa cells; isolated rabbit aortic strips provided an index of the response of vascular smooth muscle. Threshold sensitivity to AII in both tissues was 0.3-1.0 ng/ml with a peak response at about 300 ng/ml. PII3 (I-Sar-8-Ala-AII) was a competitive antagonist in both systems; 1-10 ng/ml of PII3 produced a significant parallel shift of the All dose-response curve (P < 0.01). The maximum response was not reduced; increasing doses of AII overcame the blockade, and the responses to other agonists were not influenced. PII3 did not stimulate either tissue. P
4
T
8
(4-Phe-8-Tyr-AII) was a partial agonist in the rabbit aorta; 100 ng/ml of P
4
T
8
induced competitive blockade, and contraction followed doses above 1,000 ng/ ml. Conversely, P
4
T
8
neither stimulated nor blocked the adrenal receptors, despite very high concentrations. Thus, the results of this study reveal functional differences in the All receptors in the two systems and provide an approach to designing therapeutic agents that might block only one of its two major biological effects.
Evidence for an Indirect Sympathetic Control of Atrial Stretch Receptor Discharge in the Dog
Authors: ZUCKER IRVING H. , GILMORE JOSEPH P.
Published: June 2012

Experiments were performed to determine the influence of cardiac sympathetic efferent nerve stimulation on the discharge rate of atrial type B stretch receptors in the anesthetized, open-chest dog. In all experiments, the left stellate ganglion was stimulated following volume expansion. To determine the effects of stellate stimulation, the responses of atrial receptors were observed during the withdrawal of blood in steps following intravascular volume expansion. Stimulation of the stellate ganglion decreased receptor discharge and left atrial pressure in all experiments. A change from a control left atrial pressure of 2.5 cm H
2
O (in peak left atrial
v
-wave pressure) resulted in a mean increase in receptor discharge of 6.6 ± 1.4 spikes/cardiac cycle during stellate stimulation; however, a change from a control pressure of 0.0 cm H
2
O resulted in a mean decrease in receptor discharge of 1.5 ± 1.5 spikes/cardiac cycle. The curves relating the change in atrial receptor discharge to the change in left atrial pressure during hemorrhage and the curve for these parameters during stellate stimulation were not significantly different from each other. Apparently, the decreased discharge during sympathetic stimulation was the result of a decline in left atrial pressure rather than a result of any direct effect on the receptor per se.