bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative Influence of Acute Sodium and Volume Depletion on Aldosterone Secretion in Nephrectomized Man
Authors: MCCAA ROBERT E. , BOWER JOHN D. , MCCAA CONNIE S.
Published: June 2012

Plasma aldosterone concentration can increase in anephric man during hemodialysis despite the lack of kidneys to produce renin. Because the metabolic clearance rate of aldosterone does not change during hemodialysis, aldosterone secretion must increase in response to sodium depletion, volume depletion, or both. This study was designed to determine the relative influence of sodium and volume depletion by ultrafiltration and hemodialysis on plasma aldosterone concentration in anephric man. Fluid (547 ml) was removed from 13 anephric subjects during 4 hours of ultrafiltration in the absence of hemodialysis. Plasma sodium and potassium concentration did not change during ultrafiltration, but total body sodium and potassium decreased. Plasma aldosterone concentration did not change significantly. Each subject was then hemodialyzed for 8 hours. In 5 subjects, an additional liter of fluid was removed without a significant change in plasma sodium concentration. Plasma aldosterone concentration also did not change in response to the reduction in fluid volume. In 8 subjects, an additional liter of fluid was removed, and plasma sodium concentration decreased from 138.5 to 130.0 mEq/liter. Plasma aldosterone concentration increased from 8.3 to 19.6 ng/100 ml plasma. Three additional anephric subjects were hemodialyzed against a dialysate containing 125.0 mEq sodium/liter for 8 hours. Plasma potassium and total body fluid volume were held constant. Plasma sodium concentration decreased from 138.5 to 125.0 mEq/liter, and plasma aldosterone concentration increased from 7.4 to 24.3 ng/100 ml plasma. These data indicate that acute sodium depletion by hemodialysis accompanied by decreased plasma sodium concentration without a change in plasma potassium concentration or fluid volume can stimulate aldosterone secretion independently of the renal renin-angiotensin system.
Engineering Mechanics for Successive States in Canine Left Ventricular Myocardium
Authors: STREETER DANIEL D. , HANNA WILLIAM T.
Published: June 2012

The relations between end-diastolic (
D
) and end-systolic (S) cavitary volumes (
V
c
), wall volumes (
V
10
), and cavitary dimensions have been studied in the canine and human left ventricle. However, the models selected for left ventricular myocardium do not represent the real heart adequately for a fiber-by-fiber analysis of fiber orientation and sarcomere length during successive states of the ejection cycle. In this study, the endocardial and epicardial surfaces were postulated to be a nested set of truncated ellipsoidal shells of revolution where wall volumes were preserved from
D
to S. Shell dimensions on the semiminor and semimajor axes,
R
and
Z
, respectively, were related to
V
c
and
V
w
by two representations: confocal and nonconfocal. If the focal length
C
= )
1/2
and
C
is the same for each shell, then the shells are confocal, otherwise they are nonconfocal. From measured
V
c
,
V
w
, and epicardial
Z
in
D
, shell dimensions were calculated for states
D
and S, using both confocal and nonconfocal representations, and compared with the measured dimensions. When no empirical corrections were made, the calculated endocardial
R
in S underestimated the measured
R
in S by 12%; moreover, the calculated epicardial
R
in S overestimated the measured
R
in S by 4%. Endocardial and epicardial C measured 3.73 ± 0.33 (SE) cm and 3.79 ±0.34 cm, respectively, in
D
and 3.77±0.11 cm and 3.71 ±0.10 cm, respectively, in S.
Force-Frequency Relationship
Authors: ANDERSON PAGE A. W. , MANRING ANDRES , JOHNSON EDWARD A.
Published: June 2012

The way that contractility varies between beats--the force-frequency relationship--was determined for rabbit papillary muscles held at different lengths. When the maximum rate of rise of tension in a contraction, F
max
, was used as a measure of contractility, the way contractility changed between contractions was independent of length. That is, when the values of F
max
obtained at one length were multiplied by an appropriate scaling factor, the force-frequency relationship determined at that length was indistinguishable from the force-frequency relationship determined at another length. If, however, the peak tension in a contraction was used as a measure of contractility, the Force-frequency relationship generally was not independent of muscle length. Therefore, it is proposed that the ratio of two values of F
max
obtained by perturbing the rate of stimulation at any given length should be tried as a length independent index of the inotropic state of the muscle.
Radioimmunoassay of Prostaglandin A
Authors: ATTALLAH AHMAD A. , LEE JAMES B.
Published: June 2012

A highly specific, sensitive (25 pg) radioimmunoassay for prostaglandin A is described; the assay is characterized by high reproducibility (coefficient of variation 1-2%) and low cross-reactivity with respect to PGE
1
and PGE
2
(10%), PGB
2
(15%), and PGF
2α
(0.01%). High specificity for PGA was obtained by chromatographic separation of the prostaglandins. Since it has been suggested that PGA is a natriuretic "hormone," the concentration of PGA in the renal cortex, outer medulla, and papilla was determined in rabbits on low-sodium and high-sodium diets in the presence and the absence of the prostaglandin synthetase inhibitor indomethacin. In rabbits on the low-sodium diet (12 mEq/24 hours). PGA2 was 15 ± 4 pg/mg in the cortex, 502 ± 67 pg/mg in the outer medulla, and 3740 ± 640 pg/mg in the papilla. In rabbits on saline loading (56 mEq/24 hours), cortical and outer medullary PGA2 rose to 32 ± 6 pg/mg and 1275 ± 290 pg/mg, respectively, but papillary PGA decreased to 1842 ± 480 pg/mg. PGA concentration in the outer medulla and papilla was markedly inhibited by indomethacin (50 mg/day), and this inhibition was associated with sodium retention. The results indicated that sodium induced papillary synthesis of PGA and intrarenal circulation of the prostaglandin to the outer medulla and the cortex possibly via the long veins of the outer medulla occurred. The results are compatible with PGA
2
involvement in salineinduced natriuresis.
Electrophysiological Properties of Canine Purkinje Cells in One-Day-Old Myocardial Infarction
Authors: LAZZARA RALPH , EL-SHERIF NABIL , SCHERLAG BENJAMIN J.
Published: June 2012

Electrophysiological mechanisms which underlie the ectopic ventricular beats occurring 1 day after occlusion of the anterior descending coronary artery of dogs were explored. In intact dogs, bipolar electrograms were recorded in the infarcted and normal zones. Both Purkinje and ordinary myocardial potentials were recorded from the endocardial surface of the normal zone, but only Purkinje potentials were recorded from the infarcted zone. The Purkinje potentials in the infarcted zone were diminished in amplitude and rapidity. The threshold for endocardial pacing was higher in the infarcted zone than it was in the normal zone. The refractory periods of Purkinje cells were longer in the infarcted zone than they were in the normal zone. Excised specimens of endocardial surface containing the infarcted zone were superfused with Tyrode's solution. No ordinary myocardial cells were electrically active at the endocardial surface of the infarcted zone. Purkinje cells showed diminished resting and action potentials, reduced upstroke velocity, enhanced automaticity and phase 4 depolarization, and long action potentials with prolonged phase 3. Excitability was depressed within the infarcted zone. During superfusion, even with Tyrode's solution poor in oxygen and free of dextrose, Purkinje cells recovered toward normal with respect to amplitude of resting and action potentials, upstroke velocity, automaticity, and excitability. The prolonged action potentials persisted. Repetitive firing was easily elicited within the infarcted zone. Various types of pacemaker activity were detected within the infarcted zone. Thus Purkinje cells in the infarcted zone showed distinctive alterations in electrophysiological properties which were probably related to deleterious factors that accumulated in that zone. It is likely that the arrhythmia which occurred in the intact dogs at this time originated within the altered Purkinje cells of the infarcted zone.
Dynamics of Plasma-Interstitial Fluid Distribution following Intravenous Infusions in Dogs
Authors: LEONARD JOEL I. , ABBRECHR PETER H.
Published: June 2012

The dynamic distribution of intravenously infused solutions between the plasma and the interstitial compartments was studied. A mathematical model developed to simulate infusion experiments considered transcapillary fluid and protein exchange, lymph flow, interstitial compliance, capillary surface area, and peripheral vascular resistance. The experimental arterial and venous blood pressure responses and the infusion rate were used as forcing functions. A piecewise optimization procedure resulted in excellent agreement between the simulated and experimental plasma volume responses and provided reasonable time-varying behavior for the precapillary-postcapillary resistance ratio and the capillary surface area. The model was tested with experimental data collected by infusing isotonic Tyrode's or dextran solution into nephrectomized dogs. Blood volume was measured continuously by giving a single injection of
51
Cr-labeled red cells and monitoring the blood radioactivity as it passed through an extracorporeal shunt. The model predicted qualitatively different responses for the precapillary-postcapillary resistance ratio depending on the type of solution infused and the value assumed for tissue compliance. Further analysis indicated that the assumption of a tissue space with overall high compliance (approximately 100 ml/kg mm Hg
-1
) is more realistic than are the much lower compliances previously reported. Parametric studies revealed that the capillary surface area, the precapillary-postcapillary resistance ratio, and the tissue compliance, but not the lymph flow or the transcapillary protein movement, exert a strong influence on the short-term plasma retention of infused fluids.
Reflexes from the Aortic Baroreceptor Fibers in the Cervical Vagus of the Cat and the Dog
Authors: ITO CYRIL S. , SCHER ALLEN M.
Published: June 2012

The baroreceptor fibers which arise from the aortic arch course centrally within the vagus nerve in the dog, and they usually follow this path in the cat. Near the origin of the superior laryngeal nerve, a separate branch of the cervical vagus (the cervical aortic nerve) arises. Previously, it was thought that this nerve contained all the important baroreceptor afferents. Aortic baroreceptor fibers that are not within the cervical aortic nerve were studied in the anesthetized cat and dog after cervical aortic and carotid sinus nerves had been sectioned. Some experiments were acute, but most were conducted 13-60 days after nerve section (to allow transected nerves to degenerate). After degeneration, baroreceptor activity was found in the peripheral aortic nerves in most animals. The sensory terminals of the surviving baroreceptor fibers were on the aortic arch on the left side and at the root of the right subclavian artery on the right side. In one of four chronic cats, four of eight chronic dogs after degeneration, and one of three animals in acute experiments a depressor response (8-70 mm Hg in chronic and 10 mm Hg in acute experiments) followed stimulation of the peripheral aortic nerve. The surviving aortic baroreceptor fibers coursed centrally in the cervical vagus.
Deactivation of Contraction by Quick Releases in the Isolated Papillary Muscle of the Cat
Authors: BODEM RAINER , SONNENBLICK EDMUND H.
Published: June 2012

In the isolated cat papillary muscle, the time course of activation during isometric contraction was measured using instantaneous velocity of shortening after quick releases at constant contractile element length and controlled load. Activation rose and declined ahead of isometric force. This course of activation could be altered by the mode of the quick release. Undamped quick releases increasingly deactivated contraction with time. Deactivation was reduced by damping the rapid movement of the lever after the release and by increasing the afterloads to which the releases were made, thus lessening the extent of the releases. The curves of activation obtained from releases to different afterloads converged after the first half of the rising phase of the twitch. Deactivation from quick releases was eliminated by tetanizing the muscle. Hence, the instantaneous relation of force and velocity of shortening was not unique relative to time except when the muscle was tetanized. Deactivation was also reduced by lowering the temperature, by adding 10 m
M
caffeine, or by increasing the Ca
2+
concentration in the bathing medium in the presence of 10 m
M
caffeine. These results suggest that quick releases deactivate contraction by uncoupling crossbridges which can be reformed if the Ca
2+
available to activate contractile sites is not sequestered elsewhere.
Reflex Blood Pressure Control during Acute Myocardial Ischemia in the Conscious Dog
Authors: PETERSON D. FRED , BISHOP VERNON S.
Published: June 2012

Occlusions of the left circumflex coronary artery were performed before and after surgical denervation of sinoaortic baroreceptors in conscious, resting dogs. The removal of baroreceptors dramatically compromised arterial blood pressure maintenance. Mean pressure fell 9.1 mm Hg before denervation and 33.0 mm Hg after denervation. Aortic flow was reduced somewhat more without baroreceptors, and calculated total peripheral resistance fell 15% at the peak of occlusion in denervated dogs compared with a 2% increase in intact dogs. Flow studies indicated that femoral resistance was maintained or increased under the influence of active arterial baroreceptors but that femoral resistance fell dramatically in their absence. Renal resistance fell during coronary occlusion whether or not arterial baroreceptors were functional. Under both conditions, renal flow was maintained near its resting level. Results of this study suggest an important function in the maintenance of perfusion pressure by arterial baroreceptors during left circumflex coronary artery occlusion. The elimination of the arterial baroreceptors unmasked a dilatory response that reduced total peripheral resistance and, consequently, arterial blood pressure. Vessels which supply skeletal muscle and skin collectively were critically involved, but flow to the kidneys did not appear to play an important role.
Modification of the Effects of Hypertension on Lysosomes and Connective Tissue in the Rat Aorta
Authors: WOLINSKY HARVEY , GOLDFISCHER SIDNEY , SCHILLER BERNICE , KASAK LISA E.
Published: June 2012

The relationship of Iysosomes to the vascular effects of hypertension and the possible modification of these effects by anti-inflammatory agents (methylprednisolone and aspirin), vitamin E, and estrogen were studied. Each of these agents was given to a group of hypertensive rats; untreated hypertensive rats and normotensive rats served as controls. Vessel wall morphology and dimensions of aortas from hypertensive rats were unaffected by treatment. Usual connective tissue accumulations seen in hypertensive vessels were suppressed to normotensive levels in the methylprednisolone- and estrogen-treated hypertensive groups. Two lysosomal enzymes, acid phosphatase and
N
-acetyl-β-
d
-glucosaminidase (NAGA), increased over normal levels in hypertensive vessels from 1.03 ± 0.08 (
SE
) to 2.04 ± 0.19 µmoles/aortic pair hour
-1
and from 1.10 ± 0.24 to 4.57 ± 0.38 µmoles/aortic pair hour
-1
for the respective enzymes. Normal enzyme levels in estrogen-treated hypertensive rats (1.14 ± 0.15 µmoles/aortic pair hour
-1
for acid phosphatase and 2.04 ± 0.44 µmoles/aortic pair hour
-1
for NAGA) and intermediate levels in methylprednisolone-treated hypertensive rats (1.35 ± 0.10 µmoles/ aortic pair hour
-1
for acid phosphatase and 2.48 ± 0.54 µmoles/aortic pair hour
-1
for NAGA) were found. Other treated groups showed the usual elevations associated with hypertension. These group differences were also seen after cytochemical staining for lysosomal acid phosphatase and NAGA. The parallel changes in aortic connective tissue and lysosomal enzymes in hypertension and their modification by two drugs suggest that these events are related.
Vascular Muscle Series Elastic Element Stiffness during Isometric Contraction
Authors: DOBRIN PHILIP B.
Published: June 2012

Series elastic element stiffness was studied during isometric muscle contraction in cylindrical segments of dog common carotid artery. These vessel segments were mounted in vitro and restored to in situ length. Vessel diameter was constantly monitored with a linear displacement transducer. The arteries were subjected to isometric contraction by adding norepinephrine to the bath and elevating the transmural pressure enough to maintain constant vessel diameter. Small, rapid quick release-quick stretch cycles were performed repeatedly during isometric contractions to evaluate the stiffness of the undamped series elastic element. After contraction was complete, repeated quick release-quick stretch cycles were also performed during inactivation of the muscle caused by the administration of potassium cyanide. At strains up to the peak in the length-active tension curve, series elastic element stiffness was a linear function of stress thoughout both isometric contraction and isometric relaxation for both quick releases and quick stretches. Vessels excited at strains less than that associated with the peak in the length-tension curve (100 mm Hg) exhibited similar stress-series elastic element stiffness slopes, but vessels excited at larger strains exhibited decreased or negative stress-series elastic stiffness slopes. Studies on potassium cyanide-poisoned vessels failed to indicate any alteration in the quick release properties of the connective tissue at large strains. The concomitant decline in the stress-series elastic element stiffness slope and the active isometric stress at large strains suggests (1) that the series elastic element undergoes mechanical yielding at high stresses or (2) that the series elastic element is an integral part of the force-generating apparatus.
Distribution of the Coronary Blood Flow across the Canine Heart Wall during Systole
Authors: DOWNEY JAMES M. , KIRK EDWARD S.
Published: June 2012

The transmural distribution of left coronary blood flow during systole was studied by measuring the myocardial uptake of a bolus of
86
Rb introduced into the coronary circulation when the perfusion was limited to the periods of systole. The measurement revealed a transmural gradient of systolic blood flow with a flow rate in the outer fourth of the left ventricle about twice that in the inner fourth. A gradient of flow encompassing all depths of myocardial tissue revealed that intramyocardial pressure during systole was not sufficient to completely collapse the vessels and, therefore, did not exceed intraventricular pressure. The results of this experiment indicate that intramyocardial pressure limits coronary blood flow through a vascular sluice mechanism.
Effects of Myocardial Strains on Coronary Blood Flow
Authors: DOWNEY JAMES M. , DOWNEY H. FRED , KIRK EDWARD S.
Published: June 2012

Systole causes a redistribution of coronary blood flow away from the subendocardium. In the present study the relative contribution of shortening of the myocardial fibers (wall strains) and of pressure development in the ventricular lumen to redistribution were determined. The distribution of coronary blood flow during systole in hearts ejecting into a severed aorta (large wall strains and near-zero afterload) was compared with that in isovolumetrically contracting hearts (reduced wall strains and significant afterload). A quantitative index of the distribution of coronary blood flow during systole was provided by the myocardial uptake of a bolus of
86
Rb or
42
K injected when constant-pressure perfusion of the left coronary artery was restricted with a solenoid-controlled pump to the period of systole. The coronary blood flow during systole in the subendocardium of the ejecting heart was 62% of that in the subepicardium. A similar gradient in the systolic flow with the endocardium receiving 37% of the blood flow to the epicardium was observed in the hearts contracting isovolumetrically. Removing the afterload by severing the aorta abolished the transmural differences in coronary blood flow. In the present experiment cardiac strains per se did not redistribute coronary blood flow through shear or traction forces on the coronary vasculature, but rather, coronary blood flow was affected only by compressive stresses in the myocardium. Contraction in the absence of afterload influenced overall coronary resistance, however; 18% of the resting coronary resistance was associated with shortening alone. An additional 11% of the resting coronary resistance appeared when pressure development accompanied shortening. Coronary blood flow patterns indicated two separate compressive stresses in the left ventricle. The first stress was associated with pressure development and increased with myocardial depth. The second stress was smaller; it was associated with shortening and uniformly distributed.
Intimal Thickening in Normochoiesterolemic Rhesus Monkeys Fed Low Supplements of Dietary Cholesterol
Authors: ARMSTRONG MARK L. , MEGAN MARJORIE B. , WARNER EMORY D.
Published: June 2012

Rhesus monkeys were fed a high-fat diet containing either 0, 43, or 129 µg/kcal of cholesterol for 18 months. In the monkeys on the cholesterol-supplemented diets, changes in plasma cholesterol remained within the range found in monkeys fed the cholesterol-free diet. Monkeys on the cholesterol-supplemented diets were compared with monkeys given no dietary cholesterol with range-matched plasma cholesterol; intimal thickness of the aorta and branch arteries, distribution of lipoprotein cholesterol, and tissue content of cholesterol in aorta and liver were considered. The monkeys on the cholesterol-supplemented diets showed intimal thickening with more sudanophilia and increased aortic cholesterol, a decrease in plasma high-density lipoprotein cholesterol, and an increase in low-density lipoprotein cholesterol, and the monkeys fed the higher amount of dietary cholesterol showed an increase in hepatic cholesterol. No null point for the effect of dietary cholesterol on arterial intima was found even at an intake level far below that conventionally used for the induction of experimental atherosclerosis in the nonhuman primate. The intimal changes found in response to very low cholesterol intake imply that subtle qualitative alterations in lipoproteins are of critical importance to our understanding of lesion induction.
Prostaglandin B
2
-Induced Cutaneous Vasoconstriction of the Canine Hind Paw
Authors: GREENBERG STANLEY , ENGELBRECHT JAMES A. , WILSON WILLIAM R.
Published: June 2012

The cutaneous vascular effects of prostaglandin B
2
(PGB
2
) were studied in dogs during constant-flow perfusion of the hind paw. The effects of PGB
2
(50-800 ng/kg min
-1
, ia) on systemic pressure, hind-paw perfusion pressure, and responses to local heating at 45°C (30 seconds) and cooling at 4°C (90 seconds) were measured in 44 dogs. PGB
2
increased perfusion pressure by 50 ± 19 mm Hg to 218 ± 21 mm Hg without any effect on systemic arterial blood pressure. The pressor response to cooling increased from 34 mm Hg to 53 mm Hg (50 ng/kg min
-1
PGB
2
), but the dilator response to heating was reduced significantly during infusions of PGB
2
(50 and 100 ng/kg). Acute denervation and reserpine treatment (0.5 mg/kg dog
-1
for 2 days) reduced the constrictor responses to PGB
2
. The abilities of PGB
2
to produce intense vasoconstriction, which is blocked by acute denervation and reserpine, to enhance responses to cooling, and to antagonize responses to heating make this preparation a useful model for the study of Raynaud's phenomenon and suggest that a prostaglandin, perhaps PGB
2
ss, may participate in cutaneous vasospastic disorders.
Depressed Fatty Acid and Acetate Oxidation and Other Metabolic Defects in Homogenates from Hearts of Hamsters with Hereditary Cardiomyopathy
Authors: KAKO K. JOE , THORNTON MAUREEN J. , HEGGTVEIT H. ALEXANDER
Published: June 2012

Metabolic changes in heart homogenate of Syrian hamsters with hereditary cardiomyopathy (BIO 14.6 strain) were examined. Oxidation of labeled fatty acids and acetate by myopathic homogenates was severely depressed; CO
2
production from labeled acetate was only one-fifteenth of the control value, and butyrate oxidation was suppressed to one-fourth of the control value. Although the addition of carnitine enhanced the oxidation of palmitate and octanoate by homogenates from both healthy and cardiomyopathic hamsters, the magnitude of the depression of oxidation (60-80%) in the myopathic homogenates was not influenced by carnitine. No change occurred in the rate of formation of palmitoyl-CoA from palmitoyl-
l
-carnitine or in the activity of acyl-CoA synthetases; similarly, the one-step oxidation of [1-
14
C]pyruvate, [1-
14
C]α-ketoglutarate, and succinate was unimpaired in cardiomyopathy, and the oxidation of [2-
14
C]pyruvate and [U-
14
C]α-ketoglutarate was maintained at a relatively high level (63-71% of control). In contrast, oxidation of [1, 4-
14
C]- and [2, 3-
14
C]succinate and [1-
14
C]acetyl-CoA by the myopathic homogenates was depressed to only 40% of the control values. The mechanism responsible for these defects in substrate oxidation by tissue homogenates from cardiomyopathic hearts has not been elucidated; however, significant increases in the activities of two of five hydrolytic enzymes indicate the possible involvement of lysosomes. Ventricular RNA and DNA, the ratio of RNA to DNA and the ratio of heart weight to body weight were all significantly increased, but myocardial water and triglyceride content and esterification of [1-
14
C]palmitate into neutral lipids showed no significant change.
Defective Activation of Clotting, Fibrinolytic, and Permeability-Enhancing Systems in Human Fletcher Trait Plasma
Authors: SALTO HIDEHIKO , RATNOFF OSCAR D. , DONALDSON VIRGINIA H.
Published: June 2012

When normal plasma is exposed to foreign surfaces, Hageman factor (HF, factor XII) is activated; under appropriate circumstances, it then initiates reactions leading to coagulation, fibrinolysis, increased vascular permeability, esterolytic activity, and kinin formation. However, coagulation, fibrinolysis, and increased vascular permeability were impaired in plasma from an individual with Fletcher trait, despite a normal concentration of HF that is functionally and immunologically indistinguishable from that in normal plasma. This defective clotting is completely repaired by the addition of small amounts of normal plasma, HF-deficient plasma, plasma thrombo-plastin antecedent (PTA)-deficient plasma, or activated PTA but only partially repaired by the addition of activated HF. Defective fibrinolysis and permeability-enhancing activity were partially corrected by the addition of small amounts of normal plasma, HF-deficient plasma, PTA-deficient plasma, or activated HF. A preparation of partially purified plasma kallikrein largely repaired defective coagulation and fibrinolysis in Fletcher trait plasma in the presence of kaolin. In immunodif fusion studies, no precipitin line formed between Fletcher trait plasma and monospecific antikallikrein serum. Fletcher trait plasma appeared to be deficient in a plasma prekallikrein, which most probably participates in the functioning of activated HF. These studies emphasize the intimate relationships among clotting, fibrinolysis, and enhancement of vascular permeability.
In Vivo Analysis of Adrenergic Receptor Activity of Dobutamine
Authors: ROBIE NORMAN W. , NUTTER DONALD O. , MOODY CARROLL , MCNAY JOHN L.
Published: June 2012

Studies were performed in anesthetized dogs to evaluate the cardiac and systemic effects of intravenously administered dobutamine and to determine its direct effects on the renal and femoral vascular beds. The results demonstrated that dobutamine possessed an inotropic efficacy similar to that of isoproterenol and norepinephrine; its chronotropic effect was similar to or greater than that of norepinephrine. In contrast to norepinephrine, dobutamine increased cardiac output and reduced total peripheral resistance with minimal effects on mean aortic pressure. Studies on the denervated hind limb demonstrated that dobutamine stimulated both alpha and beta receptors. The dose of dobutamine which produced a 50% increase in femoral blood flow was 180 times the required dose of isoproterenol and the dose which produced a 50% increase in contractile force was 43 times the required dose of isoproterenol. Studies on the renal vasculature demonstrated that dobutamine caused no dopamine-like renal vasodilator activity and only minor vasodilation mediated by beta receptors. We concluded that dobutamine is more cardioselective than is isoproterenol. The dobutamine-induced decrease in peripheral resistance observed in the whole dog was presumably due to increased myocardial contractility coupled with a greater net effect of beta-adrenergic vasodilation than alpha-adrenergic vasoconstriction. Studies with reserpine-treated dogs showed that all dobutamine-induced effects were due to a direct action on receptors.
Role of Positive Feedback in the Atrioventricular Nodal Wenckebach Phenomenon
Authors: LEVY MATTHEW N. , MARTIN PAUL J. , ZIESKE HARRISON , ADLER DALE
Published: June 2012

In the atrioventricular (AV) nodal Wenckebach phenomenon, there is a progressive increase in the P-R interval and a concomitant reduction in the R-P interval. Two series of experiments were conducted on anesthetized dogs to ascertain whether the changes in the P-R interval depended on the associated changes in the R-P interval. In one series of experiments, the atrium was paced at various basic cycle lengths, and a single test cycle was interposed about every 100 beats. When the test cycle was very short, the increase in the P-R interval sometimes exceeded the associated reduction in the R-P interval. During the subsequent basic cycle, although the P-P interval was much greater than it was during the test cycle, there was a further reduction in the R-P interval. When this change in the R-P interval was appreciable, AV conduction failed despite the increase in cycle length. In the second series of experiments, the AV nodal Wenckebach phenomenon was induced by rapid atrial pacing. When the stimulation mode was suddenly altered to maintain a constant R-P interval, the Wenckebach rhythm immediately ceased, although the mean heart rate had not changed significantly. Therefore, it appears that above a critical heart rate a positive feedback loop is established in which an increase in the P-R interval evokes a corresponding decrease in the R-P interval. In turn, the curtailed R-P interval that reflects a less complete recovery of AV nodal excitability elicits a still greater increase in the P-R interval. This cycle continues until an impulse is ultimately blocked. Clamping the R-P interval opens the feedback loop and terminates the arrhythmia.
Glass Microelectrode Studies on Intramural Papillary Muscle Cells
Authors: SOLBERG LLOYD E. , SINGER DONALD H. , TEN EICK ROBERT E. , DUFFIN EDWIN G.
Published: June 2012

Although the electrophysiological properties of intramural ventricular myocardial cells are important to an understanding of cardiac excitation and conduction, they have not been well defined. The paucity of information stems from limitations on the depth of penetration by glass microelectrodes and from difficulties in perfusing the deep layers. Therefore, a tissue slicing technique that satisfactorily exposes all the layers of a papillary muscle specimen from the endocardium to the epicardium was developed for electrophysiological examination. Glass microelectrodes were then used to explore these slice preparations to define the electrophysiological characteristics of intramural cells in the normal dog. Transmem-brane potentials recorded from subendocardial and deep myocardial cells in the papillary muscle slices were comparable to those recorded from standard preparations. Similarities included action potential duration and configuration, relationships among resting potential, action potential configuration, and extracellular potassium concentration, and dependency of action potential duration on cycle length. However, the average magnitudes of measured electrophysiological characteristics were consistently greater in the subsurface cells tested in papillary muscle slices than they were in the surface cells tested in the standard preparations, i.e., resting potential was 2-4 my more negative, action potential amplitude was 7-9 my larger, and maximum rate of voltage change (maximum dV/dt) was 40-140 v/sec larger. Deep myocardial tissues also exhibited enhanced responsiveness (the curve relating activation potential to maximum dV/dt of the response shifted up and to the left), cell populations with large maximum dV/dt, and estimated conduction velocities in excess of three times those in the surface cell layers. These findings provide a reasonable explanation for (1) discrepancies between previously reported values for ventricular conduction velocity, (2) rapid impulse spread to the papillary muscle tip, and (3) bidirectional activation of the papillary muscle and large trabeculae. They also suggest the possibility of functional pathways that facilitate rapid activation of the deep myocardial lavers.
Instantaneous Pressure-Volume Relationships and Their Ratio in the Excised, Supported Canine Left Ventricle
Authors: SUGA HIROYUKI , SAGAWA KIICHI
Published: June 2012

We have previously shown in the normally ejecting canine left ventricle that
E
(
t
), the time-varying ratio of instantaneous pressure,
P
(
t
), to instantaneous volume,
V
(
t
), is little affected by end-diastolic volume or aortic pressure. The present study on an excised, supported canine heart preparation indicates that the thesis on
E
(
t
) is also valid for either totally isovolumic or auxobaric beats. Intraventricular volume was measured more accurately than it was in the previous study by a new volumetric system. Regression analysis of the data showed that the instantaneous pressure-volume relationship could be approximated by the equation
P
(
t
) =
E
(
t
).[
V
(
t
) -
V
d
], where
V
d
is an empirical constant, over a wide range of intraventricular volume. Similar
E
(
t
) curves were obtained from both isovolumic and auxobaric beats for a given contractile state. When the contractile state of the preparation was enhanced by a constant-rate infusion (0.2 µg/min) of norepinephrine or isoproterenol into the coronary artery, the peak magnitude of
E
(
t
) increased 63% from 3.6 mm Hg/ml and the time to peak
E
(
t
) shortened 10% from 175 msec. We conclude that the present investigation substantiates our earlier study which established a link between
E
(
t
) and the contractile state of the heart.
Lipoprotein Uptake and Metabolism by Rat Aortic Smooth Muscle Cells in Tissue Culture
Authors: BIERMAN EDWIN L. , STEIN OLGA , STEIN YECHEZKIEL
Published: June 2012

Aortic smooth muscle cells from the rat were successfully grown in tissue culture and shown to have characteristic morphology.
125
I-labeled homologous very low density lipoproteins and high density lipoproteins were taken up by these smooth muscle cells during incubation for 48 hours at the stationary phase. Despite multiple washings, a large proportion of the lipoprotein radioactivity associated with the cells was apparently surface bound and trypsin releasable. With both lipoprotein fractions, lipid and protein uptake by the cells measured after trypsinization was related to time and to the amount of lipoprotein protein added to the medium. Compared with protein, there was a disproportionately greater entry of lipid radioactivity into the cells. Light and electron microscope autoradiography localized the label intracellularly over the cell cytoplasm, cell boundaries, and, in some cells, over lysosomes. On the basis of either protein uptake or whole particle uptake, approximately four times as much high density lipoprotein as very low density lipoprotein was taken up by the smooth muscle cells. To assess metabolism and degradation of high density lipoproteins, aortic smooth muscle cells were incubated in fresh unlabeled medium for 48 hours after exposure to
125
I-labeled high density lipoproteins. A large proportion of radioactivity released was trichloroacetic acid precipitable, suggesting some release of whole lipoprotein protein; however, these lipoproteins appeared to be modified when they were tested with anti-high density lipoprotein antiserum. Also, water-soluble radioactivity (presumably protein breakdown products) was released in amounts that averaged 3% of the protein label in the cells. These results indicate that although aortic smooth muscle cells growing in tissue culture can rapidly take up lipids and lipoproteins, catabolism of lipoprotein protein is slow. Correlative biochemical and ultrastructural analysis suggests the possibility of regurgitation of noncatabolized lipoprotein protein by reverse endocytosis.
Protective Action of Methylprednisolone on the Myocardium during Experimental Myocardial Ischemia in the Cat
Authors: SPATH JAMES A. , LANE DAVID L. , LEFER ALLAN M.
Published: June 2012

Cats subjected to coronary artery occlusion were used to study the effect of methylprednisolone on the release of lysosomal acid hydrolases and creatine phosphokinase (CPK) from ischemic myocardial tissue. Plasma CPK activity was increased significantly 2 hours after occlusion and increased eightfold 5 hours after ligation in vehicle-treated cats. Intravenous administration of methylprednisolone (30 mg/kg) 30 minutes before or 60 minutes after occlusion significantly limited the increases in plasma CPK activity to values only slightly greater than those observed in sham-operated cats. Plasma activities of the lysosomal hydrolases, β-glucuronidase and cathepsin D, were comparable in all groups of cats and did not change during the 5-hour observation period. Nevertheless, cathepsin D and β-glucuronidase activities were reduced 41% and 33%, respectively, in the ischemic portion of the myocardium of untreated cats subjected to coronary artery ligation. The CPK activity of the ischemic myocardium was reduced 43% in these cats. Pre- or posttreatment of cats with methylprednisolone prevented the decline in CPK and lysosomal hydrolase activity of ischemic myocardium. These data indicate that lysosomal disruption is a consequence of myocardial ischemia and that pre- or posttreatment with methylprednisolone prevents the leakage of myocardial lysosomal and cellular enzymes. Moreover, the methylprednisolone-induced stabilization of myocardial membranes appears to be related to the ability of glucocorticoid to limit infarct size following myocardial ischemia.
Kinetics of the Inhibitory Effect of Pepstatin on the Reaction of Hog Renin with Rat Plasma Substrate
Authors: ORTH HELMUT , HACKENTHAL EBERHARD , LAZAR JEFFREY , MIKSCHE ULRIKE , GROSS FRANZ
Published: June 2012

The reaction between hog renin and rat angiotensinogen followed Michaelis-Menten kinetics. A K
m
value of 1,109 ng angiotensin/ml was determined for the rate of angiotensin formation at pH 7.4 and 37°C. The pH optimum for the reaction of hog renin with rat angiotensinogen was between 6.8 and 7.0. Pepstatin inhibited the reaction in a noncompetitive way. The maximum inhibitory effect occurred at approximately pH 6; at values above pH 8.0, pepstatin had no inhibitory effect. The effect of pepstatin was reversible, since renin activity could be restored by 24 hours of dialysis against distilled water. A 50% inhibition of the enzymatic activity of 0.01 dog units of hog renin was obtained with 0.45 µg pepstatin/ml.
The Myocardial Depressant Effect of Beta-Receptor Blocking Agents
Authors: LIANG CHANG-SENG , HOOD WILLIAM B.
Published: June 2012

dl
-Propranolol,
d
-propranolol, and practolol were administered in increasing doses to conscious dogs before and after acute coronary artery occlusion.
dl
-Propranolol and practolol caused dose-dependent decreases in cardiac output, stroke volume, stroke work, and maximum rate of left ventricular pressure rise before and after coronary artery occlusion. These parameters were reduced 25-40% after the largest cumulative doses--1.43 mg/kg for
dl
-propranolol and 52 mg/kg for practolol--were administered. The degree of beta-receptor blockade increased in proportion to the logarithm of plasma drug concentration. After occlusion, both drugs produced identical decreases in cardiac output at equivalent degrees of beta-receptor blockade. Neither drug affected resting heart rate before infarction, and neither drug reduced the tachycardia induced by coronary artery occlusion; this tachycrotic response probably resulted from cardiac vagal withdrawal. Mean systemic arterial blood pressure and total peripheral vascular resistance increased following beta-receptor blockade before infarction, most likely because of increased peripheral vascular alpha-adrenergic activity. These two effects did not occur after coronary artery occlusion, probably because vascular alpha-adrenergic activity had already been stimulated.
d
-Propranolol produced none of these effects. We concluded that the cardiodepressant effect of beta-receptor blocking agents in the doses administered was caused by their inhibition of endogenous sympathetic tone to the heart rather than by their quinidinelike action.
The Signal Perceived by the Macula Densa during Changes in Renin Release
Authors: FREEMAN RONALD H. , DAVIS JAMES O. , GOTSHALL ROBERT W. , JOHNSON J. ALAN , SPIELMAN WILLIAM S.
Published: June 2012

Renin secretion was studied in acute experiments in dogs during occlusion of the ureter alone (experiment 1), ureteral occlusion with a superimposed intrarenal infusion of papaverine (experiment 2), or ureteral occlusion with a superimposed intravenous ethacrynic acid injection (experiment 3) and following release of the ureteral occlusion (all three experiments). In all three experiments, ureteral occlusion increased renin secretion four- to fivefold. In experiment 2, papaverine, an inhibitor of smooth muscle contractility, was infused intrarenally during the last 20 minutes of ureteral occlusion, but renin secretion was unchanged by the infusion. Renin secretion decreased rapidly and was at the control level 5, 12½, and 27½ minutes after release of the occlusion, but urinary sodium concentration and excretion rate increased markedly during this period. In experiment 3, a superimposed injection of ethacrynic acid failed to alter renin secretion during ureteral occlusion. After release of the ureter, renin secretion remained unchanged for the first 5 minutes. Although renin secretion had decreased 12½ and 27½ minutes after release of the occlusion, it was still elevated twofold above the control level. Again, sodium excretion increased markedly and urinary sodium concentration was high after ureteral release. These findings support the hypothesis that the rate of renin release is inversely related to the rate of sodium transport by the macula densa cells.
Characterization and Localization of Ventricular Arrhythmias Resulting from Myocardial Ischemia and Infarction
Authors: SCHERLAG BENJAMIN J. , EL-SHERIF NABIL , HOPE RONALD , LAZZARA RALPH
Published: June 2012

Electrocardiograms and electrograms were recorded in 18 dogs anesthetized with sodium pentobarbital. Using endocardial and epicardial plunge wire electrodes in normal and ischemic or infarcted areas, activation of Purkinje and regular muscle tissue was studied within the first 20-30 minutes and 24 hours after anterior descending coronary artery ligation. The ventricular arrhythmias in the first 20 minutes were abolished during vagally induced atrial arrest, but ventricular automaticity was unchanged from that during the control period. These rate-related arrhythmias were uniformly associated with marked diminution and delay of epicardial activation in the ischemic zone. Slowing of the heart rate caused recovery of the timing, form, and duration of these epicardial potentials with the coincident disappearance of ventricular arrhythmias. The ventricular arrhythmias of the early phase spontaneously subsided with time 20-30 minutes after ligation; concurrently, epicardial activation in the ischemic zone improved. The ventricular arrhythmias noted 24 hours after coronary artery ligation were revealed by vagally induced atrial slowing and suppressed by rapid atrial pacing, indicating the existence of enhanced ventricular automaticity. There was a loss of endocardial muscle activation; Purkinje tissue was depressed but viable in the infarcted zone. The sequence of firing during many of the multifocal ventricular ectopic beats showed that the earliest activation arose from Purkinje tissue in the infarcted zone. However, other ectopic beats appeared to arise from infarcted epicardial muscle.
Participation of Central Serotonergic Neurons in the Control of the Circulation of the Unanesthetized Rabbit
Authors: Wing LINDON M. H. , CHALMERS JOHN P.
Published: June 2012

The role of central serotonergic neurons in circulatory control was studied in rabbits given intracisternal injections of 5, 6-dihydroxytryptamine (5, 6-DHT, 300 µg/kg) to cause degeneration of central serotonergic nerve terminals and depletion of central serotonin stores. In normal rabbits, intracisternally administered 5.6-DHT produced decreases in mean arterial blood pressure (11%,
P
< 0.001) and heart rate (9%,
P
< 0.001) that were maximum 1 week after injection. Central serotonin levels were reduced to less than 50% in the spinal cords of the rabbits treated with 5, 6-DHT compared with the levels in vehicle-injected controls. Pretreatment with intracisternally administered 5, 6-DHT completely prevented the sustained increases in mean arterial blood pressure and heart rate seen after sinoaortic denervation in control rabbits. In rabbits with neurogenic hypertension following sinoaortic denervation, treatment with intracisternally administered 5, 6-DHT caused a prompt, persistent reduction in mean arterial blood pressure and heart rate. Intracisternally administered 5, 6-DHT failed to interfere with the development or the maintenance of the hypertension that follows bilateral wrapping of the kidneys with cellophane. This study suggests that central serotonergic neurons participate in the baroreceptor reflex arc, possibly at the bulbospinal level. The integrity of these neurons appears to be necessary for the development of sustained neurogenic hypertension following sinoaortic denervation but to be of minimum importance in experimental renal hypertension in the rabbit.
Effect of Theophylline and Adrenergic Blocking Drugs on the Renin Response to Norepinephrine In Vitro
Authors: NOLLY HECTOR L. , REID IAN A. , GANONG WILLIAM F.
Published: June 2012

The effects of norepinephrine, theophylline, and adrenergic blocking drugs on renin release from rat kidney slices were studied in vitro.
l
-Norepinephrine increased renin release into the incubation medium; this increase was accompanied by an increase in the renin content of the slices. Statistically significant increases in renin release were produced by 10
-5
M
and 2 x 10
-5
M
l
-norepinephrine.
d
-Norepinephrine in the same doses was ineffective. Theophylline (10
-3
M
) had no effect by itself, but it potentiated the effect of
l
-norepinephrine on renin release. The response to
l
-norepinephrine was markedly suppressed by
l
-propranolol (10
-4
M
) but not by
d
-propranolol (10
-4
M
). The α-receptor blocking agents phentolamine (10
-4
M
) and phenoxybenzamine (10
-4
M
) increased rather than decreased the effect of
l
-norepinephrine. These results are consistent with a direct intrarenal effect of norepinephrine on renin release; this effect appears to be mediated by a β-adrenergic mechanism.