bluuebunny/crossref_metadata_2025 huggingface dataset:
Microelectrode Demonstration of Wedensky Facilitation in Canine Cardiac Purkinje Fibers
Authors: BAILEY JOHN C. , SPEAR JOSEPH F. , MOORE E. NEIL
Published: June 2012

Microelectrode techniques were used to examine changes in excitability of canine Purkinje fibers at sites distal to complete conduction block. Immediately distal to a site where impulse propagation failed, it was possible to record subthreshold depolarizations. Intracellular stimulation of the Purkinje cells exhibiting these subthreshold responses with constant-current pulses of subthreshold intensity enabled full-amplitude, propagated action potentials to develop when the subthreshold stimuli were timed to occur during the slow upstroke of the subthreshold depolarization. This period of a decreased current threshold requirement for stimulation observed during the first 40-50 msec of the subthreshold depolarization was followed by a period during which suprathreshold stimuli were necessary to evoke propagated responses. Propagated action potentials which interrupted the subthreshold response during its repolarization phase demonstrated reduced maximal rising velocities. We concluded that summation of appropriately timed subthreshold stimuli could induce full-amplitude, regenerative, all-or-none responses and that the changes in excitability of subthreshold responses were not solely voltage dependent. Sodium inactivation appeared to be responsible for the depressed rate of action potentials that interrupted the subthreshold response during its repolarization phase and might participate in the coincident depressed excitability.
Impulses in Slowly Conducting Vagal Fibers from Afferent Endings in the Veins, Atria, and Arteries of Dogs and Cats
Authors: COLERIDGE HAZEL M. , COLERIDGE JOHN C. G. , DANGEL ALBERT , KIDD CECIL , LUCK JOHN C. , SLEIGHT PETER
Published: June 2012

Afferent impulses in 61 fine myelinated or unmyelinated vagal fibers arising from endings in large blood vessels ("vascular endings") were recorded in anesthetized dogs and cats. The endings had a sparse, irregular spontaneous discharge, or they were quiescent. They were stimulated by capsaicin, phenyl diguanide, or veratridine injected into the bloodstream but not by sodium cyanide or hypoxia. Unlike arterial baroreceptors and atrial receptors, which are concentrated in localized areas, vascular endings were widely distributed in the thoracic aorta, the pulmonary artery, the brachiocephalic artery, the splenic artery, the atriovenous junctions, the atrial appendages, the inferior vena cava, and the hepatic vein. Conduction velocity in 28 fibers ranged from 0.8 to 11.0 m/sec (mean 3.1 m/sec), and in 19 of these fibers the velocity was less than 2.5 m/sec (i.e., the fibers were C-fibers). Vascular endings were stimulated by distending the vessels with balloons. Endings in the pulmonary artery and the aorta did not respond to pressures within the physiological range, but they were stimulated by abnormally high pressures (pulmonary artery 60-110 mm Hg, aorta 200-215 mm Hg). The physiological role of the vascular endings is unknown.
Correlation of Antiarrhythmic Effects of Diphenylhydantoin with Digoxin-Induced Changes in Myocardial Contractility, Sodium-Potassium Adenosine Triphosphatase Activity, and Potassium Efflux
Authors: GOLDSTEIN ROBERT E. , PENZOTTI STANLEY C. , KUEHL KAREN S. , PRINDLE KIRK H. , HALL CLIFFORD A. , TITUS ELWOOD O. , EPSTEIN STEPHEN E.
Published: June 2012

To clarify the suppressant action of diphenylhydantoin (DPH) on digitalis-induced arrhythmias we studied effects of DPH and digoxin, alone and in combination, on contractile force, sodium-potassium adenosinetriphosphatase (Na
+
-K
+
ATPase) activity, and potassium (K
+
) balance in dog hearts perfused with Krebs-Ringer's solution. Neither control perfusion nor DPH alone (3 x 10
-5
M) altered Na
+
-K
+
ATPase activity or produced K
+
loss; DPH alone depressed contractile force. Digoxin alone (10
-6
M) caused a 59% rise in contractile force at the onset of arrhythmia along with a net rate of K
+
loss (K
+
efflux) of 50 ± 12, µmoles/min and a decrease in Na
+
-K
+
ATPase activity from 13.8 to 5.2 µmoles phosphorus/mg protein hour
-1
(
P
< 0.001). Perfusion with combined DPH and digoxin delayed toxicity by 13 minutes (or 82%), at which time contractile force was higher (92% above base line, P<0.05), K
+
efflux was greater (87 ± 20 µmoles/min), and Na
+
-K
+
ATPase activity was lower (2.6 µmoles/mg hour
-1
,
P
<0.05) than they were with digoxin alone. Combined DPH and digoxin perfusion lasting only until the time toxicity appeared with digoxin alone, however, yielded higher Na
+
-K
+
ATPase activity (7.7 µmoles/mg hour
-1
,
P
<0.02) and less rise in contractile force (25% above base line,
P
<0.05). Thus, DPH appeared to retard digoxin-induced inhibition of Na
+
-K
+
ATPase activity. Nevertheless, digoxin in the presence of DPH ultimately produced greater inhibition of Na
+
-K
+
ATPase activity, greater increase in contractile force, and greater K
+
efflux prior to toxicity than did digoxin without DPH. These findings suggest that the antiarrhythmic effects of DPH cannot be attributed solely to prevention of inhibition of Na
+
-K
+
ATPase activity or to diminution of K
+
efflux, two changes characteristically accompanying digoxin administration.
Morphometry of the Human Pulmonary Arterial Tree
Authors: SINGHAL SIAM , HENDERSON ROBERT , HORSFIELD KEITH , HARDING KEITH , CUMMING GORDON
Published: June 2012

From a cast of a human pulmonary arterial tree, the diameter, length, order, and end branches of all intact branches down to those 0.8 mm in diameter were measured and corrections for broken branches were made. A sample of structures smaller than these (0.8-0.1 mm) was similarly measured. The values for branches less than 0.1 mm in diameter were found by extrapolation and comparison with known data for the precapillary vessels. Therefore, data or estimates for each order of branching in the pulmonary tree were obtained and calculations of cross-sectional area, volume, and flow were made.
Evaluation of Several Geometric Models for Estimation of Left Ventricular Circumferential Wall Stress
Authors: McHALE PHILIP A. , GREENFIELD JOSEPH C.
Published: June 2012

Phasic left ventricular wall force and wall thickness were monitored with appropriate transducers to provide a direct measurement of circumferential wall stress in open-chest dogs. Left ventricular pressure and measurements of chamber geometry were used to estimate the wall stress using several geometric models. During the initial control period, peak and end-ejection measured wall stresses were 207 ± 19 and 104 ± 13 g/cm
2
, respectively. The best estimates of these values were 198 ± 18 and 117 ± 11 g/cm
2
obtained from a modified thin-wall ellipse formula in which the midwall rather than the endocardial radius was used. Wide variations in hemodynamic conditions were produced with intravenous infusions of nitroglycerin, phenylephrine, and isoproterenol. Comparison of directly measured and estimated values during all control periods and during the response to these interventions showed that both the modified thin-wall ellipse and a thick-wall ellipse were generally accurate predictors of the measured wall stress. All other models tended to underestimate measured stress. The sensitivity of the estimated wall stress computed by the models to geometric measurement errors was also evaluated. A thick-wall sphere was the most sensitive to both circumferential length and wall thickness measurement errors, and a thick-wall ellipse was the least sensitive. All models examined were relatively insensitive to base-to-apex length measurement errors.
Inactivation of Bradykinin in the Pulmonary Vascular Bed of Newborn and Fetal Lambs
Authors: FRIEDLI BEAT , KENT GERALDINE , OLLEY PETER M.
Published: June 2012

Bradykinin is largely inactivated in one passage through the pulmonary vascular bed of adult animals. We studied pulmonary inactivation of bradykinin in newborn lambs, fetal lambs at term, fetal lambs preterm, and adult ewes by comparing the systemic pressure response to infusions proximal to the pulmonary vascular bed with the response to infusions distal to the pulmonary vascular bed. A high degree of inactivation was confirmed in mature ewes (93 ± 1.2%); newborn lambs showed significantly less pulmonary inactivation (68 ± 5.2%) and fetal lambs at term showed only 46 ± 4.8% inactivation. In the preterm fetuses (gestational age 110-128 days), no inactivation could be demonstrated in the pulmonary vascular bed. The return to base-line diastolic pressure after the infusion was discontinued was much slower in the fetus than it was in the newborn and the adult animal, indicating a prolonged effect of bradykinin. The results suggest that inactivation of bradykinin is a pulmonary function that develops late in fetal life and is still less than adult levels at birth. This finding could be of particular interest if bradykinin participates in mediating the circulatory changes occurring at birth.
Redistribution of Renal Intracortical Blood Flow during Dopamine Infusion in Dogs
Authors: HARDAKER WILLIAM T. , WECHSLER ANDREW S.
Published: June 2012

We determined the effect of intravenous and renal intra-arterial infusion of dopamine on the distribution of intracortical blood flow in kidneys of anesthetized dogs. Total renal and renal intracortical blood flows in dogs receiving dopamine intravenously were quantified by the radioactive microsphere technique with reference sampling. In dogs receiving dopamine by renal intra-arterial infusion, total renal and renal intracortical blood flows were determined from radioactive microsphere and electromagnetic flowmeter data. Tissue perfusion rates for the total kidney, the renal cortex, the renal outer cortex, and the renal inner cortex increased following either intravenous or direct renal intra-arterial infusion of dopamine. Dopamine infusion by either method caused a relative redistribution of renal blood flow from the outer twothirds to the inner one-third of the renal cortex. During direct dopamine infusion into the renal artery, no significant changes in renal hemodynamics occurred in the contralateral kidney. No changes in arterial blood pressure occurred during dopamine infusion by either method. These observations imply that the change in the fractional distribution of renal intracortical blood flow following dopamine infusion is not dependent on a systemic mode of action. This pattern of flow redistribution suggests that the intrarenal dopamine-specific receptor may be in higher number in the inner cortex or that the redistribution of cortical flow after dopamine infusion may reflect differing initial physiological states of the inner and outer cortical receptors for dopamine.
A Two-Compartment Model Describing the Release and Negative Inotropic Action of Acetylcholine on the Heart
Authors: VALENTINUZZI MAX E. , HOFF HEBBEL E. , GEDDES LESLIE A.
Published: June 2012

Single-pulse stimulation of the vagus nerve in turtles (
Pseudymys floridana
) produced the well-known negative inotropic effect on the atria. After stimulation, the peak amplitudes of the atrial contractions exhibited an envelope which appeared to be proportional to the concentration of acetylcholine at the receptor sites. Postulating a quantized release of acetylcholine with each stimulus, the envelope was modeled by a two-equal-compartment configuration. In about 63% of the cases this envelope behaved as if it described a critically damped system, in 18% of the cases it behaved as if the system were slightly overdamped, and in the remaining 19% it corresponded to a lightly underdamped system. The average washout time constant per compartment calculated from the single-pulse response was 4.7 ± 0.8 seconds (
SD
). Repetitive stimulation was provisionally equated with a constant release of acetylcholine; its mathematical description was derived from the time integral of the single-pulse case, i.e., from a direct application of indicator-dilution theory. However, the average time constant obtained from this second type of fit was only 0.84 ± 0.4 seconds. This lower value was interpreted as a dynamic modification (perhaps nonlinear) due to accumulation of acetylcholine and probably associated with an increase in acetylcholine esterase activity.
Selective Stimulation of Renal Nerves in the Anesthetized Dog
Authors: LA GRANGE RONALD G. , SLOOP CHARLES H. , SCHMID HERMAN E.
Published: June 2012

The combined effects of low-frequency stimulation of the renal sympathetic nerves and reductions in renal arterial blood pressure on various hemodynamic parameters of the in situ kidney and on renal venous renin levels were determined in 17 dogs. Autoregulation of flow (measured using noncannulating electromagnetic probes) and glomerular filtration (measured using continuous extraction of
131
I-iothalamate) was followed before, during, and after nerve stimulation. Stimulation of isolated renal nerves (0.5 msec, 10-15 v, 0.1-3.0/sec) produced distinct changes in the release of renin with only minimal changes in the autoregulatory curves for glomerular filtration rate and renal plasma flow. Reducing arterial blood pressure from 150 to 50 mm Hg caused an increase in the release of renin from 4 to 35 ng/ml hour
-1
. Stimulation of the renal nerves increased renin production at both pressures (from 4 to 10 ng/ml hour
-1
at 150 mm Hg and from 35 to 50 ng/ml hour
-1
at 50 mm Hg). In fact, renal nerve stimulation elicited increases in renin release at all pressures examined. In contrast, sodium excretion following nerve stimulation was depressed at comparable sodium loads in spite of minimal changes in renal hemodynamics. It appears that the effect of the renal sympathetic nerves on renin release is evident at all pressures; however, the sympathetic nerves are proportionately more important at pressures above 100 mm Hg and the renal artery pressure plays a greater role at pressures below 115-100 mm Hg.
Myocardial Mechanical Responses and Ionic Exchange in High-Sodium Perfusate
Authors: TILLISCH J. H. , LANGER G. A.
Published: June 2012

The effects of an extracellular sodium (Na) concentration of 200 m
M
on function, ionic exchange, and water movements were examined in the vascularly perfused rabbit intraventricular septum. When the perfusate was switched from 1.42 m
M
Na to 200 m
M
Na, dP/dt fell 20.4% over 2 minutes; dP/dt then recovered to the control level. The time course of the functional recovery correlated with the uptake of Na into the slowly exchangeable fraction of the tissue, and the rate of recovery in 200 m
M
Na depended on the frequency of contraction of the preparation. During perfusion with 200 m
M
Na, a 41% increase in slow-phase Na content compared with the content during perfusion with 142 m
M
Na was observed. The hyperosmolar perfusate induced a 21% cellular dehydration within 10 minutes as estimated from measurement of 10-minute
35
SO
4
space and total tissue water. The time course of dehydration was much more rapid than the time course of functional recovery. Calcium (Ca) influx during the period when dP/dt had returned to control levels in 200 m
M
Na was the same as it was during a control period in 1.42 m
M
Na. Thus, there appears to be a Na-Ca exchange system which enhances Ca influx and thus causes an inotropic effect in response to an increase in intracellular Na concentration.
Participation of Oxygen in the Local Control of Skeletal Muscle Microvasculature
Authors: HUTCHINS PHILLIP M. , BOND ROBERT F. , GREEN HAROLD D.
Published: June 2012

The control of the local supply of oxygen to a skeletal muscle vascular bed was analyzed by: (1) determining if a relative oxygen lack causes vascular dilation, (2) ascertaining the vascular elements responsible for the dilation, and (3) attempting to elucidate the mechanism of the dilation. When the concentration of oxygen in the inspiratory air was reduced from that in room air to 18% without increasing the carbon dioxide concentration or inducing a fall in systemic arterial blood pressure, a dilation significant at the 5% level was observed in the terminal arterioles, the metarterioles, and the distribution arterioles of the cremaster muscle of the rat; all of these vessels were oriented transversely to the skeletal muscle fibers and had diameters of less than 40µ. The magnitude of the dilation, expressed as a percent of the control diameter, was inversely related to the vessel's average control diameter. No significant dilation was noted in the precapillary sphincters or the major arterioles with control diameters greater than 40µ. Intra-arterial injections of sodium cyanide produced responses that paralleled in relative magnitude those observed in similar vessels during hypoxia. The microcirculatory adjustments to mild systemic hypoxia were not altered by pharmacological blockade of sympathetic ganglia or α, β, γ, or histaminergic receptors.
Quantitative Studies of Microcirculatory Structure and Function
Authors: ZWEIFACH BENJAMIN W.
Published: June 2012

A modified version of the Wiederhielm electronic servo system for micropressure recordings was used to establish the details of the pressure drop across successive segments of the microcirculation from arterioles (150µ) to venules (200µ) in the mesentery of the cat; most of the readings were made in vessels less than 25jz in diameter. Micropressures correlated with central pressure only in arterial vessels larger than 50µ. Frequencydistribution plots of micropressures showed a wider spread in the vessels that were 50-1Oµ in diameter than they did in capillary vessels that were less than 20µ in diameter.Therefore, it appears that classification of vessels on the basis of diameter, which is at present the only practical way of comparing pressure measurements in presumably identical segments of a continuously branching system, is not adequate and makes statistical analysis difficult. In the present study, micropressures remained pulsatile throughout the bed, although the pulse pressure could be narrowed to 2-4 mm Hg in the capillaries. Simultaneous measurement of pressure in two vessels showed that the greatest pressure drop occurred in the region where arterioles (40-50)u) distributed numerous precapillary branches (10-15/x); in this region arteriolar pressures were reduced from a level of 45-65 mm Hg to about 30-35 mm Hg. These data suggest that application of the resistance term for Poiseuille flow in the microcirculation should take into account the relative sizes of the parent vessel and the branch, the entry dimensions into the branch and the length of the neck or junctional segment. Evidence found in this investigation indicated that precapillary branching configurations were self-regulatory. A small number of low-resistance, shunt pathways between arterioles and venules were regularly present, as shown by the extremely small pressure drop in 15-18% of the vessels. The data indicate that much more caution is needed in interpretation of pressure-related phenomena in the microcirculation because of their strong dependence on the anatomical and physical features characteristic of individual tissues.
Changes in Coronary Venous Inosine Concentration and Myocardial Wall Thickening during Regional Ischemia in the Pig
Authors: DE JONG JAN WILLEM , GOLDSTEIN SIDNEY
Published: June 2012

Correlations between local mechanical and metabolic events were studied during a partial decrease in flow in the left anterior descending coronary artery in 14 open-chest pigs. A decrease in flow to 28% (19-39%) of the control value was achieved with an adjustable screw clamp. A flow probe was placed around the artery. Blood samples were taken from the regional anterior coronary vein and the femoral artery. Myocardial wall thickening was measured with a harpoon type of mercury strain gauge. During ischemia, systolic myocardial wall thickening decreased to 44.5 ± 5.1% (
SE
) of its control value (
P
< 0.001). The mean concentrations of plasma potassium and whole blood inosine, hypoxanthine, and lactate in three serial 2-minute samples obtained during a 6-minute control period were compared with those obtained during a 6-minute period of partial occlusion. During ischemia, venous inosine concentration increased from 10.9 ± 0.7 µ
M
to 18.5 ± 1.8 µM (
P
< 0.005), venous hypoxanthine concentration increased from 28.5 ± 1.4 µ
M
to 33.0 ± 1.5 µ
M
(
P
< 0.005), venous potassium concentration increased from 3.77 ± 0.10 m
M
to 4.08 ± 0.13 m
M
(
P
< 0.001), and venous lactate concentration increased from 1.04 ± 0.19 m
M
to 1.52 ± 0.17 m
M
(
P
< 0.001). The arterial level of potassium increased very little. The arterial concentration of the other compounds did not change significantly during the 6-minute period of ischemia. Myocardial lactate extraction changed from a control value of 42.6 ± 6.7% to -4.6 = 12.5% (
P
< 0.05). A negative correlation (

r
s

= -0.79,
P
< 0.01) was observed between venous inosine concentration and myocardial wall thickening (percent of control) during ischemia. This study indicates that the local venous inosine concentration is a sensitive indicator of regional myocardial ischemia in the pig.
Effect of Propranolol on Blood Pressure and Plasma Renin Activity in the Spontaneously Hypertensive Rat
Authors: FORMAN BARR H. , MULROW PATRICK J.
Published: June 2012

Spontaneously hypertensive Wistar rats have normal basal levels of plasma renin activity but do not respond to sodium depletion or the stress of ether anesthesia plus laparotomy. Both age and rat strain influence the development of this hyporesponsive renin system: normal Wistar and spontaneously hypertensive rats but not Sprague-Dawley rats develop the hyporesponsive system as they age. Therefore, these rat strains may serve as useful models for studying the effects of age and hypertension on plasma renin activity. In the present study, propranolol administration up to 18 mg/kg day
-1
for 15 days did not lower plasma renin activity but did cause a paradoxical rise in blood pressure in spontaneously hypertensive rats. This paradoxical rise was prevented by placing the rats on a low-sodium diet prior to propranolol administration. The mechanism of the paradoxical rise is unknown, but we suggest that it could be the result of increased alpha-adrenergic activity in response to a fall in cardiac output.
Coronary and Hemodynamic Effects of Temporary Acute Aortic Insufficiency in Intact Anesthetized Dogs
Authors: FOLTS JOHN D. , ROWE GEORGE G.
Published: June 2012

In ten dogs with chronically implanted electromagnetic flowmeter probes, phasic aortic and circumflex coronary artery blood flows were measured before, during, and after 15-120 seconds of aortic insufficiency. The dogs were studied in the intact anesthetized state with a cardiac catheter device that produced graded amounts of temporary aortic insufficiency with 18-68% aortic regurgitation. With the onset of aortic insufficiency, there was an immediate increase in pulse pressure with retrograde aortic diastolic blood flow. During the very first cardiac cycle that demonstrated aortic insufficiency, there was a reduction in diastolic coronary blood flow with an increase in systolic coronary blood flow. Mean coronary blood flow fell very low during the first five to ten cardiac cycles. As severe aortic insufficiency continued, systolic coronary blood flow increased, diastolic coronary blood flow remained low or negative, and mean coronary blood flow returned to the normal range. Before the onset of aortic insufficiency, the ratio of diastolic coronary blood flow to systolic coronary blood flow averaged 2.2; after 2 minutes of aortic insufficiency the ratio of diastolic coronary blood flow to systolic coronary blood flow was 0.15. The amount of reduction in diastolic coronary blood flow was related to the amount of aortic regurgitation. Left ventricular work averaged 3.7 kg m/min before and 8.2 kg m/min after 2 minutes of aortic insufficiency with an average of 63% aortic regurgitation; mean coronary blood flow increased from an average of 51 ml/min before to 60 ml/min after 2 minutes of aortic insufficiency. When aortic insufficiency was terminated, coronary blood flow increased to an average of 123 ml/min.
Release of Adenosine from Ischemic Brain
Authors: BERNE ROBERT M. , RUBIO RAFAEL , CURNISH RICHARD R.
Published: June 2012

A threefold increase in tissue adenosine levels was produced by ischemia in the dog and the rat brain within 1 minute; adenosine levels increased further with longer periods of ischemia. Inosine and hypoxanthine were also increased by ischemia but to different degrees. The nucleosides and hypoxanthine appeared in cerebrospinal fluid during ischemia in the dog brain, and incubation of adenosine in normal cerebrospinal fluid failed to show the presence of degradative enzymes. Intra-arterially administered adenosine in the dog and the cat produced little or no increase in cerebral blood flow or the diameter of pial arterioles, respectively, when it was given in amounts that reduced arterial blood pressure. However, when it was applied topically to exposed pial arterioles of the cat, adenosine induced dilation that was roughly proportional to the dose used. When U-
14
C-adenosine was infused into the internal carotid arteries of the dog, no radioactivity was detectable in the cerebrospinal fluid and practically none appeared in the brain tissue. When labeled adenosine was added to dog cerebrospinal fluid, only a few counts appeared in the cerebral venous blood, whereas cerebral tissue was heavily labeled with 84-87% of the radioactivity in the form of adenine nucleotides. In the rat, after intravenous injection of labeled adenosine, the counts per gram of heart were twenty- to thirtyfold greater than those per gram of brain. These observations indicate that intra-arterially administered adenosine probably fails to cross the blood-brain barrier rapidly enough to influence cerebral blood flow but that it can be released from the ischemic brain into the cerebrospinal fluid and be reincorporated from the cerebrospinal fluid into brain nucleotides. Hence, adenosine can conceivably participate in the regulation of cerebral blood flow.
Autonomic Nervous System and Benign Essential Hypertension in Man
Authors: CUCHE JEAN-LOUIS , KUCHEL OTTO , BARBEAU ANDRÉ , LANGLOIS YVES , BOUCHER ROGER , GENEST JACQUES
Published: June 2012

The effect of upright posture as a physiological stimulus of the adrenergic nervous system was studied in 56 subjects with benign essential hypertension. The subjects received a controlled-sodium diet. Blood pressure, heart rate, catecholamines, plasma renin activity, and urinary creatinine, sodium, and potassium excretion were measured in the recumbent and upright positions. We found an alteration in the blood pressure response in subjects with benign essential hypertension; the postural increase in the mean blood pressure in normotensive subjects (3.18 ± 1.35 mm Hg) progressively disappeared and was replaced by a postural decrease in subjects with more severe stable hypertension (-6.71 ± 2.42 mm Hg). The hypertensive subjects also lacked the usual increase in urinary excretion of norepinephrine. A significant increase in plasma renin activity associated with a significant decrease in plasma norepinephrine occurred in subjects with labile hypertension with postural tachycardia. Finally, we found a highly significant correlation between the excretion of sodium and potassium in the recumbent position and the retention of both ions in the upright position.
Adenosine 3', 5'-Monophosphate-Dependent Membrane Phosphorylation
Authors: LARAIA PAUL J. , MORKIN EUGENE
Published: June 2012

The role of cyclic adenosine 3', 5'-monophosphate (AMP) in the control of microsomal calcium ion (Ca
2+
) transport was studied in microsomes prepared from rabbit heart. These cardiac microsomes contained intrinsic cyclic AMP-dependent protein kinase activity that phosphorylated serine residues in a microsomal protein component with a molecular weight of about 20,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Intrinsic phosphoprotein phosphatase activity of the microsomal membranes resulted in rapid dephosphorylation of these residues. Microsomes phosphorylated in the presence of 1 x 10
-6
M cyclic AMP exhibited enhanced Ca
2+
uptake. We conclude that reversible phosphorylation of microsomal membranes may be an important mechanism for regulation of microsomal Ca
2+
transport by cyclic AMP.
Effect of Variation of Transmural Pressure on the Frequency Response of Isolated Segments of Canine Carotid Arteries
Authors: HUTCHISON KENNETH J.
Published: June 2012

The frequency-response curve of isolated canine arterial segments at transmural pressures between 140 and 40 mm Hg showed an initial constant-amplitude portion over the lower frequency range followed by one or two major amplitude peaks (resonances) at higher frequencies. At lower transmural pressures, the response was more damped and resonances were infrequent. The amplitude of the flat portion of the curve increased as transmural pressure was decreased, and thus the dynamic modulus of elasticity calculated at 10 Hz decreased. The static modulus behaved in a similar fashion, but it was always lower than the dynamic modulus. The resonances shifted to lower frequencies as transmural pressure was decreased, and thus the dynamic modulus of elasticity calcuwall stiffness. Two series of five arteries each were examined; in one series the arteries were mounted with a fixed 50% longitudinal elongation and in the other series they were mounted with variable, mean 85%, longitudinal elongations. The difference between the two series suggests that increasing longitudinal elongation markedly increases the frequency shift induced by transmural pressure of one of the resonances and may result in coincidence of the two resonances at a given transmural pressure which varies from artery to artery.
Influences of Physical Training on the Heart of Dogs
Authors: WYATT HORACE L , MITCHELL JERE H.
Published: June 2012

To investigate the effects of physical training on cardiac dimensions and function, eight dogs were exercised for 12 weeks by treadmill running 1 hour/ day, 5 days/week. Five dogs were confined in cages as controls for an 8-week period. Heart rates were monitored by telemetry during rest and exercise. Maximum QRS spatial magnitudes were calculated from records of McFee lead electrocardiograms. Left ventricular end-diastolic dimensions were determined radiographically by the bead and clip technique. No statistically significant changes occurred during the control period. Training produced statistically significant decreases in heart rate at rest (72 beats/min to 49 beats/min,
P
< 0.005) and at a standard work load of 6.1 mph on a level treadmill (205 beats/ min to 158 beats/min,
P
< 0.005) and statistically significant increases in work load (5.4 mph to 9.1 mph,
P
< 0.005) at a standard heart rate of 194 beats/min. Improvements were rapid during the first 4 weeks of training but gradual during the remaining 8 weeks. Training caused small but statistically significant increases in left ventricular end-diastolic wall thickness (8.7 mm to 9.3 mm,
P
< 0.0025), estimated left ventricular mass (83.6 g to 91.2 g,
P
< 0.01), and maximum (McFee) QRS spatial magnitude (4.0 mv to 4.8 mv,
P
< 0.05).
A Combined Morphological and Electrophysiological Study of the Atrioventricular Node of the Rabbit Heart
Authors: ANDERSON ROBERT H. , Durrer Dirk , JANSE MICHIEL J. , VAN CAPELLE FRANS J. L. , BILLETE JACQUES , BECKER ANTON E. , DURRER DIRK
Published: June 2012

Thirteen rabbit atrioventricular nodes were studied both morphologically and electrophysiologically. Two of these nodes were subsequently reconstructed in three-dimensional fashion. From the morphological standpoint, it was shown that the atrioventricular node was divided into a smaller enclosed portion and a larger open portion by a fibrous collar derived from the central fibrous body. Three distinct nodal cell types were identified within these nodal segments. The open node was mostly occupied by transitional cells which merged proximally with the atrial myocardium. As they entered the enclosed node, some of these transitional cells merged into a knot of midnodal cells. Others passed circumferentially round this knot and together with the midnodal cells, joined with a tract of lower nodal cells. The latter cells were continuous with the His bundle anteriorly, but they also extended into the open node posteriorly. It was possible to correlate the activation sequence of the node accurately with the disposition of these cells. Using both reconstructions and techniques to mark cells from which action potentials had been recorded, it was shown that the transitional cells correlated with the AN zone of the node. Cells with N potentials were located in the environs of the midnodal cell knot. The anterior portion of the lower nodal cells correlated with the NH nodal zone. The posterior extension of the lower nodal cells and the overlay fibers of the anterior transitional cells both functioned as dead-end pathways. Histologically distinct tracts were not identified within the internodal atrial myocardium.
Time course for reversal of electrophysiological and ultrastructural abnormalities in subendocardial Purkinje fibers surviving extensive myocardial infarction in dogs.
Authors: Friedman P L , Fenoglio J J , Wit A L
Published: June 2012

The electrophysiological properties of subendocardial Purkinje fibers surviving in myocardial infarcts were studied with intracellular microelectrodes in isolated superfused preparations and correlated with subsequent light and electron microscopic studies. Transmembrane action potentials could always be recorded from one or two cell layers of subendocardial Purkinje fibers in infarcted regions 3 days to 7 weeks after coronary artery occlusion; ventricular muscle action potentials were rarely found. Microscopic studies also demonstrated several layers of intact subendocardial Purkinje fibers; the subjacent ventricular muscle cells were irreversibly injured and replaced by scar. At all time intervals, surviving Purkinje fibers had significantly reduced maximum diastolic potentials, action potential amplitudes, and depolarization velocities as well as prolonged action potential durations. These parameters normalized between 24 hours and 7 weeks after coronary artery occlusion. Surviving Purkinje fibers with electrophysiological abnormalities at 24 hours and 3 days contained vast lipid deposits. Lipid was less prevalent at 10 days when action potential characteristics had improved. By 7 weeks, action potentials were nearly normal and lipid was absent. Subendocardial Purkinje fibers surviving in infarcts are subject to conditions which cause electrophysiological and ultrastructural abnormalities. Persistent abnormalities in the electrophysiological properties of these surviving Purkinje fibers may cause persistent altered electrophysiological properties of the infarcted heart.
Effect of alterations of arterial blood pressure and heart rate on segmental dyskinesis during acute myocardial ischemia and following coronary reperfusion.
Authors: Kerber R E , Abboud F M
Published: June 2012

The effect of alterations of blood pressure and heart rate on segmental dyskinesis induced by coronary artery ligation and the influence of such manipulations on the magnitude of recovery of the syskinetic segment during subsequent coronary artery reperfusion were evaluated in 77 open-chest dogs. Wall motion was recorded by ultrasound reflected directly from the ischemic myocardial segment. Acute ischemia produced characteristic regional abnormalities in wall motion: aneurysmal bulging occurred during isometric contraction and wall velocity was markedly reduced during ventricular ejection. During 69 minutes of ischemia, a control group of dogs underwent no interventions and showed no further changes in wall motion. Tachycardia induced by atrial pacing during ischemia had no significant effect. Arterial hypertension during ischemia caused a marked reduction in wall velocity when methoxamine was used: 14 plus or minus 2 (SE) mm/sec (ischemia alone) to 6 plus or minus 1 mm/sec (ischemia + drug). In contrast, norepinephrine improved wall velocity: 11 plus or minus 2 mm/sec (ischemia alone) to 25 plus or minus 4 mm/sec (ischemia + drug). Hypertension caused by infusion of phenylephrine gave intermediate results, as did hypotension induced by either nitroprusside or hemorrhage during the ischemic period. After 60 minutes the drugs were stopped, the coronary ligation released, and the ischemic myocardium reperfused. The relative order of improvement of wall velocity with reperfusion was 11 plus or minus 2 mm/sec (ischemia alone) to 24 plus or minus 3 mm/sec (reperfusion) in the group that received norepinephrine, 12 plus or minus 3 mm/sec to 20 plus or minus 3 mm/sec in the control group with no intervention durin ischemia, 13 plus or minus 2 mm/sec to 20 plus or minus 1 mm/sec in the nitroprusside group, 9 plus or minus 2 mm/sec in the phenylephrine group, and 14 plus or minus 2 mm/sec to 12 plus or minus 1 mm/sec in the methoxamine group. The aneurysmal bulging during isometric contraction also was reduced to a greater degree by reperfusion in the group that received norepinephrine during the ischemic period than it was in the groups undergoing other interventions during ischemia. We conclude that drug-induced elevations in arterial blood pressure can have different effects on the syskinetic motion of acutely ischemic myocardium and on the degree of recovery following reperfusion depending on the particular agent used.
Comparison of 85krypton and 133xenon cerebral blood flow measurements before, during, and following focal, incomplete ischemia in the squirrel monkey.
Authors: Hanson E J , Anderson R E , Sund T M
Published: June 2012

A comparison of regional cerebral blood flow measurements made with beta- and gamma-emitting isotopes revealed good correspondence in areas of normal perfusion and reactive hyperemia but poor correspondence in areas of focal ischemia. After middle cerebral artery occlusion at normocapnia, there was a 65% reduction in regional cerebral blood flow from 1.40 plus or minus 0.27 ml/g min--1 to 0.49 plus or minus 0.10 ml/g min--1 in monkeys studied with 85Kr but only a 27% reduction in regional cerebral blood flow from 0.84 plus or minus 0.09 ml/g min--1 to 0.61 plus or minus 0.08 ml/g min--1 in monkeys studied with 133Xe. The lack of correlation within areas of focal, incomplete ischemia was attributed to an impairment of isotope delivery to the area of ischemia coupled with the inherent lack of spatial resolution of determinations made with 133Xe. This finding may partly explain the numerous discrepancies in experimental and clinical studies of the effects of alterations in the arterial partial pressure of CO2 on regional cerebral blood flow in areas of ischemia; it may also explain the failure of such studies to reflect the true severity of focal ischemia.
Effect of hemodilution on the distribution of renal blood flow.
Authors: Migdal S , Alexander E A , Bruns F J , Riley A L , Levinsky N G
Published: June 2012

We evaluated the effects of hemodilution, expansion of intravascular volume, and expansion of interstitial volume on the distribution of cortical renal blood flow, utilizing the microsphere technique. Hemodilution without volume expansion (saline exchange) produced an increase in fractional blood flow in zone 1 (outermost zone) of the cortex from 34 plus or minus 1% to 43 plus or minus 2% and a decrease in fractional blood flow in zone 4 (innermost zone) from 16 plus or minus 2% to 13 plus or minus 2%. Hemodilution without volume expansion or a decrease in plasma protein concentration (isoncotic exchange) produced a similar redistribution in blood flow in zone 1 from 34 plus or minus 2% to 41 plus or minus 2% and in zone 4 from 14 plus or minus 2% to 10 plus or minus 1%. Hemodilution with intravascular volume expansion (hyperoncotic albumin infusion) also produced a superficial shift; blood flow in zone 1 increased from 27 plus or minus 1% to 30 plus or minus 1% and that in zone 4 decreased from 19 plus or minus 2% to 15 plus or minus 1%. Previous studies have demonstrated a redistribution to the juxtamedullary area after saline expansion. Our data demonstrate that hemodilution causes flow to redistribute to the superficial rather than the deep cortex. This superficial shift appears to be secondary to decrease hematocrit rather than to dilution of plasma proteins or expansions of intravascular volume. The deep shift in cortical blood flow which occurs during saline loading is presumably a consequence of expansion of interstitial volume.
Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.
Authors: Gavras H , Brunner H R , Laragh J H , Vaughan E D , Koss M , Cote L J , Gavras I
Published: June 2012

The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.
Blood pressure regulation in end-stage renal disease and anephric man.
Authors: Onesti G , Kim K E , Greco J A , del Guercio E T , Fernandes M , Swartz C
Published: June 2012

The hemodynamic pattern of response to bilateral nephrectomy was studied in 29 patients with end-stage renal disease on maintenance hemodialysis. Four patterns of hemodynamic response were seen. In 12 patients with nonmalignant hypertension, bilateral nephrectomy reduced blood pressure and total peripheral resistance with no effects on cardiac output. In 5 patients with malignant hypertension, bilateral nephrectomy reduced blood pressure, increased cardiac index, and reduced total peripheral resistance more markedly. In these two groups, at equivalent levels of total exchangeable sodium, before and after bilateral nephrectomy, mean arterial pressure and total peripheral resistance were invaribly lower in the absence of renal tissue. In 3 additional patients with nonmalignant hypertension, the decrease in blood pressure after bilateral nephrectomy was delayed from 3 to 12 weeks. When this occurred spontaneously, it was accompanied by a decrease in total peripheral resistance. The fourth hemodynamic pattern was seen in 6 normotensive patients with end-stage renal disease. After bilateral nephrectomy, there were no significant changes in mean arterial pressure, total peripheral resistance, or cardiac output. Salt and water loading failed to elevate blood pressure significantly. Renal transplantation was performed in 3 hypertensive patients before removal of the end-stage kidney. The functioning renal homograft did not result in normal blood pressure as long as the end-stage kidneys remained in place. Removal of the end-stage kidneys significantly decreased mean arterial pressure and total peripheral resistance. In the anephric state, a sharp difference was seen in blood pressure response to salt and water loading between previously normotensive and previously hypertensive patients. Previously hypertensive patients responded with a progressive increase in blood pressure that reached hypertensive levels. Previously normotensive patients failed to elevate their blood pressure significantly. It is concluded that the vasopressor function of the kidney is the most important factor in the pathophysiology of hypertension of end-state renal disease. Expansion of body fluid plays a role, but elevates the blood pressure only in patients who were previously hypertensive. The antihypertensive function of the kidney does not appear to be a major factor in the regulation of blood pressure in end-stage renal disease.
Development and maintenance of renal hypertension in normal and guanethidine sympathectomized rats.
Authors: Douglas J R , Johnson E M , Marshall G R , Heist J , Hartman B K , Needleman P
Published: June 2012

The sympathetic nervous system has been postulated to play a role in the maintenance of renal hypertension. Permanent peripheral sympathectomy was performed by treating newborn rats for 21 days with guanethidine. Sympathectomy was confirmed by (1) relative insensitivity to tyramine, (2) lack of responsiveness to renal nerve stimulation, and (3) absence of dopamine-beta-hydroxylase immunofluorescence in renal blood vessels. Placement of a clip on the left renal artery led to the development of two-kidney renal hypertension. No differences were observed between the two-kidney renal hypertensive normal and sympathectomized rats; both had elevated plasma renin activity and vasodepression with angiotensin antagonists which were maintained up to nine weeks. Furthermore, in normal rats chronic beta-adrenergic blockade with propranolol caused no change in the development of the two-kidney renal hypertension. Similarly, no differences were seen in blood pressure, plasma renin activity, or response to antagonists between the one-kidney renal hypertensive (clip plus contralateral nephrectomy) normal and sympathectomized rats. Both showed sustained low renin hypertension up to 12 weeks. The absence of the peripheral sympathetic nervous system did not affect the development or maintenance of hypertension in either model of hypertension.
Venous smooth muscle in hypertension. Enhanced contractility of portal veins from spontaneously hypertensive rats.
Authors: Greenberg S , Bohr D F
Published: June 2012

In isolated bath studies smooth muscle from the rat portal vein was evaluated for its reactivity and contractility, and the whole vessel wall was evaluated for its extensibility. Smooth muscle from the spontaneously hypertensive rat (SHR) had the following characteristics when compared with that from normotensive controls: (1) Spontaneous phasic contractions were more frequent and developed more tension; (2) threshold concentrations for responses to prostaglandins A-2 and B-2 were lower, but those for responses to epinephrine, norepinephrine, KCl, BaCl-2, and SrCl-2 were similar; (3) high concentrations of calcium had a less depressant action on the responses to the prostaglandins but not on the responses to the other agonists; (4) maximal contractile tensions to all agonists were greater; and (5) passive extensibility was less. These differences, because they are in the venous system, cannot be secondary to the increase in wall stress of arterial hypertension. The decreased passive extensibility in this vein in SHR creates a stiffer framework on which the active contractile process is able to develop greater tension. If this increase in active tension is generalized to all veins, it could be responsible for a decrease in venous capacity which increases the rate of venous return and, hence, increases cardiac output.