bluuebunny/crossref_metadata_2025 huggingface dataset:
Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster.
Authors: Sole M J , Lo C M , Laird C W , Sonnenblick E H , Wurtman R J
Published: June 2012

Although a reduction in myocardial norepinephrine stores in cardiac hypertrophy and congestive failure is well documented, norepinephrine turnover has been inadequately studied in such hearts. We compared norepinephrine turnover in control and cardiomyopathic hamsters by following the decline in specific activity of myocardial norepinephrine after labelling with an intraperitoneal tracer dose of 3H-norepinephrine. Adult myocardial norepinephrine concentrations were not attained until 4 weeks of age in both strains. There was no difference in the rate of constant (K) for myocardial norepinephrine turnover (0.107+/-0.004 hours-1 vs. 0.100+/-0.005 hours-1) in the two strains of hamsters during the neonatal period. In young control hamsters, K fell to 0.064+/-0.004 hours-1, but that for age-matched hamsters with mild cardiac hypertrophy was 0.102+/-0.001 hours-1 (P less than 0.001). There was little change in K as control hamsters aged. With the development of more severe hypertrophy in cardiomyopathic hamsters, cardiac norepinephrine decreased and resting K rapidly increased to approach the value obtained when hamsters were subjected to immobilization stress (0.302+/-0.013 hours-1). The maximum achievable K remained the same for both control and dystrophic hamsters even during terminal disease. Prolonged immobilization led to a reduction in cardiac norepinephrine in both strains. Ganglionic blockade of failing hamsters completely restored the levels of both cardiac norepinephrine and K to control values. Splenic noradrenergic nerves showed no change in K, norepinephrine content, or maximum K during cardiac decompensation. We conclude that, in the late stages of hamster cardiomyopathy, there is a progressive and possibly specific increase in cardiac sympathetic tone which leads to a concomitant decrease in cardiac norepinephrine. With the loss of sympathetic reserve, congestive failure supervenes.
Serum dopamine beta-hydroxylase as an index of sympathetic nervous system activity in man.
Authors: Noth R H , Mulrow P J
Published: June 2012

Serum dopamine beta-hydroxylase (DBH) activity was comparable in eight adrenalectomized patients and in 41 normal volunteers (37.8 +/- 3.6 vs. 40.0 +/- 4.0 IU), but were very low in four patients with severe diabetic autonomic neuropathy (6.7 +/- 4.2). These observations suggest that the major source of DBH activity in human serum is probably the sympathetic nervous system. Serum DBH activity was also significantly lower in seven patients with low renin essential hypertension than in 17 patients with normal renin hypertension (19.9 +/- 4.3 vs. 43.9 +/- 5.0 IU, P less than 0.05). Dietary sodium depletion, a stimulus for catecholamine secretion, produced only a small increase in serum DBH activity in supine normal volunteers (26.5 +/- 10.4 to 33.9 +/- 11.4, P less than 0.05; n = 7) and in five adrenalectomized patients (33.0 +/- 12.7 to 44.1 +/- 15.2, P = 0.06). Plasma renin activity increased more than 3-fold in these same subjects, and did not correlate with serum DBH activity. Similarly, 4 hours of ambulation produced only a small increase in serum DBH activity which did not correlate with plasma renin activity. The small magnitude of these responses to physiological stimuli of the sympathetic nervous system diminishes the potential clinical usefulness of measurement of serum DBH activity. Further studies utilizing direct correlation of plasma and urine catecholamines with serum DBH activity are needed to establish its relationship to sympathetic nervous system activity.
Further characterization of the natriuretic factor derived from kidney tissue of volume-expanded rats. Effects on short-circuit current and sodium-potassium-adenosine triphosphatase activity.
Authors: Hillyard S D , Lu E , Gonick H C
Published: June 2012

Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.
Altered venous function in hypertensive rats.
Authors: Simon G
Published: June 2012

The vascular beds of the upper or lower body of rats were perfused through the aorta with oxygenated Krebs-Ringer solution containing dextran (7 g/100 ml), at 37 degrees C. Perfusion was stopped every 10 minutes, and the pressure rise in the jugular or the femoral vein was recorded during rapid infusion (15.3-90.0 ml/min) of Krebs-Ringer solution into the inferior vena cava. The following groups of rats were studied: (1) six male genetically hypertensive rats (GHR), 9-11 months old, New Zealand strain; (2) seven female GHR, 5-6 months old, New Zealand strain; (3) eight male spontaneously hypertensive rats (SHR), 4 months old, Okamoto strain; (4) five male rats with two-kidney Goldblatt hypertension (2-KGH), 30 days postclipping; (5) seven male 2-KGH rats, 65 days postclipping; (6) eight male rats with one-kidney Goldblatt hypertension (1-KGH), 40 days postclipping; (7) weight- and sex-matched normotensive control rats of the appropriate strain; and (8) weight- and sex-matched two-kidney and one-kidney, sham-clipped normotensive rats. Preliminary studies showed that rapid infusion into the venous circulation fills the veins, but there is no entry of fluid into the arterial side of the circulation. Compared to controls, the venous pressure-volume curves of GHR (male and female), SHR, 1-KGH rats and 2-KGH rats, 65 (but not 30) days postclipping, were shifted toward the pressure axis (P less than 0.05). The shift of the venous pressure-volume curves persisted following the reduction of vasoconstrictor tone by killing the rats or by the administration of sodium nitroprusside (0.1 mg/ml perfusate), or by both. The findings suggest decreased venous capacity in hypertensive rats.
Depression of atrioventricular sensitivity in the dog by successive brief bursts of vagal stimulation.
Authors: Martin P
Published: June 2012

When identical, successive single vagal stimulations, separated in time (T) by 2-60 seconds, are applied in the dog, the peak change in atrioventricular conduction time for the second stimulus, deltaAV2, is less than that of the first, deltaAV1, that is, the ratio deltaAV2/deltaAV1 less than 1.0 (the mean minimum deltaAV2/deltaAV1=0.52). It was further determined that at any one given T, the actual value of deltaAV2/deltaAV1 also was a function of the first stimulus amplitude. The same dependence of deltaAV2/deltaAV1 on the first stimulus amplitude was found when the amplitude was varied either by (1) changing the number of vagal fibers stimulated for both the first and second response, but at a constant AD (the delay in the cardiac cycle at which the stimulus was given), or (2) by stimulating the same number of fibers but changing AD for both the first and second response. Also the same characteristic of deltaAV2/deltaAV1 plotted vs. T was found either (1) when both the first and second responses were produced by stimulation of the same nerve, or (2) when stimulated of the nerve from one side produced the first response and the alternate side the second response. These data suggest that the reason for this deltaAV2/deltaAV1 time-dependent effect lies in changes in receptor responsiveness or in acetylcholine inactivation, but not in mechanisms purely internal to the nerve terminal associated with synthesis, storage, or release of acetylcholine.
The effects of des-Asp1-angiotensin II on blood pressure, plasma aldosterone concentration, and plasma renin activity in the rabbit.
Authors: Steele J M , Neusy A J , Lowenstein J
Published: June 2012

To examine the hypothesis that des-Asp-1-angiotensin II (angiotensin III) may be an important mediator of various responses to angiotensin II, both peptides were given sequentially at 25 ng/kg per min by systemic infusion to conscious rabbits, and the effects on blood pressure, plasma aldosterone concentration, and plasma renin activity were compared. The mean arterial pressure increased with angiotensin II infusion an average of 18.2 mm Hg, and with angiotensin III infusion only 3.2 mm Hg. Both peptides, however, produced a six- to sevenfold increase in plasma aldosterone concentration, and a threefold decrease in plasma renin activity. Renal clearance data suggest that the suppression of renin activity was not a consequence of renal hemodynamic change or altered sodium transport, but of direct inhibition through a receptor mediating a short feedback loop. These data in the intact rabbit, taken together with in vitro studies by others, suggest that the responses of these three organ systems to angiotensin peptides are mediated by receptors of varied specificity: those mediating vasoconstriction exhibit a greater response to angiotensin II than to angiotensin III; those mediating the secretion of aldosterone exhibit a lesser response to angiotensin II than to angiotensin III; and those mediating the suppression of renin release do not appear to discriminate between the two peptides.
Depressed function of a ouabain-sensitive sodium-potassium pump in blood vessels from renal hypertensive dogs.
Authors: Overbeck H W , Pamnani M B , Akera T , Brody T M , Haddy F J
Published: June 2012

Vasodilator responses to acute intra-arterial infusions of K+ are attenuated in dogs with chronic one-kidney perinephritic hypertension in rats with chronic two-kidney Goldblatt hypertension, and in men with essential hypertension. There is evidence that K+ evokes vasodilation by stimulating vascular smooth muscle membrane Na+-K+-activated adenosine triphosphatase, thereby increasing activity of the cellular Na+-K+ electrogenic pump. We therefore proposed that there may be an underlying decrease in the operation of this pump in vascular smooth muscle of hypertensives. The operation of the cellular Na+-K+ pump may be estimated by measurement of rubidium uptake. Thus, so further investigate our hypothesis, we measured 86Rb uptake in small mesenteric arteries and splanchnic veins from 12 dogs with chronic uncomplicated one-kidney perinephritic hypertension and from 12 normotensive control dogs. Vessels were excised under thiamylal anesthesia and incubated in cold medium (plasma or Krebs-Henseleit solution) for sodium loading and then the velocity of 86Rb uptake was estimated in the absence of or in the presence of ouabain, a specific inhibitor of the Na+-K+ pump. In neither arteries nor veins was there evidence for differences between hypertensives and normotensives in the ouabain-insensitive uptake of 86Rb. In contrast, the ouabain-sensitive 86Rb uptake was depressed by 42% in arteries (P less than 0.05) and by 49% in veins (P less than 0.01) from hypertensive dogs, if incubated in the dog's own plasma. These results indicate that the activity of a ouabain-sensitive Na+-K+ pump may be depressed in vascular tissue from dogs with chronic one-kidney perinephritic hypertension. Because the Na+-K+ pump in vascular smooth muscle is probably electrogenic, such an abnormality, by partially depolarizing the muscle cell membrane, would help to account for the elevated vascular resistance found in these dogs.
Turbulent blood flow in humans: its primary role in the production of ejection murmurs.
Authors: Sabbah H N , Stein P D
Published: June 2012

To clarify the postulate that turbulence may produce ejection murmurs, point velocity and sound were measured in the ascending aorta of 13 subjects: six with normal aortic valves, six with aortic valvular disease, and one with a Bjork-Shiley prosthetic aortic valve. Velocity was measured with a catheter-tip hot film anemometer probe, and sound was measured with a catheter-tip micromanometer. Ejection murmurs detected intra-arterially were always found to be associated with turbulent or highly disturbed flow. Conversely, in the absence of intra-arterial sound during ejection, only minor disturbances of flow were detected. A linear relation between the sound energy density and turbulent energy density was shown (r = 0.92) and a linear relation between the acoustic power output (sound intensity) and turbulent power supply (r = 0.87) also was shown. Studies in vitro of sound and point velocity distal to a porcine valve inserted within a cast of the aorta, which permitted precise centering of the transducers along the axis of flow, confirmed these observations. When the power generated by the turbulence exceeded 3 ergs/sec per cm2, the murmurs were audible at the chest wall. The clinical gradation of the intensity of the murmurs increased as the power of turbulence increased. In conclusion, in this study we have demonstrated a clear association between turbulent blood flow and systolic ejection murmurs.
Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier.
Authors: MacKenzie E T , Strandgaard S , Graham D I , Jones J V , Harper A M , Farrar J K
Published: June 2012

Acute hypertension was induced in 19 anesthetized cats by the intravenous administration of angiotensin. The caliber of pial arteries was measured by a television image-splitting technique and local cerebral blood flow by the hydrogen clearance technique. As the blood pressure was increased, pail arterioles constricted and cerebral blood flow remained relatively constant, showing that autoregulation of cerebral blood flow was intact. At mean arterial pressures of more than 170 mm Hg arteriolar dilation appeared. In smaller arterioles (initial diameter less than 100 mum) a segmental dilation (the "sausage'string" phenomenon) frequently preceded uniform dilation. This arteriolar dilation was associated with a marked increase in local cerebral blood flow indicating that the upper level of autoregulation had been breached. In no cat was vasospasm or a decrease in blood flow observed during induced hypertension. Hypertension also caused dysfunction of the bloodbrain barrier since, in 17 out of 19 of the cats examined, there was extravasation of protein-bound Evans blue into brain tissue. In only one of the 19 cats subjected to neuropathological analysis was ischemic brain damage identified and this was restricted to minimal ischemic cell change. The results indicate that severe, induced hypertension in cats produces cerebral arteriolar dilation, an increase of cerebral blood flow, and dysfunction of the blood-brain barrier. These observations may be of importance in understanding the pathogenesis of hypertensive encephalopathy.
Compression of the coronary arteries by the fibrillating canine heart.
Authors: Downey J
Published: June 2012

We performed experiments to test whether the subendocardial ischemia which reportedly accompanies elective ventricular fibrillation (VF) during cardiopulmonary bypass might be the result of mechanical compression of the coronary vessels. The left coronary artery of the open-chest, anesthetized dog was cannulated and perfused with arterial blood through an extracorporeal circuit. Coronary inflow rate was held constant with a pump and the coronary vessels were dilated maximally by infusing adenosine. Any change in perfusion pressure or the transmural distribution of flow in these hearts would have been due to changes in compression. When the hearts were stopped in diastole by vagal stimulation, infusion of microspheres 15 mum in diameter revealed a subendocardial to subepicardial (inner to outer) flow ratio (I/O) of 1.2. When the same hearts were caused to fibrillate spontaneously (not electrically maintained) the I/O fell to 0.9. Little change in coronary perfusion pressure occurred between arrest and VF. When the contractile activity during VF was attenuated by intracoronary sodium pentobarbital (120 mg) the I/O rose toward that seen during arrest. However, augmentation of muscle activity by infusion of isoproterenol during VF failed to change the I/O. Finally the I/O fell in proportion to the degree of distention in the fibrillating ventricle. The results that we observed indicate that muscular contraction during VF preferentially inhibits subendocardial flow through vascular compression.
Modulation of Ca2+ control of dog and rabbit cardiac myofibrils by Mg2+. Comparison with rabbit skeletal myofibrils.
Authors: Solaro R J , Shiner J S
Published: June 2012

Increases in free Mg2+ from 0.04 to 10.0 mM with constant pH 7.0 TO 0.10 M ionic strength, and 2 mM MgATP2- caused a rightward shift of the free Ca-relative ATPase relation for both cardiac skeletal myofibrils. The specific activity of cardiac myofibrillar ATPase over a wide range of free Ca2+ was, however, depressed in 0.04 vs. 1.0 mM Mg2+, whereas a similar decrease in free Mg2+ slightly enhanced skeletal myofibrillar ATPase. Lowering free Mg2+ from 1.0 to 0.04 mM caused similar increases in cardiac and skeletal myofibrillar bound calcium, which were largely attributable to increased calcium binding to myofibrillar myosin. Raising free Mg2+ from 1.0 to 10.0 mM caused only a slight decrease of skeletal myofibrillar bound calcium, and this change was attributable to myofibrillar myosin. The same increase in free Mg2+ caused cardiac myofibrils to bind increased amounts of calcium and this change was not attributable to myofibrillar myosin. By subtracting calcium bound to myofibrillar myosin, we were able to estimate calcium binding by myofibrillar troponin. The transition between basal and maximal ATPase in 1.0 and 10 mM Mg2+ was found to be assocciated with binding of an additional 2 mol/mol of either skeletal or cardiac myofibrillar troponin.
Plasma catecholamines during paroxysmal neurogenic hypertension in quadriplegic man.
Authors: Mathias C J , Christensen N J , Corbett J L , Frankel H L , Spalding J M
Published: June 2012

Blood pressure, heart rate, and plasma catecholamine levels were measured in 16 quadriplegic subjects with physiologically complete cervical spinal cord transections above the level of the sympathetic outflow, and in 15 normal subjects (controls). In the quadriplegics the average resting blood pressure was 107/59 (mean, 75) mmHg, heart rate was 65 beats/min, and plasma norepinephrine (NE) and epinephrine (E) levels were 0.05 and 0.005 ng/ml, respectively. In the controls average resting blood pressure was 117/79 (mean, 92) mmHg, heart rate was 61 beats/min, and resting plasma NE and E levels were 0.20 and 0.06 ng/ml, respectively. Resting blood pressure and plasma NE and E levels were significantly lower in the quadriplegics (P less than 0.01, less than 0.001, less than 0.001, and less than 0.001, less than 0.001, respectively) than in the controls. In the quadriplegics, neurogenic hypertension was induced by bladder and muscle stimulation. This resulted in a marked elevation of both systolic and diastolic blood pressure (from an average of 109/60 (mean, 75) to 168/87 (mean, 114) mmHg) as a result of uninhibited sympathetic nervous activity through the isolated spinal cord. Plasma NE consistently rose, from an average of 0.05 to 0.16 ng/ml (P less than 0.001). There was significant linear relationship between plasma NE and mean blood pressure (P less than 0.001). In the quadriplegics infusion of l-norepinephrine to raise the blood pressure to comparable levels (from 105/58 (mean, 74) to 183/93 (mean, 123) mmHg) resulted in plasma NE levels approximately 21 times higher than during muscle and bladder stimulation. It is possible that the lower resting arterial blood pressure and plasma NE and E levels in the quadriplegics in comparison to normal subjects may reflect diminished resting sympathetic nervous activity. The rise in blood pressure following increased sympathetic nervous activity was accompanied by an elevation in plasma NE. The hypertension was not secondary to the rise in plasma NE. Plasma NE in these subjects appears to be a reliable index of prevailing sympathetic nervous activity.
The stimulation of cardiac prostaglandin production by blood plasma and its relationship to the regulation of coronary flow in isolated isovolumic rabbit hearts.
Authors: Moretti R L , Abraham S , Ecker R R
Published: June 2012

Infusion of small amounts of blood plasma into isolated, isovolumic rabbit hearts perfused with Tyrode's solution resulted in coronary vasoconstriction followed by a decrease in left ventricular developed pressure and dP/dt. Maximal effects were obtained with a perfusate plasma concentration of 1%. Increasing the plasma concentration beyond 1% did not appreciably increase the coronary vasoconstriction. During perfusion with 2% plasma, the coronary flow-oxygen uptake ratio was unchanged over a range of perfusion pressures (40-100 mm Hg) and vascular resistance increased with pressure. In the absence of plasma, the coronary flow-oxygen uptake ratio increased with pressure and vascular resistance decreased. Thus, cardiac regulation of coronary flow in response to changes in perfusion pressure occurred in the presence of plasma but not in its absence. The effects of plasma were reduced with two different inhibitors of prostaglandin synthesis (5,9,11,14-eicosatetraynoic acid and indomethacin). At a perfusate concentration of 50 mug/ml, indomethacin abolished the effects of 2% plasma. Rat stomach strip bioassay for prostaglandin activity indicated that the vasoconstrictor effect of plasma was accompanied by a 4-fold increase in the release of prostaglandin activity by the isolated hearts. The vasoconstrictor effect of plasma also was accompanied by an increase in the conversion of 3H-arachidonate to radiolabeled prostaglandins E2 and F2alpha. These results indicate that a relationship exists between a coronary vasoconstrictor in plasma, cardiac prostaglandin synthesis, and the regulation of coronary flow in response to changes in perfusion pressure in isolated rabbit hearts.
The role of cyclic adenosine 3', 5'-monophosphate and calcium in the regulation of contractility and glycogen phosphorylase activity in guinea pig papillary muscle.
Authors: Dobson J G , Ross J , Mayer S E
Published: June 2012

We studied the relationships between the positive inotropic effects of isoproterenol, increased frequency of contraction or paired electrical stimulation, and cyclic AMP concentration and phosphorylase activity in isolated guinea pig papillary muscles. The minimum concentration of isoproterenol (10 nM) that augmented isometric force development increased cyclic AMP concentration. However 100 nM isoproterenol was required to increase the phosphorylase activity ratio (-AMP/+AMP) from 0.15 +/- 0.03 to 0.25 +/- 0.03. After addition of 1 muM isoproterenol to the bath, cyclic AMP increased within 0.5 minute from 0.58 +/- 0.03 to 1.04 +/- 0.13 mol/kg (wet weight), peak contractile force was elevated 2-fold at 1 minute, and the phosphorylase activity ratio rose to 0.40 +/- 0.02 in 4 minutes. Although an increase in contraction frequency (6/min to 36/ min) and paired stimulation produced more than a 3-fold increase in peak contractile force, there were no changes in cyclic AMP and phosphorylase activity. The cyclic AMP concentration during diastole was 0.60 +/- 0.04 and in midsystole, 0.55 +/- 0.03 mumol/kg. Anoxia increased the phosphorylase activity ratio from 0.19 +/-0.02 to 0.41 +/- 0.04 without elevation of cyclic AMP concentration. Removal of Ca2+ from the bathing medium prevented active force development and the anoxic increase in phosphorylase activity, but did not prevent the isoproterenol-induced increase in cyclic AMP and phosphorylase. These results suggest that cyclic AMP is a factor in the catecholamine-induced enhancement of inotropic state. However, it does not appear to play a role in the maintained augmentation of inotropic state produced by increased contraction frequency and paired stimulation, nor does the concentration of the cycle nucleotide appear to vary during the contraction cycle or during anoxia. Extracellular Ca2+ is required for contraction, the positive inotropic aciton of catecholamines and phosphorylase b to a conversion by anoxia.
Red cell velocity and plasma transit time in the cerebral microcirculation of spherocytic deer mice.
Authors: Rosenblum W I
Published: June 2012

Spherocytic deer mice provide a model of human spherocytosis. Their erythrocytes are abnormal in shape and are more rigid than normal red blood cells (RBC). Like their human counterparts, spherocytic mice are anemic. Measurements of RBC velocity in microvessels on the cerebral surface failed to reveal a difference between the velocity of cells in spherocytic as compared to normal deer mice. However, plasma transit, as measured by fluorescein microangiography, was faster than normal. Both decreased plasma transit time and increased RBC velocity are expected in nonspherocytic, anemic mice. Since the former, but not the latter, was found in the spherocytic, anemic mice, it appears that increased RBC rigidity has a greater effect on RBC movement than on plasma movement within the cerebral microcirculation. Thus iit would seem that this increased RBC rigidity prevents the increased RBC velocity that otherwise would be observed in anemia but does not prevent the decrease in plasma transit time.
Origin of epicardial ST-T wave potentials in the intact dog.
Authors: Spach M S , Barr R C
Published: June 2012

Ventricular repolarization was analyzed by measuring epicardial potential distributions in intact dogs with single or multiple ectopic foci and a minimum at the terminal site(s) of excitation. During the latter half of the T wave the distributions became more complex, and two maxima evolved from the initial one at each ectopic site. The measured epicardial potentials were simulated by means of a model of ST-T wave events that is suitable for study of single and multiple ectopic beats with fusion, a a model we call 'SI model.' Intracellular potentials around the ventricles during repolarization were calculated from measured excitation sequences and known action potential shapes. The extracellular potentials around the ventricles were computed from the intracellular ones by a simplified ventricular geometry. The satisfactory agreement between the theoretical and measured extracellular potential distribution shows that the complex changes which occur throughout the ST-T wave are predicted well on the basis of changes in the intracellular potential distributions. In contrast to the well known lability of the T wave from beat, the results show that for any single beat the events of repolarization proceed in an entirely repeatable and deterministic fashion. The results present a way to directly represent cardiac extracellular events during the ST-T wave, a method analogous to the use of isochromes during QRS, and they imply that in the future it will by possible to achieve a more precise quantitative understanding of the events of the ST-T wave than thus far has been possible for QRS.
Changes in extracellular potassium activity in response to decreased pH in rabbit atrial muscle.
Authors: Skinner R B , Kunze D L
Published: June 2012

The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean control level of 3.6 mM to a new steady state level of 3.9 mM after 1 hour. When the pH was further decreased to 6.1, extracellular K+ activity increased to a mean of 4.9 mM. Following the change in pH, the increase in extracellular K+ activity occurred over a period of 30-40 minutes at which time a stable value was reached and maintained for the next hour. On return to normal pH the extracellular K+ activity returned to control with a time constant of 20 minutes or less. Measurements of intracellular K+ activity over 1 hour showed a mean loss of 3 mM at pH 6.8 and a mean loss of 8 mM at pH 6.1. The loss was reversible within 20 minutes of return to control pH. The increase in extracellular K+ activity was accompanied by a decrease in resting membrane potential as well as decreases in maximum dv/dt and overshoot of the action potential. The action potential contour underwent complex changes consisting of decrease in the plateau and a prolongation of the time to full repolarization.
Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole.
Authors: Jalife J , Moe G K
Published: June 2012

Isolated false tendons excised form dog hearts were mounted in a three-chamber tissue bath. Isotonic sucrose solution was perfused in the central chamber to provide a region of depressed conductivity between the fiber segments in chambers 1 and 3, which were perfused with Tyrode's solution. The electrotonic influence of spontaneous or driven responses evoked in chamber 3 during the first half of the spontaneous cycle of a chamber 1 peacemaker delayed the next spontaneous discharge. This effect changed to acceleration when the chamber 3 segment fired during the second half of the spontaneous cycle. We found that subthreshold depolarizing current pulses 50-300 msec applied across the sucrose gap caused similar degrees of delay or acceleration. Furthermore, hyperpolarizing currents caused the reverse pattern. The results indicate that the discharge pattern of a parasystolic focus may be altered by the electrotonic influence of activity in the surrounding tissue. The significance of these findings is considered in relation to the mechanism of production of parasystolic rhythms.
Uptake of infarct-imaging agents in reversibly and irreversibly injured myocardium in cultured fetal mouse heart.
Authors: Schelbert H R , Ingwall J S , Sybers H D , Ashburn W L
Published: June 2012

We studied the specificity of uptake of infarct-imaging agents for reversibly or irreversibly injured myocardium independently of blood flow by using intact beating fetal mouse hearts in organ culture. Reversible injury resulted from deprivation of oxygen and glucose for 4 hours at 37 degrees C; irreversible injury, from similar deprivation at 42 degrees C. At the end of the insult, uptake of 99mTc(Sc)-labeled pyrophosphate, glucoheptonate, or tetracycline was markedly increased in irreversibly damaged and, to a lesser degree, in reversibly injured hearts. After 24 hours of recovery, necrotic hearts accumulated even more pyrophosphate and tatracycline but less glucoheptonate. Uptake of radioiodinated tetracycline increased only in irreversibly injured hearts. Pyrophosphate uptake was not reduced in hearts cultured in calcium-free medium. These finding suggest that 99mTc(Sn)-labeled pyrophosphate, tetracycline, and glucoheptonate preferentially localize in irreversibly damaged myocardium; the 99mTc(Sn) complex modifies the specificity of uptake; and the uptake of 99mTc(Sn)-pyrophosphate appears unrelated to calcium uptake.
The Collaterals of the Coronary Arteries in Normal and Pathologic Hearts
Authors: BAROLDI GIORGIO , MANTERO ORESTE , SCOMAZZONI GIUSEPPE
Published: June 2012

The collateral vessels of normal and pathologic hearts were studied by making plastic casts of the coronary vessels. The normal heart possesses conspicuous coronary anastomoses. The localization, the development and to a certain extent, the incidence was studied. The maximum increase in collateral vessels was observed in cases of coronary narrowing; a less pronounced increase was found in conditions of chronic hypoxemia.
Mechanism of Experimental Atrial Flutter
Authors: LANARI A. , LAMBERTINI A. , RAVIN A.
Published: June 2012

The mechanism of atrial flutter induced by the local application of aconitine or by the Rosenblueth-Garcia Ramos method was studied in dogs. The results were analyzed from a pharmacologic and electrocardiographic point of view. It was concluded that aconitine-induced flutter is due to a single, rapidly firing ectopic focus and electrically-induced flutter to a circus movement. Although they can be differentiated electrocardiographically by means of direct cardiac leads, they cannot be differentiated by esophageal or limb leads.
The Effect of KCl on Atrial Fibrillation Caused by Acetylcholine
Authors: BURN J. H. , GUNNING A. J. , WALKER J. M.
Published: June 2012

Atrial fibrillation can be produced in the heart-lung preparation of the dog by the slow infusion of acetylcholine and the application of electric stimuli to the auricle. The fibrillation can then be maintained indefinitely, after stimulation ceases, by continuing the infusion of acetylcholine. The fibrillation can be restored to normal rhythm by the infusion of KCl. This throws light on the action of acetylcholine in maintaining atrial fibrillation.
The Initiation of Ventricular Tachycardia and Fibrillation in Isolated Hearts by Potassium Chloride
Authors: GRUMBACH L.
Published: June 2012

An accelerating tachycardia ending in fibrillation can be initiated in isolated hearts by injections of KCl after the administration of epinephrine, but not in untreated hearts. KCl acts in two ways to do this. First, it causes an A-V block that enables epinephrine to cause a paroxysmal ventricular tachycardia. Secondly, it causes the latter to accelerate by delaying the recovery of excitability so that at least one premature systole can fall into the recovery phase of a preceding impulse. This event is necessary and sufficient for the initiation of a self-sustaining accelerating tachycardia that can end in fibrillation.
Cardiac Responses to Sympathetic Stimulation
Authors: ANZOLA JORGE , RUSHMER ROBERT F.
Published: June 2012

The cardiac responses to stimulation of sympathetic nerves to the heart were studied both in thoracotomized and in intact unanesthetized dogs. The changes in heart rate, left ventricular pressure, right and left ventricular dimensions and systemic arterial pressures were recorded. The powerful effects of sympathetic stimulation resemble cardiac responses to exercise more than those following administration of catecholamines. It is inferred that neural mechanisms may be more important for cardiac control during spontaneous activities than the circulating hormones.
Physiologic Evidence for a Dual A-V Transmission System
Authors: MOE GORDON K. , PRESTON JAMES B. , BURLINGTON HAROLD
Published: June 2012

A study of the transmission of early premature contractions between atria and ventricles and in the retrograde direction in the dog heart suggests the existence of two parallel A-V conduction pathways communicating with each other over one or more branches. The evidence is based on the excessive delay of very early premature responses in traversing the node, suggesting that a slowly conducting pathway recovers earlier than the normal "fast" pathway; on the echoing back to the chamber of origin of early premature responses; and on ventricular electrograms of "abnormal" configuration obtained during early premature responses. These observations and the hypothesis to which they lead provide a natural explanation for reciprocal rhythm and nodal paroxysmal tachycardia.
Placental Transfer of Radioactive Digitoxin in Pregnant Women and its Fetal Distribution
Authors: OKITA GEORGE T. , PLOTZ ERNEST J. , DAVIS M. EDWARDS , Curry John H. , Smith Frederick D.
Published: June 2012

Placental transfer of radioactive C
14
-digitoxin was investigated in four pregnant women. The concentration of the labeled drug and its metabolic products in the various fetal organs was determined. Less than 1 per cent of the administered glycoside was detected in the fetus as unchanged digitoxin and less than 3.5 per cent as its metabolites. The fetal heart and kidney of 11 to 12 weeks gestation had the highest concentrations. However, at near term the fetal liver, gallbladder and intestine had somewhat similar concentrations. Metabolic conversion of the cardiac glycoside by fetal liver as well as biliary excretion is indicated from the tissue distribution data.
Theory and Experiments on Schematized Models of Stenosis
Authors: BURGER H. C. , VAN BRUMMELEN A. G. W. , DANNENBURG F. J.
Published: June 2012

In this study the relation between flow and the difference of the pressures on the two sides of stenosis with sharp edges is investigated for constant and pulsatile flows. The applicability of the theory of Gorlin and Gorlin is complicated by a kind of hysteresis phenomenon in the case of pulsatile flows.
Intrinsic Deflections, Local Excitation and Transmembrane Action Potentials
Authors: SANO TOYOMI , ONO MASARU , SHIMAMOTO TAKIO
Published: June 2012

The steepest rise of the action potential obtained by an ultramicroelectrode from the most superficial subepicardial muscle fiber in situ of the tortoise was compared with the intrinsic deflection of the unipolar direct electrocardiogram and the surface electrocardiogram obtained from approximately the same region. No specific point on the intrinsic deflection, such as the highest or lowest point, could be regarded as indicating the arrival of excitation. Surface electrocardiograms obtained by the capillary ultramicroelectrode could not be regarded as simple second derivatives of the action potential, they resembled more unipolar direct electrocardiograms.
Amplifier for Linear Recording of Oxygen Saturation and Dye Dilution Curves
Authors: WIEDERHIELM CURT
Published: June 2012

An amplifier system has been designed for use with commercially available oximeter earpiece or cuvette and a direct recording oscillograph. Linear response to changes in oxygen saturation and in vivo dye concentrations are obtained with a rise time less than 0.5 sec., noise level and drift less than 2.5 per cent and accuracy comparable to Van Slyke-Neill method. Standard error of estimate between Van Slyke-Neill manometric and cuvette oximeter amplifier-recorder systems is ±2 per cent.
Extrarenal Effects of Intravenous Pitressin in Nephrectomized Rats
Authors: FRIEDMAN SYDNEY M. , NAKASHIMA MIYOSHI , FRIEDMAN CONSTANCE L.
Published: June 2012

Using inulin as indicator of the extracellular fluid volume, the effects of Pitressin on the movements of sodium and potassium were studied in the nephrectomized rat together with simultaneously determined direct blood pressure values. Pitressin caused a movement of sodium and water into cells coupled with the extrusion of some potassium during the phase of blood pressure elevation. The beginning of the phase of blood pressure decline coincided with a rapid shift of potassium into cells while the sodium and water acquired by cells in the early phase were gradually extruded. These shifts were demonstrable with as little as 10 mU. of Pitressin intravenously while the maximal effect occurred in the 30 to 50 mU. dose range. These effects may account for many of the changes observed with Pitressin in the intact animal and also may have some bearing on blood pressure homeostasis.
Increased Aldosterone Secretion in Response to Blood Loss
Authors: FARRELL GORDON L. , ROSNAGLE ROBERT S. , RAUSCHKOLB ELIZABETH W. , Banks Robert , Saleliar Milena
Published: June 2012

A marked increase in the adrenal secretion of the potent electrolyte-active steroid, aldosterone, was observed in the dog in response to loss of blood. The proportionate increase in adrenal output of alclostcrone exceeded that of hydrocortisone. The physiologic mechanism by which the increased aldosterone release is mediated remains obscure. The stimulus to increased aldosterone secretion was not a change in the serum electrolytes. Expansion of the volume of the vascular system by the infusion of large amounts of plasma substitutes failed to uniformly prevent the increased aldosterone output.
Metabolic Aspects of the Relationship Between the Contractility and Membrane Potentials of the Rat Atrium
Authors: WEBB J. LEYDEN , HOLLANDER PHILIP B.
Published: June 2012

Some of the relationships between metabolism, membrane potentials and contractility in cardiac tissue have emerged from a study of the effects of anoxia, depletion of substrate and dinitrophenol on the rat atrium. The repolarization phase of the action potential was shown to be particularly sensitive to disturbances in metabolism. Depression of metabolism resulted in a more rapid repolarization, which may provisionally be interpreted as an acceleration of K
+
efflux; restoration of metabolism reversed this effect. A concept relating membrane potentials and metabolism is presented, involving the presence of bound ATP within the membrane.
A Catheter Tip Method for Measurement of the Instantaneous Aortic Blood Velocity
Authors: FRY DONALD L. , MALLOS ALEXANDER J. , CASPER ALFRED G. T.
Published: June 2012

A method of determining the instantaneous aortic blood velocity from the pressure difference between two points along the axis of the aorta was derived from the Navier-Stokes equation. Experimental support for the derived formula was obtained in a flow model and in a living animal aorta. The flow model was a small piston pump which produced a known sinusoidal fluid velocity. The velocity computed from the formula compared well with the known values. In the living animal the formula yielded a velocity curve which compared favorably with those in the literature. The pressure difference from which the velocity was computed was obtained through a specially designed double lumen catheter attached to a differential pressure transducer. The method is applicable only to pulsatile flow.
The Catechol Amine Content of Various Organs of the Cat After Injections and Infusions of Adrenaline and Noradrenaline
Authors: VON EULER U. S.
Published: June 2012

Infusions of 2.5-7.8 µg. noradrenaline/Kg./min. over 30 min. and intraperitoneal injections of noradrenaline and adrenaline up to 2000 µg/Kg, in the cat had no effect on the catechol amine content of the heart, spleen, liver, kidney and skeletal muscle, except for a slight increase in the adrenaline content. It is concluded that these organs lack the ability to accumulate circulating catechol amines administered in physiologic dosage.
The Electrolytes of Arterial Wall in Experimental Renal Hypertension
Authors: TOBIAN LOUIS , WHITE LOIS
Published: June 2012

In rats with renal hypertension, smooth muscle cells in the wall of the aorta appear to have more water, sodium, potassium, magnesium and phosphorus per unit of cell solids than similar cells in normotensive rats. When the blood pressure of a few hypertensive rats dropped to normal as a result of a low sodium diet, the potassium and phosphorus in the arterial cells also appeared to decrease to normal levels. These studies give indications of the compositional changes in arterial smooth muscle cells that are associated with renal hypertension.
Ineffectiveness of Nitroglycerin as an Antiadrenergic Agent on the Cat Heart
Authors: POPOVICH NICHOLAS R. , ROBERTS FRED F. , CRISLIP RODNEY L. , MENGES HERMANN , ECKSTEIN RICHARD W.
Published: June 2012

The possibility that nitroglyoerin modifies the metabolic effects of the sympathomimetic amines was tested in cats. Changes in the heart rate, blood pressure, height of the electrocardiographic T-wave and myocardial oxygen consumption following the injection of epinephrine or l-arterenol were compared with changes in these indices after nitroglycerin was given with these sympathomimetic amines. The conclusion is reached that nitroglycerin does not significantly influence the effects of epinephrine or l-arterenol on the heart rate, the height of the electrocardiographic T-wave or myocardial oxygen consumption. There is no evidence in these experiments to support the concept that nitroglycerin metabolically neutralizes the myocardial anoxating properties of the sympathomimetic amines.
Sarcolemmal sodium permeability and contractile force of guinea pig papillary muscle: effects of germitrine.
Authors: Honerjäger P , Reiter M
Published: June 2012

The action potential of guinea pig papillary muscle exposed to the ceveratrum alkaloid germitrine (2 mugM) is followed by a long-lasting after-depolarization (maximal amplitude, 8 mV; half-time of decay, 32 seconds; total duration, approximately 75 seconds). This after-depolarization interrupts the terminal phase of repolarization. During repetitive stimulation (0.1-1.0 Hz; 80 nM germitrine) the after-depolarizations that follow consecutive action potentials are summed, causing persistent depolarization of up to 10 mV. The after-depolarization is reversibly abolished by tetrodotoxin (TTX). Test contractions evoked at various times during or after the germitrine-induced after-depolarization reveal a phase during which the ability of the muscle to develop force is transiently increased. This positive inotropic influence reaches its maximum 1 minute after the conditioning stimulus and thereafter decays with a half-time 4.8 times longer than the half-time of decay of the after depolarization. It is reversibly abolished by TTX and augmented by dihydro-ouabain (DHO). We conclude: Germitrine induces an after-depolarization by prolonging dramatically the Na permeability component which is mediated by the fast Na channels and normally restricted to the first few milliseconds of the action potential. The germitrine-induced selective and persistent increase of sarcolemmal sodium permeability (PNA) causes a positive inotropic effect, probably because intracellularly accumulating Na ions exchange for extracellular Ca ions.
The distribution of labeled albumin across the rabbit thoracic aorta in vivo.
Authors: Bratzler R L , Chisolm G M , Colton C K , Smith K A , Zilversmit D B , Lees R S
Published: June 2012

125I-albumin was injected intravenously into normal conscious rabbits. The rabbits were killed after 10 minutes to 24 hours, and the descending thoracic aorta was excises immediately, opened longitudinally, rinsed, and frozen. Samples of frozen aorta were sectioned paralled to the intimal surface and washed with trichloroacetic acid (TCA) prior to counting. TCA-soluble tissue radioactivity slowly increased with time, suggesting that 125I was cleaved gradually from the labeled albumin within the aortic wall. At up to 4 hours, transmural concentration profiles of TCA-precipitable radioactivity had steep gradients near the intimal surface, moderate gradients near the medial-advential border, and were relatively falt in the middle of the media. After 24 hours, the steep intimal gradient had disappeared. Concentrations were otherwise comparable to those at 4 hours. The rate of accumulation of TCA-precipitable radioactivity was rapid initially (measurable concentrations were found throughout the media after only 10 minutes) and decreased with time. The results are consistent with entry of 125I-albumin into the media from both the luminal and adventitial sides. Approximate calculations indicate that the albumin mass transfer resistance associated with the intimal endothelium is about 1 order of magnitude greater than that associated with the media.