bluuebunny/crossref_metadata_2025 huggingface dataset:
The rabbit as an animal model for the activated factor X-antithrombin III-heparin reaction.
Authors: Gitel S N , Wessler S , Medina V M
Published: June 2012

When activated factor X (Xa) inhibitory activity of serially diluted human and rabbit plasma is determined in a low salt assay, a lineare plot is obtained for human, but not for rabbit plasma. When a high salt assay is used, the dilution curves for both human and rabbit plasma are linear, and qualititive as well as quantitative differences are essentially eliminated. On Sephadex G-200 chromatography Xa inhibitory activity of human and rabbit plasma appears in two peaks. With the low salt assay the first and second peaks for human plasma contain respectively 30%, and 70% of the activity; whereas with rabbit plasma these values are greater than 95% and less than 5% of the activity. With the high salt assay the figures for human plasma are less than 5% and greater than 95%, and with rabbit plasma 65 +/- 3% and 35 +/- 3%, respectively. With the high salt system, rabbit plasma shows a continuous increase in Xa inhibitory activity with increasing heparin concentrations, similar to that obtained with human plasma. In the high salt system the relative contributions of antithrombin III to Xa neutralization in human and rabbit plasma are different. However, in experiments in which Xa inhibitory activity of antithrombin III is altered by heparin, a simple formula, Total activity (%) = 65% + 0.35 x human plasma (%), permits translation of rabbit data on the Xa-antithrombin III-heparin reaction to man. On the basis of these findings, the rabbit model can effectively be used to study the Xa-antithrombin III reaction.
Trophic influence of the sympathetic nervous system on the rat portal vein.
Authors: Aprigliano O , Hermsmeyer K
Published: June 2012

Adrenergic denervation of the rat portal vein was produced in vivo by the sympatholytic agent 6-hydroxydopamine (6-OHDA). Treatment of rats with 6-OHDA decreased the responses of the portal veins to nerve stimulation, reduced 3H-norepinephrine (NE) uptake, and decreased catecholamine fluorescence, indicating that partial adrenergic denervation was achieved. The main findings of this study indicate that the in vivo denervation produced: (1) a (time-dependent) increase in sensitivity of the veins to NE, which was not of prejunctional origin, (2) an increase in sensitivity to BaC12, and (3) a partial depolarization of the myovascular cells. The results suggest that the in vivo denervation of the portal veins by 6-OHDA produces a postjunctional alteration, which may be due to the removal of a trophic influence of the sympathetic nervous system. It is proposed that the partial depolarization and associated ionic changes may be components of the mechanism. These results provide the first direct evidence that membrane excitability changes are involved in trophic nerve-muscle interactions in blood vessels.
Action potentials, afterpotentials, and arrhythmias.
Authors: Cranefield P F
Published: June 2012

Triggered activity must be added to spontaneous activity and to circus movement as a cause for extrasystoles and tachycardias of either atrial or ventricular origin. The activity of a triggerable focus requires phase 4 depolarization caused by an afterpotential; this distinguishes it from the activity seen in circus movement. A triggerable focus becomes rhythmically active only if driven at a critical rate or by a critically timed premature impulse; this distinguishes it from a focus of spontaneous or automatic activity. The ease of triggering a triggerable focus increases in the presence of catecholamines; triggerable foci in the atrium become quiescent when exposed to acetylcholine. At the present time, fibers within the coronary sinus provide the most persuasive example of triggered activity as a possible cause of arrhythmias of clinical significance. It is possible that the coupled extrasystoles of digitalis toxicity may be triggered; there is every reason to believe that further examples of triggered arrhythmias of possible clinical significance will be discovered.
Actin-activated adenosine triphosphatase activity of native and N-ethylmaleimide-modified cardiac myosin from normal and thyrotoxic rabbits.
Authors: Banerjee S K , Morkin E
Published: June 2012

The Ca2+-ATPase activity of cardiac myosin is increased in thyrotoxic animals. However, the physiological significance of this observation is uncertain since, in living muscle, Mg-ATP is hydrolyzed by myosin under the stimulating influence of actin. In this study, we have compared the actin-activated ATPase activity of myosin from euthyroid (myosin-N) and thyrotoxic (myosin-T) rabbits and the derivatives of myosin-N and myosin-T formed by blocking the most rapidly reacting class of thiols (SH1) with N-ethylmaleimide (NEM). Also, we have studied the activity of these myosins in the presence of a complex of troponin and tropomyosin that confers calcium sensitivity on the system. Vmax for the actin-activated ATPase of myosin-T was about 168% greater than for myosin N. The apparent dissociation constant for actin, Kapp, for myosin-T was about 42% of the normal value. After NEM modification, Vmax and Kapp for NEM-modified myosin-T and myosin-N decreased, becoming essentially the same for both myosins. In the presence of troponin-tropomyosin complex, the actin-activated ATPase of myosin-T exhibited calcium sensitivity that could be reduced by thiol modification. These results suggest that the SH1 thiols or the region near these groups are important to the actin-activated ATPase of myosin-N and are essential to the increased activity of myosin-T. Also, they suggest that the changes in the enzymatic properties of myosin induced by thyroxine may be responsible for altering the contractile properties of the heart.
Behavior of cardiac receptors with nonmyelinated vagal afferents during spontaneous respiration in cats.
Authors: Thames M D , Donald D E , Shepherd J T
Published: June 2012

Activity from left atrial and left ventricular receptors with nonmyelinated vagal afferents (mean conduction velocity, 1.2 m/sec) was recorded in 13 closed-chest spontaneously breathing cats anesthetized with alpha-chloralose. The anatomic position of each receptor was determined by probing the opened heart at the conclusion of the experiment. Three of eight left atrial receptors and four of five left ventricular receptors were silent under resting conditions. The mean discharge frequency under resting conditons for the six receptors displaying spontaneous activity was 1.0 +/- 0.15 impulse/sec. Thus cardiac receptors with vagal nonmyelinated afferent have a low resting discharge in spontaneously breathing cats. The frequency and pattern of discharge of atrial but not of ventricular receptors was altered during spontaneous respiration. The atrial receptors discharged with cardiac rhythmicity during end inspiration and early expiration when transmural pressure was greatest and were silent for the remainder of the respiratory cycle. Whe respiration was augmented by CO2 breathing or blood volume was increased, the rate of discharge was a linear function of atrial transmural pressure. Eleven ventricular receptors with nonmyelinated afferents (mean conduction velocity, 1.0 m/sec) were exposed to graded volume expansion and phenylephrine infusion in eight open-chest and three spontaneously breathing cats. Raising left ventricular end-diastolic pressure alone increased the frequency of discharge, and a concomitant increase in systolic pressure caused a further increase in firing.
Multiple pathways of capillary permeability.
Authors: Renkin E M
Published: June 2012

Morphological and physiological studies indicate multiple routes for transport across capillary endothelium. However, the identification of the morphological counterparts of specific transport processes (or the assignment of specific transport roles to morphologically identifiable pathways) has been only partly achieved: the contribution of endothelial cell membranes to transport of water and small, lipid-insoluble molecules needs to be evaluated. The identification of the "small pore" pathway for water and lipid-insoluble molecules with the intercellular junctions still remains questionable. The contributions to total macromolecular transport of junctions, single vesicles (pinocytosis, cytopempsis), chains of vesicles, and fenestrae are not yet known.
Lack of correlation of plasma norepinephrine and dopamine-beta-hydroxylase in hypertensive and normotensive subjects.
Authors: Lake C R , Ziegler M G , Coleman M , Kopin I J
Published: June 2012

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.
Failure of renin suppression by angiotensin II in hypertension.
Authors: Williams G H , Hollenberg N K , Moore T J , Dluhy R G , Bavli S Z , Solomon H S , Mersey J H
Published: June 2012

Angiotensin II was infused at rates varying from 0.1 to 10 ng/kg per minute into 49 subjects with hypertension and 26 normotensive subjects and changes in blood pressure, plasma angiotensin II, and plasma renin activity (PRA) were determined after 20 and 30 minutes at each dose. Similar dose-related increases in angiotensin II and blood pressure occurred with a threshold of 1 ng/kg per minute in the normotensive and hypertensive subjects. Whereas angiotensin II induced a significant, dose-related decrement in renin activity in the normotensive subjects, with a threshold of 1.0 ng/kg per minute, no significant change in renin activity occurred in either the normal-renin or high-renin hypertensive subjects. In a separate study, nine normotensive and six hypertensive sodium-restricted subjects were given a converting enzyme inhibitor, SQ 20881, 30 microgram/kg. Despite a significantly greater fall in blood pressure (P less than 0.006) and angiotensin II concentration (P less than 0.045) in the hypertensive subjects, they did not have a greater rise in plasma renin activity. We conclude that angiotensin II reduces renin release in normal man at infusion rates that yield plasma angiotensin II levels within the physiological range but has a strikingly reduced influence on renin release in hypertension. In high-renin hypertension due to renal artery stenosis or nephrosclerosis, renin release is presumed to be relatively autonomous because of a dominant, intrarenal mechanism. The mechanism in normal-renin essential hypertension is not clear, but the abnormality could well be related to the pathogenesis of the hypertension.
Effects of norepinephine, calcium, and rate of discharge on 42K movements in canine cardiac Purkinje fibers.
Authors: Musso E , Vassalle M
Published: June 2012

We studied the effect of norepinephrine, calcium concentration, and rate of discharge in the presence of different [Ca2+]0 on radioactive potassium movements in cardiac Purkinje fibers. The following results were obtained: (1) norepinephrine increases potassium uptake in quiescent fibers and in fibers driven at constant rate, but more in the latter; (2) norepinephrine also increases potassium uptake in quiescent fibers depolarized at the plateau; (3) increasing [Ca2+]0 increases potassium uptake in fibers driven at constant rate; (4) increasing [Ca2+]0 may decrease K+ uptake in quiescent fibers; (5) increasing [Ca2+]0 decreases the rate of loss of tissue radioactivity in quiescent fibers and increases it in a driven fiber; (6) increasing the driving rate increases potassium uptake in low and high [Ca2+]0; (7) high [Ca2+]0 increases K+ uptake, especially at low rates; (8) norepinephrine is less effective in increasing K+ uptake in the presence of a high [Ca2+]0. We conclude that: (a) norepinephrine increases potassium uptake by different mechanisms; (b) calcium affects potassium movements when it is allowed to enter the cell, presumably by affecting potassium conductance; (c) the effect of an increased rate of discharge on K+ uptake may involve stimulation of active K+ uptake and may include a calcium-dependent component which is largest at high [Ca2+]0 and a slow rate of drive; (d) simultaneous application of two interventions results in a summation that is smallest when one of the mechanisms is already substantially activated.
Regional choline acetyltransferase activity in the guinea pig heart.
Authors: Schmid P G , Greif B J , Lund D D , Roskoski R
Published: June 2012

Choline acetyltransferase is the enzyme that catalyzes the biosynthesis of acetylcholine, the neurotransmitter of the pre- and postganglionic parasympathetic system. To assess the extent of parasympathetic innervation, enzyme activity was measured in specialized and contractile regions throughout the guinea pig heart. Enzyme activity in the right atrial appendage was 137 nmol g(-1) hr(-1). Activity was greatest in the region of the sinoatrial node (187 nmol g(-1) hr(-1). Also, enzyme activity was high in the regions of the atrioventricular node (153 nmol g(-1) hr(-1), the proximal conduction bundles (133 nmol g(-1) hr(-1), and the base of the anterior papillary muscle of the right ventricle (179 nmol g(-1) hr(-1), which contains the moderator band and Purkinje fibers. In contrast, the enzyme activity in the inferior interventricular septum and the free walls of the right and left ventricles, which are more predominantly contractile tissue, was 67 +/- 6,108 +/- 14, and 56 +/- 11 nmol g(-1) hr(-1), respectively. This activity is significantly lower than in the right atrial appendage. These results suggest that the density of parasympathetic innervation is similar in all the components of the conduction system, from the sinoatrial node to Purkinje tissues. Furthermore, the parasympathetic innervation of regions specialized for conduction is up to four times more dense than that of contractile regions.
The magnitude of the electromotive force of canine ventricular myocardium.
Authors: Mashima S , Harumi K , Murao S
Published: June 2012

The isolated and perfused dog heart was placed in a cubic container filled with Tyrode's solution. Ventricular ectopic beats were produced by electrical stimulation of the left ventricular wall, and initial QRS vectors of these beats were determined with orthogonal leads from the surface of the container. At the same instants, the activated area on the epicardial surface was measured by means of a large number of contiguous bipolar leads from the epicardial surface. The QRS vector and the activated epicardial area were found to be nearly porportional. By use of these results and a calibration system with artificial dipoles, the double layer moment of the ventricular activation wave was calculated as 0.13 mA.cm per unit area. This value corresponds to 60% of the maximal possible strength of the tissue electromotive force. Lowering the conductivity of the surrounding solution increased the QRS voltage but not as much as the potential caused by a constant-current dipole within the solution. The relationship between the QRS voltage and the conductivity of the medium was analyzed by a simplified model of the system and was found to correspond approximately to that of a constant-current source within a spherical heart with a resistivity 2 to 3 times that of Tyrode's solution.
The relationship of excitability to conduction velocity in canine Purkinje tissue.
Authors: Peon J , Ferrier G R , Moe G K
Published: June 2012

The relationship between interelectrode conduction time and "take-off" potential (TOP) was studied with microelectrode techniques in isolated canine false tendons. Conduction of regular or test beats initiated during phase 4 dopolarization or late phase 3 repolarization speeded as TOP decreased. Similarly, beats initiated during digitalis-induced oscillatory after potentials demonstrated more rapid conduction at lower TOP. Because of the frequency-coupled nature of the oscillations, conduction times became rate dependent. Phenytoin antagonized digitalis oscillations and reversed speeding of conduction attributable to the oscillations. No uniform relationship between speed of conduction and maximum upstroke velocity of the action potential could be demonstrated in the above experiments or when speed of conduction was varied by changes in concentration of K+ or Ca2+. However speed of conduction could be demonstrated to vary directly with changes in excitability as measured by intracellular current injection.
Evidence for a splanchnic sodium input monitor regulating renal sodium excretion in man. Lack of dependence upon aldosterone.
Authors: Carey R M
Published: June 2012

Eight normal male subjects were placed on a constant 10 mEq sodium, 60 mEq potassium diet for 5 days. At 8:00 a.m. on the 5th day, the subjects were given a standard dose of 100 mEq of sodium orally or intravenously. Subjects receiving oral sodium also received 200ml of 5% dextrose in water intravenously, and those receiving intravenous sodium also received placebo capsules orally. Water intake and posture were controlled. The subjects then returned to a free diet for 1 month and subsequently were restudied by using the opposite route of sodium administration. The subjects given the oral sodium load excreted greater quantities of sodium in their urine than those repleted intravenously. The differential natriuresis was significant as early as 2 hours after sodium loading. Plasma aldosterone concentration was similar irrespective of the route of sodium administration. Six patients with primary adrenocortical insufficiency and documented hypoaldosteronism were studied with the same protocol after 5 days of 50 mEq sodium, 60 mEq potassium intake. They also had significantly greater natriuresis after oral than intravenous sodium administration. The data suggest the presence of a splanchnic input monitor for sodium which partially regulates renal sodium excretion and is not dependent upon a turn-off mechanism for aldosterone secretion.
The interaction of human plasma glycosaminoglycans with plasma lipoproteins. II. Hemagglutination studies.
Authors: Donnelly P V , Di Ferrante N , Jackson R L
Published: June 2012

Formalinized, tannic acid-treated sheep erythrocytes coated with low density lipoproteins (LSL) or apoprotein B (apo-B) are are agglutinated by anti-apo-B immunserum. Those coated with high density lipoproteins (HDL) or apoprotein A-I(apo-A-I) are agglutinated by anti-apo-A-I immunserum. These coated formocells have been used to study the interactions of lipoproteins and apoproteins with plasma glycosaminoglycans (GAG). The sulfate-rich species of plasma GAG agglutinates cells coated with LDL, HDL, apo-B, and apo-A-I at ionic concentrations above 0.15 M. The less-sulfated species of plasma GAG does not agglutinate the coated cells but inhibits the agglutination caused by the sulfate-rich species. Treatment of the sulfate-rich GAG with papain causes a reduction in molecular weight by one-half and also causes a loss of its agglutinating activity. These results suggest that the sulfate-rich plasma GAG, consisting of two glycan chains linked to a peptide backbone, cause agglutination by binding to two or more formocells. In contrast, the less-sulfated plasma GAG, consisting of single, short glycan chains, are incapable of causing agglutination but may prevent it by covering specific binding sites present on the coated cells.
Enhancement of platelet aggregation by tranylcypromine in mouse cerebral microvessels.
Authors: Rosenblum W I , El-Sabban F
Published: June 2012

Tranylcypromine, given intraperitoneally at doses greater than or equal to 10 mg/kg, enhanced platelet aggregation in the arterioles on the cerebral surface in mice. Tranylcypromine inhibits prostacyclin synthesis in vitro. Iproniazid, which inhibits monoamine oxidase but not prostacyclin synthesis, failed to enhance platelet aggregation. The failure of iproniazid to enhance aggregation in this study rules out an effect on monoamine oxidase as the cause of tranylcypromine's action. That iproniazid inhibited aggregation indicates it has an effect opposite to that of tranylcypromine. Imidazole, a drug known to inhibit synthesis of both prostacyclin and thromboxane, failed to affect platelet aggregation. All of our data are compatible with the hypothesis that prostacyclin is an inhibitor of platelet aggregation. This hypothesis has been based largely on in vitro data, to which we now add in vivo support.
Simulation studies of the electrocardiogram. II. Ischemia and infarction.
Authors: Miller W T , Geselowitz D B
Published: June 2012

Experimental studies of the myocardial action potentials following coronary artery occlusion have shown that the resulting regional ischemia is reflected by characteristics changes in the shapes of the action potentials in the ischemic region. The principal changes are decreases in the magnitude of the resting potential and in the action potential duration. Action potentials with prolonged durations have been observed in the infarcted regions of experimental animals after the development of inverted T waves in the surface electrocardiogram (ECG). We use such abnormal action potentials in our digital computer model to study the effects of acute myocardial ischemia and infarction on the surface ECG. The heart is represented in sufficient detail to allow variations in the location and size of the ischemic injury and in the distribution of the severity of injury within the injured region. The evolution of acute infarctions is simulated by progressively modifying the abnormal action potentials assigned to the injured region. Calculated standard 12 lead ECGs and torso isopotential surface maps for simulated acute ischemia and infarction are in good agreement with patient data reported in the literature. Typical simulations include anterior and inferior transmural ischemia and infarction and anterior subendocardial ischemia. The model is used to examine relationships between torso surface potentials during ventricular activation and recovery and the site and size of the ischemic injury.
Actions of lidocaine on transmembrane potentials of subendocardial Purkinje fibers surviving in infarcted canine hearts.
Authors: Allen J D , Brennan F J , Wit A L
Published: June 2012

We compared the effects of lidocaine, 2 X 10(-5) M, on transmembrane resting and action potentials of Purkinje fibers on the endocardial surface of 24- to 72-hour-old myocardial infarcts in dogs with its actions and subendocardial Purkinje fibers in normal hearts. At both proximal (near the tip of the papillary muscle) and distal (toward the apex) recording sites in noninfarcted hearts, lidocaine had no significant effect on maximum diastolic potential (MDP) or Vmax. It shortened action potential duration (APD) only at the proximal site. In infarcted hearts, we arbitrarily divided Purkinje fibers at the infarcted distal site into two groups. Group I consisted of fibers which did not have a severely depressed MDP or Vmax but in which APD was markedly prolonged. Lidocaine had no effect on MDP of these fibers, significantly depressed Vmax, and shortened APD. Group II consisted of fibers in which MDP and Vmax were markedly reduced. Lidocaine also reduced Vmax of these fibers further (by 60%) without altering resting potential. In addition, lidocaine depressed pacemaker activity of Purkinje fibers in infarcts. The drug did not alter conduction of premature impulses in the subendocardial Purkinje network in normal hearts but increased the maximum delay of early premature impulses in Purkinje fibers in infarcted hearts and sometimes resulted in nondriven repetitive activity. Therefore, the effects of lidocaine on transmembrane potentials of Purkinje fibers in infarcts are different from its effects on fibers in normal hearts.
Relationship of aortic wall and baroreceptor properties during development in normotensive and spontaneously hypertensive rats.
Authors: Andresen M C , Krauhs J M , Brown A M
Published: June 2012

We studied the relationship between aortic baroreceptor function and aortic wall properties in normotensive (NTR) and spontaneously hypertensive (SHR) rats 10-20 weeks old. Baroreceptor discharge, static pressure-volume (P-V), and pressure-radius relationships were measured in excised aortic segments. Histological studies of wall thickness and receptor numbers also were made. Circumferential wall stress and strain were calculated, as was the incremental elastic modulus (EINC). EINC in NTR's at 100 mm Hg was similar to values reported for in vivo human, dog, and rat aortas. At 10 weeks, SHR's had significantly elevated blood pressure, but SHR and NTR aortas had similar relationships among pressures, volumes, strains, and EINC's. Differences arose subsequently and, at 20 weeks, NTR aortas had larger volumes, larger strains, and smaller EINC's at equivalent pressures, whereas SHR aortas were unchanged. Thus the reduced distensibility of SHR relative to NTR aortas, rather than being due to retrogressive changes from normal, appeared to result from a failure to pass through a phase of increased distensibility. At 10 weeks, SHR baroreceptors showed resetting in both pressure-response and strain-response curves, and it was concluded that early hypertensive baroreceptor resetting was due to primary changes in the receptors. At 20 weeks, the order of the strain-response curves for NTR and SHR baroreceptors was reversed due to a reduction in strain sensitivity of NTR baroreceptors. Resetting of NTR baroreceptors during development may have important implications as a mechanism of blood pressure control in development.
Direct evidence that the greater contractility of resistance vessels in spontaneously hypertensive rats is associated with a narrowed lumen, a thickened media, and an increased number of smooth muscle cell layers.
Authors: Mulvany M J , Hansen O K , Aalkjaer C
Published: June 2012

The mechanical and morphological properties of segments of certain precisely defined resistance vessels (approximately 150 micrometer lumen diameter) in the mesenteric bed of spontaneously hypertensive (SHR) and normotensive (WKY) rats have been compared in vitro under carefully controlled conditions and also after fixation. At a given transmural pressure, the relaxed SHR vessels (compared with the WKY vessels) would have had a 16% smaller lumen diameter (P less than 0.01) and a 49% thicker media (P less than 0.005), so that the media volume per unit segment length was 31% greater (P less than 0.05). The smooth muscle cells were arranged circumferentially in about four layers in the SHR vessels and in about three layers in the WKY vessels. The SHR active wall tension in response to potassium was 53% greater (P less than 0.02) and to norepinephrine was 50% greater (P less than 0.01) than for WKY. However, the ED50 values for the norepinephrine dose-response curves were similar (approximately 5 micrometer). Activation with potassium plus norepinephrine gave greater responses in both vessel types, than with either agent alone, but the SHR responses were on average only 19% greater than the WKY (P less than 0.10). However, under these conditions, the SHR vessels would have been able to contract against 45% greater transmural pressures (P less than 0.001) because of their smaller lumen. On maximal activation, the mean force developed by each cell (approximately 3.85 micro N) was the same in both vessel types, even though on average (P = 0.10) the SHR cells had a 21% greater cross-sectional area. The results support the Folkow hypothesis that in genetic hypertension the increased peripheral resistance is associated with structural changes in the resistance vessels.
The relation between arterial viscoelasticity and wave propagation in the canine femoral artery in vivo.
Authors: Milnor W R , Bertram C D
Published: June 2012

The influence of arterial dimensions and viscoelasticity on pulse wave propagation has been expressed in many theoretical models of blood flow in arteries, but few experimental tests of these theories in vivo have been reported. The measurements required for such tests include not only the arterial viscoelasticity, diameter, and wall thickness, but also the true propagation coefficients and impedances, for comparison with the values "predicted" by solution of the model equations. We made such measurements in 16 experiments on the femoral artery in nine anesthetized dogs. A two-point pressure and flow technique was used to measure wave propagation, and an ultrasonic micrometer was used to measure vessel diameter as a function of time and pressure. Measured attenuation constants ranged from 0.010 at 1.3 Hz to 0.075 at 12.7 Hz, and were more than twice as large as those predicted by two representative linear models. True phase velocity, which increased from 6.71 m/sec at 1.3 Hz to 10.54 m/sec at 12.7 Hz, agreed closely with the values computed by the Cox model but were lower than those given by the Jager model. The resistive, but not the reactive, component of longitudinal impedance was significantly greater than predicted by the models at all frequencies. The experiments do not identify the source of these discrepancies. The use of linear models to calculate pulsatile blood flow from pressure gradients in relatively small vessels, or to calculate attenuation and characteristic impedance from arterial viscoelasticity in vessels of any size, produces significant errors.
Ontogenetic increase of the maximal rate of rise of the chick embryonic heart action potential. Relationship to voltage, time, and tetrodotoxin.
Authors: Iijima T , Pappano A J
Published: June 2012

The maximal rate of rise (Vmax) of the embryonic chick ventricular action potential increased about 2-fold from 112 +/- 6 V/sec and 113 +/- 5 V/sec on the 4th and 6th incubation days, respectively, to 217 +/- 7 V/sec on the 12th incubation day. Neither the steady state inactivation (hinfinity) of Vmax, the temperature-dependent shift of hinfinity, nor the time constant for recovery (tauRec) of Vmax changed significantly when Vmax had doubled. Inhibition of Vmax by tetrodotoxin (TTX) was the same in hearts from the 4th, 6th, and 18th incubation days. The relation between Vmax and TTX concentration could be described by a one-to-one binding curve with an apparent dissociation constant of 2 X 10(-8) M. The increase of Vmax, a valid measure of the early inward Na+ current (iNa) during the rising phase of the cardiac action potential, can be attributed to an elevated maximal Na+ conductance (-gNa) during ontogenesis. These results indicate that the physicochemical properties of the gNa unit responsible for the rapid rising phase of the action potential and of the TTX binding site associated with it may remain constant during a period of embryonic development when -gNa increased significantly.
Sympathetic control of major coronary artery diameter in the dog.
Authors: Gerová M , Barta E , Gero J
Published: June 2012

The diameter of a major coronary artery, the ramus interventricularis ventralis (RIV), was measured in dogs with arrested hearts perfused by an extracorporeal circulation. The resting diastolic diameter was 1.78 +/- 0.07 mm (mean +/- SE) at a diastolic pressure of 74.2 +/- 3.4 mm Hg. Bilateral supramaximal stimulation of fibers leaving the cranial pole of the stellate ganglion decreased the diameter by 71.2 +/- 8.9 micrometer, i.e., 4.0 +/- 0.5% of the resting diameter. Stimulation of the left stellate ganglion contributed 59.8 +/- 5.7% of the maximum response; that of the right contributed 40.3 +/- 5.5%. Stimulation of the thoracic ganglia (T2-4) resulted in a 1.2 +/- 0.4% decrease in coronary vessel diameter. RIV failed to respond to bilateral caudal cervical ganglion stimulation. After iv administration of phentolamine, 1-2 mg/kg, no response to sympathetic stimulation could be elicited. Therefore, it appears that alpha-receptors are activated by the release of the sympathetic neurotransmitter to sympathetic stimulation and that beta-receptors are not involved in the response of RIV to sympathetic stimulation.
The effects of geometry, elasticity, and external pressures on the diastolic pressure-volume and stiffness-stress relations. How important is the pericardium?
Authors: Mirsky I , Rankin J S
Published: June 2012

The concept of an incremental elastic modulus is applied in the quantification of passive elastic stiffness-stress relations of intact heart muscle, and a transmural pressure-volume relation for the left ventricle is subsequently derived in terms of geometry, muscle elasticity, and external pressures to assess their importance. Physiological and clinical applications of this method indicate that: (1) stiffness-stress relations obtained on the basis of pressure-volume data from dog hearts are not significantly different from those obtained from muscle strips excised from these same hearts; (2) shape and the presence of right ventricular, pericardial, or pleural pressures are of secondary importance in an assessment of passive elastic stiffness; and (3) dramatic shifts in the left ventricular intracavity pressure-volume relations following drug interventions are primarily due to the presence of substantial pericardial pressures; however, the transmural pressure-volume relations are not markedly altered, implying no alteration in the intrinsic ventricular compliance.
The role of adenosine in prolonged vasodilation following flow-restricted exercise of canine skeletal muscle.
Authors: Belloni F L , Phair R D , Sparks H V
Published: June 2012

A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held constant at 12.5 +/- 1.3 ml/min per 100 g which was about 14% of the expected free flow for this exercise level. Skeletal muscle tissue adenosine was measured with the an enzymatic, spectophotometric assay of trichloroacetic acid extracts of congruent to 50 mg biopsy samples. Tissue adenosine rose from 2.30 +/- 0.90 nmol/g in resting muscle to 22.5 +/- 5.8 nmol/g by the end of the 22-minute exercise. Following exercise, tissue adenosine fell toward its baseline value with a time course very similar to the early portion of the return of skeletal muscle vascular resistance to its control level. Thus, skeletal muscle adenosine content (1) increases to a sufficient magnitude and (2) falls with an appropriate time course to be at least partly responsible for the early portion of prolonged vasodilation seen after flow-restricted exercise of skeletal muscle.
Protracted ventricular tachcardia induced by premature stimulation of the canine heart after coronary artery occlusion and reperfusion.
Authors: Karagueuzian H S , Fenoglio J J , Weiss M B , Wit A L
Published: June 2012

The effects of premature ventricular stimuli were studied in two groups of dogs with infarcts, one group subjected to permanent occlusion of the left anterior descending coronary artery and the other to temporary occlusion for 2 hours. In dogs with permanent occlusion, spontaneous ventricular arrhythmias occurred after 3-6 hours. In 13 dogs with temporary occlusion, ventricular arrhythmias occurred immediately after reperfusion and then persisted. In five dogs with temporary occlusion, ventricular arrhythmias did not occur spontaneously until 13-15 hours after occlusion. On days 2-9 after surgery, after sinus rhythm had returned, the ventricles of each awake dog were stimulated. After permanent occlusion, premature stimuli occurring on the T wave usually induced from one to 10 repetitive responses on days 2-4. Protracted ventricular tachycardia (lasting greater than 10 seconds) was induced in only two of 10 dogs. The response to premature stimuli was similar after temporary occlusion when ventricular arrhythmias did not occur spontaneously until 13-15 hours after occlusion. Protracted tachycardia was not induced. In the dogs with temporary occlusion, which initially had continuous arrhythmias, premature stimuli occurring on the T wave on days 3-5 after surgery induced both repetitive responses and protracted ventricular tachycardia. Stimuli applied to the ventricles during tachycardia terminated it. Histological studies on all infarcts showed that, after permanent occlusion, necrosis was uniform; after temporary occlusion, viable myocardium survived in the necrotic region. These salvaged myocardial fibers may provide reentrant pathways, causing long-lasting tachycardia.
Heart adaptation to acute pressure overload: an involvement of endogenous prostaglandins.
Authors: Chazov E I , Pomoinetsky V D , Geling N G , Orlova T R , Nekrasova A A , Smirnov V N
Published: June 2012

The purpose of this investigation was to study the relationships between the contractile behavior of the heart and myocardial prostaglandins. Using an open-chest model in rabbits, we assayed the left ventricular tissue content to prostaglandins (PG) E and F2 alpha at various intervals following acute pressure overload created by graduated aortic stenosis. The results suggest that the rabbits could be divided into two distinct groups based on specific hemodynamic changes following coarctation (systolic and diastolic pressure, dP/dt, and contractility index). The first group included rabbits whose adaptation to pressure overload was expressed as a gradual increase in the contractility index. The second group was comprised of rabbits that developed heart failure following coarctation. The increase in contractility in response to overload in the first group was paralleled by an increase in the content of PGE and PGF 2 alpha in the left ventricle, whereas, in rabbits with heart failure, the prostaglandin level did not rise above that of the control hearts. It is suggested that an increased endogenous prostaglandin content may be an important factor in adaptation to acute overload.
Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart.
Authors: Vary T C , Angelakos E T , Schaffer S W
Published: June 2012

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.
Distribution, surface density, and membrane area of diadic junctional contacts between plasma membrane and terminal cisterns in mammalian ventricle.
Authors: Page E , Surdyk-Droske M
Published: June 2012

The surface density of diadic junctional complexes (DJC) between plasmalemma and terminal cisternal membrane, as well as the areas of plasmalemmal and cisternal membrane involved in DJC, have been determined morphometrically in external plasmalemmal envelope and T-system of rabbit, rat, and mouse ventricular heart muscle. In all three species, both the surface density and the plasmalemmal area of DJC are 4- to 6-fold greater in the T-system than in the external plasmalemmal envelope. The surface density and DJC membrane area per unit cell volume and per unit myofibrillar volume increase in the order rabbit less than rat congruent to mouse and are not related simply to basal heart rate or intraventricular pressure. The results show that if Ca2+ release is a function of terminal cisterns, then, in ventricular heart muscle, most of the Ca2+ thus released for myofibrillar activation must originate from cisterns associated with the T-system. They make it necessary to consider the possibility that the 20--50% of plasmalemma in the T-system that is involved in excitation-contraction coupling may be unavailable for other processes; and they show that interspecies differences in surface density and membrane area of DJC/unit cellular and myofibrillar volume correlate with differences in Ca2+- activated Ca2+ release in skinned fibers and with differences in rate of tension development described for intact rat and rabbit ventricular muscle.
Increased sheep lung vascular permeability caused by Escherichia coli endotoxin.
Authors: Brigham K L , Bowers R , Haynes J
Published: June 2012

We infused Escherichia coli endotoxin, 0.07-1.33 microgram/kg, intravenously into chronically instrumented unanesthetized sheep and measured pulmonary arterial and left atrial pressures, lung lymph flow, lymph and blood plasma protein concentrations, and arterial blood gases. Endotoxin caused a biphasic reaction: an early phase of pulmonary hypertension and a long late phase of steady state increased pulmonary vascular permeability during which pulmonary arterial and left atrial pressures were not increased significantly and lung lymph flow was 5 times the baseline value. Lymph: plasma total protein concentration ratio during the late phase (0.76 +/- 0.04) was significantly (P less than 0.05) higher than during baseline (0.66 +/- 0.03). The lymph response was reproducible. Lung lymph clearance of endogenous proteins with molecular radii (r) 35.5 to 96 A was increased during the steady state late phase of the reaction, but, as during baseline, clearance decreased as r increased. The endotoxin reaction was similar to the reaction to infusing whole Pseudomonas bacteria, except that endotoxin had less effect on pressures during the steady state response and caused a relatively larger increase in lymph clearance of large proteins. We conclude that E. coli endotoxin in sheep causes a long period of increased lung vascular permeability and may have a greater effect on large solute pathways across microvessels than do Pseudomonas bacteria.
The prolonged pressor response to renin in the nephrectomized rat.
Authors: Boyd G W
Published: June 2012

Angiotension I dose-response curves and renin clearances were studied in nephrectomized and paired sham-nephrectomized control rats under pentobarbital anesthesia. Both threshold and slope of the angiotensin dose-response curves were decreased 22 hours after nephrectomy. In addition, the ratio of renin clearance (determined during renin infusions) in the 22-hour-nephrectomized rat to that in paired 22-hour sham-nephrectomized controls was 0.50 +/- 0.03 (mean +/- SEM, P less than 0.001, n = 12 pairs). The finding of reduced renin clearance was confirmed by an indirect assessment of "effective renin clearance" based on a comparison of the blood pressure decline after renin injections with angiotensin I dose-response curves in the same rat. Overall, approximately half of the 50% fall in renin clearance could be accounted for by an immediate effect of removal of the kidney on renin clearance. This role of the kidney in renin clearance was confirmed by the finding of a renal venous-arterial renin ratio of 0.9 +/- 0.03 (P less than 0.005) during renin infusion in normal rats. It is concluded that both changes in the angiotensin I dose-response curve and decrease in plasma renin clearance contribute to the postnephrectomy prolongation of the renin pressor response in the rat.
Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node.
Authors: Taniguchi T , Fujiwara M , Lee J J , Hidaka H
Published: June 2012

Transmural stimulation of, or application of nicotine to, the isolated rabbit sinoatrial (SA) node resulted in initial negative and late positive chronotropy. Simultaneous application of acetylcholine and norepinephrine produced a similar biphasic chronotropic effect. These procedures produced an initial increase in cyclic guanosine 3':5'-monophosphate (cyclic GMP) and a delayed elevation in cyclic adenosine 3':5'-monophosphate (cyclic AMP). The initial and late effects on rate and nucleotide levels were inhibited by pretreatment with atropine and propranolol, respectively. Pretreatment with atropine shortened the time of maximum increase in cyclic AMP level and heart rate from 3 to 1 minute after the simultaneous application of acetylcholine and norepinephrine and enhanced the positive chronotropic effect. Physostigmine prolonged the duration of the increase in cyclic GMP and negative chronotropic effect after the simultaneous application. These results suggest that when acetylocholine and norepinephrine are present simultaneously in the SA node region, the former interacts predominantly with muscarinic receptors and stimulates the cyclic GMP system, which in effect delays the cyclic AMP elevation and reduces the positive chronotropic effect of norepinephrine. However, these effects of acetylcholine cannot be explained solely on the basis of changes in the cyclic GMP level, because sodium nitroprusside produced a marked elevation of the cyclic GMP levels without decreasing the heart rate and did not affect the norepinephrine-induced increase in pacemaker rate and cyclic AMP. Sodium nitroprusside may affect cyclic GMP pools other than those susceptible to acetylcholine. These cyclic GMP pools may not exert chronotropic effects.
Cellular thin filament protein contents and force generation in porcine arteries and veins.
Authors: Cohen D M , Murphy R A
Published: June 2012

We estimated the cellular myosin, actin, and tropomyosin contents of vascular smooth muscle from (1) seven major arteries, (2) seven large veins, and (3) the first through third order branches of the uterine vasculature to determine whether variations in the contractile apparatus contribute to the functional diversity of vascular smooth muscle. We obtained the estimates by quantitative densitometry of stained polyacrylamide gels after electrophoresis of sodium dodecyl sulfate-treated tissue homogenates. No differences in cellular myosin content were found (18.7 +/- 1.0 mg/g cell wet weight in arteries vs. 17.2 +/- 0.7 in veins). However, the actin and tropomyosin contents were higher in arteries (49.7 +/- 2.9 and 13.1 +/- 0.8 mg/g cell, respectively) than in veins (25.5 +/- 1.4 and 7.0 +/- 0.3 mg/g cell). These differences persisted in the smaller uterine vessels. The higher contents of thin filament proteins in arteries, compared with veins and several other smooth muscle tissues previously studied, may underlie the high force generating capacity of arterial smooth muscle.