bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct effect of beta-adrenergic stimulation on renin release by the rat kidney slice in vitro.
Authors: Weinberger M H , Aoi W , Henry D P
Published: June 2012

Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic acid to the incubation medium. Significant dose-related stimulation of renin release was observed with epinephrine and norepinephrine in concentrations from 1.5 times 10(-9) to 1.5 times 10(-7)M and with isoproterenol in concentrations from 2 times 10(-9) to 2 times 10(-7)M. No significant stimulation was seen with 10(-10)M concentrations of the three agents. Methoxamine (10(-6)M) stimulated renin release significantly (P less than 0.01). The stimulation observed with epinephrine, norepinephrine, or isoproterenol was blocked by d,l- and l-propranolol (2 times 10(-4)M) but not by d-ropranolol (2 times 10(-4)M) or phentolamine (9 times 10(-4)M). Methoxamine-induced stimulation was abolished by d,l-propranolol but not by phentolamine. These data that the in vitro kidney slice system is responsive to physiological concentrations of catecholamines when they are protected from degradation. The results further demonstrate a direct stimulatory role for beta-adrenergic agents on renin release and suggest that alpha-adrenergic effects seen in vivo are mediated indirectly by hemodynamic, vascular, or functional changes in the kidney.
Myocardial sodium extraction at varied coronary flows in the dog. Estimation of capillary permeability of residue and outflow detection.
Authors: Guller B , Yipintsoi T , Orvis A L , Bassingthwaighte J B
Published: June 2012

Sudden injections of boluses containing both 131I-albumin and 24NaCl were made into the coronary artery inflow of isolated blood-perfused dog hearts. Indicator dilution curves were recorded using gamma emissions from both the intact heart and the coronary sinus outflow, with plasma flows, Fs, ranging from 0.3 to 1.8 ml/g min-1. Three measures of sodium extraction, E, during transcapillary passage were obtained from each site by comparison of the sodium and albumin curves. The most useful estimates of E were "instantaneous extractions" obtained from the later part of the upslope and the peak of the venous dilution curves (coronary sinus) or from the corresponding early phase of washout of the externally monitored curves (intact organ). Extractions were lower at higher flows. Permeability-surface area products, PS, were computed (1) by the formula PS equals -Fsloge(1 - E), (2) by fitting the observed dilution curves with a Krogh capillary-tissue cylinder model, and (3) by the approximating formula PS equals -Fsloge (1 - 1.14E). The two latter approaches provided a correction for back diffusion of tracer from tissue to blood. For sodium, the values of PS averaged 0.88 +/- 0.36 (SD) ml/g min-1, (n equals 52). At high flows, with Fs greater than 1.0 ml/g min-1, the values of PS averaged 1.01 +/- 0.38 ml/g min-1 (N equals 11). Assuming S equals 500 cm2/g and plasma to be 93% water, our findings suggest capillary permeabilities for sodium of about 3.1 times 10(-5) cm/sec.
Effect of exercise on dilution estimates of extravascular lung water and on the carbon monoxide diffusing capacity in normal adults.
Authors: Goresky C A , Warnica J W , Burgess J H , Nadeau B E
Published: June 2012

Previous studies in exercising animals have demonstrated that the extravascular lung water accessible to measurement by dilution methodology increases in the transition from rest to low-level exercise and thereafter does not change with progress to high-level exercise. In normal humans, similar systematic examination is essential to provide a background for the interpretation of changes in measured extravascular lung water in pathophysiological states. Moreover, such an examination might provide new insight into the mechanisms underlying the change in the pulmonary diffusing capacity with exercise. We therefore measured both the pulmonary extravascular lung water (by use of the triple indicator-dilution technique) and the diffusing capacity for carbon monoxide in 11 subjects, seated on an exercise bicycle, at rest and usually during two levels of exercise. The central blood volume increased by 50% with a tripling of the cardiac output. The accessible lung water increased from an average of 2.16 g/kg to 2.55 g/kg in the transition from rest to low-level exercise, but it did not increase further at the higher level of exercise. The simultaneously measured diffusing capacity for carbon monoxide (single breath and steady state) continued to increase over the whole range of cardiac outputs. We infer that the proportion of the pulmonary parenchyma perfused by blood flow increases slightly in the transition from rest to low-level exercise but increases no further at the higher level of exercise. The continued increase in the pulmonary diffusing capacity over the range in which the estimated lung water values do not change appears to imply that part of this increase may be blood flow dependent rather than dependent on the recruitment of additional surface for exchange.
Control of renin secretion in the dog. Effects of furosemide on the vascular and macula densa receptors.
Authors: Corsini W A , Hook J B , Bailie M D
Published: June 2012

Experiments were undertaken to investigate further the effect of furosemide on renin secretion in the anesthetized dog. To separate the effects of the macula densa and the baroreceptor mechanisms, experiments were conducted in kidneys made nonfiltering by combining 2.5 hours of renal ischemia with ureteral ligation. Furosemide, in a dose of 5 mg/kg, increased renin secretion and decreased renal resistance in dogs with a nonfiltering kidney. Prior dilation of the nonfiltering kidney with either acetylcholine or papaverine prevented changes in both resistance and renin secretion. However, following dilation of the intact filtering kidney with acetylcholine, furosemide caused an increase in renin secretion. Infusion of d,l-propranolol decreased renin secretion in both the filtering and the nonfiltering kidneys. Following propranolol treatment, furosemide increased renin secretion in the filtering kidney but had no effect on renal resistance. These experiments indicate that furosemide stimulates renin secretion by both the macula densa and the baroreceptor mechanisms. The data suggest that stimulation of the sympathetic nervous system may alter renin secretion by modulating the renal baroreceptor, but sympathetic innervation does not appear to be involved in the macula densa mechanism.
Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung.
Authors: Bucens D , Pain M C
Published: June 2012

An isolated perfused canine lung preparation in which determinants of vascular caliber could be individually controlled was developed. The relation of pulmonary arterial (Pa), venous (PV), and alveolar (PA) pressures was such that Pa greater than PA greater than PV throughout the whole lung. The addition of isoprenaline to the perfusate abolished vascular reactivity. Once stability was reached, vascular cross-sectional area remained acceptably constant for 2.25 hours as judged by normalized conductance. The influence of perfusate hematocrit, blood gas tensions, and pH on pressure-flow relations was then studied in 15 isolated canine lungs. The hematocrit-vascular conductance relation was derived at constant perfusion pressure. Conductance varied linearly with hematocrit over a range of 16.5 to 89.5%. Mean pulmonary arterial blood gas tensions were: PO2 = 121 mm Hg, PCO2 = 28 mm Hg, and pH = 7.46. Acute respiratory acidosis (PO2 = 30 mm Hg, PCO2 = 81 mm Hg, pH = 7.17) and lactic acidosis and hypoxemia (PO2 = 32 mm Hg, PCO2 = 21 mm Hg, pH = 6.96) did not significantly alter this relation. Transformation of the conductance-hematocrit data indicated that hematocrit was the most important determinant of relative apparent viscosity of the blood. Both acute respiratory and lactic acidosis failed to significantly increase relative viscosity within the range of hematocrit usually found in secondary polycythemia.
Effect of the angiotensin II blocker 1-Sar-8-Ala-angiotensin II on renal artery clip hypertension in the rat.
Authors: Macdonald G J , Boyd G W , Peart W S
Published: June 2012

Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.
Dissociation constant of the norepinephrine-receptor complex in normotensive and hypertensive rats.
Authors: Strecker R B , Hubbard W C , Michelakis A M
Published: June 2012

Previous reports have suggested that smooth muscle obtained from the thoracic aorta of spontaneously hypertensive rats is less responsive to vasoconstrictive agents than that obtained from normotensive rats. The present study was undertaken to determine whether the responsiveness of aortic muscles from normotensive and spontaneously hypertensive rats correlates with a difference in the affinity of the adrenergic receptors for norepinephrine and whether antihypertensive therapy alters the affinity of the adrenergic receptors for norepinephrine. The affinity of the adrenergic receptors for norepinephrine was determined by computing the dissociation constant of the norepinephrine-receptor complex (KDR). The values computed for KDR in aortic muscles from normotensive and spontaneously hypertensive rats that had received no antihypertensive therapy were 1.07 X 10(-7)M and 1.17 X 10(-7)M, respectively. The values computed for KDR in aortic muscles from normotensive and spontaneously hypertensive rats that had received antihypertensive therapy were 1.38 X 10(-7)M and 1.29 X 10(-7)M, respectively. The differences in these values for KDR are not significant. These results indicate that the difference in the contractility of aortic muscles from normotensive and spontaneously hypertensive rats is not related to an alteration in the affinity of the adrenergic receptors for norepinephrine and that the affinity of the adrenergic receptors for norepinephrine is not altered by antihypertensive therapy. Thus, it appears that the etiology of hypertension cannot be directly correlated with a difference in the affinity of the adrenergic receptors for norepinephrine.
Expansion of extracellular space in the nonischemic zone of the infarcted heart and concomitant changes in tissue electrolyte contents in the rat.
Authors: Polimeni P I , Al-Sadir J
Published: June 2012

The alterations in electrolyte content that occur in an infarcted zone of the heart have also been reported to occur in a similar manner, although to a far less degree, in the distant, apparently normal zones of the heart. These alterations in the nonischemic myocardium have usually been tabulated without comment, presumably because their magnitudes approach values of statistical dispersion. Our measurements of electrolyte content in the normal zone of the infarcted rat heart confirmed that all of the electrolyte contents were slightly modified. There was a rise in sodium, calcium, and chloride and a decline in potassium and magnesium. In addition, the extracellular space ([14C]sucrose) in this zone was elevated by nearly 15%. We have postulated a mechanism for this elevation based on an increase in the net filtration rate through myocardial capillaries. The expansion of the extracellular space can account for all of the electrolyte changes in the normal zone with the exception of the alteration in calcium. Therefore, there is no basis for assuming that these myocardial alterations reflect general movements of electrolytes down their electrochemical gradients. We suggest that the increment in the nominal concentration of cellular calcium is related to a compensatory mechanism that allows the reduced mass of functional myocardium to contract more vigorously.
Muscle stiffness determined from canine left ventricular pressure-volume curves.
Authors: Glantz S A , Kernoff R S
Published: June 2012

We measured pressure-volume curves in nine excised dog ventricles and stress-strain curves in two to five muscle specimens from each ventricle to verify a derived formula that relates muscle stiffness to the ventricular pressure-volume curve. The assumptions underlying this formula are: (1) the ventricle is a uniform spherical shell, (2) all muscle fibers carry average stress and deform as if they were at the midwall, (3) static equilibrium exists, (4) internal pressure induces the only load, and (5) the muscles exhibit an exponential stress-strain curve given by the equation sigma(epsilon) = alpha(ebeta epsilon - 1), where sigma = stress, epsilon = strain, and alpha and beta are constants. There was no significant difference between the stiffness constant, beta, inferred from the left ventricle pressure-volume curves (14+/-4.3[SD]) and that measured directly from the muscle stress-strain curves (16+/-2.8).
Hypotensive effect of clonidine during sodium depletion in the rat.
Authors: Pals D T
Published: June 2012

Clonidine was nonhypotensive in conscious unrestrained rats maintained on a normal sodium intake. In contradistinction, clonidine caused a dose-related hypotension in conscious unrestrained rats subjected to sodium depletion via furosemide. The plasma renin activity of normal and sodium-depleted rats was reduced after the administration of clonidine (100 mug/kg, iv) by 22.8% and 34.4%, respectively. Intravenous infusion of an angiotensin II antagonist, 1-Sar-8-Ala-angiotensin II, caused a significant reduction of arterial blood pressure in sodium-depleted rats but not in normal rats. Similarly, bilateral nephrectomy reduced arterial blood pressure and completely abolished the hypotensive effect of clonidine in sodium-depleted rats. Subcutaneous administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in sodium-depleted rats than it did in normal rats. Treatment of normal and sodium-depleted rats with 6-hydroxydopamine reduced the arterial blood pressure of both groups to approximately 85 mm Hg and completely abolished the hypotensive effect of clonidine in the sodium-depleted rats. The data presented in this paper are consistent with the conclusion that clonidine acts at some site in the sympathetic nervous system of sodium-depleted rats to inhibit renal nerve activity with a resultant suppression of renin secretion and a reduction of the angiotensin II-maintained arterial blood pressure. A similar sequence of events occurring in normal rats would not result in hypotension because their arterial blood pressure is not maintained by angiotensin II.
Atrial rhythm during ventricular fibrillation in the dog.
Authors: Scher A M , Heethaar R M , Zimmerman A N , Meijler F L
Published: June 2012

Depolarization of the atrioventricular junctional tissues and of the atrial septum was examined in the perfused dog heart before and during ventricular fibrillation by (1) recording the potentials from the junctional tissues in the regions of the interatrial and interventricular septum and examining the relationship of activity at these sites to atrial depolarization, (2) computing histograms and autocorrelograms of atrial firing intervals to study atrial rhythmicity, and (3) plotting the sequence of atrial septal depolarization. The junctional tissue was generally randomly depolarized by the fibrillating ventricles. The histograms and autocorrelograms indicate that during ventricular fibrillation the atrial depolarization intervals do not remain constant, but vary widely. This seems to be due to the retrograde excitation from the junctional tissues. Plots of the depolarization sequences of the interatrial septum also indicate that retrograde depolarization takes place. The junctional tissues decrease the number of impulses that can pass from ventricle to atrium, and they similarly decrease the number of impulses that pass in an antegrade direction during atrial fibrillation.
The effect of procaine amide on components of excitability in long mammalian cardiac Purkinje fibers.
Authors: Arnsdorf M F , Bigger J T
Published: June 2012

The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K+]0 = 4.0 mM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical observation that PA may exert both artiarrhythmic and arrhythmogenic effects. The primary mechanism by which PA modifies excitability would seem to differ considerably from that of the structurally similar local anesthetic agent lidocaine.
Ventricular elastic modulus as a function of age in the Syrian golden hamster.
Authors: Kane R L , McMahon T A , Wagner R L , Abelmann W H
Published: June 2012

Analysis of passive right and left ventricular pressure-volume curves for hearts of 72 Syrian golden hamsters studied in vitro showed increases in ventricular weight, volume, and compliance at mid-age. Both ventricles were filled by syringe pumps at a constant rate. Ventricular compliance (dV/dP) was determined by electronic differentiation of the intraventricular pressures and formation of the ratio (dV/dt)/(dP/dt) as a continuous function of intraventricular pressure between 0 and 30 mm Hg. By relating, with justification, the left ventricle to a thin-walled elastic sphere, ventricular elastic moduli, E, for different ages were compared at constant levels of myocardial wall stress, sigma. The elastic modulus E proved to be a linear function of sigma. The slope of the E-sigma plot yielded a stiffness constant, K, for each age group. Body weight, heart weight, end-diastolic volume, and dV/dP all varied by more than 200% up and then down as a function of age, but K was not a significant function of age. These results suggest that the aging heart does not normally undergo substantial alterations in passive properties that affect the muscle cells and fibers themselves, but rather that the observed changes in compliance are primarily attributable to alterations in ventricular size.
Effect of vagal stimulation on the overflow of norepinephrine into the coronary sinus during cardiac sympathetic nerve stimulation in the dog.
Authors: Levy M N , Blattberg B
Published: June 2012

In anesthetized dogs with the chest open, supramaximal stimulation of the left cardiac sympathetic nerves at 2 and 4 Hz produced an increase of 40-50% in ventricular contractile force (CF) and of 40-65% in coronary sinus blood flow. At these frequencies of stimulation, norepinephrine (NE) overflow into the coronary sinus was 29.8 +/- 5.1 (SE) and 54.9 +/- 13.2 ng/min, respectively. Concurrent, supramaximal vagal stimulation, at a frequency of 15 Hz, had no significant effect on coronary sinus blood flow, but caused a 25% reduction in CF and a 30% decrease in NE overflow. The changes in CF and NE overflow evoked by vagal stimulation were prevented by atropine. These results are consistent with the hypothesis that there are muscarinic receptors on the postganglionic sympathetic terminals in the walls of the ventricles. Acetylcholine released during vagal stimulation combines with these receptors, causes a reduction in the liberation of NE, and thereby attenuates the positive inotropic response.
Effect of hindlimb isolation procedure on isogravimetric capillary pressure and transcapillary fluid dynamics in dogs.
Authors: Brace R A , Guyton A C
Published: June 2012

We measured isogravimetric capillary pressure (Pci) and plasma colloid osmotic pressure (pip) in isolated dog hindlimbs. A very rapid isolation technique and a perfusion technique involving no weight change were developed in order to compare the effects of different isolation procedures. Also, a "previous isolation procedure" (PIP) was used to approximate isolation procedures previously reported; this procedure included (A) anesthesia for 1 to 1 1/2 hours before limb isolation, (B) 1/2 hour of denervation before isolation, and (C) perfusion after isolation for 1/2 hour at an arterial pressure of 100 mm Hg and a venous pressure of 6 mm Hg. These different procedures altered average (+/- SE) capillary pressure and fluid dynamics in the hindlimb as shown in the foly pressure in the intact resting dog hindlimb may be 8 mm Hg below plasma colloid osmotic pressure, or about 9 mm Hg, and that many reported values have been heavily influenced by the isolation technique.
Cardiac performance in rats with renal hypertension.
Authors: Averill D B , Ferrario C M , Tarazi R C , Sen S , Bajbus R
Published: June 2012

To evaluate cardiac performance in renal hypertension more precisely we determined cardiac function curves for 12 normotensive rats and 11 other rats with two-kidney Goldblatt hypertension. The hypertensive group (BP = 134 +/- 8 mm Hg) showed significant cardiac hypertrophy (44 +/- 1% increased ratio of heart weight to body weight, P less than 0.01) and markedly increased left ventricular stroke work with a moderate but not significant increase in left ventricular end-diastolic pressure (LVEDP) (5.9 +/- 0.8 vs. 4.7 +/- 0.4 mm Hg). We evaluated cardiac function by recording left ventricular end-diastolic pressure, stroke volume (SV), and cardiac output (CO) (by electromagnetic flowmeter) during rapid alteration in venous return. Analysis of variations of stroke volume vs. left ventricular end-diastolic pressure showed that renal hypertension is accompanied by a significant decrease in ventricular performance [SV = 0.0190 + 0.0509 LVEDP - 0.0025 (LVEDP)2 + 0.0001 (LVEDP)3] compared to the normotensive group [SV = 0.0430 + 0.0644 LVEDP - 0.0040 (LVEDP)2 + 0.001 (LVEDP)3]. The alterations in stroke volume and cardiac output were associated with a lack of significant changes in the work performed at matched end-diastolic pressures. The data indicate that chronic renal hypertension is accompanied by a depression of cardiac reserve which is not revealed by measurements of cardiac output and left ventricular end-diastolic pressure at rest. This impairment in cardiac function might be related to either diminished cardiac contractility or reduced left ventricular compliance; the latter possibility is in accord with our finding of a 2-fold increase in the hydroxyproline content (P less than 0.001) and a significant decrease in the DNA concentration of ventricular tissue.
Atrial receptors with nonmedullated vagal afferents in the cat. Discharge frequency and pattern in relation to atrial pressure.
Authors: Thorén P N
Published: June 2012

The response of 14 atrial receptors with nonmedullated vagal afferents to changes in atrial pressure was determined in anesthetized thoracotomized cats. Recordings were made from 11 single fibers and three two-fiber filaments. Mean conduction velocity was 0.9 m/sec (range, 0.35 to 2.2 m/sec). During the control period, either no activity was detected or there was a sparse discharge (mean, 1.4 impulses/sec), which occasionally was related to the a or v waves. As atrial pressure was increased by transfusion or by occlusion of the aortic, pulmonary arterial, mitral, and tricuspid orifices, an increased rate of firing occurred, often related to the atrial v wave. The threshold for individual receptors was between 2 and 3 mm Hg (mean pressure) in the right atrium, and 5 and 12 mm Hg in the left atrium. The maximal firing rate was 5-11 impulses/sec for right atrial and 10-20 impulses/sec for left atrial receptors. The receptors were localized by probing the opened heart, and were identified in both atria, in the interatrial septum, and in the atrial-venous junctions. Thus receptors connected to vagal C fibers are present throughout both atria and are activated by moderate changes in pressure.
Mechanical stimuli exciting type A atrial vagal receptors in the cat.
Authors: Recordati G , Lombardi F , Bishop V S , Malliani A
Published: June 2012

The activity of type A right atrial vagal receptors was recorded from the right cervical vagus in cats anesthetized with sodium pentobarbital, immobilized with gallamine, and with their chests open. Nerve impulses initiated by receptor activation were recorded simultaneously with instantaneous right atrial pressure and dimensional changes under various hemodynamic conditions. Atrial volume changes induced by infusion of saline, bleeding, and occlusion of the inferior vena cava did not alter consistently the systolic activity of the receptors. Electrical stimulation of the right stellate ganglion significantly increased the frequency of discharge during systole, whereas electrical stimulation of the left thoracic vagus significantly reduced the frequency of discharge. These inotropic interventions produced similar effects when the heart was paced at a fixed rate. Pacing the right atrial appendage increased the systolic discharge of the receptors only when at high rates the atrium contracted against closed atrioventricular valves. To investigate the influence of tonic efferent sympathetic activity on spontaneous receptor discharge, three receptors were studied before and after bilateral surgical stellectomy, and in cats with their chest closed three receptors were studied before and after infusion of propranolol. Both of these interventions markedly reduced the systolic activity. In addition to having effects on systolic activity, injection of saline, vagal stimulation, and sympathetic "denervation" always activated the receptors during filling. Our results indicate that: (1) the systolic discharge of type A receptors is a function of the active tension developed by atrial muscle during contraction; and (2) the pattern of discharge of the receptors during the atrial cycle depends on both the degree of atrial distention and the state and extent of contraction.
Pumping ability of the hypertrophying left ventricle of the spontaneously hypertensive rat.
Authors: Pfeffer M A , Pfeffer J M , Frohlich E D
Published: June 2012

Cardiac pumping ability was assessed during the natural development of left ventricular hypertrophy by elevating venous pressure by infusing Tyrode's solution intravenously to produce peak cardiac output. This experiment was performed on spontaneously hypertensive rats (SHR) of three age groups (11, 24, and 83 weeks). From 11 to 24 weeks, peak cardiac output of SHR increased in direct proportion to the abnormally increased ventricular mass; Thus peak cardiac output per gram of left ventricle (LV) remained stable. Similar results were obtained for two strains of normotensive rats at each of the same three age groups. Thus, in the normotensive animal peak cardiac output per gram of LV remained stable over a wide range of ages and varying left ventricular weights. However, with progressive elevation of arterial pressure in aging SHR (83 weeks), we observed severe ventricular hypertrophy (100% increases in left ventricular to body weight ratio). In this oldest SHR group, unlike age-matched normotensive rats, there was a marked reduction in the pumping ability per gram of LV. Thus, during the natural development of left ventricular hypertrophy SHR demonstrated both a stable stage of hypertrophy in which the increased left ventricular mass maintained its pumping ability, and a later stage of deterioration in which there was a loss of the normal relationship between ventricular mass and pumping ability.
Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial measurement of blood flow to ischemic regions in dogs.
Authors: Rivas F , Cobb F R , Bache R J , Greenfield J C
Published: June 2012

This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope-labeled microspheres, 7-10 mum in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with dwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 +/- 0.03 (SE), 0.39 +/- 0.05, and 0.53 +/- 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmuarl layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured.
Combined effects of rate membrane potential, and drugs on maximum rate of rise (Vmax) of action potential upstroke of guinea pig papillary muscle.
Authors: Chen C , Gettes L S
Published: June 2012

We studied the effect of increasing the rate of stimulation on the maximum rate of rise of the action potential upstroke (Vmax) in guinea pig papillary muscles at various resting membrane potentials and after the addition of quinidine and lidocaine to the perfusate. Increasing rate caused a decrease in Vmax due to interaction of three factors: (1) a metabolic factor, presumably resetting of the Na-K pump, which caused a decrease in Vmax at all levels of resting potential between -90 and -60 mV, (2) a transient decrease in resting potential which influenced Vmax when the resting potential was less negative than approximately -80 mV, and (3) the recovery characteristics of Vmax which contributed to the decrease in this variable when rate was faster than 5/sec. As a result of these factors the steady state curve relating membrane potential to Vmax was itself rate-dependent. Lidocaine and quinidine exaggerated the rate-dependent decrease in Vmax; however, their effects differed. The effect of quinidine was consistent with its known depressant effect on the Na-K pump. The lidocaine effect was consistent with a slowing of recovery of Vmax. Our results help to explain the effects of an increase in rate on Vmax and conduction velocity in normal, partially depolarized, and drug-treated fibers
The influence of combined intra-aortic balloon counterpulsation and hyperosomotic mannitol on regional myocardial blood flow in ischemic myocardium in the dog.
Authors: Watson J T , Fixler D E , Platt M R , Nall B B , Jett G K , Willerson J T
Published: June 2012

We investigated the combined effectiveness of intra-aortic balloon counterpulsation and hyperosmotic mannitol (25%) on regional myocardial blood flow during acute coronary insufficiency. Cardiac output and paced heart rate were held constant in chloralose-anesthetized dogs during right heart bypass. Acute coronary insufficiency was produced by ligation of the proximal left anterior descending coronary artery (LAD). Regional myocardial blood flow was measured using radioactive microspheres. Left ventricular end-diastolic pressure, mean aortic pressure, maximum left ventricular dp/dt, and hematocrit were unchanged by combined mannitol infusion and balloon pumping. Studies of combined treatment with balloon pumping and mannitol immediately after the second of two 13-minute consecutive reversible ligations of the LAD demonstrated that (1) collateral coronary blood flow increased 46% (P less than 0.02) in ischemic myocardium compared with mannitol infusion along during the first LAD ligation, and (2) collateral coronary blood flow increased 27% (P less than 0.05) in ischemic myocardium compared with balloon pumping along during the first LAD ligation. Studies in which combined treatment was delayed until 20 minutes after LAD ligation demonstrated that collateral coronary blood flow was elevated by 33% (P les than 0.05) in ischemic myocardium compared to control studies in which balloon pumping alone had no effect. The results suggest that the increase in collateral coronary blood flow was in part a result of an increased transmural pressure gradient produced by balloon diastolic augmentation and the ability of mannitol to reduce coronary vascular resistance in ischemic myocardium.
Experimental myocardial infarction in the cat. I. Reversible decline in contractility of noninfarcted muscle.
Authors: Mathes P , Romig D , Sack D , Erhardt W
Published: June 2012

The contractile state of the noninfarcted myocardium was examined in adult cats after myocardial infarction produced by ligation of several branches of the left coronary artery. At 2 days, 7 days, and 6 weeks after infarction, and after determination of intracardiac pressures, papillary muscles were exicised from the noninfarcted segment of the right ventricle and attached to a myograph for analysis of contractile function. One week after infarction there was a decline in actively developed force at Lmax, caused by a decrease in the rate of force development. In addition, the response to procedures that augment myocardial contractility, such as paired stimulation and increasing the frequency of electrical stimulation, was significantly depressed. Two days after infarction, changes were less significant, although similar in direction. Six weeks after infarction, developed force at Lmax had returned to normal values. The response to procedures augmenting contractility also had returned to normal. There appears to be a distinct, reversible loss of contractility in the remaining viable myocardium in the early phase after experimental infarction.
External detection and visualization of myocardial ischemia with 11C-substrates in vitro and in vivo.
Authors: Weiss E S , Hoffman E J , Phelps M E , Welch M J , Henry P D , Ter-Pogossian M M , Sobel B E
Published: June 2012

To characterize externally detectable changes in myocardial metabolism of free fatty acids (FFA) and glucose associated with ischemia, isovolumically beating rabbit hearts were perfused under conditions of selected flows with cyclotron-produced, short-lived (t1/2 - 20.4 minutes), 11C-labeled isotopes of glucose and FFA. Tension-time index decreased 83% and lactate production increased from 0.5 +/- 1.9 (SE) to 5.3 +/- 2.1 mumol/min per g of dry weight reflecting myocardial ischemia after flow was reduced from 20 to 5 ml/min. After 30 minutes of low flow the myocardial accumulation of 11C-octanoate, expressed as the extraction fraction, declined from 56 +/- 15% to 30 +/- 3%, reflecting metabolic suppression of FFA extraction during low flow. Effects attributable exclusively to prolonged residence time were excluded. Similar results were obtained with 11C-palmitate. The myocardial avidity for 11C-palmitate was demonstrable by rectilinear whole body scanning in dogs given 5 mCi of the agent intravenously. Diminished 11C-palmitate uptake in zones of myocardium rendered ischemic for 20 minutes prior to reflow in intact dogs was delineated by electrocardiographically gated positron-emission transaxial computer reconstruction tomography. Thus, diminished 11C-FFA extraction, externally detectable, accompanies decreased perfusion in isolated perfused hearts, and decreased 11C-FFA uptake reflecting myocardial ischemia in vivo can be evaluated noninvasively by positron-emission transaxial tomography.
Modification by prostaglandins E1 and E2, indomethacin, and arachidonic acid of the vasoconstrictor responses of the isolated perfused rabbit and rat mesenteric arteries to adrenergic stimuli.
Authors: Malik K U , Ryan P , McGiff J C
Published: June 2012

In isolated perfused rabbit mesenteric arteries, prostaglandin (PG) E1 and E2, 1-5NG/ML, did not alter the basal perfusion pressure, but reduced the vasoconstrictor responses to sympathetic nerve stimulation; the responses to injected norepinephrine were reduced by PGE1 and variably affected by PGE2. In contrast, in rat mesenteric arteries PGE1 and PGE2, 1-5 ng/ml, potentiated the vasoconstrictor responses to nerve stimulation and to injected norepinephrine. In rabbit mesenteric arteries, the inhibitor of PG synthesis, indomethacin, augmented the responses to sympathetic nerve stimulation and to injected norepinephrine, whereas in rat mesenteric arteries indomethacin inhibited the responses to both adrenergic stimuli. Arachidonic acid, a PG precursor, reduced the vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine in rabbit, whereas in rat, potentiation of the responses to adrenergic stimuli occurred. Since these effects of arachidonic acid were abolished by the simultaneous infusion of indomethacin, they appear to be mediated through conversion of arachidonic acid to PG. We conclude that prostaglandins modulate adrenergic transmission in mesenteric arteries and this effect is species dependent.
The effect of the pattern of cardiac sympathetic activity on myocardial contractile force and norepinephrine overflow in the dog heart.
Authors: Levy M N , Blattberg B
Published: June 2012

The left of right cardiac sympathetic nerves in open-chest, anesthetized dogs were stimulated at mean frequencies of 2 or 4 Hz. The stimuli were applied intermittently, in patterns with repetition rates or either 60/min or 15/min, to simulate the spontaneous patterns of sympathetic neural activity that occur synchronously with the cardiac or respiratory cycles, respectively. With either repetition rate, intermittent stimulation of the left sympathetic nerves was about 10-20% less effective in enhancing myocardial contractile force (CF) and about 10% less effective in increasing coronary sinus blood flow than was steady stimulation at the same mean frequency. With right-sided stimulation, there was no appreciable difference between steady and intermettent stimulation patterns with respect to the effect on heart rate. With either left-or right-sided stimulation, the rate of norepinephrine (NE) overflow into the coronary sinus blood was 20-40% less with intermittent than with steady stimulation. Cocaine administration did not materially affect this difference in NE overflow. It was concluded that the higher instantaneous frequencies that prevail during intermittent stimulation result in a reduction in the rate of NE release at the sympathetic postganglionic nerve endings in the heart.
The decay of the potentiated state in sheep and calf ventricular myocardial fibers. Influence of agents acting on transmembrane Ca2+ flux.
Authors: Bass O
Published: June 2012

Paired pulse stimulation increases the contractile strength of mammalian myocardium. If stimulation is discontinued the "potentiated state" takes several minutes to decay, as shown by the first contraction following resumption of stimulation. From earlier experiments it has been inferred that contractile force depends on Ca2+ released from intracellular stores rather than on an influx of Ca2+ associated with a given action potential. This view now receives support from the following findings: (1) Ni2+ and Co2+, known to inhibit Ca2+ influx during the action potential, when applied during a 2-minute rest period, are practically without effect on the strength of the first beat but strongly depress steady state contractions. (2) Caffeine, known to enhance Ca2+ efflux from and inhibit Ca2+ uptake into intracellular stores, greatly accelerates the decay of the potentiated state during a rest period. (3) Na+ -poor solution, known to inhibit Ca2+ efflux, has a strong positive inotropic effect. Paired pulse stimulation fails to increase contractile strength in Na+ -poor solution, and a rest period of many minutes is practically without effect on the amplitude of the first beat after resumption of stimulation. The results indicate that contraction is due to Ca2+ released from internal stores whose degree of filling can be altered.
Two levels of resting potential in canine cardiac Purkinje fibers exposed to sodium-free solutions.
Authors: Wiggins J R , Cranefield P F
Published: June 2012

Canine cardiac Purkinje fibers exposed to sodium-free solutions containing 16 mM CaCl2, 20 mM tetraethylammonium chloride, 108 mM tetramethylammonium chloride, and 2.7 mM KCl may be quiescent at a resting potential of either -50 mV or -90 mV. The membrane potential of these fibers can be switched from -50 mV to -90 mV by a hyperpolarizing current pulse and from -90 mV to -50 mV by a depolarizing current pulse. The transition from -50 mV to -90 mV depends on a voltage-dependent increase in potassium conductance, that conductance being low at -50 mV and high at -90 mV. A reduction in potassium conductance causes the fiber to depolarize from -90 mV to -50 mV because of the presence of an inward current which apparently is carried mainly by Ca. Fibers that show a high resting potential cannot be excited except by depolarizing stimuli strong enough to move the membrane from -90 mV to a threshold potential of about -40 mV. Fibers that show a low resting potential are more easily excited and may show rhythmic activity sustained by afterpotentials that appear only if the low membrane potential is accompanied by a low potassium conductance. Slow changes in membrane potential also are seen; these changes may result from movements of chloride.
An electrogenic sodium pump and baroreceptor function in normotensive and spontaneously hypertensive rats.
Authors: Saum W R , Brown A M , Tuley F H
Published: June 2012

Postexcitatory depression (PED) and adaptation were examined in slowly adapting aortic baroreceptors of normotensive rats (NTR) and spontaneously hypertensive rats (SHR); an aortic arch-aortic nerve preparation in vitro was used. PED was elicited either mechanically by employing single or double pressure steps, or electrically by antidromic stimulation of the aortic nerve. During PED the axon of the receptor was capable of conducting action potentials and the receptor itself could respond to increased pressures. The relationship between duration of PED and number of impulses preceding it was hyperbolic. In NTR's and SHR's PED was abolished by ouabain or solutions containing no potassium, neither of which affected the steady state pressure-volume relationship of the aorta. These interventions, which are known to block electrogenic pumps, also lowered the pressure threshold and increased the curvature of the steady state pressure-frequency curve. Furthermore, lithium, another agent that blocks electrogenic pumps, also abolished PED. Thus, PED is attributed mainly to an electrogenic sodium pump which operates normally in baroreceptors. We found that adaptation from peak transient to steady state frequency did not appear to be altered significantly when the pump was blocked. Blockage of the pump by ouabain is responsible for the baroreceptor reflex effects elicited by this drug. We conclude that resetting and reduced sensitivity in SHR baroreceptors are not attributed to significant differences in electrogenic pump activity.
Intact vesicles of canine cardiac sarcolemma: evidence from vectorial properties of Na+, K+-ATPase.
Authors: Besch H R , Jones L R , Watanabe A M
Published: June 2012

Most biological membranes are functionally asymmetric. To study biochemical control of cardiac transsarcolemmalion fluxes, it would be of obvious advantage to use isolated vesicles of sarcolemma which retains the low passive permeability characteristics of intact sarcolemma because in such vesicles the membrane should exhibit its normal asymmetric character with respect to enzymic activities. The purpose of this investigation was to attempt identify such vesicles in a cardiac microsomal (membrane vesicular) preparation. We studied activation by Na+ and K+ of Na+, K+-ATPase and its associated K+-phosphatase activities, using as substrates ATP or p-nitrophenylphosphate (pNPP) in the presence of Mg2+. Optimal concentrations of K+ alone (10 mM) stimulated p-nitrophenylphosphatase (pNPPase) activity 1.8-fold, and over 80% of the increase could be inhibited by ouabain. Optimal Na+ plus K+ concentrations (100 mM and 10 mM, respectively) stimulated the rate of ATP hydrolysis 2-fold, but only 11 +/- 1.1% of the increased activity was ouabain-sensitive. Optimal pretreatment with sodium dodecyl sulfate (SDS) (0.3 mg/ml) rendered both activities completely sensitive to inhibition by ouabain and reduced the basal Mg2+-ATPase activity by 70-90%. The K+-stimulated pNPPase activity doubled after preincubation in SDS, but the ATPase activity stimulated by Na+ plus K+ fell by 50% under these conditions. A similar pattern of apparent activation was produced by preincubation with deoxycholate (DOC), except that basal Mg2+-dependent activities were resistant to destruction by this detergent. The incremental responses to activation by ions and substrates, and inhibition by oubain, are consistent with the hypothesis that permeability-intact vesicles of sarcolemma are present in the isolated preparation, and that detergent activation renders the vesicles highly permeable to the ions, substrates, and ouabain.