bluuebunny/crossref_metadata_2025 huggingface dataset:
The renin-angiotensin-aldosterone system in rabbits with congestive heart failure produced by aortic constriction.
Authors: Morris B J , Davis J O , Zatzman M L , Williams G M
Published: June 2012

Severe constriction of the suprarenal abdominal aorta of 3-kg rabbits to 3.7+/-0.2 mm2 and maintenance of a daily sodium intake of 10 mE q by infusion of 0.9% sodium chloride resulted in a progressive increase in central ear arterial pressure to 106+/-3 (SEM) mm Hg (control=79+/-1). This was accompanied by a progressive increase in left ventricular end-diastolic pressure to 22+/-2 mm Hg (control=3+/-1), plasma renin activity to 21+/-5 ng of angiotensin/hour per ml (control=5+/-1), plasma aldosterone concentration to 99+/-23 pg/ml (control=14+/-4), and plasma sodium concentration to 142+/-1 mEq/liter (control=136+/-1). Urinary excretion of sodium decreased to 3.9+/-0.7 mEq/day and marked fluid retention occurred. We also found that these changes were accompanied by a decrease in hematocrit to 24+/-2% (control=40+/-1), formation of 36+/-9 ml of fluid in the thoracic cavity, 33+/-9 ml of ascites, pulmonary congestion and edema, hepatic congestion, and enlargement and hypertrophy of both the left and right ventricles. All rabbits died of ventricular failure at a time that was partly related to the degree of aortic constriction and that ranged from 2 to 12 days. The model we have established is chronic, highly reproducible, easy to produce, and inexpensive, and resembles the clinical syndrome of right and left congestive heart failure in man. Furthermore, the studies provide evidence for an important role of the renin-angiotensin-aldosterone system in the fluid retention that leads to pulmonary and systemic venous congestion after suprarenal aortic constriction.
Platelet aggregation in the cerebral microcirculation: effect of aspirin and other agents.
Authors: Rosenblum W I , El-Sabban F
Published: June 2012

After a certain period of time filtered ultraviolet light produces platelet aggregation in microvessels on the cerebral surface of the mouse, but only when sodium fluorescein is first injected intravascularly to provide a light-absorbing, heat-generating target. The platelet aggregates fluoresce. They occur only in the illuminated field and adhere to arteriolar and venular walls. Vasoconstriction is not detected prior to or up to 30 seconds after aggregation. Electron microscopy reveals damaged endothelium and undamaged red cells, as well as aggregates consisting almost exclusively of platelets in varying stages of aggregation, pseudopod formation, and degranulation. The time between onset of the noxious stimulus and recognition of the first aggregate can be measured as the vessels are observed microscopically. This "time of aggregation" is prolonged by pentobarbital as opposed to urethane anesthesia, and also is related to time elapsed after craniotomy. We also found that aspirin and indomethacin significantly prolong time to first aggregate, but only on the arteriolar side of the circulation. This is so even though the composition of the aggregates is the same on both the arteriolar and venular sides. Heparin has no effect.
Effects of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for alpha- and beta-adrenergic actions.
Authors: Rosen M R , Hordof A J , Ilvento J P , Danilo P
Published: June 2012

We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. Control spontaneous rates for adults and neonates did not differ significantly. There was a biphasic response to all agonists such that rate decreased at low and increased at high concentrations. The decrease was greater with phenylephrine and epinephrine than with isoproterenol. The increase in rate was greater with isoproterenol and epinephrine than with phenylephrine. Propranolol shifted the dose-response curves downward and to the right for all agonists; phentolamine, shifter the curves upward and to the left. Epinephrine and isoproterenol dose-response curves for the neonates were upward and to the left of those for adults. Phenylephrine curves were identical for adults and neonates. Thus there are alpha- and beta-adrenergic effects on Purkinje fiber automaticity; the former decrease and the latter increase rate. Furthermore, the effects on automiticity of beta-adrenergic amines are greater in the neonates than in the adult.
Effects of physical training on end-diastolic volume and myocardial performance of isolated rat hearts.
Authors: Bersohn M M , Scheuer J
Published: June 2012

We studied the performance of ventricular muscle and cardiac function of hearts from rats conditioned by swimming (CH) and from sedentary rats (SH) in an isolated working heart apparatus modified to measure end-diastolic volume by dye dilution. Instantaneous aortic flow, left ventricular (LV) pressure and oxygen consumption were measured. Heart rate and mean aortic pressure were kept constant, and atrial filling pressure was varied from 5 to 20 cm H2O. Heart weights of SH and CH were equal and end-diastolic pressures and volumes were similar at all atrial pressures. However, ejection fraction, calculated circumferential fiber velocity, peak systolic pressure, peak aortic flow, cardiac output, and stroke work were all greater in CH than in SH, and the differences increased as atrial pressure was increased. Maximal negative dP/dt was greater in CH than SH at all preloads (P less than 0.001). Oxygen consumption of CH was increased in proportion to the increase in work. These results indicate that the improved pumping performance of CH is due to a change in ventricular muscle function. Faster relaxation is a prominent effect of physical training on the rat heart and may foster more complete filling at high heart rates.
Influence of prostaglandin E2, indomethacin, and reserpine on renal vascular responses to nerve stimulation, pressor and depressor hormones.
Authors: Fink G D , Chapnick B M , Goldberg M R , Paustian P W , Kadowitz P J
Published: June 2012

The effects of prostaglandin E2 (PGE2) indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE2, 0.03 and 0.3 microgram/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. Responses to nerve stimulation were decreased to a greater extent than responses to norepinephrine. At lower concentrations the effects of PGE2 on pressor responses and on vascular resistance could be separated. Reserpine decreased the histochemical evidence of adrenergic innervation and reduced the response to renal nerve stimulation, enhanced the response to norepinephrine, and was without effect on the response to angiotensin. Indomethacin decreased depressor responses to arachidonic acid, produced a small increase in renal vascular resistance but did not enhance renal pressor responses. The increase in renal vascular resistance after indomethacin was not modified by reserpine pretreatment. Indomethacin enhanced the renal response to bradykinin. These data show that PGE2 possesses the ability to modulate pressor responses in the kidney. However, experiments with indomethacin suggest that endogenous prostaglandins neither modulate pressor responses nor mediate the response of the renal vascular bed to bradykinin. In addition, these data suggest that the increase in renal resistance after indomethacin is not dependent on the adrenergic nervous system.
The capillary and sarcolemmal barriers in the heart. An exploration of labeled water permeability.
Authors: Rose C P , Goresky C A , Bach G G
Published: June 2012

Although the exchange of labeled water between blood and tissue in the heart has usually been assumed to be flow-limited, the outflow patterns of labeled water, relative to intravascular references, in a multiple indicator dilution experiment, have appeared to be anomalous in terms of the models used to explain the transport of less permeable substances. Data showing a change in the shape of the labeled water outflow curve after vasodilation and after the infusion of toxic doses of 2,4-dinitrophenol led us to propose a new model for labeled water permeation which includes barriers at both the capillary wall and the sarcolemmal membrane. This model explains adequately the form of the outflow curve, provides parameters related to the permeability at the two barriers, and gives an estimate of the ratio of the intracellular to interstitial space. Dinitrophenol infused intra-arterially in a dose sufficient to cause S-T elevation in the electrocardiogram is found to reduce the sarcolemmal water permeability by an order of magnitude, but to have no effect on capillary water permeability. We conclude that water transport in the heart is barrier-limited at both the capillary and sarcolemmal membranes and that sarcolemmal water permeability is probably mediated at least in part by a structure sensitive to the effects of dinitrophenol, presumably a protein channel. Since the outflow patterns of inert gases resemble that of labeled water, it is possible that oxygen distribution is also barrier-limited.
Effects of therapy on maximal walking time following femoral ligation in the rat.
Authors: Conrad M C
Published: June 2012

Maximal walking times at a constant rate of 10 m/min were compared in normal rats, normal rats that had been exercised daily for 6 weeks, and rats that had undergone bilateral femoral artery ligation followed by 6 weeks of either an oral vasodilator, absence of sympathetic impulses to the extremities, cold exposure, or daily exercise. Rats maintained on the vasodilator could walk no farther than untreated, ligated rats. Both chronic cold exposure and sympathectomy significantly increased maximal walking distances of ligated rats and daily exercise increased maximal walking distances 7-fold. Rats that had received 6 weeks of exercise training following femoral artery ligation could walk longer than normal untrained rats; therefore, the increased exercise tolerance could not be explained solely by the restoration of normal large artery conductance by enlargement of collaterals bypassing the femoral occlusion.
Diffusion permeability of an isolated rete mirabile.
Authors: Rasio E A , Bendayan M , Goresky C A
Published: June 2012

The rete mirabile of the swimbladder of the eeel is a countercurrent exchange organ composed of alternately disposed and venous capillaries. A countercurrent perfusion of these was set up by isolating arterial input and outflow, and venous input and outflow, and perfusing each set of capillaries with oxygenated albumin-containing Krebs-Ringer bicarbonate buffer. Constant arterial infusions containing tracer albumin, inulin, 3-O-methylglucose, urea, and water were begun and tracer concentrations at the outlets of arterial and venous beds were determined. Capillary permeabilities were determined from the resulting steady state values. The method of calculation of permeability values from the data acquired in the rete involves no approximations and appears to yield unequivocal values. For the solutes, the values appear compatible with transcapillary passage by free diffusion. No evidence of increasing restriction (in comparison to the diffuse coefficients) was found over the range of molecular sizes explored. The permeability for labeled water, in relation to the solutes, was too high, and this augmentation was attributed to the larger surface available for its exchange. Despite this larger value, labeled water did not undergo flow-limited exchange. A significant barrier to its distribution is present in this capillary system.
Regional oxygen saturation of small arteries and veins in the canine myocardium.
Authors: Weiss H R , Sinha A K
Published: June 2012

Oxygen saturation of small arteries and veins (20-500 micron) was determined microspectrophotometrically in the hearts of 12 pentobarbital-anesthetized open-chest dogs. Hearts were removed, quick frozen in liquid propane, and O2 saturation was determined in blood vessels on a regional basis between and within ventricular walls. No significant differences existed in arterial O2 saturation between right, left, and septal walls or regionally within any wall by depth or in base-to-apex comparisons. Although there was variation in arterial saturation, it was independent of vessel size. Arteries were followed by serial section into the left ventricular wall for distances up to 7.5 mm without significant saturation change. The average venous saturations of the right, septal, and left ventricular walls were not significantly different. No regional differences in venous saturation were found within any ventricular wall in comparisons between base and apex. In the left ventricle, subepicardial venous saturation (29.8%) was significantly higher than subendocardial saturation (16.4%). In veins traced from the surface, saturation decreased with depth. Greater variability of saturation was found in small compared to large veins. The greater O2 extraction in the subendocardium may indicate a higher O2 consumption than in the subepicardium.
Fluid dynamics of coronary artery stenosis.
Authors: Mates R E , Gupta R L , Bell A C , Klocke F J
Published: June 2012

A large-scale model of the coronary circulation, instrumented to permit detailed pressure and velocity measurements, has been used to study flow through isolated stenotic elements in large coronary arteries. Pulsatile aortic and instantaneous peripheral resistance were stimulated with servovalves. A variety of axisymmetric and asymmetric stenoses were studied and flow separation was found to occur for all but very mild stenoses. Pressure recovery downstream of the stenosis throat was limited and, in some cases, no recovery was observed. Pressure drop was primarily dependent upon the minimum area of the stenosis and relatively independent of stenosis geometry. Flow was quasi-steady at normal heart rates, and simple steady flow theory proved adequate to describe the pressure drop through the stenosis. The theory yielded results that agreed well with published data for dogs and appears promising for predicting effects of hemodynamic variables on a given stenotic lesion. Thus, principal findings of the study are that a relatively severe stenosis behaves essentially like an orifice and that a simple quasi-steady theory appears adequate to predict effects of a stenosis on coronary flow.
The role of canine superficial ventricular muscle fibers in endocardial impulse distribution.
Authors: Myerburg R J , Gelband H , Nilsson K , Castellanos A , Morales A R , Bassett A L
Published: June 2012

Thin sections of canine right and left ventricular endocardium and myocardium were studied in a tissue bath to compare conduction properties of intraventricular specialized conducting tissue [Purkinje fibers (PF)], the superficial layers of subendocardial ventricular muscle (SVM), and the deeper ventricular muscle (DVM) below this level. The study was carried out because of observations that some areas of the endocardium, which are devoid of either specialized conducting tissue or of PF-VM junctions between specialized conducting tissue and ventricular muscle, conduct relatively rapidly, favoring specific orientations of propagation. Preparations containing PF, SVM, and DVM were studied electrophysiologically and histologically. A technique of stripping limited areas of endocardium was used to expose DVM in order to determine its intrinsic calculated conduction velocity. In 12 preparations, the average calculated conduction velocity in PF was 1.62 m/sec, and the average in DVM was 0.26 m/sec. The SVM conduction velocity was intermediate between the two, averaging 0.98 m/sec when propagation was parallel to SVM fiber orientation. Conduction velocity transverse to SVM fiber orientation was not significantly different from DVM conduction velocity. Histologically, the most superficial layers of VM were oriented uniformly in the direction of rapid subendocardial conduction, in contrast to DVM fibers in which orientation varied. It is concluded that the geometric arrangement of SVM fibers may provide a means for rapid subendocardial conduction and impulse distribution at a conduction velocity intermediate between PF and DVM in areas devoid of specialized conducting tissue.
Relative effect of CO2 on canine coronary vascular resistance.
Authors: Case R B , Felix A , Wachter M , Kyriakidis G , Castellana F
Published: June 2012

We determined the effect of alterations in coronary arterial PCO2 on coronary vascular resistance (CVR) at a constant coronary sinus (CS) PO2 and the effect of coronary arterial PO2 variation on CVR at a constant CS PCO2. A linear but opposing effect on CVR was found for both gases. The sensitivity of CVR to O2 change, represented as CVR/CS PO2, was approximately twice that of the ratio CVR/CS PCO2. (0.0852 +/- 0.006 vs. -0.0362 +/- 0.005). The entire range of CVR variation obtainable through CO2 variation was as great as that resulting from O2 variation. During randomized variation of O2 and CO2, CVR can be mathematically related in a multiple linear expression to CS PO2 and CS PCO2.
Neurogenic vasodilation of cat cerebral arteries.
Authors: Lee T J , Hume W R , Su C , Bevan J A
Published: June 2012

Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, gamma-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response.
Renal function of conscious spontaneously hypertensive rats.
Authors: Beierwaltes W H , Arendshorst W J
Published: June 2012

Renal clearance studies were performed in conscious 13-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before and during volume expansion by intravenous infusion of isotonic saline. Mean arterial pressure and filtration fraction were greater in SHR, whereas fractional and absolute excretion of sodium and water, glomerular filtration rate, and renal plasma flow in SHR and WKY were not statistically different. This was the case during hydropenia and volume expansion. We did not observe as exaggerated natriuresis after intravenous loading when unanesthetized SHR were compared with the response of WKY. These observations suggest that the kidneys of genetically hypertensive rats of the Okamoto-Aoki strain have adapted to an elevated renal perfusion pressure or that hypertension is required to normalize renal function so that excretion is appropriately matched with intake.
Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion.
Authors: Bricknell O L , Opie L H
Published: June 2012

In Langendorff-perfused rat hearts, the perfusion pressure was reduced from 100 cm H2O to 20 cm H2O for 30 minutes to produce a model of global ischemia with a residual oxygen uptake. The release of lactate dehydrogenase (LDH) and the occurrence of ventricular arrhythmias during reperfusion were dependent on the substrate. Glucose-perfused hearts had the highest rates of glycolytic ATP production (2.5 mumol/g per min) during ischemia with normal contents of tissue cyclic adenosine 3',5'-monophosphate (cAMP) and, during reperfusion, the release of LDH was lowest and severe ventricular arrhythmias did not occur. In pyruvate-perfused hearts, glycolysis was inhibited during ischemia, the rate of production of glycolytic ATP was only 0.5 mumol/g per min. and tissue cAMP doubled; during reperfusion, LDH release was 14-fold higher and ventricular arrhythmias were more severe. Total tissue contents of ATP and phosphocreatine were similar in glucose- and in pyruvate-perfused hearts. In hearts perfused with acetate, there was virtually no glycolytic ATP synthesized during the last 5 minutes of ischemia and cAMP increased further. Acetate- and palmitate-perfused hearts showed greatest release of LDH and had severest arrhythmias during reperfusion, suggesting that it was the metabolic and not the detergent effects of palmitate that were operating. Lipolysis was not a major factor in the cause of reperfusion LDH release. A role of glycolytic ATP in the maintenance of membrane integrity is postulated.
Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.
Authors: Stalcup S A , Pang L M , Lipset J S , Odya C E , Goodfriend T L , Mellins R B
Published: June 2012

Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus.
Isometric relaxation of rat myocardium at end-systolic fiber length.
Authors: Wiegner A W , Bing S H
Published: June 2012

In a "physiologically sequenced" contraction (PSC), which loads the isolated muscle preparation in a manner which approximates that of the intact heart, isometric relaxation precedes isotonic relaxation and occurs at minimum ("end-systolic") length. We studied the effects of inital muscle length, load, temperature, calcium, and isoproterenol on the isometric relaxation phase of physiologically sequenced contractions to define the determinants of the rate of isometric relaxation of rat left ventricular myocardium. At the baseline temperature (28 degrees C), relaxation was found to be nonexponential, and the maximum rate of decline of force (-dF/dtmax) was used to evaluate changes in relaxation. Three factors, shortening, end-systolic length, and total load, were examined as possible mechanical determinants of -dF/dtmax. We found that -dF/dtmax is linearly related to end-systolic muscle length for lengths below 94% of Lmax; -dF/dtmax is also strongly related to total load for lightly loaded contractions, but peaks at loads of approximately 80% of peak developed force and declines thereafter. Shortening is poorly correlated with -dF/dtmax. The slope of the linear portion of the relation between -dF/dtmax and end-systolic length appears to be independent of muscle-loading conditions and sensitive to factors known to alter relaxation.
The effects of variations in conductivity and geometrical parameters on the electrocardiogram, using an eccentric spheres model.
Authors: Rudy Y , Plonsey R , Liebman J
Published: June 2012

The effects of variations in the volume conductor properties of the torso on the electrocardiogram were studied by means of a theoretical eccentric spheres model. The model includes a blood cavity, cardiac muscle layer, pericardium, lung region, skeletal muscle layer, and subcutaneous fat. The source of the field is a double-layer spherical cap located within the myocardium. The following effects regarding the electrocardiogram (ECG) potentials were determined: (1) blood augments the potential, but less than predicted by simpler published models; (2) in anemia, high potentials are expected, whereas in polycythemia, voltages are reduced; (3) abnormally low lung conductivity (emphysema) causes low surface potentials whose magnitude is controlled by the low conductivity skeletal muscle layer; (4) low voltages result both from low and high pericardial conductivities; (5) the surface potential increases with increasing myocardial conductivity; (6) low skeletal muscle conductivity (Pompe's disease) causes high surface potentials; (7) obesity lowers the potential only slightly; (8) a thick myocardium, protruding into the lung region, slightly augments the potential; (9) an increase in the thickness of the myocardium at the expense of the blood cavity causes a decrease in potential; (10) the potential increases with increasing heart size; and (11) the location of the heart within the torso has a very significant effect on the surface potential distribution.
Contribution of prostaglandins to muscle blood flow in anesthetized dogs at rest, during exercise, and following inflow occlusion.
Authors: Beaty O , Donald D E
Published: June 2012

The role of locally formed cyclo-oxygenase products (endoperoxide intermediates, prostaglandins, or prostacyclins) in resistance to blood flow was studied in the hindlimbs of anesthetized dogs during rest, during exercise, and following release of inflow occlusion. Meclofenamic acid, indomethacin, or sodium meclofenamate reduced mean resting blood flows of 86, 113, and 118 ml/min to 54, 82, and 67 ml/min, respectively. Inhibitors of prostaglandin synthesis reduced the vasodilator response to arachidonic acid by 81%. In addition, prostaglandin synthesis inhibitors attenuated the hyperemic responses following inflow occlusions in the resting hindlimb. The attenuation was most marked following a 1-second occlusion (74%) and progressively less following a 10-second (44%) and a 300-second (24%) occlusion. However, the portion of the total postocclusive hyperemic response attributable to prostaglandins was constant and independent of occlusion duration. Inhibition of prostaglandin synthesis did not affect the hyperemia of exercise, but reduced significantly the postocclusion hyperemia that followed the release of a 1-second (63%) and a 2-second (43%) period of inflow occlusion in the exercising hindlimb; attenuation was minor following a 10-second occlusion (10%). In three of four exercising hindlimbs, the portion of the postocclusion hyperemia attributable to prostaglandins was inversely related to the duration of the occlusion. These data indicate that locally synthesized cyclo-oxygenase products, possibly prostaglandins, are important in the maintenance of blood flow in resting but not exercising muscle, contribute significantly to postocclusive hyperemia in resting and exercising hindlimbs, and mediate the hyperemia that follows occlusions of 5 seconds or less in resting and 2 seconds or less in exercising hindlimbs.
Influence of aging on left ventricular hemodynamics and stiffness in beagles.
Authors: Templeton G H , Platt M R , Willerson J T , Weisfeldt M L
Published: June 2012

We studied the influence of aging on the contractile performance, stiffness, and contraction time of the canine left ventricle. Eight young (27 +/- 2.5 months, mean +/- SE) and seven old (128 +/- 20.5 months) beagles were placed on complete cardiopulmonary bypass, the arterial pressure was adjusted to 80 mm Hg, and the heart contracted isovolumically at a paced rate of 120 beats/min. Diastolic pressure-volume curves were established for each unpaced left ventricle at the beginning of each experiment, and the volume at the knee of the curve was used during the subsequent data collection when the heart was paced. Stiffness was measured with a sinusoidal forcing function, which imposed a sinusoidal displacement of 1 ml at 20 Hz into a balloon placed in the left ventricle. In each ventricle, stiffness was related linearly to pressure during the cardiac cycle, and was greater for any given pressure in the older beagles. Contraction duration was prolonged in the older dogs. In an additional seven old beagles during right heart bypass time, and duration of contraction were longer than in seven young beagles. Aging of the beagle heart is associated with an increase in left ventricular systolic and diastolic stiffness and prolonged duration of contraction.
Cellular mechanisms of normal growth in the mammalian heart. II. A quantitative and qualitative comparison between the right and left ventricular myocytes in the dog from birth to five months of age.
Authors: Legato M J
Published: June 2012

This paper describes and contrasts the changes in myocytes taken from the right and left ventricules of dog heart over the first 5 months of life. The development of the two populations of cells differs in important respects: sarcomeric volume, the proportion of the myocyte occupied by the contractile apparatus, and the volume and surface area of the transverse tubular system all were greater on the average in the left than in the right ventricle (P less than 0.001). Other intracellular structures also changed significantly as development progressed, but did so in both chambers; the surface area and surface-to-volume (s/v) ratio of both right and left ventricular myocytes increased with age (P less than 0.001) as did mitochondrial and mitochondrial-myocyte volume (P less than 0.001). The surface area (P less than 0.01) and the s/v ratio of the mitochondria (P less than 0.001) also increased with development. Nuclear and nuclear myocyte volume grew smaller with age in both chambers (P less than 0.002), as did the surface area (P less than 0.001) and the s/v ratio of the nucleus (P less than 0.01). Not only does myocyte composition change quantitatively, striking changes in intracellular architecture and the appearance and arrangement of intracellular organelles occur during postnatal life.
The hemodynamic effects of prostaglandins in the rat. Evidence for important species variation in renovascular responses.
Authors: Gerber J G , Nies A S
Published: June 2012

The hemodynamic effects of prostaglandins E2, F2alpha, D2, and I2, and of indomethacin and arachidonic acid were studied in Sprague-Dawley rats, by means of the radioactive microsphere technique. In contrast to effects in other species, PGE2, PGD2, and arachidonic acid were renal vasoconstrictors in the rat, although PGE2 and arachidonic acid reduced total vascular resistance. PGF2alpha and indomethacin had no effect on the renal vasculature, but PGI2 produced renal and systemic vasodilation. These data indicate that if prostaglandin-mediated renal vasodilation occurs in the rat, PGI2 may be the substance responsible. In view of the species differences in renal vascular responses to the prostaglandins, the rat may not be an appropriate model for study of the prostaglandin system as it relates to other species.
Influence of cardiac fiber orientation on wavefront voltage, conduction velocity, and tissue resistivity in the dog.
Authors: Roberts D E , Hersh L T , Scher A M
Published: June 2012

When the canine epicardium is stimulated, the spread of epicardial excitation is 2.4 times faster parallel to the long axes of the cardiac fibers than perpendicular to them. Likewise, gross tissue resistivity is lower parallel to fibers by a factor of 3.2, and the voltage across the depolarization wave is approximately three times as great in the longitudinal direction. Equations are presented which relate these variables. Theoretical considerations confirm the experimental finding that the potentials around a wave of depolarization cannot be accounted for by the conventional hypothesis that the wavefront is a uniform double-layer current source.
Some bases of differences in vascular response to sympathetic activity.
Authors: Bevan J A
Published: June 2012

Basic patterns of neuroeffector organization vary widely in the vasculature, in general, with vessel diameter and type, and confer distinctive properties. The smaller the vessel, the more intimate the neuroeffector relationship, the more localized the action of the released transmitter, and the more important myogenic conduction compared to transmitter diffusion for the coordination of vascular effector response. Seemingly superimposed upon these basic general patterns are other variable features, conferring upon vessels of similar size and type diversity of function. These variables include sensitivity and magnitude and possible location of alpha- and beta-receptors and their subtypes, presence and nature of intrinsic vascular tone, and the density and pattern of adrenergic innervation to mention the more important. Functional diversity in neuroeffector characteristics can, to some extent, be understood in relation to embryological development, neurotrophic influences, effector regulation of innervation, and the mural response to an increase in intravascular pressure.
Biochemical determinations of cholinergic innervation in cerebral arteries.
Authors: Florence V M , Bevan J A
Published: June 2012

Endogenous choline acetyltransferase (ChAT) activity and high affinity (HA) 3H-choline uptake can be assayed specifically and used to quantify cholinergic neuronal mechanisms. In general, arteries at the base of the brain in the cat and rabbit were distinguished by high and in the dog by lower ChAT activity and 3H-choline levels of uptake. There was a linear relationship between the mean values of the observations from of the two assays on given cerebral arteries from the three species (r = 0.871,P less than 0.001). Since ChAT activity and HA 3H-choline uptake essentially are confined to cholinergic nerve terminals, our results imply that the Circle of Willis and its main branches in the cat, rabbit, and dog are cholinergically innervated.
Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats.
Authors: Warshaw D M , Mulvany M J , Halpern W
Published: June 2012

We studied alterations in structural and mechanical properties of mesenteric arterial resistance vessels from young (6-week) and old (50-week) spontaneously hypertensive (SHR)and matched normotensive Wistar-Kyoto (WKY) rats. Emphasis was placed upon relating the active tension capabilities of these vessels to their smooth muscle cell content. Cylindrical segments, 0.7 mm long with internal diameters of 150 micrometer, were mounted in a myograph capable of recording circumferential vessel wall tension and dimensions. Comparisons of vessel morphology and mechanics were performed at a normalized internal circumference, L1,where active tension (delta T1) is near maximum. Arterial wall and medial hypertrophy were observed in young and old SHR. Since the percent smooth muscle cells within the media for SHR was similar to that of WKY, both increased smooth muscle cell and connective tissue content account for the medial hypertrophy. These differences in SHR vessels were reflected directly in their passive and active mechanical properties. Fully relaxed vessels from SHR were less compliant, and upon activation at L1 (high potassium depolarization), delta T1 was not different for young SHR and WKY, but values for old SHR were 35% greater (P less than 0.05) than for WKY. When relating the active force generation of the vessel to the actual smooth muscle cell area, values for smooth muscle cell stress (force/area) were similar for SHR and WKY at both ages. In addition, similarities were observed for active dynamic mechanical measurements of Young's modulus and half response time. Genetic hypertension in rats therefore appears to be associated with the development of increased vessel contractility determined by a greater number of smooth muscle cells which possess contractile properties similar to those of normotensive vessels.
Effects of ischemia on tissue metabolites in red (slow) and white (fast) skeletal muscle of the chicken.
Authors: Klabunde R E , Mayer S E
Published: June 2012

Brief periods of ischemia have been shown to produce marked reactive hyperemia in both red (slow) and white (fast) skeletal muscle. However, evidence is lacking for specific vasodilator metabolites which are rapidly produced in ischemic skeletal muscle. The present study examined the effects of 1 and 3 minutes of ischemia on creatine phosphate (CrP), adenine nucleotide metabolism, and anaerobic glycolysis in red anterior (ALD) and white posterior latissimus dorsi (PLD) muscles of the chicken. Tissue metabolite concentrations were determined from perchloric acid or trichloroacetic acid extracts using enzymatic assay or high pressure liquid chromatography. CrP or adenine nucleotides were not significantly altered in either muscle following 1 or 3 minutes of ischemia. However, adenosine increased by 611% in the ALD at 1 minute. Following 3 minutes of ischemia, adenosine concentrations were elevated by 439% and 201% in the ALD and PLD, respectively. The PLD showed the greatest increases in inosine and IMP. Inorganic phosphate increased by 67% and lactate increased by 142% in the ALD at 3 minutes. The PLD, which is reported to have a high anaerobic glycolytic capacity, showed no increase in lactate. These results support the hypothesis that adenosine may be a mediator of akeletal muscle reactive hyperemia following short periods of ischemia.
Time course of increased collateral arterial and venous endothelial cell turnover after renal artery stenosis in the rat.
Authors: Ilich N , Hollenberg N K , Williams D H , Abrams H L
Published: June 2012

We induced left renal artery stenosis in rats and studied collateral arterial formation by angiography, histology, and radioautography with tritiated thymidine. Endothelial cell turnover was estimated by radioautography with tritiated thymidine in the periureteric blood supply of 10 normal and 38 collateral-forming kidneys 1 to 100 days after stenosis. Periureteric arterial endothelial cell labeling showed a highly significant (P less than 0.005) increase, apparent within 1 day and gradually falling as the vessels grew, until a baseline was reached in 35 days. A smaller but statistically significant increase in the labeling index also was found in endothelial cells of the renal vein during the first week (P less than 0.01), and had a similar time course. A marked increase in epithelial cell labeling in the ureters draining the stenotic kidneys also was evident (P less than 0.005). Thus, collateral vessel development is characterized by active DNA synthesis in the cellular elements which is maximal during the first week. A humoral factor is implicated in the vascular response by the parallel proliferation of venous and uretic cellular elements that are unlikely to experience the biophysical forces, such as increased blood flow or tangential wall force, which might stimulate proliferation in ther arterial vessels.
Sympathetic modulation of hypercapnic cerebral vasodilation in dogs.
Authors: D'Alecy L G , Rose C J , Sellers S A
Published: June 2012

We measured cerebral blood flow using both the radioactive microsphere technique and the cerebral venous outflow technique in dogs anesthetized with chloralase. The effect of sympathetic stimulation on cerebral blood flow was observed during both normocapnia and prolonged hypercapnia using both blood flow techniques. The increase in blood flow with hypercapnia was the same with both methods. During hypercapnia the venous outflow method showed a 38% decrease and microspheres an 18% decrease in cerebral blood flow with sympathetic stimulation. At normal CO2, stimulation caused a decrease in cerebral venous flow: no change was observed with the microsphere method. Analysis of the blood flow patterns to extracerebral tissues and evaluation of extracerebral arterial reference samples failed to prove the existence of axial streaming and subsequent skimming of microspheres within the cephalic circulation. It is concluded that direct electrical stimulation of the sympathetic innervation of the cerebral vessels is capable of reducing cerebral blood flow even during a profound hypercapnic vasodilation.
Calcium and magnesium sensitivity of the carotid baroreceptor reflex in cats.
Authors: Kunze D L
Published: June 2012

The systemic blood pressure response to changes in carotid sinus pressure has been examined during variations in the calcium and magnesium concentration of the perfusate of the isolated sinus. The threshold for the blood pressure response was increased by 16 +/- 0.8% when calcium was raised from 1.1 mM (control) to 2.2 mM and increased by 27 +/- 1.8% when calcium was raised to 3.3 mM. The threshold was reduced by 21 +/- 0.7% in zero calcium and 13 +/- 0.8% in 0.55 mM Ca2+. The sensitivity (slope of the linear portion of the pressure response curve) of the reflex was not significantly changed except at 3.3 mM Ca2+ where it was reduced by 16 +/- 2.9%. Magnesium had directionally similar effects of a lesser magnitude. Earlier work described the reduced sensitivity and threshold of the baroreceptor reflex when sodium concentration in the carotid perfusate was reduced. The present study shows that reducing calcium attenuates the effect of lowered sodium and increasing calcium augments it. These results are discussed in terms of possible ionic influences on the receptor potential and spike generation.
Correlation between acute reductions in myocardial blood flow and function in conscious dogs.
Authors: Vatner S F
Published: June 2012

Decreases in regional endocardial function (ultrasonic dimension technique) and blood flow (radioactive microsphere technique) were correlated in 14 conscious dogs with acute graded levels of coronary stenosis. Coronary stenosis affected overall ventricular function only slightly, but induced gradual reductions in regional blood flow (BF) and segment length (SL) shortening in the ischemic zone. The relationship was best fit by an exponential function relating % change in SL to % change in BF; i.e., SL(% delta) = -161.6 e -0.047BF(% delta) (r = 0.92). In 14 segments, where no change in function was observed, blood flow fell by 6 +/- 1%. However, 10--20% reductions of blood flow impaired function significantly. Severe reduction of blood flow was required to reduce function completely. In 12 segments exhibiting paradoxical motion, blood flow fell by 95 +/- 2%, a value greater (P < 0.01) than in four akinetic segments, i.e., those with no shortening or lengthening (-82 +/- 4%). These data, which show on one hand that only 10-20% reductions in blood flow impair function significantly and that, on the other hand, severe reductions in blood flow are required to abolish active shortening completely, indicate sensitive coupling between blood flow and function in the conscious dog with acute myocardial ischemia.
Direct evidence for myogenic autoregulation of the renal microcirculation in the hamster.
Authors: Gilmore J P , Cornish K G , Rogers S D , Joyner W L
Published: June 2012

We transplanted neonatal hamster renal tissue into a hamster check pouch chamber and subjected the renal tissue to increases and decreases in extravascular pressure. A decrease in extra-vascular pressure decreased, and an increase in extravascular pressure increased, the diameter of preglomerular arterioles. Thus, the change in preglomerular arteriolar diameter was directly related to alterations in extravascular pressure. Neither saralasin nor indomethacin affected these changes, whereas papaverin prevented them. The efferen arterioles responded passively to changes in extravascular pressure; i.e., the changes in their diameter were inversely related to changes in extravascular myogenic autoregulation of preglomerular vessels.
Ionic currents during hypoxia in voltage-clamped cat ventricular muscle.
Authors: Vleugels A , Vereecke J , Carmeliet E
Published: June 2012

To explore the mechanisms underlying the shortening of the cardiac action potential in hypoxia, we studied the effect of hypoxia on the ionic currents in cat papillary and trabecular muscles using the single sucrose gap-voltage clamp technique. For potentials positive to -70 mV, hypoxia induces an increase in time-independent outward current. The changes in the tail current suggest that time-dependent outward current is not increased but, rather, reduced. Because the time course of ik remains unchanged, we concluded that the shortening of the action potential is not a result of a change in the time-dependent outward current. In the potential range of the plateau, the amplitude of the slow inward current is not affected by hpoxia. Its time constant of inactivation appears slightly decreased. The prolongation of the action potential by epinephrine during hypoxia is accompanied by an increase in the slow inward current. As a result of these studies, we conclude that the shortening of the cardiac action potential in the early stage of hypoxia results from an increase in K+ outward background current.
Reflex cardiovascular and respiratory effects of serotonin in conscious and anesthetized dogs.
Authors: Zucker I H , Cornish K G
Published: June 2012

Cardiovascular and respiratory effects of intra-left atrial or intra-left ventricular injection of serotonin were studied in conscious dogs (n = 8), anesthetized closed-chest dogs (n = 13) and anesthetized open-chest dogs (n = 9). Serotonin (50-200 microgram), injected as a bolus, resulted in an initial bradycardia and hypotension followed by a delayed tachycardia and hypertension in the conscious dogs. The hypertension was seen as an increase of 21.5 +/- 2.7 (mean +/ SE) mm Hg from a control pressure of 102.5 +/- 1.9 mm Hg, whereas the initial decrease in pressure was 22.6 +/- 1.9 mm Hg. The tachycardia was 23.3 +/- 3.9 beats/min above a control heart rate of 104.9 +/- 3.9 beats/min whereas the bradycardia was 58.5 +/- 3.7 beats/min below control. There was a significant attenuation of the hypotension in both groups of anesthetized dogs. In fact, no hypotension was elicited in the open-chest anesthetized dogs. Open-chest anesthetized dogs showed only a hypertensive response (mean increase 67.2 +/- 5.5 mm Hg). Stimulation of respiration was seen in all groups of dogs. In conscious dogs there was a 214.8 +/- 15.4% increase in respiratory depth and a 20.8 +/- 3.1 breaths/min increase in respiratory rate. Atropine significantly reduced the bradycardia and abolished the hypotension in conscious dogs. Bilateral cervical vagotomy did not abolish the response in open-chest anesthetized dogs. We conclude that the so-called "hypertensive coronary chemoreflex" is altered dramatically by the state of the preparation and by anesthesia.