bluuebunny/crossref_metadata_2025 huggingface dataset:
Spread of contraction in rabbit ear artery preparations in response to stimulation by norepinephrine.
Authors: Vonderlage M
Published: June 2012

To investigate the spread of contraction in the rabbit ear artery, changes in segment diameter were measured after local stimulation. No spread of contraction was produced by direct current or local application of norepinephrine (NE). Repetitive electrical stimulation caused contraction which spread far from the point of excitation. Since 2 x 10(-7) g/ml tetrodotoxin (TTX) or 10(-5) M phentolamine prevented this spread of contraction, we concluded that it depends on normal function of periarterial nerves and of the alpha-adrenergic receptors at the site of the smooth muscle cells. To check this conclusion and exclude the possibility of myogenic propagation, which normally is due to the conduction of action potentials, the relation between membrane potential of smooth muscle cells and the rapid phase of the contractile response after rapid addition of NE was investigated. In both polarized and depolarized tissues NE induces a biphasic contractile response with no difference in latency. Membrane potential does not change during mechanical latency after the rapid addition of 5 x 10(-9) - 5 x 10(-6) g/ml NE. There are only slight differences in contraction amplitude and maximum rate of tension development when strips from polarized and depolarized tissues incubated in Ca2+-free solution are stimulated by NE. These findings support the conclusion that spread of contraction is not due to myogenic propagation.
Inotropic actions of isoproterenol in cat ventricular muscle. Effects of extracellular potassium.
Authors: Wiggins J R
Published: June 2012

The inotropic actions of isoproterenol in cat papillary muscles or trabeculae bathed in a salt solution containing 4 mM KCl were compared to those in similar muscles bathed in a salt solution containing 22 mM KC1. Although isoproterenol evoked the same increase in force of contraction in both groups of muscles, the time course of contraction differed markedly. In muscles bathed in 4 mM KC1, isoproterenol caused a concentration-dependent decrease in time-to-peak force, but in muscles bathed in 22 mM KCl, isoproterenol caused a concentration-dependent increase in time-to-peak force. These data suggest that ventricular muscle activated by slow response action potentials may utilize a different mechanism of excitation-contraction coupling than do muscles activated by Na-dependent action potentials.
Hydrolase activities in the rat aorta. V. Comparison to activities in liver and kidney after thyroidectomy and relation to dynamic clearance of circulating low density lipoproteins.
Authors: Katz-Feigenbaum D , Braun L , Wolinsky H
Published: June 2012

Thyroid hormones influence circulating low density lipoprotein (LDL) levels in humans; they could have an effect on LDL catabolism. Male rats were thyroidectomized (H); half were treated for 7 days with 2 micrograms triiodothyronine/100 g body weight (T) and both groups were compared to controls (C). Aorta, liver, and kidney were assayed for cellular marker enzymes, including lysosomal acid cholesteryl esterase (ACE). Specific activities of ACE (mU/mg DNA; mean +/- SD) were: Aorta, C, 0.19 +/- 0.01; H, 0.16 +/- 0.01; T, 0.21 +/- 0.01; Liver: C, 15.55 +/- 1.49; H, 9.16 +/- 1.54; T, 15.43 +/- 2.28; Kidney: C, 1.70 +/- 0.23; H, 1.04 +/- 0.13; T, 2.08 +/- 0.35. Half lives for injected unmodified 125I-labeled human LDL were 11.5 +/- 0.7 hour in C, 16.2 +/- 3.1 in H, and 12.9 +/- 0.9 in T groups. Fractional catabolic rates (FCR) of LDL in %/hr were 6.5 +/- 0.6 in C; 4.8 +/- 0.5 in H, and 6.0 +/- 0.3 in T. Reductively methylated 125I-labeled human LDL had half-lives of 14.9 +/0 1.4 hour in C and 15.1 +/- 1.6 hour in H and the FCR of this modified LDL was 5.3 +/- 0.5 %/hr in C and 5.2 +/- 0.7 %/hr in H groups. Thus, thyroidectomy results in marked decreases in ACE specific activity of liver and kidney and a marked decrease in FCR and prolonged half-life of non-modified LDL (all P less than 0.05). On the other hand, methylated LDL showed a similarly reduced FCR and prolonged half-life in control and thyroidectomized rats (P less than 0.05). This suggests a major effect of thyroid deficiency on receptor-mediated uptake of LDL in vivo and demonstrates the influence of hormonal status on dynamic clearance and catabolism of LDL.
The effect of an isovolumic left ventricle on the coronary vascular competence during reflow after global ischemia in the rat heart.
Authors: Humphrey S M , Thomson R W , Gavin J B
Published: June 2012

During global ischemia in isolated rat hearts, the development of contracture, due to irreversible myofilament sliding, causes reduction of left ventricle luminal volume. Also, a considerable area of the myocardium cannot be reperfused after 1 hour's global ischemia. The purpose of this study was to reduce myofilament sliding by placing a fluid-filled isovolumic balloon in the left ventricular cavity of isolated rat hearts and assess the extent of reflow, after 60 minutes' ischemia, by perfusion of a 1% fluorescein tracer solution. Light and electron microscopy was used to determine the state of the vasculature and myofibrillar apparatus. In hearts without the left ventricular balloon (control) the ischemia produced a no-reflow zone comprising 45% of the myocardial wall. In contrast, if an isovolumic balloon was in place during the ischemic period, only 6% of the wall was involved. The volume of the capillary bed in the subendocardium of the control hearts was about 60% of that in th isovolumic hearts. In the isovolumic ("isometric") mode, ischemic contracture was associated with more severe myocardial cell injury than in the corresponding control ("isotonic") mode. Our results support the concept that intramyocardial pressure generated by ischemic contracture plays a major role in the production of the no-reflow phenomenon in globally ischemic rat hearts, and indicate that it is the series elastic component of cardiac muscle which imparts the stiffness necessary to prevent reopening of coronary vessels after a severe ischemic insult.
Evidence against significant resting sympathetic coronary vasoconstrictor tone in the conscious dog.
Authors: Chilian W M , Boatwright R B , Shoji T , Griggs D M
Published: June 2012

The primary objective of this study was to ascertain whether resting coronary blood flow is under tonic restraint due to sympathetically mediated alpha-adrenergic coronary vasoconstriction. To accomplish this, we first developed and verified a technique for selectively sympathectomizing the posterior region of the canine left ventricle. This technique entailed the topical application of phenol in a thin line to specific sites on the myocardium and epicardial vessels. As part of the verification, we demonstrated that left stellate nerve stimulation caused increases in the myocardial extraction ratios for oxygen and lactate in the normally innervated region (I) of the ventricle, but not in the sympathectomized region (Sx). We then measured regional myocardial blood flow with microspheres in phenol-treated animals under conscious, resting conditions. The animals were acclimated to the laboratory environment, and their arterial plasma norepinephrine levels averaged 135 +/- 37 pg/ml. heart rate (81 +/- 3 bpm) and mean aortic pressure (100 +/- 2 mm Hg) were not significantly affected by beta-adrenergic blockade or combined alpha- and beta-adrenergic blockade in these animals. Blood flow in I and Sx averaged 0.87 +/- 0.08 ml/min per g and 0.85 +/- 0.07 ml/min per g, respectively, and the difference was not statistically significant. The endocardial-to-epicardial blood flow ratio in I and Sx averaged 1.23 +/- 0.03 and 1.29 +/- 0.04, respectively, and the difference was not statistically significant. The results were not significantly affected by beta-adrenergic blockade or combined alpha- and beta-adrenergic blockade. We were unable to confirm previous evidence in the literature of significant resting sympathetic coronary vasoconstrictor tone in the conscious animal.
Flow through collapsible tubes at high Reynolds numbers.
Authors: Lyon C K , Scott J B , Anderson D K , Wang C Y
Published: June 2012

The pressure-flow relationships of collapsible tubes were studied utilizing the Starling resistor model. Reynolds numbers much higher than previously reported were used to simulate high cardiac output states. Alterations which occur in vivo, including longitudinal tension, stretch, tubing diameter, length, and outflow resistance were also simulated and systematically investigated. The pressure-flow curves showed an initial rising phase, a plateau phase, as well as a late-rising phase which has not been reported previously. Self-induced oscillations occurred during the plateau phase and persisted throughout the late-rising phase. These perturbations were markedly increased by longitudinal tension and stretch, but were attenuated by increased diameter, length, and outflow pressure. These instabilities may prove to be an explanation for the "venous hum."
Myocyte growth without physiological impairment in gradually induced rat cardiac hypertrophy.
Authors: Julian F J , Morgan D L , Moss R L , Gonzalez M , Dwivedi P
Published: June 2012

A surgical technique was developed to place sutures around the pulmonary arteries of young rats (about 1 month old and 100 g body weight). As the operated rats grew, the pulmonary arteries were gradually constricted, leading after 4-6 weeks to the development of severe right ventricular hypertrophy with free wall weights about twice those from control rats. There were no signs of heart failure or cardiac decompensation. Collagen concentrations were the same in operated and control rats. Myocytes were isolated from right ventricles by enzymatic digestion. Autoradiographic studies showed considerable uptake in non-myocyte nuclei. Myocyte sarcomere lengths were unchanged. However, myocyte lengths and areas increased sufficiently to account for the increase in free wall weights observed. Physiological studies were done on isolated papillary muscles and ventricular strands, which were subsequently fixed. The force-generating capability at optimum length, magnitude of active compliance, and maximum speed of shortening (using four different techniques) were measured in each isolated muscle. There were no significant changes observed between operated and control rats. Microscopic examination of the muscle cross-sections confirmed that average myocyte area in the muscles obtained from operated rats was significantly increased. The results show that it is possible to obtain considerable increases in average myocyte size (by about a factor of 2) while still maintaining normal physiological function.
The effects on atrial electrophysiology and structure of surgically induced right atrial enlargement in dogs.
Authors: Boyden P A , Hoffman B F
Published: June 2012

We evaluated the relationship between susceptibility to arrhythmias caused by right atrial (RA) enlargement and alterations in transmembrane potentials and ultrastructure. RA enlargement was produced in eight dogs (TI) by excising the septal cusp of the tricuspid valve through a right atriotomy and constricting the pulmonary artery. This procedure resulted in RA dilation and hypertrophy. Four sham-operated dogs (S) also were studied. Neither TI nor S dogs developed spontaneous atrial arrhythmias. Atrial overdrive (OD) and premature stimulation (PS) were used to initiate and terminate arrhythmias. At 2 weeks and for 20 to 30 weeks after surgical preparation, TI dogs were more susceptible to arrhythmias than S dogs. The duration of arrhythmias exceeded 10 minutes more often in TI dogs than in S dogs. Sixty-one percent of all arrhythmias in the TI dogs had rates of 320-450 impulses/min, and electrogram and ECG characteristics of atrial flutter (type II rhythm), whereas no S dogs developed rhythms with these slower rates. The type II rhythms were persistent, 30% lasting longer than 30 minutes, while 22% lasted more than 60 minutes. Transmembrane potentials recorded in vitro from the RA free wall of TI dogs, and responses to norepinephrine and acetylcholine were not different from control. Histological and ultrastructural studies on TI atria showed hypertrophy of fibers and some increase in connective tissue between cells. These results suggests that altered susceptibility to long-lasting arrhythmias need not be associated with significant abnormalities of cellular electrophysiology.
Effect of Choline and Cholesterol on Lipoprotein Patterns of Rats
Authors: WILGRAM GEORGE F. , LEWIS LENA A. , BEST CHARLES H.
Published: June 2012

Serum lipid values (low-density lipoproteins, alpha lipoproteins and serum cholesterol) are decreased in choline deficiency. It is believed that this is due specifically to a choline lack rather than to a nonspecific effect of a deficiency. The addition of cholesterol to a choline deficient diet does not lead to hyperlipemia and hypercholesterolemia. It appears that dietary choline is one of the many requirements necessary for production of hyperlipemia and hypercholesterolemia. A metabolic interdependence between choline and cholesterol is pointed out in rats.
Myocardial Failure in Experimental Hypothermia
Authors: LOMBARDO THOMAS A. , RADIGAN LEO R. , MORROW ANDREW G.
Published: June 2012

Hypothermic animals subjected to total venous inflow occlusion and open cardiotomy develop elevations in right atrial mean pressure and postmortem evidences of myocardial failure. Acetyl strophanthidin, given before inflow stasis, prevented myocardial failure and increased survival. Myocardial failure was attributed to anoxia resulting from decreased coronary blood flow and alterations in the oxygen content of the blood supplying the myocardium. Perfusion of the coronary system with small quantities of oxygenated blood obtained from donor animals permitted open cardiotomy with survival.
Androgen Inhibition of Atherogenesis in Pullets
Authors: COOK D. L. , EDGREN R. A. , HARRIS T. W.
Published: June 2012

Continuous testosterone propionate administration, but not pretreatment, inhibited cholesterol-induced coronary atherogenesis in pullets. This inhibition was associated with depression of the plasma total cholesterol, phospholipids. c/p ratio and turbidity. Aortic atherogenesis was not affected.
Factors Concerned in the Early Stages of Thermal Shock
Authors: DOBSON ERNEST L. , WARNER GEORGE F.
Published: June 2012

The present study is concerned with the early stages of burn injury and demonstrates that the factor of plasma volume reduction does not adequately account for the prompt, precipitous fall in cardiac output.
An Electric Device for Instantaneous and Continuous Computation of Aortic Blood Velocity
Authors: FRY DONALD L. , NOBLE FRANK W. , MALLOS ALEXANDER J.
Published: June 2012

An electric device is described which computes the instantaneous aortic blood velocity from the pressure difference between two points along the aorta. The pressure difference was obtained from a specially designed double lumen catheter attached to a differential pressure gage. The aortic blood velocity curves obtained from 20 dogs compare closely with most of those appearing in the literature.
Use and Application of the Cuvette Densitometer as an Oximeter
Authors: SABISTON DAVID C. , KHOURI EDWARD M. , GREGG DONALD E.
Published: June 2012

A method has been developed for the continuous recording of oxygen saturation in blood by the use of a cuvette densitometer. The device consists of a light source, a cuvette through which the blood flows and a photosensitive element. It is simple to operate and has an acceptable sensitivity and stability. The instrument is applicable to a number of investigative problems.
Bilateral Cerebral Blood Flow and Oxygen Consumption in Man by use of Krypton
85
Authors: MUNCK OLE , LASSEN NIELS A.
Published: June 2012

Side-to-side differences of estimated cerebral blood flow and oxygen consumption are found in most of 38 bilateral studies with the method of Kety and Schmidt using Kr
85
as inert gas instead of nitrous oxide. The results indicate that bilateral values reflect the blood flow and oxygen consumption of the whole brain much more reliably than unilateral values. Accurate, bilateral determinations may prove of value, especially for the individual evaluation of the results obtained in a given subject.
Effect of Aramine-Induced Smooth Muscle Contraction on Length-Tension Diagrams of Venous Strips
Authors: LEONARD EDWARD , SARNOFF STANLEY J.
Published: June 2012

The elastic properties of helically cut strips of peripheral veins of dogs were studied. Length-tension diagrams of relaxed venous strips are compared With those obtained when the smooth muscle of the strip is contracted in the presence of a long-acting sympathomimetic agent, Aramine. Sustained strong, muscular contraction is always associated with a change in the shape of the length-tension curve and a marked decrease in the extensibility of the tissue. The contribution to total strip tension of the smooth muscle relative to that of other tissue elements appears to be greater in this preparation than it is in certain previously described arterial tissues. Aramine causes smooth muscle contraction of the isolated vein strip in concentrations comparable to those probably achieved in vivo. This fact supports the hypothesis that Aramine can alter the pressure-volume characteristics of the venous bed in intact animals.
Efficiency of Oxidative Phosphorylation of Heart Muscle Mitochondria from Digitalized Guinea Pigs
Authors: PLAUT KATHARINE ARMSTRONG , GERTLER MENARD M. , PLAUT G. W. E.
Published: June 2012

Fifty-four normal adult male guinea pigs were divided into two groups: (a) a control group of 29 was injected with a carrier solution and (b) an experimental group of 25 was injected with the carrier solution which contained digitoxin nativelle. Serial electrocardiographs revealed no significant changes in the control group; in the experimental group, changes indicated only therapeutic digitalis effect and no toxic phenomena. The efficiency of oxidative phosphorylation of isolated cardiac mitochondria from the digitalized animals has been compared with that from control animals. No significant differences could be observed between the digitalized and non-digitalized animals. It would appear that the administration of therapeutic amounts of digitoxin nativelle does not affect the energy-generating mechanisms of normal guinea pig heart mitochondria.
Effect of Exercise and Coronary Artery Narrowing on Coronary Collateral Circulation
Authors: ECKSTEIN RICHARD W.
Published: June 2012

The effect of chronic coronary arterial narrowing on the coronary collateral circulation has been studied in rested and exercised dogs. The data indicate that moderate and severe arterial narrowing results in extensive collateral development proportional to the degree of narrowing, further that exercise leads to even greater anastomoses. The results also show that while mild arterial narlowing fails to initiate collateral growth by itself, the addition of exercise promotes an effective collateral circulation. An attempt is made to define the gross factors in the development of collateral vessels and to correlate them with the concept that exercise may play a beneficial role in building collateral vessels in patients with coronary disease.
A Study of Circulatory Dynamics by Means of Crystal Radiation Detectors on the Anterior Thoracic Wall
Authors: HUFF REX L. , PARRISH DANIEL , CROCKETT WAYNE
Published: June 2012

A description is given of simultaneous tape records from four well-shielded crystal detectors placed on the anterior chest in the projections of the right atrium, pulmonary artery, ventricles, and lung vessels alone. Single intravenous injections of J
131
human serum albumin were made. Cardiac outputs calculated from the observed data compare favorably with those obtained by catherization. Use of the tape recorder with slow playback speeds allows for unique storage, transformation and interpretation of data. Characteristic curves obtained from patients with congenital and valvular heart disease are analyzed.
Inhibitory Effect of "Isocholesterol" on the Absorption of Cholesterol
Authors: BEST MAURICE M. , DUNCAN CHARLES H. , Watheii Joan D.
Published: June 2012

The presence on carbon-3 of a free hyclroxyl group that may be esterified is a common characteristic of the known sterol inhibitors of cholesterol absorption. The 30-carbon sterols found in wool fat possess such a group, but differ from the previously demonstrated inhibitors of cholesterol absorption in that they do not form insoluble precipitates with digitonin. To determine whether these substances would influence cholesterol absorption, "isocholesterol," a mixture of 30-carbon wool fat sterols, has been fed to the albino rat alone and in combination with cholesterol.
Experimental Coronary Occlusion in Dogs and Its Effect Upon the Cardiac Glycogen Fractions
Authors: MERRICK ARTHUR W.
Published: June 2012

A chemical quantitative analysis of the acid-soluble and acid-insoluble fractions of myocardial glycogen following an episode of acute infarction is presented. Both glycogen forms are depleted from the more seriously occluded area. The labile fraction similarly is decreased in the ischemic zone surrounding the infarct while the acid-insoluble moiety maintains a normal level.
Capacitive Properties of Body Tissues
Authors: SCHWAN HERMAN P. , KAY CALVIN F.
Published: June 2012

The electric capacity of various tissues surrounding the heart has been investigated in living dogs, using frequency ranges from 10 to 10,000 c.p.s. Electrode polarization, a serious source of error in such measurements, has been corrected for. Discussion of our results and of resistivity data previously obtained in body tissues proves that the electric properties of body tissues are primarily resistive ones.
Role of Venous Return in the Cardiovascular Response Following Injection of Ganglion-Blocking Agents
Authors: TRAPOLD JOSEPH H. , Sullivan Joan G. , Hawkins James L.
Published: June 2012

The reduction of arterial pressure in anesthetized dogs following the injection of ganglion-blocking agents is dependent primarily upon a reduction in arterial vasomotor activity and secondarily upon a reduction in venous return associated with an increase in vascular capacity. When venous return is maintained at control levels, the administration of the blocking agents of this study invariably produce a decrease in total peripheral resistance (TPR). Ordinarily in the intact animal such a decrease in TPR is not observed due to a marked reduction in cardiac output which produces a secondary increase in TPR. The results of this study further suggests that the venous and arterial systems may differ in their sensitivity to the effects of ganglion-blocking agents.
Radiopotassium Indicator-Dilution Studies During Angiocardiography
Authors: CONN HADLEY L. , JOYNER CLAUDE R. , HEIMAN DONALD F. , ZINSSER HARRY F.
Published: June 2012

In an attempt to learn more about the physiologic changes in the cardiovascular system during angiocardiography and the nature of mixing of radio-opaque dyes with blood, radiopotassium and Diodrast I
131
dilution curves were obtained before and during angiocardiography. Studies in patients without vulvuar disease and with mitral valvular disease indicated an increased cardiac output during angiocardiography, but the increases were not statistically greater than those following control injections. No difference in indicator-dilution patterns of potassium and Diodrast was demonstrable, suggesting identical circulatory mixing pattterns.
Hemodynamic Effects of Quantitatively Varied Experimental Mitral Regurgitation
Authors: BRAUNWALD EUGENE , WELCH GEORGE H. , SARNOFF STANLEY J.
Published: June 2012

Mitral regurgitation was produced in the open-chest dog by permitting blood to flow from left ventricle through a flow meter into the left atrium during systole. The hemodynamic effects of known amounts of regurgitation were studied. Two liters per minute of mitral regurgitant flow had relatively little effect on effective cardiac output, aortic pressure, left atrial pressure and on the left ventricular function curve.
Effect of the Sampling System on the Shape of Indicator Dilution Curves
Authors: LACY WILLIAM W. , EMANUEL RICHARD W. , NEWMAN ELLIOT V.
Published: June 2012

This paper describes the distorting effects produced by various sizes of polyethylene tubing and various flow rates on a square wave input of dye concentration. The importance of an accurate sampling system when recording dilution curves for analysis of their shape is emphasized and the distortion caused by inadequate sampling systems is demonstrated in vivo.
Autocorrelation of Electrocardiographic Activity during Ventricular Fibrillation
Authors: ANGELAKOS E. T. , SHEPHERD G. M.
Published: June 2012

Mathematical analysis of periodic and semiperiodic functions by the use of special electronic computers was applied to electrocardiographic recordings of ventricular fibrillation from hypothermic dogs. Preliminary experiments revealed a definite periodic component 1 to 3 min. after onset of fibrillation which practically disappeared in 5 min.
Effects of capsaicin and bradykinin on afferent fibers with ending in skeletal muscle.
Authors: Kaufman M P , Iwamoto G A , Longhurst J C , Mitchell J H
Published: June 2012

Capsaicin, injected into the arterial supply of the skinned hindlimb of dogs, evokes reflex increases in cardiovascular function. Moreover, the cardiovascular reflexes evoked by capsaicin are very similar to those evoked by static exercise. The afferent fibers initiating these reflex increases have not been identified electrophysiologically, although their endings are believed to be located in skeletal muscle. We have, therefore, attempted to determine which afferent fibers are stimulated by capsaicin. In anesthetized dogs, we recorded impulses from afferent fibers with endings in either the gastrocnemius or gracilis muscles and injected capsaicin (10-30 microgram/kg) into the abdominal aorta. Capsaicin stimulated 24 of 34 group IV (C fiber) endings, but only 5 of 19 group III (A delta fiber) endings. By contrast, bradykinin (0.5-1.5 microgram/kg) stimulated 17 of 33 group IV endings and 9 of 19 group III endings. Impulse activity for the 24 group IV afferents stimulated by capsaicin increased from 0.7 +/- 0.1 to a peak of 9.3 +/- 1.4 imp/sec. Firing started 6 +/- 1 seconds after injection and remained above control levels for 24 +/- 5 seconds. Capsaicin had no significant effect on the firing rate of 30 group I and II muscle afferents. Our results suggest that group IV muscle afferents are primarily responsible for causing the reflex increases in cardiovascular function evoked by injecting capsaicin into the arterial supply of the skinned hindlimb of dogs. Moreover, capsaicin is likely to be a useful pharmacological tool with which to determine the reflex autonomic effects caused by stimulation of group IV muscle afferents.
Comparison of the adrenal and renal responses to angiotensin II fetal lambs and adult sheep.
Authors: Robillard J E , Gomez R A , VanOrden D , Smith F G
Published: June 2012

The adrenal and renal responses to similar increases in plasma angiotensin II (AII) were studied in chronically catheterized fetal lambs (112-131 days gestation: term 145 days) and adult nonpregnant sheep. The rate of AII infusion was adjusted to compare the effect of similar rises in plasma AII concentration between fetuses and adult ewes. Increases in plasma AII were associated with a decrease in plasma renin activity (PRA) in both fetuses (5.55 +/- 1.53 to 2.11 +/- 0.59 ng/ml per hr, P less than 0.05) and adult ewes (1.28 +/- 0.34 to 0.62 +/- 0.16 ng/ml per hr, P less than 0.05), but the percent changes in PRA for similar increases in plasma AII were not different when fetuses were compared to adult ewes. Contrary to the effect of AII on PRA, the increase in plasma AII did not produce parallel changes in plasma aldosterone concentration when fetuses were compared to adult ewes. The percent changes in plasma aldosterone concentration for similar increases in AII concentration were significantly higher in adult ewes (+165 +/- 37%) than in fetuses (+58 +/- 15%)(P less than 0.01). Finally, there were no significant changes in fetal urinary excretion of PGE and PGF2alpha when a significant rise (P less than 0.05) was observed in adult ewes at the highest level of plasma AII concentration. In summary, the present results tend to suggest that there are differences between fetuses and adult ewes in the response to AII, the response being smaller in fetuses.
Coronary vasodilation after a single ventricular extra-activation in the conscious dog.
Authors: Schwartz G G , McHale P A , Greenfield J C
Published: June 2012

This study was undertaken to determine if coronary blood flow can be regulated in response to a transient increase in cardiac metabolic demand. Eight conscious dogs with experimentally produced complete heart block, a chronically implanted electromagnetic flow probe on the left circumflex coronary artery, and fluid-filled catheters for measurement of left ventricular and aortic pressures were studied. At a paced heart rate of 60 beats/min, a single ventricular extra-stimulus was introduced with a delay of 150-200 msec from the preceding R-wave. The extra-stimulus produced a ventricular extra-activation, but not a discrete mechanical extra-systole. The ensuing beats exhibited systolic potentiation, manifest by a 50 +/- 8% increase from control in maximum left ventricular dp/dt in the first potentiated beat, presumably accompanied by increased myocardial oxygen demand. In the diastole immediately following the first potentiated systole, the coronary vascular resistance index (mean aortic pressure/mean coronary flow in that diastole) fell significantly from control by 12 +/- 2%. The results indicate that a transient increase in cardiac metabolic demand is followed immediately by a compensatory coronary vasodilation that occurs within the same cardiac cycle.
Effects of pH on Na+-Ca2+ exchange in canine cardiac sarcolemmal vesicles.
Authors: Philipson K D , Bersohn M M , Nishimoto A Y
Published: June 2012

Using highly purified sarcolemmal vesicles isolated from dog ventricles, we examined the effects of pH on Na+-Ca2+ exchange. The initial rate of Nai+-dependent Ca2+ uptake is a sigmoid function of pH. The Ca2+ uptake is inhibited at pH 6 and stimulated at pH 9 (as compared with uptake at pH 7.4). This dependence on pH suggests that the ionization state of a histidine residue may be important in Na+-Ca2+ exchange. The effects of H+ on Nai+-dependent Ca2+ uptake are partially competitive with Ca2+, although this relationship is complex. Nao+-dependent Ca2+ efflux is also sensitive to H+ and increases monotonically with pH. These effects of pH appear to be due to intrinsic interactions with the Na+-Ca2+ exchange system and are not due to an alteration of Na+-H+ exchange or membrane permeability. The effects of pH on vesicular Na+-Ca2+ exchange are apparent only at low Ca2+ and Na+ concentrations. Thus modulation of vesicular Na+-Ca2+ exchange by pH is manifest only under ionic conditions which exist intracellularly in intact myocardium. Since the negative inotropy caused by acidosis is thought to reflect a fall in internal pH, these results suggest that alteration of sarcolemmal Ca2+ transport (medicated by Na+-Ca2+ exchange) by internal pH may contribute to the regulation of myocardial contractility by pH.
Contribution of thromboxane to renal resistance changes in the isolated perfused hydronephrotic rabbit kidney.
Authors: Kawasaki A , Needleman P
Published: June 2012

Thromboxane A2 is not produced in normal rabbit kidneys, but its synthesis is induced in numerous renal pathological states. The presence of this potent vasoconstrictor could readily compromise renal hemodynamics. We found that the thromboxane synthetase inhibitor, OKY-1581 (sodium-3-[4,3-pyridylmethyl)phenyl]-2-methylacrylate) is effective in the perfused hydronephrotic kidney in selectively inhibiting thromboxane production without altering prostaglandin E2 or prostacyclin release. The vasoactive peptides bradykinin and angiotensin cause the hydronephrotic kidney to produce thromboxane A2, which results in a profound renal vasoconstriction which is reversed by pretreatment with OKY-1581. Thus, OKY-1581 provides a powerful tool which can be used to assess the participation of thromboxane in pathophysiological states and to ascertain the therapeutic potential of thromboxane synthetase inhibitors in numerous disease states.
Electrotonic interactions across an inexcitable region as a cause of ectopic activity in acute regional myocardial ischemia. A study in intact porcine and canine hearts and computer models.
Authors: Janse M J , van Capelle F J
Published: June 2012

We recorded 60 DC simultaneous electrograms from isolated porcine and canine hearts in the first minutes after coronary occlusion. Ventricular premature beats (VPB) originated from the normal side of the ischemic border, which was frequently separated from the central ischemic area showing delayed activity by a small zone of inexcitable tissue. We attempted in a computer model to generate VPB's at one side of an area showing conduction block. In computer simulations,,, the presence of elements capable of automatic activity greatly facilitated the induction of VPB's. By coupling automatic elements to nonautomatic elements, overt pacemaking activity could be suppressed. Subthreshold depolarizations transmitted through a zone of conduction block could, when properly timed, trigger the latent automatic elements into overt automatic activity, resulting in single or repetitive VPB's. The ventricular premature beats in the intact hearts with acute regional ischemia may be caused by "triggered automaticity" in which the trigger is provided by the "injury current" flowing from ischemic cells showing delayed repolarization via a segment of inexcitable ischemic cells in the border zone to normally perfused cells with suppressed automaticity.
Determination of coronary collateral flow by a load line analysis.
Authors: Wyatt D , Lee J , Downey J M
Published: June 2012

We have examined the feasibility of determining coronary collateral blood flow in an open-chest dog by a "load line" type of analysis as is often employed to analyze transistors and vacuum tubes. The load line equation states that collateral flow is given by the quantity: [Formula: see text] where PcP is peripheral coronary pressure, AOP is aortic pressure, Qret is retrograde flow, and K is a constant. The validity of this equation was critically tested in a series of dog experiments in which the collateral vessels were found to approximate a linear resistance, the source pressure for the collaterals (K in the equation) was found to be 0.8 of aortic pressure, and the retrograde flow with zero back pressure was found to account for all of the collateral flow. Finally, we found that estimates from the equation correlated well with direct microsphere measurements of collateral flow. All of these findings support the use of the proposed technique which determines collateral flow by three easily measured laboratory parameters.
Effects of coronary arterial pressure on left ventricular end-systolic pressure-volume relation of isolated canine heart.
Authors: Sunagawa K , Maughan W L , Friesinger G , Guzman P , Chang M S , Sagawa K
Published: June 2012

In the excised canine left ventricle, the end-systolic pressure-volume relationship (ESPVR) has been shown to be approximately linear over the working range of loading conditions when coronary arterial pressure (CAP) is maintained constant, independent of loading conditions. To investigate the ESPVR under the more intact physiological condition in which the CAP varies with loading on the left ventricle, we studied the effect of changes in CAP on the ESPVR in 10 excised cross-circulated canine ventricles which were contracting isovolumically. The ESPVR, determined from isovolumic contractions at four different volumes, was reasonably independent of CAP as long as CAP remained above a critical pressure (67.0 +/- 22.1 mm Hg). Below this pressure, the slope of ESPVR decreased although the volume axis intercept (V0) remained unaltered. These findings indicate that under physiological conditions, where there is a close coupling of CAP to systolic left ventricular pressure, the ESPVR should become nonlinear in the low preload or afterload regions. When CAP was varied with the left ventricular pressure in five ventricles, the ESPVR indeed became nonlinear in the low-load region. We conclude that the ESPVR in intact conditions is reasonably linear in the physiological load range, but it can be nonlinear in the low-load range.
High force development and crossbridge attachment in smooth muscle from swine carotid arteries.
Authors: Dillon P F , Murphy R A
Published: June 2012

In experiments designed to achieve maximal activation, the active force/cell cross-sectional area in tissues prepared from the swine carotid media was 6.7 +/- 0.3 (sd) X 10(5) N/m5. This value exceeds that reported for other vertebrate muscle cells and is striking because of the low smooth muscle myosin content. The hypothesis that high force generation may, in part, reflect an increase in the crossbridge duty cycle, i.e., the fraction of the cycle during which force is generated, was tested by determining the rate of force redevelopment after a step shortening and the ration of the load-bearing capacity of the contractile system to the developed stress during the course of isometric contractions. Maximal crossbridge cycling rates estimated by the rate of force redevelopment occurred 30 seconds after the onset of a high K+-induced contraction, and decreased thereafter, although the load-bearing capacity or maximum active stress was maintained. These results from isometric experiments support the hypothesis and provide further evidence that attached, non-cycling crossbridges contribute to force maintenance in tonically contracting arterial smooth muscle.
Effects of duration and severity of arterial hypertension and cardiac hypertrophy on coronary vasodilator reserve.
Authors: Wangler R D , Peters K G , Marcus M L , Tomanek R J
Published: June 2012

Cardiac hypertrophy is associated with a decrease in coronary reserve. However, factors which may modulate the interaction between myocardial growth and vascular proliferation, such as duration and severity of hypertrophy, have not been evaluated. We measured myocardial perfusion with microspheres in conscious, chronically instrumented. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats at 3, 7, and 15 months of age; and in SHR stroke-prone (SHR-SP) rats at 13-14 months of age. Myocardial perfusion was measured with microspheres in awake rats at rest and during maximal coronary dilation produced by dipyridamole infusion (2.0 mg/kg per min, iv). Arterial pressure was significantly elevated (P less than or equal to 0.05) in all hypertensive groups (vs. age-matched WKY), both at rest and during dipyridamole infusion. Left ventricular mass in the SHR rats was increased significantly (P less than or equal to 0.05) by 14%, 28%, and 29% at 3, 7, and 15 months, respectively. Left ventricular mass in the SHR-SP group was increased by 50% (P less than or equal to 0.05) compared to the 15-month-old WKY. Left ventricular minimal coronary vascular resistance (per gram) was significantly greater (P less than or equal to 0.05) in SHR at 7 months, and in the SHR-SP group (66% and 60%, respectively). Right ventricular minimal coronary vascular resistance was significantly greater (P less than or equal to 0.05) in SHR at 7 and 15 months (50%), and in the SHR-SP group (122%), compared to 15-month-old WKY. The results indicate the following: (1) the increase in minimal coronary vascular resistance between SHR and WKY rats was greatest when left ventricular hypertrophy peaked (7 months) and was no longer present after left ventricular hypertrophy had stabilized. (2) In 14-month-old SHR-SP rats, with more severe left ventricular hypertrophy and hypertension, minimal coronary vascular resistance was considerably higher than in SHR of approximately the same age. (3) Long-term arterial hypertension was associated with a higher right ventricular minimal coronary vascular resistance. Resistance appeared to change in proportion to the severity of hypertension, and the changes were independent of the presence of right ventricular hypertrophy.
Regulation of large coronary arteries by beta-adrenergic mechanisms in the conscious dog.
Authors: Vatner S F , Hintze T H , Macho P
Published: June 2012

We examined, in conscious dogs, the effects of beta-adrenergic stimulation on measurements of left circumflex coronary arterial diameter and blood flow and on calculations of late diastolic coronary resistance (LDCR) and left circumflex coronary internal cross-sectional area (CSA). Isoproterenol (0.1 microgram/kg) initially decreased mean arterial pressure by 25 +/- 2% (mean +/- SEM), and LDCR by 62 +/- 4%, and increased heart rate by 82 +/- 10%, left ventricular (LV) dP/dt by 79 +/- 12%, and mean coronary blood flow by 85 +/- 5%, while CSA rose slightly. The peak effects on CSA (24 +/- 2%) occurred later, along with decreases in mean arterial pressure (7.4 +/- 1.0%) and LDCR (25 +/-5.3%) and increases in coronary blood flow (14 +/- 2%), LV dP/dt (12 +/- 3%), and heart rate (24 +/- 4%). Pirbuterol (1.0 microgram/kg) induced changes that were qualitatively similar to those induced by isoproterenol. Prenalterol (20 micrograms/kg), a cardioselective beta 1-adrenergic receptor agonist, did not affect mean arterial pressure, but increased heart rate by 40 +/- 5%, LV dP/dt by 72 +/- 10%, mean coronary blood flow by 34 +/- 11%, and CSA by 26 +/- 3%, and decreased LDCR by 29 +/- 5+. Isoproterenol and pirbuterol, but not prenalterol, increased coronary sinus O2 content and decreased A-VO2 difference. After beta 1-adrenergic receptor blockade with atenolol (1 mg/kg), prenalterol no longer induced significant effects, whereas isoproterenol and pirbuterol decreased mean arterial pressure similarly to what was observed prior to blockade, but did not increase LV dP/dt, and induced attenuated increases in mean coronary blood flow, CSA, and decreases in LDCR. Thus, in the intact, conscious animal, large coronary arteries are regulated by beta-adrenergic mechanisms. Surprisingly, a major fraction of large coronary arterial dilation appeared to be either directly or indirectly due to beta 1-adrenergic receptor mechanisms, although beta 2-adrenergic effects were also significant.
Calcium depletion in rabbit myocardium. Ultrastructure of the sarcolemma and correlation with the calcium paradox.
Authors: Frank J S , Rich T L , Beydler S , Kreman M
Published: June 2012

The ultrastructure of the Ca-depleted myocardial sarcolemma (via Ca-free and Ca-free plus EGTA perfusion at 28 degree C and 37 degree C) was studied in the vascularly perfused interventricular septum of the rabbit. Thin-section and freeze-fracture electron microscopy was used. Two major structural defects in the sarcolemma were found. (1) Ninety percent of the Ca-depleted cells have between 30 and 40% of their glycocalyx separated from the bilayer. With tannic acid staining, the separation is seen to occur between the external lamina and the surface coat. (2) Freeze-fracture data showed an apparent decrease in intramembrane particles on the P face of unidirectionally shadowed replicas. Quantitation of rotary-shadowed replicas showed no decrease in density of intramembrane particles. It was concluded from this that there was no loss of intramembrane particles, but rather a reorientation in the plane of the bilayer after Ca depletion. Both glycocalyx and bilayer changes were present after perfusion of the heart for only 5 minutes (37 degree C) with Ca-free perfusate. With low temperature and Cd substitution, separation of the glycocalyx occurred in less than 1% of the cells. After Ca depletion at 18 degree C, the density of intramembrane particles on the P face was not significantly different from controls. Cd substitution did not prevent the decrease total intramembrane particles per square micron, but the larger intramembrane particles had similar densities (154/micrometer2) as control (181/micrometer2), and as Ca-depletion with hypothermia (180/micrometer2). These findings indicate that structural changes in the glycocalyx and the bilayer can be totally prevented by hypothermia. Cd, on the other hand, prevents glycocalyx separation and affords protection only to the large intramembrane particles. Upon reperfusion with Ca, the intramembrane particles undergo the further alteration of aggregation, while numerous vesicles can be seen in the fracture plane of the membrane.
Effects of extracellular calcium ions, verapamil, and lanthanum on active and passive properties of canine cardiac purkinje fibers.
Authors: Pressler M L , Elharrar V , Bailey J C
Published: June 2012

The effects of alteration of extracellular calcium ion concentration ([Ca++]o) were studied in isolated false tendons using microelectrode techniques. Several determinants of cellular excitability and conduction velocity were affected by extracellular calcium. Increasing [Ca++]o from 2 to 8 mM resulted in: (1) a progressive decrease in interelectrode conduction velocity (2) a 7-mV shift of the maximum upstroke velocity-membrane potential relation toward less negative potential, (3) an increase in rheobasic current, (4) a 14-mV shift of the voltage threshold for all-or-none depolarization to less negative potentials, (5) a 52% increase in internal longitudinal resistance per unit length, and (6) a 27% decrease in the capacitance filled by the foot of the action potential from 4.90 to 3.56 microF/cm2. Blockade of the slow inward current by Mn++ or verapamil did not alter the [Ca++]o-induced effects on the maximum upstroke velocity-membrane potential relation. Cable properties were determined during alteration of [Ca++]o in the presence of verapamil (3 X 10(-6) and 1 X 10(-5) M) or in the presence of La+++ (0.2 mM). Verapamil increased membrane resistance X unit length but did not affect internal longitudinal resistance per unit length. La+++ had no effects on either membrane resistance X unit length or internal longitudinal resistance per unit length. Verapamil did not block the increase in ri induced by elevation of [Ca++]o. However, no change in ri occurred during an increase of [Ca++]o when La+++ was present. The results suggest that [Ca++]o-induced changes in internal longitudinal resistance may occur by the influx of calcium ions through the Na+/Ca++ exchange mechanism.
Role of endothelial cell cytoskeleton in control of endothelial permeability.
Authors: Shasby D M , Shasby S S , Sullivan J M , Peach M J
Published: June 2012

Increased permeability of the pulmonary microvasculature is felt to cause acute noncardiogenic lung edema, and histological studies of edematous lungs show gaps between apparently healthy endothelial cells. To determine whether alterations in endothelial cell cytoskeletons would alter endothelial permeability, we exposed monolayers of pulmonary artery endothelial cells grown on micropore filters to cytochalasin B or D. Cytochalasin exposed monolayers demonstrated a 2- to 3-fold increase in endothelial permeability that was readily reversible by washing the monolayers free of cytochalasins. Parallel phase contrast and fluorescence microscopy demonstrated retraction of cell cytoplasm and disruption of bundles of microfilaments in cytochalasin exposed cells. These changes also were readily reversed after washing the cells free from cytochalasins. To test the relevance of these findings to an in situ microvasculature, we added cytochalasin B to the perfusate of isolated rabbit lungs and observed that cytochalasin B caused a high permeability lung edema. These studies suggest that endothelial cell cytoskeletons may be important determinants of endothelial permeability.