bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of positron emitters in vivo characterized with a beta probe
Authors: Lerch R. A. , Ambos H. D. , Bergmann S. R. , Sobel B. E. , Ter-Pogossian M. M.
Published: December 2017

To facilitate characterization of regional myocardial kinetics of positron-emitting tracers in vivo without distortion by activity outside the region of interest, a probe was developed and evaluated for monitoring radioactivity by detection of positrons themselves. These particles (beta particles) have a maximal range in tissue of only few millimeters rather than the larger range of gamma photons emitted as a result of positron annihiliation. Regional myocardial time-activity curves were determined in open-chest dogs after intracoronary injection of 0.5-1.5 mCi [15O]H2O, a tracer used for measurement of myocardial blood flow, or 6.0-8.0 mCi [11C]palmitate, a tracer used for noninvasive assessment of myocardial metabolism. Time-activity curves after [11C]palmitate injection clearly delineated specific components of myocardial tracer clearance previously identified in vitro in isolated perfused hearts. Myocardial washout of [15O]H2O was monoexponential for more than 2 min without distortion induced by recirculating tracer in ventricular blood. Reproducibility of measured tracer clearance rates during monoexponential clearance was high based on duplicate determinations for both tracers. The beta-detector probe developed overcomes several intrinsic limitations of gamma-probe systems or well counting of serial myocardial biopsies for studies of positron-emitting tracers in vivo and should facilitate assessment of factors of influencing tracer kinetics in vivo relevant to positron-emission tomography.
Importance of injection site for coronary blood flow determinations by microspheres in rats
Authors: Wicker P. , Tarazi R. C.
Published: December 2017

Because coronary blood flow (CBF) determinations require that blood and microspheres be uniformly mixed in the root of the aorta, we developed a technique of left-atrial (LA) catheterization in rats and compared the variability of results obtained by LA injection and left-ventricular (LV) injection as regards systemic [cardiac output (CO)], proximal (coronary), and distal (renal, cerebral) flows in anesthetized animals. CBF values averaged 410 +/- 224 and 358 +/- 99 (SD) ml.min-1.100 g-1 from LV and LA injection, respectively, or 5.7 +/- 2.9 and 4.9 +/- 1.3 (SD) %CO. The variability with LA injection was significantly lower than with LV injection as shown by the marked differences in standard deviations obtained with the two methods (224 vs. 99 ml.min-1.100 g-1 or 2.9 vs. 1.3 %CO, P greater than 0.01). In contrast, no significant difference in variability was found for either CO or more distal regional flows. These results indicate that LV injections might be adequate for systemic flow and regional flows to relatively distal beds but that accurate measurements of CBF require LA injection of microspheres.
Effect of tilting on adipose tissue vascular resistance and sympathetic activity in humans
Authors: Linde B. , Hjemdahl P.
Published: December 2017

To study baroreceptor reflex control of human adipose tissue circulation, head-up tilting (to 80 degrees for 10 min) was performed in eight healthy volunteers. Blood flow in subcutaneous adipose tissue and skeletal muscle on the arm was evaluated by local clearance of 99mTcO4-. The isotope depots were maintained at heart level throughout the experiment. Tilting induced rapid increases in plasma norepinephrine and epinephrine, heart rate, and diastolic but not mean arterial pressure. There was rapid vasoconstriction in both adipose tissue and skeletal muscle followed by vasoconstrictor escape during tilting and a brief period of hyperemia after tilting. The vascular resistance index [mean arterial pressure/disappearance rate (kappa) of 99mTc (%/min)] increased from 16 +/- 2 to 41 +/- 9 U (P less than 0.05) in adipose tissue and from +/- 3 to 44 +/- 15 U (P less than 0.05) in skeletal muscle. Tilting caused an initial decrease followed by an increase in arterial plasma glycerol without concomitant changes in plasma immunoreactive insulin. The vascular and glycerol responses to tilting closely resemble canine subcutaneous adipose tissue responses to sympathetic nerve stimulation. The present experiments show baroreceptor reflex-induced vasoconstriction in human adipose tissue, which presumably is mediated by sympathetic nerve activity.
Isoproterenol-induced myocardial dysfunction in dogs with coronary stenosis
Authors: Gallagher K. P. , Kumada T. , Battler A. , Kemper W. S. , Ross J.
Published: December 2017

Stress-induced regional myocardial ischemia in the presence of mild coronary stenosis was studied in five dogs 2-4 wk after implantation of pairs of ultrasonic crystals to measure left ventricular wall thickening (% delta WT) and subendocardial segmental shortening (% delta L). Isoproterenol (0.2 micrograms.kg-1.min-1) was infused before and after production of coronary stenosis, which produced no resting dysfunction. During isoproterenol infusion with coronary stenosis % delta WT and subendocardial % delta L were significantly decreased although blood flow was comparable to conditions at rest, indicating that the demand for blood flow exceeded supply. Linear regression analysis of mean transmural blood flow versus % delta WT during isoproterenol demonstrated that wall thickening was significantly related to changes in mean blood flow: y (percentage wall thickening) = 27.5 X (transmural blood flow) -8.2 (r = 0.83); likewise % delta L was significantly related to subendocardial blood flow during isoproterenol infusion: y (percentage shortening) = 17.1 X (subendocardial blood flow) -0.4 (r = 0.85). These results indicate that both regional % delta WT and % delta L sensitively reflect the adequacy of myocardial perfusion even during stress-induced changes in myocardial O2 demands and blood flow.
Inhibition by theophylline of the early component of canine ventricular contraction
Authors: Endoh M. , Iijima T. , Motomura S.
Published: December 2017

Changes in mechanical characteristics of the isolated canine ventricular muscle were investigated during interaction of isoproterenol with theophylline or caffeine. An early and a late component with time to peak tension of 80 and 150 ms, respectively, were differentiated in a single contraction of the muscle stimulated at 0.5 Hz at 37 degrees C during the interaction of isoproterenol and theophylline, or isoproterenol and caffeine. Isoproterenol increased preferentially the early component and affected only slightly the late one. Theophylline or caffeine elevated the early component less than the late one. In the presence of theophylline + isoproterenol or caffeine + isoproterenol the peak tension was achieved by a late component, whereas the increase in the early one induced by isoproterenol in 3 X 10(-7) M and higher was depressed significantly. During the interaction the rate of twitch relaxation was accelerated further rather than depressed. Changes in action potential indicate that the calcium influx via the myocardial cell membrane during depolarization was increased: the peak plateau potential was significantly elevated by theophylline alone and further by theophylline + isoproterenol. These results indicate that theophylline and caffeine (2 mM) may act intracellularly to inhibit the isoproterenol-induced promotion of the early component without impairing the isoproterenol-induced acceleration of relaxation in the canine ventricular muscle.
Alterations in mechanical properties of rat papillary muscle during maturation
Authors: Capasso J. M. , Remily R. M. , Sonnenblick E. H.
Published: December 2017

Myocardial performance was measured during maturation using isolated left ventricular papillary muscles from female Wistar rats. Muscles were studied isometrically and isotonically, stimulated at 0.1 Hz, perfused with Tyrode solution having an external calcium concentration of 2.4 mM, and maintained at 30 degrees C. Heart and body weight increased rapidly during the first 6 mo and then stabilized. Peak isometric developed tension, time to peak isometric developed tension, and time to half relaxation increased substantially during the 1- to 10-mo period with little change in the peak rate of isometric tension rise and peak rate of isometric tension fall. No difference in resting tension was noted among any groups. Force-velocity curves from muscles from 2-, 6-, and 10-mo-old animals show a significant age-related decrease in the isotonic velocity of shortening by as much as 21% between 2 and 10 mo of age. Thus maturation profoundly affects the contractile state of cardiac muscle, with force of contraction increasing and velocity of shortening decreasing as a function of age in the rat.
Myocardial responses to alpha-adrenoceptor stimulation with methoxamine hydrochloride in lambs
Authors: Lee J. C. , Fripp R. R. , Downing S. E.
Published: December 2017

This study was undertaken to evaluate the effects of methoxamine on left ventricular performance, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) in lambs. Measurement of maximum rate of rise of left ventricular pressure (LV dP/dtmax), left ventricular end-diastolic pressure (LVEDP), CBF, and MVO2 were made in nine lambs using a hemodynamically controlled preparation. The lambs were given atropine sulfate (1 mg), tetraethylammonium chloride (100 mg), and practolol (4 mg/kg) to provide parasympathetic, ganglionic, and beta-adrenergic blockades. Aortic pressure and blood flow and heart rate were held constant in each lamb. Dose-related increases in LV dP/dtmax and decreases in LVEDP were observed after progressively larger doses of methoxamine ranging from 0.4 to 6.0 mg/kg were given. These positive inotropic responses were eliminated by giving phentolamine (2 mg/kg). CBF, myocardial O2 extraction, and MVO2 did not change significantly. A positive inotropic action of methoxamine was also demonstrated in five additional animals by obtaining ventricular function curves. Initially the mean stroke volume at LVEDP 10 cmH2O (SV10) was 4.11 +/- 0.16 (SE) ml. This value increased to 5.09 +/- 0.28 ml after methoxamine (P less than 0.01). After phentolamine, SV 10 fell to 4.37 +/- 0.08 ml (P less than 0.05). These observations support the hypothesis that alpha-adrenergic receptors are present and mediate a substantial positive inotropic action on neonatal lamb myocardium.
Effects of antihistamines and indomethacin on hyperosmolar-induced vasodilation
Authors: Pinsky M. R. , Smith P. L. , Bleecker E. R. , Bromberger-Barnea B.
Published: December 2017

The circulatory effects of iv injections of hyperosmolar solutions were studied both in intact dogs with aortic flow probes and in dogs using a standard right heart-bypass preparation. Serial iv injections of 20 ml of 10% NaCl or 50 ml of 25% mannitol produced reproducible episodic vasodilation characterized by falls in mean aortic pressure from 99 +/- 10 (SE) to 61 +/- 6 Torr and increases in aortic flow from 2.20 +/- 0.06 1/min to 3.12 +/- 0.28 (P less than 0.01). Systemic vascular resistance decreased (P less than 0.01) with each injection and serum osmolarity increased (P less than 0.01); however, there was a poor correlation between these two variables (r = -0.24). Because the mechanism of these physiological changes is unclear, the following experiments were performed to determine whether they were due to the release of vasoactive chemical mediators. We measured arterial and venous plasma histamine, a mediator released systemically in IgE-mediated anaphylactic reactions, but found no changes in histamine levels. Furthermore, pretreatment with both H1 and H2 blockers (diphenhydramine and cimetidine), agents that blocked histamine-induced hypotension, did not prevent hyperosmolar vasodilation. Also, indomethacin (a cyclooxygenase pathway inhibitor of prostaglandin synthesis) did not affect hyperosmolar vasodilation or the fall in systemic vascular resistance. Therefore, hyperosmolar vasodilation is not caused by the systemic release of histamine or by the effects of prostaglandins. The mechanism of these reactions is unknown, but it may be due to direct local effects of hyperosmolar solutions on vascular smooth muscle, perhaps mediated by local fluid and electrolyte shifts.
Modulation of rabbit carotid baroreflex during positive end-expiratory pressure
Authors: Sepe F. J. , Magnusson M. R. , Stinnett H. O.
Published: December 2017

Modification of carotid baroreflex heart and vascular responses during increased lung positive end-expiratory pressure (PEEP) were measured anesthetized aortic-denervated rabbits. Static carotid intrasinus pressure (ISP) was varied in increments of 12.5 mmHg over 25-140 mmHg during lung inflation conditions ranging from spontaneous breathing (SB) to positive-pressure respiration at 0.0-7.5 cmH2O PEEP. To distinguish cardiopulmonary vagally and nonvagally mediated influences, heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were measured and compared before and after sequential vagotomy and beta- and alpha-receptor blockade. When compared with responses of SB animals the HR-ISP relationship was not significantly altered during controlled respiration (CR) with PEEP before or after vagotomy. With CR and then PEEP, MAP-ISP relationship curves and linear slope values (ISP range 62-113 mmHg) were significantly depressed when compared with those of SB rabbits. Before vagotomy slope values were -1.61 (SB), -1.22 (CR + 0.0 cmH2O PEEP), and -0.82 (CR + 7.5 cmH2O PEEP); respective values after vagotomy were -2.26, -0.96, and -0.64. Results of CO and TPR responses during low ISP and PEEP demonstrated components of both vagally and nonvagally mediated influences from inflation sensitive cardiopulmonary receptors.U
New method for measuring QRS duration using high-frequency electrocardiography
Authors: Bhargava V. , Goldberger A. L.
Published: December 2017

Definition of QRS onset and offset is a basic problem in electrocardiography. Current techniques rely either on subjective estimates or on computer algorithms using QRS derivative or spatial vector velocity parameters. We developed a spectral method based on the observation that the QRS complex, unlike the P wave, PR segment, or ST-T complex is comprised of significant frequencies greater than 50 Hz. Accordingly, we adapted a microprocessor-based electrocardiograph (ECG) system with a signal-averaging program to reduce noise and a 50-300 Hz digital filter. Leads I and aVF were simultaneously acquired by computer in 40 subjects with a wide range of QRS duration (55.5-161 ms). Excellent correlation (r = 0.98) was noted between high-frequency QRS duration measurement and careful visual determinations made at high gain and expanded time scale. The high-frequency ECG appears to provide an objective physiological definition of the QRS complex based on spectral content not on morphology or slope.
On-line cardiac mapping: an analog approach using video and multiplexing techniques
Authors: Parson I. , Mendler P. , Downar E.
Published: December 2017

A video and multiplexing system is described that provides a source of display in real-time, slow-motion, and stop-frame modes of ventricular activation. The displayed image, consisting of a matrix of 112 dots, is arranged to represent a polar projection of the ventricles. The dots brighten at the time of local cardiac activation, which is sensed by an electrode array monitoring the myocardium. Experiments in in situ canine hearts have provided detailed depictions at 8.3-ms intervals of the ventricular activation sequence during sinus and ventricularly paced rhythm. The origin of ventricular paced beats can be located with an accuracy of less than 5 mm. Coronary occlusion produces a defect in the displayed image that outlines the ischemic area and demonstrates regions of delayed conduction. This approach to ventricular mapping provides a detailed on-line display of activation with a recording capacity of 1 h. The system offers a practical, inexpensive alternative to computerized methods of investigating ventricular arrhythmias in both the experimental and intraoperative environment.
Effects of hemorrhage on umbilical venous return and oxygen delivery in fetal lambs
Authors: Itskovitz J. , Goetzman B. W. , Rudolph A. M.
Published: December 2017

The effect of acute hemorrhage (21.7 +/- 1.6%, mean +/- SE of the estimated blood volume) on the distribution of the umbilical venous return (UVR) and oxygen delivery to fetal organs (radionuclide microsphere technique) was studied in 10 chronically catheterized fetal lambs. Hemorrhage decreased UVR and total oxygen delivery to the fetus by 23 and 28%, respectively (P less than 0.001). A greater proportion of the UVR bypassed the liver through the ductus venosus (DV) (P less than 0.01). Consequently, DV blood flow was relatively maintained, and liver blood flow and oxygen delivery derived from the UVR decreased by 41 and 45%, respectively (P less than 0.002). The proportion of cardiac output constituted by DV blood increased by 30% (P less than 0.01). The changes in the distribution of the DV blood were similar to the changes in the distribution of cardiac output. As a result the proportion of organ blood flow and oxygen delivery derived from DV blood increased by 30% in both the upper and lower body organs. These studies show that fetal hemorrhage has a marked effect on the distribution of the UVR to the liver. The preferential distribution of the DV blood to the heart and brain is maintained but not enhanced. Our results indicate that changes in distribution of the DV-derived blood and oxygen following fetal hemorrhage is determined primarily by the responses of the arterial circulation, i.e., circulatory afterload.
Dimensional analysis of right and left ventricles during positive-pressure ventilation in dogs
Authors: Cassidy S. S. , Mitchell J. H. , Johnson R. L.
Published: December 2017

Our purpose was to determine the effects of controlled ventilation with positive end-expired pressure (PEEP) on ventricular dimensions and to relate changes in shape to changes in stroke volume and left ventricular volumes. Left and right ventricular dimensions were measured using biplane cinefluorography of dogs with radiopaque markers implanted in their hearts, and left ventricular volumes were derived from left ventricular dimensions by assuming that the left ventricle conformed to the shape of a nonprolate ellipsoid. As PEEP increased from 0 to 5, 10, and 15 cmH2O, stroke volume fell 36%, and all three left ventricular end-diastolic dimensions fell, with apex-base falling 5%, anterior-posterior falling 7%, and septal-lateral falling nearly twice as much, 12%. This resulted in a 11.3 cm3 fall in left ventricular end-diastolic volume. The right ventricular end-diastolic dimensions changed in opposite directions with respect to each other as the level and PEEP was raised to 15 cmH2O; one axis fell 3.2 mm, and the midpoint of the right ventricular free wall moved outward by 1.7 mm. Thus the fall in cardiac output (and stroke volume) during PEEP was associated with a fall in left ventricular end-diastolic volume and a change both left and right ventricular configurations. It is not known whether the left ventricular septal-lateral narrowing is the consequence of lateral wall compression by the lungs or encroachment on the left ventricle by the septum.
Left ventricular dimensions and function during right ventricular pressure overload
Authors: Badke F. R.
Published: December 2017

The effects of right ventricular (RV) pressure overload on left ventricular (LV) function is controversial. Therefore, we examined LV dimensions and shortening after acute and chronic pulmonary artery (PA) constriction in six conscious dogs, preinstrumented with LV and RV catheters, an LV micromanometer, a PA inflatable cuff occluder, and ultrasonic crystals to measure an LV anteroposterior, a septal-lateral, and a free wall segment chord. Studies were performed before, immediately after, and 2, 4, and 6 wk after PA constriction. With acute cuff inflation, RV systolic- and end-diastolic pressures rose, but LV end-diastolic pressure fell. Both septal-lateral end-diastolic length and systolic shortening declined 4.1 +/- 0.7 mm and 5.9 +/- 2.3% respectively (P less than 0.01), whereas the anteroposterior and segment chords were unaffected. With chronic RV pressure overload septal-lateral shortening but not end-diastolic length returned to control levels. Also the first derivative of LV pressure (LV dP/dt) fell 540 +/- 164 mmHg/s by 6 wk compared with control, but this decline was reversed by volume expansion with dextran. We conclude that RV pressure overload displaces the septum toward the LV free wall; acutely this displacement is primarily at end diastole, but chronically it occurs at end systole as well, maintaining the septal contribution to LV ejection. Thus chronic RV pressure overload is associated with significant changes in LV diastolic shape but maintenance of normal LV function.
Diastolic myocardial stiffness in gradually developing left ventricular hypertrophy in dog
Authors: Serizawa T. , Mirsky I. , Carabello B. A. , Grossman W.
Published: December 2017

The effects of gradually developing left ventricular pressure overload on diastolic myocardial stiffness were studied in a chronic moderate hypertrophy model. A snug aortic band was placed beneath the left coronary artery in six puppies 4.5 wk of age, and hemodynamic studies were performed 33.5 wk later. In all six dogs, moderate pressure gradients (10-58 mmHg) developed across the constriction, and angiographic area of the aortic constriction was significantly smaller than for a control group, 4.9 +/- 0.5 vs. 8.4 +/- 0.8 mm2/kg, (mean +/- SE, P less than 0.05). Increases occurred in left ventricular (LV) wall thickness (1.08 +/- 0.07 vs. 0.83 +/- 0.04 cm, P less than 0.05), LV wall mass (5.2 +/- 0.3 vs. 4.1 +/- 0.2 g/kg, P less than 0.05), and wall thickness-to-radius ratio (0.67 +/- 0.04 vs. 0.50 +/- 0.03, P less than 0.01), whereas no differences were noted in LV end-diastolic pressure (11 +/- 1 vs. 9 +/- 1 mmHg), LV end-diastolic volume (LVEDV, 2.06 +/- 0.22 vs. 2.35 +/- 0.15 ml/kg) or ejection fraction (71 +/- 4 vs. 71 +/- 3%). The values of LV wall mass, LVEDV, and aortic constriction are normalized to body weight. Diastolic LV myocardial stiffness was examined in terms of the elastic stiffness-stress relations. There were small and insignificant differences in end-diastolic stress (17.3 +/- 1.5 vs. 20.4 +/- 3.8 g/cm2), myocardial stiffness constant (Km, 13.7 +/- 5.6 vs. 11.2 +/- 3.3), and end-diastolic elastic stiffness (221 +/- 67 vs. 221 +/- 79 g/cm2) between hypertrophied and control hearts. No significant differences in the elastic stiffness of hypertrophied and normal muscle were observed over the common stress range of 5-25 g/cm2. We conclude that moderate left ventricular hypertrophy in chronic, gradually developing pressure overload is an adaptation process associated with normal myocardial stiffness.
An extracorporeal reservoir device for continuous monitoring of tissue volume change
Authors: Chen H. I.
Published: December 2017

The conventional use of a gravimetric or plethysmographic method for continuous monitoring of tissue volume changes has some inherent problems related to organ exteriorization, denervation, and tissue handling. A new method using an extracorporeal reservoir is devised for indirect measurement of tissue volume changes. When the organ is perfused with constant flow and the venous outflow is collected in a reservoir, the reservoir volume reaches a steady level by pumping out equal amount of blood entering the reservoir. Under this condition, every perturbation causing a change in tissue volume will result in a reservoir volume change of the opposite direction. Two different pressure-regulating systems are also designed for the control of arterial perfusion pressure. Because volume change is not allowed to occur inside the regulating system, the device still guarantees that the reverse change in reservoir volume reflects the tissue volume change on alteration of arterial perfusion from constant-flow to constant-pressure condition. The method has been tested in six canine ileum segments by comparing the reservoir volume with the tissue volume recorded with direct gravimetric measurement. Experimental trials include venous pressure elevation, arterial perfusion changes, and intra-arterial infusion of vasoactive agents. The tests indicate that the tissue volume changes can be faithfully measured from the reverse change in reservoir volume. The technical advantages and possible applications of the reservoir method in the realm of hemodynamic and microcirculatory studies are also discussed.
Rat gracilis muscle preparation for combined macro- and microvascular research
Authors: Swain D. P. , Lalone B. J.
Published: December 2017

A skeletal muscle preparation for the study of single vessel and whole organ vascular responses is presented. After surgical isolation from anesthetized rats, the gracilis muscle preparation is autoperfused via cannulation circuits. This allows the measurement of, and experimental control over, such macrovascular parameters as arterial and venous pressures and total muscle blood flow. In addition, the preparation is thin enough to allow the simultaneous study of microvessels by transilluminated microscopy. Such dual capabilities allow the preparation to be used in a wide variety of investigations and, in particular, as a primary tool in correlating microcirculatory responses with those of the whole organ in experiments designed to elucidate local control mechanisms of skeletal muscle vasculature. An example of such is demonstrated for reactive hyperemia responses simultaneously obtained at arteriolar and muscle venous effluent locations.
Ion-selective electrode studies of cell Na components in vascular smooth muscle of WKY and SHR
Authors: Friedman S. M. , McIndoe R. A. , Spieckermann G.
Published: December 2017

Vascular smooth muscle cells of the rat tail artery were enriched with Na by overnight incubation at 10 degrees C in K-free physiological salt solution (K-free PSS). The cells were then returned to normal PSS in a series of steps so as to define the effect of varying temperature between 3 and 37 degrees C, the effect of ouabain, the effect of readmitting K+ in the continuing presence of ouabain, and, finally, the effect of removing ouabain in the continuing presence of K+. The effects were measured with flow-through Na+ and K+ glass-cannula electrodes as changes in a superfusate moving slowly past the artery. Where possible, confirmatory evidence was obtained by conventional incubations followed by chemical analysis of the tissues. About 10 mmol Na+/kg dry wt is transferred out of the cells when temperature is raised from 3 to 37 degrees C. Exposure of the tissue to ouabain while the tissue is still in the K-free state produces a further loss of about 8 mmol Na+/kg dry wt and 4 mmol k+/kg dry wt. Readmittance of K+ in the continuing presence of ouabain induces a further loss of about 25 mmol Na+/kg dry wt in exchange for an uptake of about 13 mmol K+ measured electrometrically or about 20 mmol K measured chemically. Finally, the removal of ouabain is followed by an extrusion of about 155 mmol Na+/kg dry wt in exchange for an uptake of 133 mmol K%. The ouabain-insensitive exchange of Na+ and K+ is enhanced in spontaneously hypertensive rats as compared with normotensive rats.
Effect of pulsatile pressure and metabolic rate on intestinal autoregulation
Authors: Shepherd A. P. , Riedel G. L.
Published: December 2017

In the intestine, raising venous pressure elicits a precapillary vasoconstriction that has been ascribed to a myogenic mechanism. Such myogenic responses occur more frequently and have a greater magnitude if arterial pressure is pulsatile. This laboratory reported that the ability of the gut to autoregulate blood flow in response to perfusion pressure manipulations is enhanced if metabolic rate is stimulated by transportable intraluminal solutes. Since both myogenic and metabolic mechanisms may participate in local control, we attempted to delineate the relative contributions the two mechanisms make to autoregulation. In one set of experiments, pulse pressures of 20 and 40 mmHg evoked a slight but statistically significant vasoconstriction. In a second series of experiments, pressure-flow curves were determined in isolated canine small bowel. The ability of the gut to autoregulate was compared at pulse pressures of 0, 20, and 40 mmHg and at basal and elevated metabolic rates. Altering pulse pressure had no systematic effect on the ability of the intestine to autoregulate blood flow. In contrast, increasing metabolic rate consistently enhanced autoregulation at each of the pulse pressures studied. Therefore, these results indicate that although a myogenic mechanism may best account for the response to elevated venous pressure, autoregulation as expressed in pressure-flow curves is more strongly influenced by the prevailing metabolic rate than by stretch stimuli such as arterial pressure pulsations.
Na+-induced intestinal interstitial hyperosmolality and vascular responses during absorptive hyperemia
Authors: Bohlen H. G.
Published: December 2017

The coupled active transport of Na+ with sugars and amino acids could cause intestinal villus interstitial hyperosmolarity, which contributes to absorptive hyperemia. However, for the villus hyperosmolarity to cause a major vascular response, a mild-to-moderate hyperosmolarity must occur in the vicinity of the major resistance vessels of the submucosa. Interstitial Na+ activity was measured throughout the small intestinal wall of rats with monensin ion-selective electrodes during glucose absorption. In the upper half of villi, the resting [Na+] was 201 +/- 5 (SE) mM and increased to 267 +/- 6 mM during luminal exposure to 25-300 mg/100 ml glucose. The submucosal resting [Na+] was 144 +/- 1 mM and increased to 177 +/- 3 mM during luminal glucose exposure. The time courses of Na+ appearance and submucosal arterial dilation were almost identical. Calculations of tissue osmolarity indicate an increase in villus osmolarity of 150-200 mosM and 79-90 mosM in the submucosa during glucose absorption. The data are interpreted to indicate that villus hyperosmolarity during glucose absorption increased submucosal osmolarity and a naturally occurring osmotic dilatory component of absorptive hyperemia could exist.
Evidence for persistent activation of cardiac slow channels in low-calcium solutions
Authors: Linden J. , Brooker G.
Published: December 2017

Action potentials were recorded from frog ventricular strips superfused with calcium-free solutions. Very long action potentials (3-60 s) were induced by chelating residual calcium with 1-5 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA). The kinetics of changes in action potential duration suggest that calcium influences action potential duration at an intracellular site. In low-calcium solutions isoproterenol was found to lengthen action potentials. The lengthening effect of isoproterenol became progressively greater as [Ca2+] was reduced by elevating [EGTA]. In the presence of 2 mM EGTA, 0.1 microM isoproterenol increased action potential duration from 4.3 +/- 0.4 to 43 +/- 14 s. Verapamil produced a greater than 90% reduction in the duration of very long action potentials (60 s) induced by EGTA, isoproterenol, or both. After rapid or prolonged depolarizations in low-calcium solutions the last 10-30 mV of repolarization took 10-15 s. We speculate that this slow phase of repolarization may be a manifestation of persistent slow channel activation. The data suggest that in low-calcium solutions slow channels can remain activated for many seconds.
Flow dependence of norepinephrine extraction by isolated perfused rat lungs
Authors: Roth R. A.
Published: December 2017

Disposition of perfused norepinephrine (NE) was studied in isolated rat lungs at several perfusate flows, including that occurring in vivo. Lungs were ventilated with 95% O2-5% CO2 and perfused at 37 degrees C with recirculating medium initially containing 90 nM [14C]NE. In agreement with previous studies the fraction of NE removed in a single pass through the pulmonary vasculature was 0.30 +/- 0.03 by lungs perfused at low flow (10 ml/min; 7.2 ml.min-1.g lung-1). This extraction ratio decreased with increasing flow, so that in lungs perfused at 45 ml/min (31.8 ml.min-1.g lung-1) the extraction ratio was 0.09 +/- 0.01. The concentration of NE metabolites in the perfusate reservoir increased with time of perfusion. The rate of appearance of deaminated and O-methylated metabolites in the recirculating perfusion medium was not markedly influenced by flow. NE that accumulated in lung was metabolized before reentry into the perfusion medium. These results indicate that extraction of NE by rat lung is markedly dependent on flow and suggest that removal of NE by lung is not highly efficient at normal organ perfusion rates.
Estimation of local myocardial stress
Authors: Janz R. F.
Published: December 2017

Two formulas are presented for estimating local average circumferential stress in the left ventricle from the cavity pressure and various quantities, available from the angiogram, which characterize the size and shape of the cavity and ventricular wall. The advantages of these formulas are as follows: 1) they are based on thick-wall shell theory; 2) they are intended for application at positions in the ventricular wall other than the base; and 3) they are based on a more general representation of ventricular geometry than a sphere, cylinder, or ellipsoid. Except for one location, both formulas predict average circumferential stresses that agree to within 25% with the corresponding stresses in a finite element model of an aneurysmal ventricle. In addition, at the equator of a thick-wall ellipsoid, the formulas are identical in form to a previously derived formula that has been shown to predict stresses that are in fair to good agreement with measured stresses in the open-chest dog heart.
Contractile behavior of rat myocardium after reversal of hypertensive hypertrophy
Authors: Capasso J. M. , Strobeck J. E. , Malhotra A. , Scheuer J. , Sonnenblick E. H.
Published: December 2017

The effects of renovascular hypertension and its reversal on the contractile performance of papillary muscles from rats has been examined. Hypertension of 10 wk duration caused a 48% increase in heart weight and significant prolongations of isometric time to peak tension (TPT), time to half relaxation, and time to peak shortening (TPS). A significant depression in the velocity of shortening was observed in the 10-wk group. However, muscles from hypertensive rats were still able to maintain normal levels of peak isometric developed tension and peak shortening; this may be due to the observed prolongation of TPT and TPS, respectively. In addition, calcium-activated actomyosin ATPase activity was depressed in hearts of hypertensive animals. Reversal of hypertension was studied at 20 wk after the onset of hypertension (10 wk of hypertension followed by 10 wk of normotension). Contractile and biochemical alterations observed in hypertensive animals were reversed in rats undergoing this regime. Thus reversal of a gradually applied pressure overload resulted in the regression of mechanical and biochemical abnormalities associated with the pressure overload myocardial hypertrophy.
Denervation of arterial chemoreceptors and baroreceptors in fetal lambs in utero
Authors: Itskovitz J. , Rudolph A. M.
Published: December 2017

Arterial baroreceptors and chemoreceptors were denervated in eight fetal lambs in utero. Carotid sinus and carotid body denervation was accomplished by stripping the carotid artery rostral and caudal to the origin of the occipital and lingual arteries. Aortic bodies were denervated by section of the superior laryngeal nerve and aortic nerve in the neck. The anatomy relevant to the technique is presented. The effectiveness of the denervation was tested by injection of 20 micrograms phenylephrine. The slowing of the fetal heart rate normally present in the intact lambs was abolished in the denervated fetuses. Denervation of the carotid and aortic chemoreceptors abolished the reflex bradycardia following injection of 200 micrograms cyanide or following acute hypoxemia produced by uterine blood flow reduction for 20 s. These results indicate that the baroreflex and chemoreflex can be elicited in utero and eliminated by the method we described. The preparation we present allows the study of the role of the arterial chemoreceptors and baroreceptors in normal fetal cardiovascular regulation and in fetal responses to stress.
Active hepatic capacitance responses to neural and humoral stimuli in dogs
Authors: Bennett T. D. , MacAnespie C. L. , Rothe C. F.
Published: December 2017

Active changes in hepatic capacitance were studied in pump-perfused dog livers during hepatic nerve stimulation or during intrahepatic arterial infusion of histamine (0.01-1 mg/l) or epinephrine (0.05 mg/l). Hepatic nerve stimulation at 5 pulses/s (pps) reduced hepatic blood volume by 76 +/- 39 (SD) ml/kg tissue and decreased the apparent hepatic compliance 36% from a control value of 25.6 +/- 9.3 ml.kg-1.mmHg-1, with constant flow perfusion. With a constant hepatic arterial pressure, 5 pps stimulation decreased hepatic arterial flow to 16% of control; the volume expelled was 91 +/- 33 ml/kg. Epinephrine caused hepatic artery constriction, the active expulsion of 71 ml/kg of blood, and a decrease of about 30% in hepatic compliance. Histamine dramatically reduced the hepatic vascular compliance, decreased the portal venous conductance, increased hepatic arterial conductance, and caused the apparent hepatic blood volume to double. Increased hepatic venous pressure, hepatic nerve stimulation, epinephrine, and, especially, histamine caused a significant filtration of fluid from the hepatic vasculature. We conclude that significant active capacitance changes and transsinusoidal fluid filtration can be induced in the canine liver by neural and hormonal stimuli.
Structure and function of specific regions in the canine atrioventricular node
Authors: Woods W. T. , Sherf L. , James T. N.
Published: December 2017

The functional subregions of the rabbit atrioventricular (AV) node have been examined in detail, but it has not been possible to subject the normal canine AV node to such rigorous scrutiny. Arterial perfusion and beveled microelectrodes have now allowed us to explore the anatomic and functional regions of the isolated canine AV node. The atria and AV junctional tissues of 20 young dogs were excised and selectively perfused with physiological solution through the nutrient arteries to the sinus node, AV node, and His bundle. AV node action potentials had shapes similar to those of the rabbit AV node and were conducted slowly (56 +/- 7 mm/s); slowest conduction (16 +/- 14 mm/s) was observed in the distal AV node where diastolic depolarization was always recorded and where maximum upstroke velocity of the action potential was slowest. From subsequent anatomic studies of the same preparations we found that the proximal region of the canine AV node was predominantly composed of interwoven slender transitional cells and that the distal region contained bundles of transitional cells and small but conspicuous aggregations of P-cells. The proximal portion of the canine AV node appeared to be organized for triage of atrial input during sinus rhythm. Electron microscopic examinations revealed numerous relatively long (greater than 1.0 micrometers) gap junctions between proximal AV node cells. The large gap junctions may provide an anatomic basis for electrotonic interaction during summation and conduction of AV node inputs. The distal AV node is the site of slowest AV conduction and also where most forms of AV junctional rhythm originate.
Ultrastructural and enzymatic development of fetal guinea pig heart
Authors: Rolph T. P. , Jones C. T. , Parry D.
Published: December 2017

The activities of some enzymes of glycolysis, the citric acid cycle, and amino acid metabolism have been measured in the fetal guinea pig heart over the last third of gestation and correlated with heart ultrastructural development. There is little change in glycolytic enzyme activity except for a two- to threefold increase in phosphofructokinase activity. Mitochondrial content and enzyme activities are low in the early fetal heart, and, although content is similar in the late fetus and adult, enzyme activities increase twofold postnatally, indicating fetal heart mitochondria are incompletely developed. The activities of aspartate and particularly alanine aminotransferase are low in the fetal heart. Over the last third of gestation the myofibrillar content of the fetal myocyte increases twofold to the adult value by term. Associated with this is a fourfold rise in myofibrillar and sarcoplasmic reticulum Ca2+-ATPase activity. Na+-K+-ATPase activity is similar in the late fetal and adult heart but one-third lower in the early fetal heart.
Active and passive capillary control in red muscle at rest and in exercise
Authors: Honig C. R. , Odoroff C. L. , Frierson J. L.
Published: December 2017

Capillary control was quantified in dog gracilis muscles from in situ. About 550 capillaries/mm2, one-third the total number present, were perfused with erythrocytes simultaneously at rest; two-thirds the total could be perfused during maximal vasodilation. The functional capillary reserve was about 600/mm2. Capillary distribution at rest reflects a passive, random process at individual capillaries and an active process that coordinates perfusion of small groups of capillaries. The latter creates long diffusion distances. These are unaltered by denervation, or flow per se, but are abolished by adenosine. Twitch contraction at 4/min recruited about 400 capillaries/mm2 without any change in flow. Capillaries opened selectively where diffusion distances were longest. The same changes occurred within 5 s during work at 4/s, even if flow was held constant. If flow could increase, about 200 additional capillaries/mm2 were slowly recruited, without change in capillary distribution. Conclusions are that 1) hemodynamics and active vasomotion contribute equally to capillary density at rest; 2) active papillary control in exercise is ungraded and solely responsible for eliminating metabolically significant diffusion paths; 3) flow and capillary density can be controlled independently by proximal and terminal arterioles, respectively.
A mathematical model of primary pacemaking cell in SA node of the heart
Authors: Bristow D. G. , Clark J. W.
Published: December 2017

Application of voltage-clamp techniques to cardiac primary pacemaker tissue is currently a subject of considerable interest in cardiac electrophysiology. Information regarding the electrical behavior of this type of membrane is by no means complete, yet sufficiently detailed information is available in the literature that would allow the formulation of a reasonably quantitative model to represent the electrical activity of primary pacemaker tissue. In this study the well-known McAllister-Noble-Tsien (MNT) model of the cardiac Purkinje fiber is modified to account for the electrical activity of the primary pacemaking cell (P-cell) of the sinoatrial (SA) node in the heart. Modification is accomplished by appropriately deleting (or inactivating) selected inward- or outward-current channels in the MNT model and adjusting the range of voltage dependence of the various channel-gating variables. Wherever possible, this is accomplished by taking into account voltage-clamp and other electrophysiological data from experiments on the SA node. The resultant model mimics published data quite well and is capable of characterizing the free-running behavior of the primary pacemaker as well as its response to injected currents.
Synergistic effects of pressure, distal resistance, and vasoconstriction on stenosis
Authors: Santamore W. P. , Kent R. L. , Carey R. A. , Bove A. A.
Published: December 2017

The synergistic effects of perfusion pressure, distal resistance, and arterial vasoconstriction on stenotic hemodynamics were examined using an in vitro arterial preparation. Canine carotid and coronary arteries were attached to a perfusion apparatus. Perfusion pressure and distal resistance were controlled independently. Arterial vasoconstriction was induced by perfusing the artery with a 100 mM K solution. A stenosis was created by partially inflating a balloon catheter within the artery. Pressure proximal and distal to the arterial segment and flow were measured. For the coronary arteries the combination of high perfusion pressure, high distal resistance, and arterial vasodilation decreased stenotic resistance to 0.79 +/- 0.10 mmHg . ml-1 . min, whereas low perfusion pressure, low distal resistance, and arterial vasoconstriction increased stenotic resistance to 22.40 +/- 4.90 mmHg . ml-1 . min (P less than 0.01). These large changes in stenotic resistance were accompanied by maximum and minimum flow rates of 86.1 +/- 6.0 and 5.5 +/- 1.1 ml/min, respectively (P less than 0.01). Qualitatively similar results were obtained with the carotid arteries. Thus perfusion pressure, distal resistance, and arterial vasoconstriction acted synergistically to greatly influence the severity of the stenosis.
Muscular blood flow distribution patterns as a function of running speed in rats
Authors: Laughlin M. H. , Armstrong R. B.
Published: December 2017

Muscle blood flow (BF) was measured using the radiolabeled microsphere technique within and among nine major muscles of rats before exercise and during treadmill walking or running at speeds of 15, 30, 45, 60, and 75 m/min. Measurements were made during exercise after 1 min of steady walking or running. Male Sprague-Dawley rats were chronically instrumented with 2 Silastic catheters, one in the ascending aorta via the right carotid artery for microsphere infusion and one in the left renal artery for arterial reference blood sample withdrawal. The preexercise results demonstrated that 1) BF to deep slow-twitch muscles was three to four times that to peripheral fast muscles (e.g., soleus and gastrocnemius BFs were 138 and 33 ml . min-1 . 100 g-1, respectively); 2) BFs to red portions within mixed muscles were three to four times those to white portions (e.g, red and white gastrocnemius BFs were 54 and 18 ml . min-1 . 100 g-1, respectively; and 3) there was a direct relationship (P less than 0.05) between BFs to muscles and their slow-twitch oxidative fiber populations. The results obtained during exercise demonstrated that 1) at the slowest speed studied (15 m/min) BFs to the red portions of muscles increased, whereas BFs to the white portions of the same muscles decreased; 2) BFs to all muscles (except soleus) were increased during running at 75 m/min when there was a range of flows of 30 ml . 100 g-1 . min-1 (white gastrocnemius) to 321 (vastus intermedius), 3) at all running speeds the increases in BF to muscles were directly related to the fast-twitch, high-oxidative fiber populations of the muscles; and 4) BFs to visceral tissues and fat were decreased during exercise.
Intra-arterial histamine increases blood-brain transport in rats
Authors: Gross P. M. , Teasdale G. M. , Graham D. I. , Angerson W. J. , Harper A. M.
Published: December 2017

The neurotransmitter histamine is located in multiple compartments in the brain and may influence cerebral vessels during some conditions. We made measurements of cerebrovascular transport of labeled sucrose, alpha-aminoisobutyric acid (AIB), and horseradish peroxidase during sustained infusion of histamine into the internal carotid artery of anesthetized rats. Histamine increased the rates of transport of sucrose and AIB up to 237% in several brain regions and in different areas of cerebral cortex. The effect was dose dependent, was reversible within 2 h, and was mediated primarily by histamine H2-receptors. An increase in cortical water content occurred, and electron microscopic examination revealed that perivascular astroglial processes were swollen. There was a twofold increase in the number of endothelial pits and vesicles in cortical capillaries perfused by histamine. We conclude that histamine can influence the function of the blood-brain barrier.