bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal stability and precision of ventricular defibrillation threshold data
Authors: Babbs C. F. , Whistler S. J. , Yim G. K.
Published: December 2017

Over 200 measurements of the minimum damped sinusoidal current and energy for transchest electrical ventricular defibrillation (ventricular defibrillation threshold) were made to determine the stability and precision of threshold data in 15 pentobarbital-anesthetized dogs. Threshold was determined by repeated trials of fibrillation and defibrillation with successive shocks of diminishing current, each 10% less than that of the preceding shock. The lowest shock intensity that defibrillated was defined as threshold. In three groups of five dogs each, threshold was measured at intervals of 60, 15, and 5 min over periods of 8, 5, and 1 h, respectively. Similar results were obtained for all groups. There was no significant change in mean threshold current with time. Owing to a decrease in transchest impedance, threshold delivered energy decreased by 10% during the first hour of testing. The standard deviations for threshold peak current and delivered energy in a given animal were 11% and 22% of their respective mean values. Arterial blood pH, Pco2, and Po2 averaged change of pH, PCO2 and PO2 were not significantly different from zero. The data demonstrate that ventricular defibrillation threshold is a stable physiological parameter that may be measured with reasonable precision.
Hydraulic conductivity of the endothelial and outer layers of the rabbit aorta
Authors: Vargas C. B. , Vargas F. F. , Pribyl J. G. , Blackshear P. L.
Published: December 2017

Pressure-driven fluid flow across the arterial wall was measured to determine wall hydraulic conductivity (Lp) before and after removal of the endothelium. The thoracic aortas of rabbits, anesthetized with Nembutal, were cannulated, perfused with oxygenated Ringer solution, and removed. With one cannula connected to a capillary manometer and the other closed, the manometer meniscus shift could be used as an indication of fluid loss through the wall plus vessel volume increase (creep). The latter effect, when measured, accounted for about one-fourth of the total volume displacement. The Lp given in cm/(s.cmH2O) +/- SD, was 3.30 +/- 0.96 x 10(-8). Another method employed continuous weighing of a closed aortic segment to obtain fluid loss, and yielded an Lp of 4.07 +/- 1.3 x 10(-8), and after mechanically removing the endothelium, the Lp became 7.73 +/- 2.8 x 10(-8). Using the above data, an Lp could be calculated for aortic endothelium of 8.6 x 10(-8). This suggests that about half the total transmural pressure drop occurs across the endothelium. Scanning electronmicrographs were used to check the condition of the endothelium.
Measurement of endogenous norepinephrine overflow from canine saphenous veins
Authors: Muldoon S. M. , Tyce G. M. , Moyer T. P. , Rorie D. K.
Published: December 2017

A method for the measurement of norepinephrine (NE) overflow from isolated superfused canine saphenous veins is described. This method involves concentrating NE present in the superfusate, followed by measurement of its concentration by high-performance liquid chromatography with electrochemical detection. The limit of sensitivity of the method (defined as a signal-to-noise ratio of 5) was 25 pg. NE concentration measured by this method correlated well (r = 0.95) with that measured by standard fluorometric methods. Electrical stimulation caused an initial overflow of a mean of 115 X 10(-18) mol NE/mg of vein per pulse; this was associated with an increase in isometric tension. With continued stimulation, less NE overflowed into the superfusate, although tension was not reduced appreciably.
Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress
Authors: Kvetnansky R. , McCarty R. , Thoa N. B. , Lake C. R. , Kopin I. J.
Published: December 2017

Blood pressure, heart rate, and circulating levels of norepinephrine, epinephrine, and corticosterone were measured before and during the first or seventh period of immobilization stress (150 min per day) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive male rats. A catheter was inserted into the tail artery of each rat to permit direct measurement of blood pressure and heart rate and serial sampling of blood in conscious, unhandled animals. During the first immobilization, SHR rats had significantly higher circulating levels of norepinephrine, epinephrine, and corticosterone than did WKY rats. One day after the sixth immobilization, basal levels of norepinephrine and epinephrine were significantly higher and mean blood pressure was significantly lower in repeatedly stressed SHRs compared to unstressed SHRs. In addition, adaptation to the repeated stress in SHRs was attended by reduced adrenomedullary secretion and an increased blood pressure response. These results demonstrate that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.
Natural biventricular hypertrophy in normotensive rats. I. Physical and hemodynamic characteristics
Authors: Pfeffer M. A. , Pfeffer J. M. , Dunn F. G. , Nishiyama K. , Tsuchiya M. , Frohlich E. D.
Published: December 2017

The Wistar-Kyoto strain of normotensive rats (WKY) is being used as a control animal for studies involving the spontaneously hypertensive rats (SHR). A subset of the WKY demonstrating an inheritable transmission of biventricular cardiac hypertrophy (BVH) has been identified. The cardiac enlargement is pronounced, with right and left ventricular weights greater than twice normal in some animals. This natural development of BVH appears to be in response to an increased cardiac output. Blood pressure is normal and, therefore, peripheral resistance is reduced. Left ventricular injection of 15-micrometer radioactively labeled microspheres demonstrated that WKY with BVH had a substantial shunt fraction of their cardiac output (45 +/- 7% radioactivity recovered in the lungs vs. 3 +/- 2% in normal WKY). This subset of WKY with BVH provides a natural model of volume-load hypertrophy. In addition, investigators using the WKY for comparison with SHR should exclude animals with BVH.
Instantaneous pressure-volume relationship of right atrium during isovolumic contraction in canine heart
Authors: Lau V. K. , Sagawa K. , Suga H.
Published: December 2017

We studied the contraction of the right atrium in an excised cross-circulated heart preparation. Atrial volume and instantaneous atrial pressure were measured in a water-filled balloon fitted in the spontaneously contracting right atrium. The relation of instantaneous pressure to volume was analyzed by collecting pressure data from multiple isovolumic contractions with different volumes but measured at multiple identical time points in the contraction cycle. The relation was found to be quasi-linear during most of atrial systole and diastole. A linear regression formula P(t) = K(t)[V- VD(t)] was therefore fitted to the data. K(t) and VD(t) of the regression formula are the slope and the volume axis intercept in the pressure-volume plane, respectively. When the atrium beat spontaneously at a regular sinus rhythm with no inotropic intervention. K(t) increased during systole and decreased during diastole, whereas VD(t) decreased during systole and increased during diastole. The average value of K was 13 +/- 1.7 (SE) mmHg . kg . ml-1 at the end of diastole and 33 +/- 0.02 (SE) mmHg . kg . ml-1 at the end of systole. The average value of VD was 0.303 +/- 0.017 (SE) ml . kg-1 at the end of diastole and 0.212 +/- .025 (SE) ml . kg-1 at the end of systole. Enhancement of contractility with epinephrine or Ca2+ significantly increased the value of K at the end of systole, but it did not significantly affect either K at the end of diastole or VD at the end of systole and diastole.
Graphical estimation of ventricular wall force and stress from pressure-volume diagram
Authors: Suga H. , Sagawa K.
Published: December 2017

A graphical method is proposed for assessment of ventricular wall circumferential total force and mean stress from the ventricular pressure-volume diagram. A family of force or stress isopleths are first drawn in the pressure-volume plane using a geometric model of the left ventricle and an appropriate version of the Laplace equation. A pressure-volume loop of the ventricle to be analyzed is then drawn in this pressure-volume plane. Total circumferential force in the ventricular wall or its mean circumferential stress can now be read directly from the intersections of the pressure-volume loop with the force or stress isopleths.
Cardiac output and mean transit time using the phase plane of dye-dilution curves
Authors: Fonseca-Costa A. , Zin W. A.
Published: December 2017

Thirty-five indicator-dilution curves were recorded in dogs following the injection of indocyanine dye into the femoral vein, right atrium, pulmonary artery, or left ventricle. Sampling was from the femoral artery through a dichromatic cuvette densitometer. The exponential decay constant of each dye-dilution curve was calculated by a new method utilizing the phase plane and compared with the value obtained by the Stewart-Hamilton procedure. A high level of correlation was found between the two methods. Mean difference between areas was only 1.04 mg.1(-1).s (r = 0.999) and between mean transit times 0.02 s (r = 0.999). The phase plane method has the additional advantage of demonstrating the portion of exponential decay, enabling the elimination of indicator-dilution curves and abnormal downslopes.
Autonomic control of right atrial contractile strength in the dog
Authors: Stuesse S. L. , Wallick D. W. , Levy M. N.
Published: December 2017

The combined effects of parasympathetic and sympathetic stimulation on right atrial contractile strength were assessed in open-chest, pentobarbital-anesthesized dogs. A factorial experimental design was employed to quantify the percent changes in atrial contractile strength in spontaneously beating and paced hearts as a function of the frequencies of vagal and stellate ganglion stimulation. In 7 of 10 dogs, there was a substantial interaction between the two autonomic divisions; the sympathetically mediated inotropic effect became less pronounced as the background level of vagal stimulation increased. The relationship between stimulation frequencies and atrial contractile strength was not significnatly altered by pacing the hearts.
Contributions of nerves and metabolites to exercise vasodilation: a unifying hypothesis
Authors: Honig Carl R.
Published: December 2017

Page H705: Carl R. Honig. “Contributions of nerves and metabolites to exercise vasodilation: a unifying hypothesis.” Pages H716 and H717: Figs. 12 and 13 should be interchanged
Effect of damaged ends in papillary muscle preparations
Authors: Donald T. C. , Reeves D. N. , Reeves R. C. , Walker A. A. , Hefner L. L.
Published: December 2017

The mechanical characteristics of the central segment of isolated cat papillary muscle were determined with recently developed equipment. Two small sharpened stainless steel pins, inserted transversely through the muscle, were used to mark the ends of a segment not damaged by attachments. Installation of the pins did not affect the performance of the muscle. The distance between the pins was measured and controlled to produce isometric and afterloaded isotonic contractions of the segment of the muscle between the pins. Data from such contractions were compared with traditional whole muscle measurements made on the same preparation. The isometric length-tension curve of the central segment was significantly higher than that of the whole muscle, and there was no plateau of developed force at long lengths in five of six muscles studied. In the resting state, the segment was more compliant than the whole muscle for physiologic lengths and much stiffer for longer lengths. Segment velocity and shortening were significantly higher than whole muscle velocity and shortening at comparable loads.
Prejunctional cholinergic modulation of adrenergic neurotransmission in the cardiovascular system
Authors: Vanhoutte P. M. , Levy M. N.
Published: December 2017

In the heart and in the blood vessel walls, complex adrenergic-cholinergic interactions occur both prejunctionally, at the level of the autonomic nerve terminals, and postjunctionally, at the level of the responding cells themselves. The principal prejunctional interaction appears to be an inhibition of the release of norepinephrine from adrenergic nerve terminals by the acetylcholine liberated from nearby cholinergic nerve endings. This inhibitory effect is mediated by muscarinic receptors located on the postganglionic sympathetic nerve terminals. The inhibitory effect of acetylcholine on cardiac and vascular tissues are therefore achieved in part by a direct influence of the cholinergic neurotransmitter on the cardiac and vascular muscle cells, and in part by an indirect influence on sympathetic neurotransmission.
Lipoprotein lipase activity in rat heart and adipose tissue during endotoxic shock
Authors: Bagby G. J. , Spitzer J. A.
Published: December 2017

The present studies were designed to delineate changes in heart and adipose tissue lipoprotein lipase (LPL) activity following the administration of E. coli endotoxin. Plasma triglyceride levels were elevated in animals given endotoxin compared to saline-injected controls. Heart LPL activity decreased from 126.4 mumol fatty acid released per gram wet wt per hour in control rats to less than 22.5 mumol . g-1 . h-1 by 7 h following the injection of endotoxin. Although endotoxin was administered in doses producing 0-100% mortalities in a 24-h period, myocardial LPL activity was depressed to the same extent (75-80%) regardless of dose. The response of adipose tissue was less pronounced. Epididymal fat pad LPL activity fell significantly over the 24-h observation period in control and endotoxin-treated rats with the latter group somewhat more depressed 7 h after treatment. The findings are consistent with the suggestion that hypertriglyceridemia often observed during endotoxic shock may be related to depressed LPL activity; the degree of depression is probably tissue dependent.
Transient tension responses of heart muscle in Ba2+ contracture to step length changes
Authors: Saeki Y. , Sagawa K. , Suga H.
Published: December 2017

To characterize mechanical properties of activated heart muscle, kitten papillary muscles in Ba2+ contracture were stretched or released stepwise, and the transient tension responses were analyzed. Various amplitudes of step length change (0.1-1.0% of Lmax) were tested from different initial lengths and at different temperatures. The tension response to either stretch or release showed four different phases, which were nearly symmetric when the input length change was 0.1% of Lmax. When the length changes was 1%, the second phase of stretch response became shorter, whereas that of release became longer. The third phase of stretch response was prolonged, whereas that of release response became obscure. The peak tension (F1) in the first phase was linearly related to the amplitude, whereas those in the second and third phase were not. Increasing temperature markedly decreased F1 and shortened the second and third phase independently of initial muscle length. These results were consistent with those properties of heart muscle in Ba2+ contracture previously characterized with sinusoidal length changes.
Effects of estradiol on release and disposition of norepinephrine from nerve endings
Authors: Hamlet Martha A. , Rorie Duane K. , Tyce Gertrude M.
Published: December 2017

Studies were performed to determine whether estradiol (E2) has a direct action on the release and disposition of norepinephrine (NE) from adrenergic nerve endings in isolated superfused canine saphenous veins. [3H]NE and is labeled metabolites were separated by column chromatography with measurement by liquid scintillation spectrometry. An increase in the spontaneous overflow of total 3H, [3H]NE, and [3H]dihydroxyphenylglycol ([3H]DOPEG) that occurred with 1 and 10 microgram/ml E2 in the superfusing medium suggested that E2 either induced NE release or interfered with intraneuronal NE storage. During electrical stimulation (ES), release of [3H]NE and [3H]DOPEG exceeded controls with 1 and 10 microgram/ml E2 in the superfusate, yet total 3H was little changed. The evoked release of [3H]DOPEG showed less of an elevation over its spontaneous efflux in E2-treated veins than in nontreated veins, suggesting that E2 may block neuronal reuptake of released NE. The efflux of O-methylated deaminated metabolites during and after ES was decreased by E2 treatment, suggesting also an inhibition of extraneuronal uptake of NE.
Influence of CO2 on cardiovascular response to hypoxia in conscious dogs
Authors: Koehler Raymond C. , McDonald Brian W. , Krasney John A.
Published: December 2017

The modulating effect of CO2 on the circulatory response to hypoxia in chronically instrumented conscious dogs was examined over a wide range of arterial partial pressure of O2 [PaO2 (from 80 to 25 Torr)] during a 41-min rebreathing period at three CO2 levels: hypocapnia (from PaCO2 of 32 to 18 Torr), eucapnia (32 Torr), and mild hypercapnia (40 Torr). Eucapnic and hypercapnic hypoxic responses were also measured after sinoaortic denervation (SAD) to assess the arterial chemoreceptor and baroreceptor reflex contributions. Elevating PaCO2 attenuated the tachycardia during hypoxia and produced progressively greater systemic, renal, and splanchnic vasoconstriction before but not after SAD. Vagal block converted the rises in renal and splanchnic flows observed during hypocapnic hypoxia to declines. The increase in left ventricular dP/d tmax was not affected by varying PaCO2 either before or after SAD. Coronary flow increased an additional onefold during hypoxia when PaCO2 was elevated both before and after SAD, but the tension-time indices did not differ significantly. These results indicate that: a) cardiopulmonary vagal afferents effectively counteract chemoreflex-induced vasoconstriction during hypocapnic hypoxia; b) chemoreflex vasoconstriction predominates in the renal and splanchnic beds when PaCO2 is elevated; c) the sinoaortic reflexes restrain the heart rate, but not the contractility response to hypoxia when PaCO2 is increased; and d) the augmented coronary vasodilation produced by CO2 is probably mediated by local CO2-hypoxic interactions.
Development of Crotalaria pulmonary hypertension: hemodynamic and structural study
Authors: Meyrick B. , Gamble W. , Reid L.
Published: December 2017

In awake rats with indwelling catheters, the development of pulmonary hypertension after feeding Crotalaria spectabilis seeds is followed. Hypoxemia is excluded as a factor. Other hemodynamic changes are found before hypertension. After 7 days, pulmonary artery pressure (Ppa) is normal, 17.17 +/- 0.30 (SE) mmHg and from 14 days significantly increased (P < 0.01). Oxygen consumption (Vo2) is significantly increased by day 7 (control 22.72 +/- 2.13 ml . min-1 . kg-1; Crotalaria 42.47 +/- 2.95; P < 0.001). and cardiac index (CI) is significantly above normal after 7, 14, and 21 days (control 350 +/- 31 ml . min-1 . kg-1; 7 days Crotalaria 476 +/- 28; P < 0.02); pulmonary vascular resistance (PVR) increases to six times normal at day 33 (control 0.033 +/- 0.003 U/kg; 33 days Crotalaria 0.194 +/- 0.020; P < 0.001). The pulmonary arteries of these same rats were studied by quantitative morphometric techniques. The first change, muscle in smaller and more peripheral arteries than normal, is detected when Vo2 and CI are increased. Increased medial thickness of arteries < 200 micrometer diameter follows with Ppa rises. Even later, the larger arteries increase their media as the number of peripheral arteries falls and right ventricular hypertrophy becomes apparent, and hypertension and increased PVR are well established.
Aortic transmural serum protein transport: effect of concentration, time, and location
Authors: Fry D. L. , Mahley R. W. , Oh S. Y. , Swyt C. R.
Published: December 2017

The diffusive transport of certain 125I-labeled purified serum proteins, canine (C), human (H), and porcine (P) serum albumin (A), as well as human high-density lipoprotein (HDL), into the isolated deendothelialized intimal-medial thoracic aortic preparation was measured as a function of protein concentration (c0), intimal surface exposure time (T), and location (z) along the vessel at 21 degrees C. Selected proteins were studied in each of 11 canine preparations and 1 porcine preparation. The resulting uptake (M, nmol/cm2) was measured by direct gamma counting of specially excised fixed tissue specimens, and the transmural concentration distributions [c(xi), nmol/cm3] were calculated from electron probe X-ray microanalysis of the silver distributions across specially prepared microautoradiographs. The results showed 1) that the processes associated with the diffusive transport of CA, HA, PA, and HDL into the intimal-medial system are independent of c0, i.e., uptake is proportional to c0, 2) that the uptake of CA for short times appeared to be linear with T 1/2, 3) that the apparent wall-plasma partition coefficient for albumin rangers between 0.1 and 0.2, 4) that the apparent tissue albumin diffusion coefficient is approximately 2.7 X 10(-8) cm2/s, 5) that the transport processes for HA and CA are indistinguishable, 6) that the processes for the transport of HDL are two times slower than those for HA or CA, and 7) that the transport rate for albumin tends to decrease with z.
Abnormal electrocardiograms in rats deficient in copper
Authors: Klevay L. M. , Viestenz K. E.
Published: December 2017

According to a new hypothesis based on epidemiologic observations, iatrogenic maneuvers, natural occurrences, and animal experiments, absolute or relative deficiency of copper is of prime importance in the etiology of ischemic heart disease. Male weanling rats were made copper deficient with a purified diet containing 0.79 microgram Cu/g diet and containing all other nutrients known to be essential. Deficiency was verified by a 39% increase in cholesterolemia. Electrocardiograms of copper-deficient rats showed several abnormalities including S-T segment depression for one-third to one-half of the R-R interval, bundle branch block with R waves three times normal height and width, Q waves, and second- and third-degree heart block. Copper deficiency shortened the lives of the rats by 73%. Copper deficiency is the only nutritional insult that has produced rapid unfavorable alterations in lipid metabolism, cardiac and arterial anatomy, and cardiac electrophysiology. Copper metabolism may be important in the etiology of ischemic heart disease and in the arrhythmias associated with the consumption of liquid-protein diets.
Intracellular recording of in situ ventricular cells during ventricular fibrillation
Authors: Akiyama T.
Published: December 2017

Transmembrane action potentials (AP) from ventricular cells during ventricular fibrillation (VF) have not been systematically studied. We have recently developed a motion-compensated micropipette holder that holds a micropipette and moves in synchrony with heart motion. AP of subepicardial ventricular cells were recorded in 14 open-chest anesthetized dogs prior to occlusion (control) of left anterior descending artery (LAD) and during first 10 min of reperfusion-induced VF. During control, characteristics (means +/- SE) of AP are: excitation rate (R), 112 +/- 4 beats/min; resting potential (Vr), -79.3 +/- 1.0 mV; overshoot potential (Vov), 17.9 +/- 1.8 mV; 90% AP duration (APD), 251 +/- 8 ms. During VF, AP from the reperfused areas are: R, 173 +/- 27 beats/min; Vr, -60.6 +/- 2.2 mV; Vov, 3.4 +/- 2.9 mV; APD, 134 +/- 9 ms (significantly different from control at P less than 0.001, except R). During VF, cells from the reperfused areas are made inexcitable with verapamil, but not by tetrodotoxin. In conclusion, during VF accurate AP recording is possible from in situ heart, and subepicardial cells in reperfused areas seem to have AP of slow-channel type.
Developmental changes in impulse conduction in the canine heart
Authors: Rosen M. R. , Legato M. J. , Weiss R. M.
Published: December 2017

We studied the age-related changes that occur in conduction in Purkinje fiber bundles (PF) from adult and 8-wk-old dogs. As PF are stretched, conduction velocity increases to a maximum when bundle length is approximately 1.5 times control. Conduction velocity in adult PF was significantly faster than that in 8-wk PF at all bundle lengths, the maximum being 2.32 +/- 0.45 m/s (mean +/- SD) in adult and 1.56 +/- 0.59 m/s in 8-wk-old dogs. At greater than 1.5 times control length, conduction velocity decreased, as did resting potential, action potential amplitude, and upstroke velocity. At 1.5 times control length, the ratio of PF to collagen in the bundles increased, and structural changes consistent with both unbuckling and unfolding of the cell membranes were seen. At greater degrees of stretch, cleft size diminished, and intracellular edema was noted. In sum, structural changes in cardiac PF can explain the changes in conduction velocity that occur with stretch. At all degrees of stretch, however, velocity is faster in PF from adult than from young dogs.
Carotid sinus distension and superior cervical ganglion transmission
Authors: Tuttle R. S. , McCleary M.
Published: December 2017

The functional relationship between sinusal distension and the sympathetic innervation of the feline carotid sinus was investigated by neurophysiological techniques. A balloon catheter was used to distend the sinus region while recording evoked postganglionic activity from the superior cervical ganglion. When the SCG was stimulated at 1.0 or 10.0/s, balloon inflation reduced postganglionic action potential height by 25-50% and increased ganglionic negativity. These effects were subsequently abolished by section of one of the remaining intact postganglionic trunks. This evidence suggests that a pressure-modulated reflex arc, similar to the intestinointestinal reflex, might exist between the carotid sinus and superior and cervical ganglion.
Restoration of cardiac function and myocardial flow by collateral development in dogs
Authors: Cohen M. V. , Yipintsoi T.
Published: December 2017

Hemodynamics of instrumented beagles with 75-85% stenoses of the left circumflex (LCf) coronary artery were evaluated before and during transient LCf balloon occlusion at rest and during treadmill running. Studies were done after surgery and 3 mo later. Myocardial blood flow was measured with radioactive microspheres during the LCf occlusions. Nine dogs (group I) had patent LCf arteries at the second study, and six (group II) had occluded vessels. Transient LCf occlusion during running in group I at weeks 1 and 12 and in group II at week 1 caused significant left ventricular failure, whereas the same protocol in group II dogs at week 12 produced minimal hemodynamic changes. Left ventricular failure precipitated by coronary occlusion during exercise diminished from week 1-12 in those animals with increasing LCf collateral flow, but actually increased in the animals with diminishing collateral flow. In group II dogs after chronic LCf occlusion total flow to LCf myocardium as well as inner-to-outer layer ratios were normal both at rest and during exercise. Thus coronary collaterals do preserve myocardial function, limit adverse hemodynamic responses to myocardial ischemia, and restore postocclusion tissue flows to normal even during the stress of exercise.
Sodium-dependent hypertension produced by chronic central angiotensin II infusion
Authors: Bruner C. A. , Weaver J. M. , Fink G. D.
Published: December 2017

Experiments were performed to characterize the hypertension produced by chronic intracerebroventricular (ICV) infusion of angiotensin II (ANG II) in conscious rats. Infusion of ANG II into a lateral cerebral ventricle for 5 days (1 or 6 micrograms/h) produced dose-dependent increases in mean arterial pressure associated with increased water intake. No consistent changes in heart rate, urinary electrolyte excretion, or water balance were observed. Similarly, no alterations in plasma sodium and potassium concentration, plasma osmolality, or plasma ANG II levels were seen during ICV ANG II infusion. Controlling fluid intake at 40 ml/day did not alter the development of hypertension in this model. Hypertension was found to be sodium dependent, with high sodium intake augmenting the increase in arterial pressure in response to chronic ICV ANG II. Although plasma aldosterone concentrations were increased in some situations during ICV ANG II infusion, adrenalectomy failed to alter the course of hypertension. This study demonstrates that chronic selective stimulation of brain ANG II receptors by means of continuous ICV infusion of ANG II produces sodium-sensitive increases in arterial pressure associated with, but not dependent on, increased fluid intake. This form of hypertension cannot be attributed to sodium and water retention, elevations in plasma aldosterone, or leak of significant amounts of ANG II from cerebrospinal fluid into the peripheral circulation.
Evidence that capillary perfusion heterogeneity is not controlled in striated muscle
Authors: Damon D. H. , Duling B. R.
Published: December 2017

We tested the hypothesis that the heterogeneity of capillary blood flow distribution in striated muscle is inversely proportional to tissue blood flow by examining the patterns of red blood cell flow in the capillaries of hamster tibialis anterior muscles. Capillary red blood cell velocities and capillary red blood cell fluxes were measured as indexes of blood flow and red blood cell distribution in vasoconstricted and vasodilated vascular beds of resting and working striated muscle. Standard statistical parameters describing dispersion of data (standard deviation and coefficient of variation) in addition to measured and normalized histograms were compared across treatments. With vasodilation the standard deviations of both variables increased linearly with the means, and measured distributions became broader. The coefficients of variation and normalized distributions of both variables did not differ across treatments. These observations do not support the idea that the heterogeneity of capillary perfusion is controlled. Rather they suggest that fractional flow dispersion among capillaries is constant and independent of muscle blood flow and/or O2 demand.
Aortic baroreceptor discharge during nonhypotensive hemorrhage in anesthetized dogs
Authors: Hakumaki M. O. , Wang B. C. , Sundet W. D. , Goetz K. L.
Published: December 2017

We tested the hypothesis that arterial baroreceptor discharge remains constant during nonhypotensive hemorrhage. Aortic baroreceptor activity was recorded from anesthetized dogs during slow, continuous hemorrhage until 24 ml blood/kg body wt had been removed. The relationship between simultaneously recorded hemodynamic variables and single-unit aortic baroreceptor activity was evaluated by a unique computer program that sampled all variables 500 times/s and analyzed data from each consecutive cardiac cycle throughout the entire experiment. In three hemorrhages performed on three dogs, aortic blood pressure did not decrease during the experiment (nonhypotensive hemorrhage), but aortic nerve activity decreased progressively when data from individual cardiac cycles having identical mean aortic pressures were compared. Reduced baroreceptor activity correlated closely with progressive reductions in pulse pressure. In other hemorrhages, mean aortic pressure decreased by a variable amount; decreases in recorded single-unit baroreceptor activity occurred during each of these hemorrhages also. In summary, hemorrhage consistently caused decreases in the activity of aortic baroreceptors regardless of whether mean aortic pressure decreased or remained constant during hemorrhage. We conclude that experimental techniques employing nonhypotensive hemorrhage do not provide an effective method for selectively studying reflexes from cardiopulmonary receptors in the absence of changes in arterial baroreceptor input.
An index for estimation of oxygen consumption in rat heart by hemodynamic parameters
Authors: Hutter J. F. , Piper H. M. , Spieckermann P. G.
Published: December 2017

To find a suitable index for the estimation of O2 consumption of rat hearts by use of hemodynamic parameters, isolated hearts were perfused under different working conditions. Coronary flow, arteriovenous O2 difference, cardiac output, and ventricular pressure curve were recorded and continuously fed into a computer. O2 consumption and different hemodynamic parameters such as dP/dtmax, maximum ventricular pressure, pressure-time integral, and heart rate were computed on-line. With the use of these data of 64 different steady states, numerous formulas containing hemodynamic parameters were tested with respect to their ability to predict O2 consumption. The best fit of the data was obtained by a linear combination of the products of rate times dP/dtmax and rate times pressure-time integral of one beat (r = 0.993). Indexes containing approximations of wall stress were not found to improve the predictive ability.
Contraction regulates myosin synthesis and myosin content of cultured heart cells
Authors: McDermott P. , Daood M. , Klein I.
Published: December 2017

Cultured neonatal rat heart cells are a useful model for studying the regulation of myocyte growth. The myosin content of heart cells increases between days 1 and 4 in culture. To determine if contraction per se can regulate myocyte growth, myosin content and protein synthesis were compared in spontaneously contracting and noncontracting cultured heart cells. Myosin content, assayed as the total myosin ATPase activity per culture dish, was significantly increased in contracting cells after 3, 4, and 5 days in culture. Protein synthesis was measured by incorporation of [14C]lysine into total cell protein and into sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved myosin. Contraction stimulated both total cell protein content and protein synthesis by day 3 in culture. Compared with heart cells arrested with 50 mM KCl, myosin synthesis was significantly increased by 96, 112, and 46% at days 2, 3, and 4, respectively. Similar results were observed when myosin content and protein synthesis in contracting myocytes were compared with cells arrested with either 25 mM KCl or 10(-5) M verapamil. The present studies suggest that contraction increases the myosin content in cultured heart cells and that this increase is mediated via a stimulation of myosin synthesis in association with cell growth.
Cardiopulmonary blood volume and plasma renin activity in normal and hypertensive humans
Authors: London G. M. , Guerin A. P. , Bouthier J. D. , London A. M. , Safar M. E.
Published: December 2017

Plasma renin activity (PRA) and systemic and forearm hemodynamics were studied during acute changes in cardiopulmonary blood volume and central venous pressure in 20 subjects, including 9 normotensive controls and 11 essential hypertensive patients of the same age. Changes in cardiopulmonary blood volume and central venous pressure were induced by a "head-down" tilt and thigh-cuff inflation. Blood pressure, pulse pressure, and heart rate did not change during cardiopulmonary blood volume variations, whereas significant changes in cardiac output, forearm blood flow, and PRA were observed. A significant negative correlation between cardiopulmonary blood volume (CPBV) and PRA existed, and slope of this correlation of delta PRA/delta CPBV was estimated as a sensitivity index of control of renin release. Sensitivity of neural control of renin release was not statistically different in normal subjects and hypertensive patients. In two groups, sensitivity of this reflex mechanism similarly decreased with age. Aging seems to be an important factor influencing the sensitivity of neural control of renin release, both in normal and essential hypertensive humans.
Innervation of bat heart: cholinergic and adrenergic nerves innervate all chambers
Authors: O'Shea J. E. , Evans B. K.
Published: December 2017

Adult Miniopterus schreibersii were anesthetized with chloroform, and in vitro preparations of cardiac chambers were prepared. Stimulation of intramural nerves in right ventricles paced at 6 Hz caused an inhibition (56.3 +/- 3.5% decrease on basal force) mediated by cholinergic nerves and an excitation (91.5 +/- 9.9% increase on basal force) mediated by adrenergic nerves. Mean pD2s (-log effective concentration, 50%) for ventricular beta-adrenoceptors and muscarinic cholinoceptors were 6.99 +/- 0.03 and 6.42 +/- 0.07, respectively. The inhibition of ventricular contractility, by nerve stimulation or exogenous acetylcholine, occurred even after blockade of beta-adrenoceptors. The results were comparable to those obtained on atria. In some experiments, the heart was perfused in situ and paced via electrodes on the ventricle: stimulation of the right vagus nerve decreased right ventricular contractility by up to 90%. The results show that, at least in this hibernating mammal, there is an adrenergic innervation of the ventricle. The presence of a cholinergic vagal innervation capable of inhibiting the basal force of ventricular contraction has not been shown in any other mammal.
Ganglionic blockade in conscious dogs with chronic caval constriction
Authors: Sweet W. D. , Freeman R. H. , Davis J. O. , Vari R. C.
Published: December 2017

Chronic constriction of the thoracic inferior vena cava decreases venous return and cardiac output, increases the secretion of renin and aldosterone, and produces sodium retention with ascites and edema formation. The arterial pressure is maintained at normotensive levels in this caval model by an increase in total peripheral resistance. The objective of the present study was to compare renal and hemodynamic responses to ganglionic blockade in the conscious thoracic caval dog to responses obtained in another low-output model, the chronic sodium-deplete dog, and also to the responses obtained in the normal sodium-replete dog. The control base-line pressures averaged 103 +/- 2, 110 +/- 3, and 110 +/- 3 mmHg, respectively, in the sodium-replete, sodium-deplete, and thoracic caval dogs (P greater than 0.05). Ganglionic blockade in the conscious dog with caval constriction resulted in a sustained 20- to 30-mmHg fall in the arterial pressure; a sustained fall of 20 mmHg occurred in the sodium-deplete dogs. In contrast, ganglionic blockade failed to decrease the blood pressure at any time in the normal sodium-replete animals. Effective renal blood flow and creatinine clearance failed to demonstrate sustained changes after ganglionic blockade in any group of dogs; renal sodium excretion increased only in the normal sodium-replete dogs. These results suggest an enhanced contribution of the sympathetic nervous system to blood pressure maintenance in both the sodium-deplete and the caval dogs. Although the data fail to demonstrate an important contribution of the adrenergic system in the chronic sodium retention in these two experimental models, decreases in renal perfusion pressure may have blunted any potential natriuresis in these animals following ganglionic blockade.
Coronary flow in heart-lung preparation affected by cardiopulmonary nerves and arterial PCO2
Authors: Kainuma M. , Ichimura I. , Shigei T. , Ishikawa N.
Published: December 2017

Studies on coronary vasodilator drugs utilizing heart-lung preparations (HLP) have been disturbed by a spontaneous gradual increase in coronary blood flow. With the purpose of finding out what would cause the gradual increase, the time course of coronary sinus blood flow (CSBF) was investigated in 20 dog HLPs under four experimental conditions, according to whether cardiopulmonary nerves (CPN) were severed or not and whether CO2 content in the inspiratory gas was high (95% O2-5% CO2) or low (50% O2-50% room air). The gradual increase in CSBF was observed, accompanied by a significant increase in 6-ketoprostaglandin F1 alpha in the arterial blood, only when CPN were intact and, simultaneously, inspiratory CO2 was high. Nevertheless, the hemodynamic parameters, except CSBF, were almost similar under four conditions. These results suggested that CSBF in HLP could be affected via a synthesis and/or a release of prostaglandin I2 by the interaction of CPN and arterial PCO2.
Alpha 1-adrenergic blockade increases coronary blood flow during coronary hypoperfusion
Authors: Liang I. Y. , Jones C. E.
Published: December 2017

Coronary hypoperfusion was elicited in alpha-chloralose-anesthetized open-chest dogs by reducing left coronary perfusion pressure to 50 mmHg. Left coronary blood flow, as well as left ventricular oxygen extraction, oxygen consumption, and contractile force were measured. The reduction in perfusion pressure caused significant reductions in coronary flow, oxygen consumption, and peak reactive hyperemic flow. During hypoperfusion in 11 dogs, intracoronary infusion of the specific alpha 1-adrenergic antagonist prazosin (0.1 mg/min) increased coronary flow and oxygen consumption by 22 and 16%, respectively. Peak increases were observed after 6–8 min of prazosin infusion (0.6–0.8 mg prazosin), and both increases were statistically significant (P less than 0.05). In seven additional dogs, beta-adrenergic blockade with propranolol (1.0 mg ic) did not significantly affect the actions of prazosin. In five additional dogs, the specific alpha 2-adrenergic antagonist yohimbine (1.3 mg ic) in the presence of propranolol (1.0 mg ic) did not affect coronary flow or oxygen consumption during coronary hypoperfusion. Those results suggest that an alpha 1- but not an alpha 2-adrenergic constrictor tone was operative in the left coronary circulation under the conditions of these experiments.
Effect of graded reductions in uteroplacental blood flow on the fetal lamb
Authors: Skillman C. A. , Plessinger M. A. , Woods J. R. , Clark K. E.
Published: December 2017

Graded reductions in uteroplacental blood flow (UBF), produced by an externally adjustable vascular occluder, were studied in unanesthetized pregnant sheep. This method was designed to simulate the physiological occurrence of reduced UBF to study its effects on fetal status. Sheep were divided into four groups in which average percent changes (+/- SE) in UBF, as measured by electromagnetic flow probes, were 7 +/- 2, -24 +/- 1, -49 +/- 1, and -63 +/- 2% for 1 h. Maternal and fetal cardiovascular (heart rate and blood pressure) and blood gas measurements of PO2 and PCO2, pH, and O2 content were determined before, during, and after recovery from UBF reduction. UBF reduction had no significant effect on maternal measurements. Changes in fetal PO2 and O2 content were directly related to the extent of vascular occlusion (P less than or equal to 0.05). Fetal pH markedly decreased after 1 h of 49% UBF reduction (P less than or equal to 0.05) and within 10 min after 63% UBF reduction (P less than or equal to 0.05). Fetal bradycardia (P less than or equal to 0.05) resulted from 63% reduction in UBF. Fetal heart rates at recovery were greater than base-line heart rate values (P less than or equal to 0.05) in the three groups whose UBF was restricted. The results of the present study suggest that the uterus of the pregnant ovine is perfused in sufficient excess to protect the fetus during short-term reductions of less than 50% UBF.
Failure of pyruvate to salvage myocardium after prolonged ischemia
Authors: Gutterman D. D. , Chilian W. M. , Eastham C. L. , Inou T. , White C. W. , Marcus M. L.
Published: December 2017

Thrombolytic therapy for acute coronary occlusion may be more effective if combined with substrate-enhanced reperfusion. In this study, we examined the utility of pyruvic acid, an important metabolic substrate, in salvaging ischemic myocardium. Twenty-six anesthetized dogs underwent 3 h of circumflex coronary occlusion followed by 90 min of reperfusion with administration of intracoronary pyruvate or vehicle. To test the sensitivity of the model in detecting differences in infarct size, eight additional dogs underwent coronary occlusion of shorter duration (45 min), an intervention that is known to reduce infarct size. Collateral perfusion to the ischemic zone during coronary occlusion was similar in experimental and control groups. Whereas a shorter duration of occlusion (45 min) decreased the infarct-to-risk area ratio by 54% compared with a longer duration of occlusion (90 min), neither early (15 min prior to occlusion) nor late (3 h after occlusion) onset of intracoronary infusion of pyruvate shifted the infarct-risk relationship (control: y = 74x - 8.7, r = 0.99; early infusion: y = 0.76x - 9.5, r = 0.85; late infusion: y = 0.58x - 5.5, r = 0.79). The failure of intracoronary administration of pyruvate to limit infarct size raises questions as to its potential clinical utility in the setting of acute myocardial ischemia.
5-Hydroxytryptamine delays relaxation time of norepinephrine-induced vasoconstriction
Authors: Manzini S. , Maggi C. A. , Meli A.
Published: December 2017

The effect of low concentration of 5-hydroxytryptamine (5-HT; 0.03-0.3 microM) on cellular and extracellular Ca2+ -dependent norepinephrine (NE; 5 microM)-induced vasoconstriction was assessed in isolated perfused rabbit ear artery. The most remarkable effect of 5-HT is a concentration-dependent enhancement of the duration of the extracellular Ca2+ -dependent NE-induced vasoconstriction. This effect of 5-HT is still present in 6-hydroxydopamine-pretreated arteries and in the presence of deoxycorticosterone and is not mimicked by the K+ channel blocker tetraethylammonium. Administration of nifedipine (0.3 microM) and EDTA (1 mM) failed to antagonize 5-HT-induced prolongation of relaxation kinetics of extracellular Ca2+ -dependent NE-induced vasoconstriction. On the other hand, this phenomenon was abolished by caffeine (15 mM) and markedly reduced by dibutyryl cyclic AMP (3 mM). 5-HT (0.3 microM), but not NE (30-50 nM), enhanced the vasoconstriction elicited by caffeine (15 mM) that was procaine sensitive and unaffected by nifedipine. These results suggest that 5-HT prolonged relaxation kinetics of NE-induced vasoconstriction through an impairment of cellular mechanisms that decrease the myoplasmic level of free Ca2+. A similar mechanism could be of relevance for 5-HT enhancement of vascular smooth muscle responsiveness to vasoactive agents.
Transmural coronary flow reserve patterns in dogs
Authors: Grattan M. T. , Hanley F. L. , Stevens M. B. , Hoffman J. I.
Published: December 2017

To investigate transmural variations in coronary flow reserve, we studied 20 anesthetized dogs with a Gregg cannula in the left main coronary artery. In 11 dogs, radionuclide-labeled microspheres were injected over a range of perfusion pressures in the control state and during maximal coronary vasodilation produced with chromonar or adenosine. In another nine dogs, control, reactive hyperemic, and adenosine-vasodilated flows were compared at the same perfusion pressures. Adenosine dilated vessels more than did reactive hyperemia, which in turn vasodilated more than did hypoperfusion. Adenosine or chromonar vasodilated more than did hypoperfusion alone in all layers of the heart at perfusion pressures as low as 30 mmHg (P less than 0.05). This effect was greatest in the subepicardium and least in the subendocardium and varied with perfusion pressure (P less than 0.05). Subendocardial-to-subepicardial flow ratios declined with diminishing perfusion pressure despite the fact that flow reserve was present in all layers. We conclude that exhaustion of flow reserve is not the mechanism by which subendocardial ischemia occurs.