bluuebunny/crossref_metadata_2025 huggingface dataset:
Central adrenergic mechanisms in hemorrhage-induced vasopressin secretion
Authors: Brooks D. P. , Share L. , Crofton J. T.
Published: December 2017

The effect of central administration of specific adrenergic agonists and antagonists on hemorrhage-induced vasopressin secretion was studied in conscious rats. The intracerebroventricular (icv) injection of the alpha 2-antagonist yohimbine, the alpha 1-antagonist corynanthine, or the beta-agonist isoproterenol failed to alter the vasopressin or blood pressure responses to two sequential 10% reductions in blood volume. Administration of the beta-antagonist propranolol, however, resulted in a significant attenuation of the vasopressin response to hemorrhage, with little effect on the blood pressure response. The alpha 2-agonist, butylated hydroxytoluene (BHT) 933, caused an enhanced vasopressin response to hemorrhage, with a resulting improved maintenance in blood pressure. The results indicate that both alpha 2- and beta-adrenoreceptors may be involved in the pressure-volume control of vasopressin secretion.
Depressor response during experimental portal hypertension in dog
Authors: Moursi M. M. , D'Alecy L. G.
Published: December 2017

Elevation of splanchnic portal pressure in dogs results in an apparently reflexic response manifest as an active reduction in mean arterial pressure (AP). The results from 14 dogs separated into a tachycardic (TACH) heart rate (HR) response (P less than 0.005, n = 6) group and a bradycardic (BRAD) HR response (P less than 0.005, n = 8) group. Both groups showed similar reductions in AP and cardiac output (CO); however, stroke volume (SV) was reduced to a greater extent (P less than 0.029) in the TACH group. Atropine eliminated or reversed the bradycardia in the BRAD group and propranolol blocked the tachycardia in the TACH group. When portal hypertension was repeated in the BRAD group after atropine, similar reductions (P less than 0.01) were observed in AP, SV, and CO but total peripheral resistance (TPR) no longer increased. Reductions in SV or CO due to reduced venous return only partially explain the AP changes. These data suggest the reflex activation of several mechanisms that contribute to rather than completely oppose the reduction in AP anticipated with a reduction in venous return. They include an atropine-sensitive negative chronotropic effect and a negative inotropic effect as well as adjustments in TPR. We thus propose a reflex mechanism that is activated by increased splanchnic pressure and contributes to an active lowering of mean arterial pressure.
Evidence for circulating factors as a cause of venous hypertrophy in spontaneously hypertensive rats
Authors: Greenberg S. , Gaines K. , Sweatt D.
Published: December 2017

Pages H421–H430: S. Greenberg, K. Gaines, and D. Sweatt. “Evidence for circulating factors as a cause of venous hypertrophy in spontaneously hypertensive rats.” Page H423: Equation 3 was incorrect due to a typographical error in which the appropriate parentheses were omitted. The correct equation is A = W/(l x d) or A = (W/l)/d. This (correct) equation was used to calculate the data, which are therefore correct.
Quantitative fluorescence microscopy on single capillaries: alpha-lactalbumin transport
Authors: Huxley V. H. , Curry F. E. , Adamson R. H.
Published: December 2017

We have extended the use of a microscope densitometric technique [Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H495-H505, 1983] to measure the solute permeability coefficients (Pa) of fluorescently labeled solutes in single perfused capillaries of frog mesentery. The method enables the transcapillary flux of solutes larger than 10,000 mol wt to be measured under conditions where the forces that determine both solute and water flows across the capillary wall are known. The Pa for alpha-lactalbumin (mol wt 14,176, Stokes radius 2.02 nm) increased from a mean value of 2.1 X 10(-6) cm/s when capillary pressure was 3.0 cmH2O (no net filtration) to greater than 4.0 X 10(-6) cm/s when capillary pressure was 15 cmH2O. Taking a value of 0.35 for the solvent drag reflection coefficient for alpha-lactalbumin, we conclude that the increased solute flux represents solvent drag through a water pathway with a hydraulic conductivity of 3.6 X 10(-7) cm X s-1 X cmH2O-1. Our data conforms to the hypothesis that alpha-lactalbumin is transported across the capillary wall by restricted diffusion and solvent drag in a pathway that carries 90% of the transcapillary water flow (the principle water pathway). In vitro and in vivo calibration experiments have been carried out to test the assumption that the measured fluorescent light intensity is proportional to the number of fluorescent molecules in the measuring window of the photometer.
Regional differences in pleural lymphatic albumin concentration in sheep
Authors: Albertine K. H. , Schultz E. L. , Wiener-Kronish J. P. , Staub N. C.
Published: December 2017

We used quantitative reflectance autoradiography to compare the concentration of albumin in visceral pleural lymphatics at the cranial and caudal ends of the sheep's lung in the vertical (60 degrees head-up) and horizontal (supine) positions. Twelve to fourteen hours after injecting 125I-albumin intravenously we placed four anesthetized sheep in the vertical position to establish a microvascular hydrostatic pressure gradient along the vertical height of the lung. We placed two anesthetized sheep in the horizontal position. Four hours later, we fixed the left lung and removed visceral pleural tissue blocks from the cranial and caudal ends, separated by a 15-cm distance, along the costovertebral margin. We measured the silver grain density in the pleural lymphatic autoradiograms by dark-field reflectance microspectrophotometry. In the vertical position, the lymph albumin concentration at the cranial end (top) of the lung averaged 2.5 +/- 0.4 g/dl compared with the caudal end (bottom), which averaged 1.8 +/- 0.3 g/dl. The difference (42% greater at the top than the bottom) is significant (P less than 0.05). The computed gradient in perimicrovascular interstitial albumin osmotic pressure was 0.26 +/- 0.13 cmH2O/cm lung height. There were no differences between the cranial and caudal lymphatic groups in the two horizontal sheep. We conclude that in the sheep lung there is a gradient in perimicrovascular albumin concentration due to the vertical gradient in microvascular hydrostatic pressure.
Hemodynamic effects of endurance training on canine left ventricle
Authors: Ramo P. , Kettunen R. , Hirvonen L.
Published: December 2017

To investigate the effects of endurance training on myocardial performance seven beagle dogs (exercise group, EG) were trained by treadmill running for 6–7 wk. Before and after experimental period the EG and control group (CG, n = 7) underwent a standard submaximal exercise test (SMT), and hemodynamic status was checked during anesthesia by catheterization technique exposing the animals to different loadings: pacing, volume loading, and isoproterenol infusion. The increase of heart rate during SMT was about 30 beats/min less in the EG than in the CG. A highly linear relationship between stroke work and end-diastolic volume was observed within the groups (for EG r = 0.953, for CG r = 0.846), but the slope of the regression line obtained for EG appeared to be significantly (P less than 0.001) greater. In EG isoproterenol induced increases in end-diastolic (27%), end-systolic (37%), and stroke volumes (19%), but, on the contrary, decreases of these volumes in CG (19, 15, and 22%, respectively); ejection fraction remained unchanged for both EG and CG. Ventricular stroke work was significantly greater in EG. Systemic vascular resistance decreased in EG in every loading test. The results indicate an improved pump performance, which is related not only to the heterometric autoregulatory adjustments, but also to extracardial adaptations.
Low Ba-induced pacemaker current in well-polarized cat papillary muscle
Authors: Delmar M. , Jalife J.
Published: December 2017

It has previously been reported that superfusion of normally quiescent mammalian ventricular muscle with low concentrations of Ba (less than 0.3 mM) can induce spontaneous activity with maximum diastolic potentials (MDP) that are similar to the normal resting potential (-80 mV or larger). The mechanism for this activity was studied in cat papillary muscle sucrose-gap preparations under current clamp and voltage-clamp conditions. Hyperpolarizing current pulses decreased or abolished the amplitude of the pacemaker potential in a voltage-dependent manner. When Ba concentration was increased to 2 mM the MDP depolarized by approximately 20 mV. Hyperpolarizing steps under these conditions abolished the diastolic depolarization, also in a voltage-dependent manner. Voltage clamping the preparation at the MDP during superfusion of 0.2 mM Ba revealed a time-dependent, inwardly directed current. Hyperpolarizing voltage-clamp steps from a holding potential of -50 mV showed that this current was maximal at approximately -70 mV and frequently reversed at membrane potentials of approximately -95 to -115 mV. The time course of this current was biexponential, and the time constant of the faster component decreased with larger hyperpolarization. When the same voltage-clamp protocol was repeated in the presence of 2 mM Ba, no time-dependent current change was detected. In four out of five experiments, Cs (2.5 mM) reduced (but never abolished) the amplitude of the low Ba-induced current. Our results do not support the hypothesis that a hyperpolarization-induced current (iF-like current) is responsible for the automaticity in well-polarized ventricular muscle at low Ba concentrations. Instead, our data suggest that this pacemaker activity is the result of a Ba-induced, time-dependent blockade of the inward rectifier potassium current (iK1).
Coordinated changes in contractility, energetics, and isomyosins after aortic stenosis
Authors: Lecarpentier Y. , Bugaisky L. B. , Chemla D. , Mercadier J. J. , Schwartz K. , Whalen R. G. , Martin J. L.
Published: December 2017

To investigate possible alterations of myocardial performance in young rats, cardiac hypertrophy was induced by stenosis of the ascending aorta (AS) in three groups of 25-day-old rats that were compared with three groups of sham-operated controls (C). The cardiac overload duration was 8-10 days, 1 mo, and 2 mo in groups 1, 2, and 3, respectively. Mechanics and energetics were studied in left ventricular papillary muscles, and determination of the V1 and V3 isomyosin pattern was achieved in the same papillary muscle. The majority of quantitative changes concerning the cardiac growth process, contractility, and isomyosin shifts occurred within 8-10 days of stenosis. At this point, the degree of left ventricular hypertrophy relative to C was 53 +/- 6%, whereas maximum unloaded shortening velocity (Vmax) decreased significantly (2.8 +/- 0.1 in C vs. 1.9 +/- 0.1 Lmax/s in AS), peak power output (Emax) decreased (1.8 +/- 0.3 in C vs. 0.6 +/- 0.1 in AS), and the curvature of Hill's hyperbola increased (1.3 +/- 0.4 in C vs. 2.0 +/- 0.7 in AS); moreover, the percent V1 isomyosin decreased significantly (98 +/- 1 in C vs. 51 +/- 3% in AS) and the percent V3 isomyosin increased significantly (2 +/- 1 in C vs. 26 +/- 2% in AS). Beyond 8-10 days of AS, additional changes in cardiac hypertrophy and in mechanical and biochemical parameters were less marked.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of brief sympathetic stimuli and heart period on atrial contractile force
Authors: Martin P. , Ishikawa S.
Published: December 2017

We studied the dynamic interaction between the independent effects of sympathetic stimuli and heart period on atrial contractile force with three experiments: 1) we measured the inotropic response to brief sympathetic stimuli when the heart was paced; this represented the pure sympathetic effect on contractile force. 2) We measured the responses to identical stimuli when the heart was not paced; this represented the effect of the combined influences. 3) We measured the contractile responses to the identical sequences of changing cycle lengths that were recorded (expt 2) but in the absence of sympathetic activity; this represented the pure effect of changing cardiac cycle length on contractile force. We subtracted the paced from the unpaced responses. This difference represented the linear elimination of the pure sympathetic effect from the combined responses. We then compared this difference with the responses to changing cycle lengths that were measured in the absence of sympathetic activity (expt 3). The values were not equal from 2.5 through 22.5 s after the stimulus of experiment 1 of the protocol above. We performed a similar comparison after expressing the results in the frequency domain. The values were significantly different for most of the frequency spectrum where the greatest power was concentrated. We therefore conclude that there is a significant interaction between the effects of sympathetic activity and changing heart periods, and this interaction determines the resultant inotropic state on any specific beat.
Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin
Authors: Shepherd R. E. , Lang C. H. , McDonough K. H.
Published: December 2017

A dose-dependent impairment of intrinsic myocardial performance has been observed following in vivo administration of endotoxin. The present study reports a dose-dependent increase in plasma catecholamines following endotoxin (ET) that may impair beta-adrenergic responsiveness. Hearts were removed from pentobarbital-anesthetized rats 4 h after a bolus injection of saline or ET (1,000, 100, or 10 micrograms/100 g body wt) and were studied as isolated cell preparations following collagenase digestion. Responsiveness of isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in myocytes prepared from hearts of animals injected with 10 and 100 micrograms ET was decreased when compared with control rats and was significantly blunted in myocytes prepared from animals receiving 1,000 micrograms ET. Similar sensitivities of the cAMP system existed, as judged by similar half-maximum effective concentration values. cAMP accumulation in the presence of 1 microM forskolin was depressed in myocytes from the 1,000-microgram ET animals; beta-adrenergic receptor density was decreased 25% (P less than 0.05) in myocytes from high-dose ET animals when compared with control animals. This was accompanied by a nonsignificant reduction in the affinity of binding sites for (+/-) [3H]CGP 12177. The blunted myocyte hormonal responsiveness following ET challenge appears to be related to the decreased activity of the adenylate cyclase that may be attributed to alterations in both receptor density and in the adenylate cyclase itself.
Regional sciatic nerve blood flow response to limb movement
Authors: Sugimoto H. , Monafo W. W. , Shimazaki S.
Published: December 2017

The regional blood flow in the sciatic nerves (NBF), biceps femoris muscles (MBF), and hind limb skin (SBF) was measured simultaneously in anesthetized, normal rats, in other rats immediately after 15 min of electrical stimulation of one sciatic trunk (10 shocks/s), and in a group of similarly stimulated but previously curarized rats. These experiments were done to quantitate NBF during direct nerve stimulation in both the presence and absence of associated vigorous limb twitching, as these relationships have not previously been examined. Tissue blood flows were measured by an “indicator-fractionation” technic, using the distribution of [14C]butanol. NBF in normal controls was 11.1 +/- 1.4 ml X min-1 X 100 g-1; MBF was 6.8 +/- 0.6 ml X min-1 X 100 g-1. In the stimulated limb of noncurarized rats, NBF rose to 19.8 +/- 3.5 ml X min-1 X 100 g-1. MBF was elevated approximately tenfold. SBF also rose. In stimulated limbs of curarized rats, NBF was also approximately double the resting normal value, 23.2 +/- 4.8 ml X min-1 X 100 g-1, but MBF was then only slightly increased. We conclude that sciatic NBF increases appreciably when this nerve is stimulated, irrespective, for the most part, of whether limb motor activity is increased. The vascular mechanisms which regulate NBF differ from and are largely independent of those regulating MBF.
Effects of sympathectomy on heart size and function in aortic-constricted rats
Authors: Siri F. M. , McNamara J. J.
Published: December 2017

Effects of chemical sympathectomy with 6-hydroxydopamine on left ventricular mass, norepinephrine content, and performance in aortic-constricted and sham-constricted rats were examined. Sympathectomy did not affect mean arterial pressure but it led to lower final body weights in aortic-constricted rats. Of the hypertensive aortic-constricted rats, those that had also been sympathectomized showed greater increases in left ventricular weight-to-body weight, right ventricular weight-to-body weight, and lung weight-to-body weight ratios. Left ventricular norepinephrine content was depressed by either sympathectomy or aortic constriction and was severely depleted by their combination. Sympathectomy had no effect on maximal cardiac output or left ventricular stroke work during rapid saline infusion. In aortic-constricted rats, however, it lowered heart rate during the infusion and increased left ventricular end-diastolic pressure at peak stroke work. This evidence suggests that elimination of the adrenergic nervous system's chronotropic influence promotes greater left ventricular filling, and the resultant increase in preload may importantly contribute to the stimulation of cardiac hypertrophy.
Time course of systolic loading is an important determinant of ventricular relaxation
Authors: Zatko F. J. , Martin P. , Bahler R. C.
Published: December 2017

We studied the dependency of left ventricular relaxation on the timing of an abrupt increase in systolic load. In 10 canine isolated heart-lung preparations, a load step of 15 mmHg was imposed at specific intervals throughout systole, and the time of loading was defined as the interval from the R wave to the completion of the load step (R-load interval). Preload was held constant. The right atrium was paced at a cycle length of 450 ms. The decay of left ventricular pressure during isovolumic relaxation was described by a single exponential time constant (Texp). Load effects on isovolumic relaxation were expressed as a percent change in Texp as compared with Texp of the beat preceding the load intervention. Loads imposed early in systole consistently prolonged Texp [mean delta Texp = +17.01 +/- 1.64% (SE) for R-load intervals less than or equal to 120 ms]. Load changes late in systole consistently abbreviated Texp [mean delta Texp = -9.49 +/- 0.86% (SE) for R-load intervals greater than or equal to 130 ms]. The transition from augmentation to diminution of Texp always occurred when the R-load interval was 120-130 ms. The mean time interval of electromechanical systole for the test beats was not significantly different (P greater than or equal to 0.05) from that of the control beats [R-load intervals less than or equal to 120: test = 247.0 +/- 27.8 (SD) ms; control = 246.6 +/- 26.8 (SD) ms] [R-load intervals greater than or equal to 130: test = 243.3 +/- 29.1 (SD) ms; control = 243.8 +/- 28.4 (SD) ms].(ABSTRACT TRUNCATED AT 250 WORDS)
Microvessel hematocrit: measurement and implications for capillary oxygen transport
Authors: Desjardins C. , Duling B. R.
Published: December 2017

Microvascular preparations of the hamster cheek pouch and cremaster muscle were used to establish the relationship among three measures of red cell distribution: 1) the systemic hematocrit defined as the volume percentage of red cells sampled from a toe clip; 2) the tube hematocrit defined as the instantaneous volume fraction of red cells in a microvessel segment of measured length and diameter; and 3) the discharge hematocrit defined as the volume percentage of red cells that flowed into micropipettes inserted into microvessels. The results show the tube hematocrit is low and highly variable in the presence of a nearly constant systemic hematocrit. The discharge hematocrit, in contrast, consistently approximated systemic values in blood taken from arterioles or venules with diameters of 6–98 micron. Indeed, the mean ratio of the discharge to the systemic hematocrit did not differ from unity (P greater than 0.25). The observed similarity between the discharge and systemic hematocrit indicates that red cells are distributed uniformly across capillary networks. Differences between the absolute value and variance of the tube hematocrit compared with the discharge hematocrit imply that the anatomical volume of a microvessel can differ from the volume available to cells and plasma within a microvessel. Thus moment-to-moment variation in the tube hematocrit or capillary red cell spacing may be indicative of a change in the effective capillary flow cross section and not solely on the inflow hematocrit.
Mechanisms for altered carnitine content in hypertrophied rat hearts
Authors: Reibel D. K. , O'Rourke B. , Foster K. A.
Published: December 2017

Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and elevated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-[14C]carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by approximately 20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels.
Atrioventricular nodal accommodation: rate- and time-dependent effects
Authors: Loeb J. M. , deTarnowsky J. M. , Whitson C. C. , Warner M. R.
Published: December 2017

To characterize intrinsic rate- and time-dependent properties of the atrioventricular (AV) node, we examined whether AV interval (AVI) would be comparable at identical heart rates (HR) reached using different types of stimulation paradigms. We compared changes in AVI during five consecutive 30-s, 20 beat/min increases in HR from control with AVI changes induced by 30-s single-step protocols to each of the same levels. In addition, HR was maintained at each level for 30, 60, 90, 120, and 150 s to control for the influences of time. Chloralose-anesthetized dogs (n = 16) were autonomically decentralized and instrumented to record electrocardiogram, blood pressure, and multiple intracardiac electrograms. Computer-generated HR steps were begun 20 beats/min above control, while continuously recording AVI. The beat-by-beat changes in AVI within each step were quantitated for all protocols. Differences between AVI during single- and multiple-step protocols were most pronounced during the first 15 s of atrial pacing. Accommodation in AVI (change in AV conduction time associated with an increased but constant heart rate) was evident during both protocols. The degree of accommodation during multiple-step protocols was modulated by the cumulative effects of earlier HR; however, a similar degree of accommodation occurred at higher HR irrespective of protocol used. Finally, the time to onset of loss of 1:1 AV conduction was significantly shorter when HR was increased using a multiple-step protocol. Thus the intrinsic response of the AV node to HR change is dependent on absolute level of HR, duration of rate change, and the potential cumulative effects of any earlier HR steps.
Characterization of pulmonary arterial input impedance with lumped parameter models
Authors: Grant B. J. , Paradowski L. J.
Published: December 2017

The purpose of this study is to evaluate systematically the ability of lumped parameter models to approximate pulmonary arterial input impedance (Zin) and estimate characteristic impedance (Zc) and pulmonary arterial compliance (Cart). To assess goodness of fit, the parameters of each model were adjusted so that the model's impedance approximates the Zin measured in anesthetized cats. To assess the ability of the model to estimate Zc and Cart, the lumped parameter models were fitted to Zin calculated from a distributed parameter model of the feline pulmonary vasculature. In addition, we assessed the concordance between the lumped parameter model estimates of Zc and Cart. The results indicate that no one model was superior; any of four models would be a reasonable choice. A four-element model was used to compare Zin measured at different phases of the respiratory cycle. Small differences in the impedance spectra were found that have not been previously reported. We conclude that lumped parameter models can be used to provide close approximations to Zin, to estimate Zc and Cart, and to provide a useful approach for statistical comparisons of impedance spectra.
Ibuprofen prevents thrombin-induced lung vascular injury: mechanism of effect
Authors: Perlman M. B. , Johnson A. , Malik A. B.
Published: December 2017

We compared pulmonary vascular responses with thrombin-induced pulmonary microembolism in awake sheep pretreated with ibuprofen or meclofenamate. Control sheep with lung lymph fistulas (n = 6) were challenged with 80 U/kg of alpha-thrombin, the native enzyme. Two groups of similarly prepared sheep received the cyclooxygenase inhibitors, ibuprofen (n = 4) or meclofenamate (n = 4), before the thrombin challenge. Thrombin-induced pulmonary microembolism in control sheep increased pulmonary lymph flow and lymph protein clearance (lymph flow X lymph-to-plasma protein concentration ratio). These lymph changes were associated with sustained increases in mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) and a decrease in circulating neutrophil count. The steady-state pulmonary hemodynamic and lymph responses to thrombin persisted after cyclooxygenase inhibition with meclofenamate, although the increases in pulmonary lymph flow and lymph protein clearance were delayed. In contrast, ibuprofen reduced pulmonary lymph flow, lymph protein clearance, Ppa, and PVR responses. Neutrophil count in control and meclofenamate groups remained below base line after thrombin, whereas neutrophil count returned to base line in the ibuprofen group within 90 min after thrombin. Ibuprofen resulted in a greater decrease in vitro neutrophil adherence to pulmonary endothelium induced by serum generated by clotting whole blood with alpha-thrombin as compared with meclofenamate. Results indicate that ibuprofen attenuates the increases in Ppa and PVR and markedly attenuates the increase in pulmonary transvascular protein clearance after thrombin. The protective effect of ibuprofen may be due to reduction of neutrophil sequestration in lung.
Source of intrinsic innervation of canine ventricles: a functional study
Authors: Blomquist T. M. , Priola D. V. , Romero A. M.
Published: December 2017

Recently it has been suggested that the parasympathetic innervation of the ventricles is by way of postganglionic axones that emanate from ganglion cells in the atria, reaching the ventricles by traversing the atrioventricular (AV) groove. We designed a series of experiments to test this hypothesis. Phenol (89%) was applied to the AV groove and surrounding 5 mm of epicardium in 21 dogs on cardiopulmonary bypass. The effects of intracoronary acetylcholine (ACh; 1-5 micrograms) and intracoronary nicotine (NIC; 25–100 micrograms) on cardiac isovolumic pressures were evaluated after beta-blockade. In another series of experiments, eight dogs were exposed to phenol in the same way and allowed to recover for 7–10 days. Atrial and ventricular responses to NIC were unaffected by phenol application to the AV groove in the acute animals when compared with application of saline alone. However, in the chronic animals, pretreatment with phenol 7–10 days previously reduced the ventricular responses to NIC by 70% while leaving the atrial responses intact. These data indicate that the intrinsic cardiac nerves (ICN) of the canine ventricles consist primarily of postganglionic parasympathetic axones which arise from supraventricular ganglia and cross the AV groove.
Myocardial blood flow and VO2 in conscious lambs with an aortopulmonary shunt
Authors: Toorop G. P. , Hardjowijono R. , Dalinghaus M. , Gerding A. M. , Koers J. H. , Zijlstra W. G. , Kuipers J. R.
Published: December 2017

We measured myocardial blood flow (QLVFW) and O2 consumption of the left ventricular free wall (VO2, LVFW) in 13 chronically instrumented, 7-wk-old lambs with an aortopulmonary left-to-right shunt (S) and in 10 control lambs without a shunt (C). The measured VO2, LVFW was compared with the calculated values obtained by two predictive indexes, the rate-pressure product (RPP) and the pressure-work index (PWI). Measured VO2, LVFW in S lambs was significantly higher than in C lambs [983 +/- 104 (SE) vs. 475 +/- 57 mumol X min-1 X 100 g LV-1, P less than 0.001]. This was achieved by the significantly higher QLVFW (294 +/- 33 vs. 145 +/- 15 ml X min-1 X 100 g LV-1, P less than 0.002), since the arteriovenous O2 difference across the left ventricular free wall was similar in both groups of lambs. Total coronary blood flow per unit body mass in S lambs was higher than in C lambs (14.1 +/- 1.5 vs. 5.6 +/- 0.6 ml X min-1 X kg-1, P less than 0.001), not only because of the increased VO2, LVFW per unit muscle mass, but also because of the increased total heart weight (102.4 +/- 6.4 vs. 81.2 +/- 4.9 g, P less than 0.02). Correct estimation of VO2, LVFW by means of the RPP and the PWI was only possible in C lambs. In S lambs the estimated values were significantly lower than the measured ones.(ABSTRACT TRUNCATED AT 250 WORDS)
Prostanoids and pial arteriolar diameter in hypotensive newborn pigs
Authors: Leffler C. W. , Busija D. W.
Published: December 2017

Effects of hypotensive hemorrhage on pial arteriolar diameter and cortical subarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface (cortical subarachnoid CSF). Prostanoids in the CSF were determined by radioimmunoassay. Measurements of pial arterioles were made during normotension (63 +/- 4 mmHg) and hypotension (28 +/- 3 mmHg). Hypotension caused pial arteriolar diameters to increase from 162 +/- 22 to 193 +/- 22 microns. During normotension, the cortical subarachnoid prostanoid concentrations were (in ng/ml) prostaglandin E2 (PGE2) 2.6 +/- 0.7, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) 1.7 +/- 0.4, thromboxane B2 (TXB2) 0.25 +/- 0.02. Hypotension caused 6-keto-PGF1 alpha to increase 245 +/- 104% and PGE2 to increase 132 +/- 38%. TXB2 increased slightly (37 +/- 21%). Topical application of PGE2 and prostacyclin caused marked dilation of pial arterioles. Treatment of hypotensive newborn pigs with indomethacin caused constriction of pial arterioles to diameters not significantly different from the normotensive diameters. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow during hypotension in piglets.
Venule distension properties in Wistar, Wistar-Kyoto, and spontaneously hypertensive rats
Authors: Lang D. J. , Johns B. L.
Published: December 2017

The purpose of this study was to determine whether venule distension characteristics are modified in denervated venules in the spontaneously hypertensive rat (SHR) during the developmental stage of hypertension. The distension of denervated first-order venules (1V) and small collecting veins (SCV) in the intestine of 7- to 8-wk-old SHR, Wistar-Kyoto (WKY), and Wistar rats were measured with intravital microscopy during venous pressure elevation. Diameter strain and distensibility were calculated for the 1V and SCV from vessel diameter and servo-null pressure. The Wistar 1V underwent larger strains and distensibilities than the WKY or SHR vessels, which had similar characteristics. For the SCV, the Wistar and WKY strains and distensibilities were similar, with the SHR different from these at only certain pressure elevations. Thus no consistent patterns of altered distension characteristics were found in denervated SHR SCV or 1V compared with its controls. This study does not distinguish between changes in local active and passive factors in the vessel wall which may influence distension. Our results may be consistent with disease mechanisms in the 7- to 8-wk-old SHR which leave these local factors unchanged or with mechanisms which have local venular effects that counterbalance each other, leaving the distension behavior of the denervated venules unchanged.
Intracellular [Ca2+] related to rate of force development in twitch contraction of heart
Authors: Yue D. T.
Published: December 2017

The relation between the rate of rise of tension (dF/dt) and intracellular free Ca2+ concentration ([Ca2+]i) during twitch contraction was investigated in mammalian ventricular myocardium. [Ca2+]i was assessed from luminescence emitted by ferret papillary muscles microinjected with the calcium-regulated photoprotein aequorin. Evidence was found that during the phase of rising tension following maximum positive dF/dt, there was an approximately linear relationship between dF/dt at a given instant and the estimated [Ca2+]i at that same instant. A single such instantaneous relationship held true for physiological contractions of widely varying strength (n = 5 preparations), up to 65.3 +/- 6.0% (means +/- SE) of maximal Ca2+-activated force, as assessed from maximally activated cardiac tetani. Furthermore, the identical relationship determined from physiological contractions also held true for virtually the entire rising phase of tension in contractions with [Ca2+]i transients slowed (approximately 4- to 5-fold) by exposure of muscles to 5 microM ryanodine (n = 5 preparations). That a unique relation applies to contractions of both vastly different strength and time course provides evidence that the correlation between instantaneous dF/dt and [Ca2+]i is not merely fortuitous but indicates a fundamental property of myocardium. Such a property provides considerable insight into many features of physiological contraction and may represent a central clue as to the mechanism of activation in mammalian cardiac muscle.
Developmental changes in the response of cardiac Purkinje fibers to SC-72-14
Authors: Morikawa Y. , Rosen M. R. , Meiri H. , Robinson R. B.
Published: December 2017

We used standard microelectrode techniques to study the effects of SC-72-14, a monoclonal antibody to eel electroplax, and tetrodotoxin (TTX) on the electrophysiological properties of neonatal and adult canine Purkinje fibers. SC-72-14, 7 ng/ml, depressed maximum upstroke potential (Vmax) and membrane responsiveness of adult but not neonatal fibers. In contrast, we previously had shown TTX to have a greater effect on neonatal than adult fibers (29). Even in the presence of SC-72-14, TTX continued to have a greater effect on the neonatal fibers. The effects of TTX and SC-72-14 were cumulative over the concentration range studied, and our results are consistent with their acting at different sites.
Hepatic arterial pressure-flow autoregulation is adenosine mediated
Authors: Ezzat W. R. , Lautt W. W.
Published: December 2017

Pressure-flow autoregulation, although weak, was seen in the hepatic artery (HA) of every cat that also showed dilation to infused adenosine. Several means of quantitating autoregulation are described and evaluated, and all indices showed that the selective adenosine antagonists, 8-phenyltheophylline and 8-(p-sulfophenyl)theophylline, inhibited autoregulation as well as the vasodilator response to exogenous adenosine and the hepatic arterial buffer response (HABR; vasodilation of HA in response to reduced portal flow). The mechanism of HABR is proposed to be dependent on washout of locally produced adenosine into portal blood; reduced portal flow causes adenosine accumulation and dilation of HA. The present data suggest that local levels of adenosine can also be washed into HA blood so that reduced arterial flow will also lead to raised adenosine levels and arterial vasodilation. Thus the mechanisms of the HABR and HA pressure-flow autoregulation are suggested to be the same, i.e., washout of locally produced adenosine, probably from the space of Mall just prior to entry of the vessels into sinusoids.
Microsphere reference flow samples during systemic flow adjustment
Authors: Geffin G. A. , O'Keefe D. D. , Denenberg A. G. , Daggett W. M.
Published: December 2017

Regional myocardial blood flow measurements in the right heart bypass preparation can be particularly valuable, since this preparation provides control of the main hemodynamic determinants of coronary blood flow. We examined the validity of aortic reference flow samples in relation to coronary samples during continuous systemic flow adjustment for aortic pressure control in six dogs on right heart bypass, anesthetized with chloralose and urethan. Microsphere concentrations were compared in paired reference flow samples drawn from the aortic arch and from a coronary artery for 119 left atrial microsphere injections. During left subclavian artery infusion and during femoral artery infusion at rates above 2,000 ml/min, there were high percentage errors in microsphere concentration between paired samples, consistent with aortic sample dilution by systemically infused blood. In 52 injections during withdrawal or femoral infusion below 2,000 ml/min, at cardiac outputs of 390-4,800 ml/min, the percentage error was 0.001 +/- 1.18% (SE); the absolute value of this error was below 20% in 96%, and below 10% in 77% of these injections. Linear regression related these coronary to aortic microsphere concentrations by the equation Y = 1.005X - 1.64, r = 0.997, Sy.x = 13.2 (5.9%). (Sy.x represents the standard deviation from regression.) These data indicate that valid aortic reference flow samples can be obtained within specific hemodynamic conditions during systemic flow adjustment in the right heart bypass preparation.
Statistical and graphical evaluation of erythrocyte volume distributions
Authors: McLaren C. E. , Brittenham G. M. , Hasselblad V.
Published: December 2017

A protocol for the statistical and graphical evaluation of erythrocyte volume distributions has been developed using expectation-maximization methods for distribution parameter estimation. In a reference sample group of 50 healthy individuals, none of the red cell volume distributions determined by an aperture impedance method differed significantly from a log normal model. Measurements in 211 patients with anemia provided evidence that similar statistical methods could be used for the characterization of abnormal red cell volume distributions. Graphical displays accurately summarize the quantitative information derived from the analysis of volume distributions and show a reference distribution fitted to the observed distribution against the range of distributions found in healthy individuals. This protocol provides a specific, statistically valid implementation of the general principles for the analysis of cell volume distributions proposed by the International Committee for Standardization in Hematology.
Measurement of hemoglobin oxygen saturation in capillaries
Authors: Ellsworth M. L. , Pittman R. N. , Ellis C. G.
Published: December 2017

We present a computer-aided videodensitometric method for the determination of oxygen saturation in red blood cells flowing through capillaries of the hamster cheek pouch retractor muscle. The optical density (OD) of red blood cells is determined at two wavelengths. At the first, 431 nm, there is a maximum difference between absorption by oxygen deoxyhemoglobin. At the second, 420 nm, absorption is equal for the two absorbing species (isosbestic wavelength). In capillaries of the retractor muscle a relationship between oxygen saturation (S) and the following OD ratio was obtained as S = -1.71 (OD431/OD420) + 2.20. The error (95% confidence interval) in oxygen saturation associated with a determination of the OD ratio is estimated to be +/- 4.8%. The computerization of the method employs a frame-by-frame analysis of the light intensity over a selected capillary segment. The light intensity waveform along the segment is digitized and the minimum (I) and maximum (I0) light intensities are used to compute an optical density (OD = log10 [I0/I]). These minimum and maximum intensities correspond to the presence and absence of a red blood cell, respectively. The method permits the off-line analysis of videotaped scenes and provides a means of assessing the extent of temporal and spatial heterogeneity of oxygen saturation in selected capillary networks. The method has been developed for use in capillaries in transilluminated striated muscle but should be generally applicable to the measurement of capillary oxygen saturation in other tissues.
Mechanism of alpha-adrenergic excitation in bovine lymphatic smooth muscle
Authors: McHale N. G. , Allen J. M. , Iggulden H. L.
Published: December 2017

Measurements were made, using the double sucrose-gap technique, of electrical and mechanical responses of bovine lymphatic smooth muscle to constant current pulses. After beta-blockade with 10(-6) M propranolol, stimulation of the alpha-receptors with norepinephrine (5 X 10(-6) M) depolarized the membrane and decreased membrane conductance. The depolarization and decrease in membrane conductance persisted in Li+- and choline-substituted low-Na+ solution, in methanesulfonate-substituted low-Cl- solution, and in Ca2+- free solution containing 1 mM ethyleneglycol-bis(beta-aminoethylether)-N, N'-tetraacetic acid. Tetraethylammonium (10 mM) did not itself affect membrane resistance nor did it block the increase in resistance due to norepinephrine. In contrast, cesium (10 mM) increased membrane resistance and prevented norepinephrine from increasing this further. As well as these effects on membrane resistance, norepinephrine (5 X 10(-6) M) increased the duration of the action potential, and this was accompanied by an increased force of contraction. Tetraethylammonium prolonged the action-potential plateau and potentiated norepinephrine's effect. These results suggest that norepinephrine is likely to increase the efficiency of lymphatic pumping due to both its positive inotropic effect and the improved safety margin for propagation resulting from the increase in membrane resistance. The latter effect may be due to the suppression of an outward K+ current.
Hemodynamic alterations in chronically conscious unrestrained diabetic rats
Authors: Carbonell L. F. , Salom M. G. , Garcia-Estan J. , Salazar F. J. , Ubeda M. , Quesada T.
Published: December 2017

Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.
Cardiorespiratory response to cyanide of arterial chemoreceptors in fetal lambs
Authors: Itskovitz J. , Rudolph A. M.
Published: December 2017

Cardiorespiratory response to the stimulation of the carotid and aortic receptors by sodium cyanide was examined in fetal lambs in utero at 0.8 (120 days) gestation. Injections of 50-400 micrograms cyanide into the inferior vena cava or the carotid artery of intact fetuses elicited bradycardia and respiratory responses that varied from a single gasp to rhythmic respiratory movements but no significant change in arterial blood pressure. Carotid sinus denervation eliminated the cardiorespiratory response to intracarotid injection of cyanide and sinoaortic denervation abolished the response to inferior vena caval injection. It is concluded that in fetal lamb in utero the aortic and carotid bodies are active, and hypoxic stimulation of these chemoreceptors results in cardiorespiratory response characterized by slowing of fetal heart rate, respiratory effort, and no consistent change in arterial blood pressure.
Response to brief coronary stenosis in conscious dogs after ventricular sympathectomy
Authors: Jones C. E. , Liang I. Y. , Mass H. J. , Gwirtz P. A.
Published: December 2017

Left ventricular responses to 2-min circumflex occlusion were studied in conscious dogs. In nonsympathectomized controls at 2, 4, and 8 wk after surgery for cardiac instrumentation, segmental shortening in the posterior ventricle significantly decreased by 111, 87, and 81% of the preocclusion values, respectively (P less than 0.05). The decrease in shortening was associated with increases in end-diastolic pressure of 9, 9, and 8 mmHg (P less than 0.05), decreases in the maximal rate of pressure generation of 305, 272, and 340 mmHg/s (P less than 0.05), and increases in heart rate of 28, 21, and 20 beats/min, respectively (P less than 0.05). After 2 and 4 wk of ventricular sympathectomy, posterior segmental shortening declined by 38 and 31%, respectively (P less than 0.05), but these decreases were less than in controls (P less than 0.05). Shortening did not change during occlusion after 8 wk of sympathectomy. Diastolic pressure increased by 6 mmHg (P less than 0.05), and the rate of pressure generation decreased by 232 mmHg/s (P less than 0.05) in the 2-wk sympathectomized ventricle. These variables did not change significantly after 4 and 8 wk of sympathectomy. After 2, 4, and 8 wk of sympathectomy, the increases in heart rate during circumflex occlusion were not different from controls (P greater than 0.05). Thus chronic sympathectomy preserved ventricular function during occlusion. This effect was attributable to a reduced preocclusion mechanical performance with a reduction in blood flow requirement and to an increased collateral perfusion, as indicated by a higher peripheral coronary pressure during occlusion in sympathectomized ventricles.