bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of ouabain-induced arterial muscle contraction
Authors: Toda N.
Published: December 2017

Ouabain caused dose-related contractions in helically cut strips of cerebral, mesenteric, renal, and femoral arteries isolated from dogs and monkeys; the contractions were elicited at lower concentrations in cerebral than in the peripheral arteries. Contractions induced by ouabain were abolished by exposure of cerebral arteries to Ca2+-free media. Contractions induced by Ca2+ in Ca2+-free media were potentiated by ouabain. Substitution of LiCl for NaCl and reduction of [K+]0 suppressed the contractile response of cerebral arteries to ouabain. Pretreatment of dogs with reserpine abolished the response of peripheral arteries to ouabain but not the cerebroarterial response. Phentolamine also abolished the response of peripheral arteries. Once oubain-induced contractions were stabilized, the alpha-antagonist caused a marked relaxation in peripheral but not in cerebral arteries. Ouabain-induced contractions appear to be mediated by an increase in the Ca2+ influx that results mainly from an inhibition of the electrogenic Na+ pump in low concentrations (cerebral arteries) and from a release of norepinephrine from nerves in high concentrations (mesenteric, renal, and femoral arteries).
Aspirin and indomethacin enhance platelet aggregation in mouse mesenteric arterioles
Authors: Rosenblum W. I. , El-Sabban F. , Ellis E. F.
Published: December 2017

The cyclooxygenase inhibitors aspirin and indomethacin enhanced platelet aggregation in mesenteric vessels, suggesting that the normal mesentery produces an antiaggregatory prostaglandin. Testing of mesentery incubate in mouse platelet-rich plasma disclosed an antiaggregatory material with the properties of prostacyclin. Chromatography showed that mesentery made several radiolabeled products from [3H]arachidonic acid, including one that cochromatographed with 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable hydrolysis product of prostacyclin. Gas chromatography-mass spectrometric analysis of mesentery incubate showed the presence of 6-keto-PGF1 alpha, synthesized from the mesentery's endogenous arachidonic acid. The enhancement of platelet aggregation in mesenteric vessels contrasts with earlier data showing that in similarly injured mouse cerebral vessels aggregation was retarded by both aspirin and indomethacin. This divergent effect of cyclooxygenase inhibitors in different vascular beds may depend on the relative importance of prostacyclin in the different beds or on the capacity of cyclooxygenase inhibitors to influence this prostacyclin production in different beds. Caution is urged before acceptance of a central role for PGI2, however, because of the capability of microvasculatures and adjacent tissue to synthesize a number of other products whose interaction with platelets and with aspirin and indomethacin remains to be elucidated.
Protective actions of naloxone in hemorrhagic shock
Authors: Curtis M. T. , Lefer A. M.
Published: December 2017

The opiate antagonist, naloxone, was infused at 8 mg x kg-1 x h-1 in cats to determine its effect in hemorrhagic shock. Hemorrhaged cats treated with naloxone maintained postreinfusion mean arterial blood pressure at a higher value compared to those receiving only the vehicle. Final pressures were 77 +/- 9 mmHg for cats receiving vehicle compared to 120 +/- 6 mmHg for cats receiving naloxone. These values represent 58 +/-7 and 98 +/- 6% of initial pressures for vehicle- and naloxone-treated cats, respectively (P < 0.001). Naloxone also moderated increases in circulating lysosomal hydrolase activity (4- vs. 23-fold increase) and total plasma proteolysis (33 vs. 100% increase). Plasma myocardial depressant factor activity was also significantly reduced in naloxone-treated hemorrhaged cats compared to shock cats given 0.9% NaCl (16 +/- 3 vs. 58 +/- 4 U, respectively; P < 0.001). Studies on cat papillary muscles demonstrated that naloxone at concentrations slightly higher than estimated plasma values during shock exerted a moderate positive inotropic effect. Our results show that naloxone improved the hemodynamic and biochemical state of cats in hemorrhagic shock. Inhibition of proteolysis and stabilization of lysosomal membranes appear to be ivolved in the protective action of naloxone, along with the well-known opiate-antagonistic action of this agent.
Time dependency of ventricular fibrillation thresholds determined using trains of stimuli
Authors: Winkle Roger A. , Jaillon Patrice , Griffin Jerry C. , Schnittger Ingela
Published: December 2017

When determining ventricular fibrillation threshold (VFT), considerable time elapses from beginning a VFT measurement until the actual occurrence of ventricular fibrillaion (VF). We have defined this elapsed time as the "time to VF" and examined the effect of varying time to VF on the measured value of VFT. We induced VF in anesthetized dogs with a 100-Hz train of 16 4-ms stimuli applied to the right ventricular epicardium. The time to VF was varied by changing either the increment of fibrillation current increase (0.5, 1.0, or 2.0 mA) from one train to the next and/or the number of atrial paced beats between trains (6-192 beats). For 0.5-mA current increments, as time to VF increased from 66 to 454 s, VFT fell progressively from 15.3 ± 4.8 to 6.7 ± 1.1 mA. When time to VF exceeded 454 s, VFT increased again. Current increments of 1.0 and 2.0 mA had a similar time dependency of VFT. For any time to VF the VFT was lower when small current increments (i.e., more trains) were used to induce VF. Pretreatment with reserpine in six dogs abolished the time dependency. We conclude that time elapsed from the beginning of a VFT determination until VF actually occurs and the total number of trains used are important determinants of the VFT, probably because of local catecholamine release by the stimuli.
Time-dependent heart period and contractility responses to successive brief vagal stimuli
Authors: Martin Paul
Published: December 2017

The vagosympathetic trunks of anesthetized propranolized dogs were stimulated with brief electrical bursts, and heart period (P-P interval), atrioventricular conduction (P-R interval), and pressure generated on a balloon anchored in the atrium (AP) were measured. Two vagal stimulus bursts were given separated by an integral number of cardiac cycles but with each placed at the same relative time in the cardiac cycle. The time between stimulus bursts ( T) varied from 2 to 60 s. For all cardiac variables over this time span, the peak response to the second stimulus (P2) was less than that of the first (P1) i.e., the ratio P2/P1 was less than unity. The maximum depression of P2/P1 for all variables occurred at a T of about 5 s. The effect of changing the time in the cardiac cycle at which the stimulus was given, and the effect of stimulus intensity on the P2/P1 ratio was also measured. Previous experiments observing the P-R interval alone suggested that synthesis and release of acetylcholine were not involved in the time dependent P2/P1 effect. The present results suggest that neuroeffector mechanisms at the target cellular level are also not involved in the depression of P2/P1. A time-dependent increase in acetylcholine inactivation is consistent with the present results, but an antagonism between primary and secondary inhibitory effects also cannot be ruled out.
Contractile and biochemical correlates of β-adrenergic stimulation of the aged heart
Authors: Guarnieri T. , Filburn C. R. , Zitnik G. , Roth G. S. , Lakatta E. G.
Published: December 2017

The age dependence of contractile and associated biochemical parameters of basal- and catecholamine-stimulated myocardial contractile performance was investigated using isolated perfused septa from adult and senescent rats. Base-line maximum rate of force development (dF/dt), β-receptor number and affinity, cAMP levels, and cAMP-dependent protein kinase activity were not different in the two age groups. During maximal isoproterenol stimulation, the increase in dF/d t was 40% less in the senescent hearts, and the cAMP levels and cAMP activation of protein kinase increased two fold but to the same extent in both age groups. The maximum contractile response to dibutyryl cAMP (DBcAMP) in the senescent was half that observed in the adult hearts. However, adult and senescent septa responded equally to an increase in perfusate [Ca2+] to 1.0 mM, which enhanced contractility to the same extent as that obtained with isoproterenol and DBcAMP in adult septa. These data taken together suggest that the factors that limit the contractile response to catecholamines in the senescent heart act subsequent to protein kinase activation but proximal to the 2+-troponin interaction.
Early kinetics of large molecule transport between plasma and lymph in dogs
Authors: Watson Philip D. , Bell Donald R. , Renkin Eugene M.
Published: December 2017

Using a mathematical model in which the interstitial space resembled a gel filtration column, Watson and Grodins (Microvasc. Res. 16: 19-41, 1978) predicted that molecules larger than serum albumin should have an early approach to steady state in lymph faster than that of serum albumin. This hypothesis was tested in dogs anesthetized with pentobarbital sodium by use of radiolabeled albumin and fibrinogen and a fluorescent dextran and by collecting lymph from cannulas in the prepopliteal lymphatics of the hind paws. The steady-state lymph-plasma concentration ratios (R), measured chemically, were 0.24 ± 0.02 (SE, n = 16) for albumin and 0.040 ± 0.004 (n = 16) for fibrinogen. In 5 h, albumin and fibrinogen tracers had reached approximatly 25 and 50% of their steady-state levels, respectively. The dextran (mol wt 1.5 x 10(5)) behaved like fibrinogen. The data support the hypothesis that the interstitium has nonrestricting pathways, and that there are gel regions that have a low permeability to very large molecules.
Exclusion of plasma proteins in interstitium of tissues from the dog hind paw
Authors: Bell Donald R. , Watson Philip D. , Renkin Eugene M.
Published: December 2017

Exclusion of plasma albumin and fibrinogen from portions of the extravascular sucrose space in tissues of the hind paw of anesthetized dogs was studied by use of radioactive traces. Thirty hours after a bolus injection of the labeled proteins, tracer concentrations were measured in plasma, prenodal popliteal lymph, and samples of hind paw skin, tendon, muscle, and toe pad. In a few experiments, constant plasma levels of tracer sucrose were maintained for 2 h before terminal sampling. In all experiments a vascular volume marker was given 15 min before termination. A linear correlation was found between the amounts of extravascular protein tracers in the tissue samples and their concentrations in lymph from the same paw, as would be expected if their actual interstitial concentrations were closely related to their lymph concentrations. For albumin, the extravascular distribution volume calculated at lymph concentration was less than the sucrose space for all tissues except toe pad. For fibrinogen, the extravascular distribution volume was less than albumin and sucrose for all tissues except skin. Differences in pattern and degree of exclusion may reflect the differences in interstitial gel-phase composition and structure.
A method to identify implanted radiopaque markers despite rotation of the heart
Authors: Davis Peter L. , Raff Gilbert L. , Glantz Stanton A.
Published: December 2017

Radiopaque endocardial markers implanted by catheter are a useful tool for investigating cardiac function because one can follow the motion to a specific element to myocardium in three dimension. This motion is computed by recording each marker's X-ray shadow with a biplane radiographic system. It is necessary to identify which marker is which on both views to complete this computation. Rotation of the heart with respect of the X-ray system can change the pattern of markers so dramatically that one cannot identify each marker's shadow with confidence. We describe a method to predict where each marker's shadow will be on the X-ray images after the heart rotates, permitting identification of each marker in biplane radiographs, even after extreme changes in the heart's orientation.
Free-wall shortening and relaxation during ejection in the canine right ventricle
Authors: Pouleur H. , Lefevre J. , Van Mechelen H. , Charlier A. A.
Published: December 2017

Relations between shortening, velocity of shortening, and relaxation of inflow and outflow segments of the right ventricular (RV) free wall (FW) were examined during ejection in 12 open-chest dogs after pharmacologic blockade by recording RV pressures, RVFW dimensions (piezoelectric crystals), and pulmonary blood flow. At heart rates of 113 +/0 8 (SD) beats/min, investigated segments remained isometric or even lengthened before the end of ejection. Tension-length data in the outflow tract converged at the time of peak systolic tension toward a common linear relation (average slope 65 +/- 10 cmH2O/mm, average intercept 5.9 +/- 0.9 mm), but markedly deviated from this line at the end of ejection. Consistent relations between peak tension and mean velocity of shortening were only observed during the first part of ejection. In addition the rate of segmental isometric relaxation, estimated from RV pressure fall was load dependent (e.g., +60% increase in relaxation rate when RVFW end-diastolic segment length increased from 12.9 +/- 0.8 to 13.5 +/- 0.8 mm). We conclude that under normal conditions, the tension-velocity-length relations of the RVFW are comparable to those of the left ventricle during the first part of ejection only. We also conclude that RV relaxation is load dependent and that a significant part of RV ejection occurs during RVFW relaxation.
Limitations in predicting oxyhemoglobin saturation of dog blood from PO2
Authors: Saito D. , Olsson R. A.
Published: December 2017

This study compared oxyhemoglobin saturation (SO2) and O2 content (CO2) estimated from O2 tension (PO2) by the Rossing-Cain nomogram (J. Appl. Physiol. 21: 195-201, 1966) with SO2 and CO2 estimated by a galvanometric O2 analyzer in blood samples from eight dogs. The nomogram consistently and significantly overestimated SO2 over the range of 20-60%. The greatest absolute difference, which averaged 10% saturation, was between 40 and 59% saturation. Between 30 and 39% saturation, the difference averaged 30% of SO2 estimated galvanometrically. CO2, calculated as the product of SO2, hemoglobin concentration (cyanmethemoglobin method), and hemoglobin O2 capacity, was significantly overestimated by the nomogram by as much as 1.2 ml/dl between 2 and 9.9 ml/dl. Between 14 and 21.9 ml/dl, the nomogram underestimated CO2 by as much as 1.2 ml/dl. We conclude that because coronary venous SO2 and CO2 values normally lie in the range of greatest error, estimates of these values based on PO2 are particularly unsuited for studies of myocardial O2 usage.
Adrenal contribution to cardiac responses elicited by acute hypoxia in piglets
Authors: Lee J. C. , Werner J. C. , Downing S. E.
Published: December 2017

The adrenal contribution to cardiac responses elicited by acute hypoxia was assessed in 16 piglets, 1-12 wks old, anesthetized with pentobarbital (30 mg/kg). External cardiac work was held constant and parasympathetic blockade was produced in each animal with atropine (1 mg). Hypoxia was produced by addition of N2 to the respirator. In a sham-adrenalectomy group (n = 6) left ventricular (LV) dP/dtmax increased significantly during hypoxia (PaO2 approximately 30 mmHg) to 3,680 +/- 414 mmHg/s from control values of 2,686 +/- 317 mmHg/s (P < 0.01). Heart rate rose from 171 +/- 6 to 186 +/- 7 beats/min (P < 0.02). These responses were not significantly altered by ganglionic blockade with trimethaphan camsylate (0.5 mg x kg-1 x min-1). Equally large increases of LV dP/dtmax appeared when heart rate was held constant by pacing. beta-Adrenoreceptor blockade with practolol (4 mg/kg) sharply reduced but did not eliminate the response. In contrast, no changes in LV dP/dtmax or heart rate were observed during hypoxia in adrenalectomized piglets (n = 6). These findings indicate that the increased cardiac contractility during acute hypoxia in piglets is dependent on the integrity of the adrenal glands and that there is minimal contribution from cardiac sympathetic nerves.
Errors in calculated oncotic pressure of dog plasma
Authors: Gabel J. C. , Scott R. L. , Adair T. H. , Drake R. E. , Traber D. L.
Published: December 2017

Several equations to calculate plasma oncotic pressure (pi) from the total protein concentration (C) have been previously described. These equations were derived empirically from samples with a wide range of C obtained by diluting or concentrating normal plasma samples. To test these equations over a range of naturally occurring C, we measured C and pi of plasma samples from 40 dogs. C ranged from 5.3 to 8.7 g/dl and averaged 6.5 +/- 0.1 (mean +/- SE) and pi averaged 17.9 +/- 0.3 mmHg. The regression equation was pi = 78.14 + 1.67 C (r = 0.74). pi increased with C much less than predicted with the commonly used equations. The albumin-to-globulin concentration ratios (A/G), determined in 27 of the dogs, decreased with increasing C (A/G = 1.56-0.128 C, r = 0.62). The lower A/G at the higher C's could cause the lower than predicted increase in pi with C, because the equations were developed from data in which A/G was constant.
Computation of transport function using multiple regression analysis
Authors: Nakai M.
Published: December 2017

A multiple regression analysis, which allows a simultaneous introduction of smoothing, was adopted for a numerical deconvolution process to obtain the transport function from a pair of indicator dilution curves. This process solves concurrently restricting linear quadratic or cubic equations that are fitted to small sections of the transport function curve, an equation that forces the tail part to zero, and uses conditions that restrict the area under the transport function to unity. Each restricting linear equation can be manually stressed by adjusting its corresponding weight iteratively so that unreasonable oscillations emerging on any particular portion of the transport function curve can be suppressed. Stability of the method was tested with various pairs of dilution curves in terms of mathematical models and with those experimentally obtained from the dog portal circulation. The deconvolution by means of the regression analysis with simultaneous smoothing was shown to be far less sensitive to observational errors in the dilution curves or sampling rates than that by means of the direct method without the regression analysis. Multiple regression analysis with simultaneous smoothing was also applied to the deconvolution process using the multiple fitting functions developed by Knopp et al. (Ann. Biomed. Eng. 4: 44-59, 1976). This process was shown to perform a stable deconvolution as well.
Effect of temperature on hydraulic conductivity of single capillaries
Authors: Curry F. E.
Published: December 2017

Paired determinations of the hydraulic conductivity (Lv) of individually perfused capillaries in frog mesentery were measured at 22-25 and 5-8 degrees C. The mean value of the ratio of the hydraulic conductivity at 22-25 to that at 5-8 degrees C was 1.76 +/- 0.22 (SE) in 10 capillaries perfused with albumin in the Ringer perfusate and 1.81 +/- 0.11 in six capillaries perfused with Ringer alone. The ratio of Lp can be accounted for in terms of a 1.60-fold increase in water viscosity between 22-25 and 5-8 degrees C. The results conform to the hypothesis that the structure of the principal pathway for water across the capillary wall is invariant with temperature; models of the water pathway that imply a change in the number of pathways or a change in pathway structure with temperature are incompatible with these results. Temperature gradients across the tissue are negligible in these experiments; calculations show that in the presence of temperature gradients, which occur during tissue cooling or rewarming, transcapillary water flows due to thermoosmosis are likely to occur.
Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery
Authors: Rabinovitch M. , Gamble W. J. , Miettinen O. S. , Reid L.
Published: December 2017

To study the influence of age and sex on the hemodynamic and structural response of the pulmonary vascular bed to chronic hypobaric hypoxia, “infant” Sprague-Dawley rats from 8 days old and “adult” rats from 9 wk old, each group including both sexes, were exposed to half atmospheric pressure for 1 mo and then allowed to recover in room air for up to 3 mo. During hypoxic exposure, pulmonary artery hypertension (Ppa) developed in all groups. The level of Ppa was similar in both male and female infant and in male adult rats but was significantly lower (P < 0.01) in the female adult rats. After recovery in room air, only partial regression of Ppa had occurred in all groups (P < 0.001). In male and female adult rats, recovery values were similar but infant rats had more residual Ppa than adults (P < 0.001). The structural changes that developed during hypoxia, especially the abnormal presence of muscle in small and peripheral intra-acinar arteries, were more severe in male adult rats compared with female adults (P < 0.01) and in infants of both sexes compared with male adults (P < 0.01). After recovery, residual structural changes were present in all rat groups but were most severe in the infants (P < 0.01).
Continuous measurement of coronary artery diameter in situ
Authors: Tomoike H. , Ootsubo H. , Sakai K. , Kikuchi Y. , Nakamura M.
Published: December 2017

The diameter of the coronary artery was measured in dogs in situ by an ultrasonic dimension gauge using 10-MHz piezoelectric crystals. Underestimation in measurements due to crystal rotation was limited to < 1% by adding a convex lens to the crystal. A pair of small 10- and 5-MHz crystals were sutured to the adventitia of the left circumflex coronary artery (LCX) and the descending aorta (Ao), respectively. Using cuff occluders for vessel constriction of the inferior vena cava (IVC) or the Ao, curvilinear relationships between pressure and diameters were obtained. Phasic changes of the aortic as well as coronary diameter were grossly similar to changes in the pressure wave. After intravenous administration of dipyridamole, aortic pressure (AP) decreased by 17% along with 3% decline of the Ao and LCX diameter, however, after nitroglycerin given by the same route, LCX diameter increased by 5% (P < 0.05) despite 16% and 2.3% reductions in AP and Ao diameter, respectively. This ultrasonic technique, which allows continuous measurement of the diameter of small vessels, should provide a new tool for the study of coronary circulation.
Right ventricular distension and left ventricular compliance
Authors: Lorell B. H. , Palacios I. , Daggett W. M. , Jacobs M. L. , Fowler B. N. , Newell J. B.
Published: December 2017

The constraint of the right ventricle (RV) on the end-diastolic pressure-volume (PV) relationship of the nonischemic and ischemic left ventricle (LV) was studied. The model used was the isovolumic beating LV, with separately perfused ejecting RV with controlled RV distension. The effect of augmented RV distension on the nonischemic LV PV relationship was examined. A change from mild [right ventricular end-diastolic pressure (RVEDP) = 1.5 mm Hg] to severe (RVEDP = 16 mmHg) RV distension resulted in a significant leftward shift of the LV PV relationship. Ischemia was produced for 90 min by reducing flow in the cannulated left main coronary artery and the effect of two levels of stable RV distension on the PV relationship of the ischemic LV was examined. Mild RV distension and moderate (RVEDP = 6 mmHg) RV distension were used. In both groups, there was a progressive leftward shift in the LV PV relationship that was significant by 60 min of ischemia. No change was seen in nonischemic controls. Ventricular relaxation, as described by the time constant of isovolumic relaxation, T, was impaired throughout ischemia but was not sufficiently prolonged to explain the above changes. Thus, the time course of change in the LV PV relationship during ischemia differs from that previously reported after pacing-induced ischemia in humans. Neither the external constraint of the RV nor incomplete relaxation explains this difference.
Bainbridge reflex in conscious, unrestrained, and tranquilized baboons
Authors: Vatner S. F. , Zimpfer M.
Published: December 2017

The effects of volume loading were examined in conscious, unrestrained, and tranquilized baboons (20-25 kg) 1-3 mo after instrumentation with miniature left ventricular pressure and diameter gauges. The response to volume loading was accompanied by significant increases (P less than 0.01) in cardiac rate (32 +/- 4 beats/min) in tranquilized baboons. When rapid saline infusion was accomplished in conscious unrestrained baboons by means of activating a remote-controlled interrogator, heart rate also rose significantly (41 +/- 8 beats/min, P less than 0.01). After cholinergic blockade with atropine, ganglionic blockade with hexamethonium, bilateral vagotomy, or combined cholinergic and beta-adrenergic blockades, volume loading failed to increase heart rate. In two smaller (12-14 kg) intact conscious baboons with relatively high spontaneous heart rates, volume loading did not alter heart rate. These experiments suggest that the Bainbridge reflex exists in larger primates with relatively low spontaneous heart rates.
Effects of changes in arterial O2 content on cerebral blood flow in the lamb
Authors: Jones M. D. , Traystman R. J. , Simmons M. A. , Molteni R. A.
Published: December 2017

The effect of variations in arterial O2 content (CaO2) on the cerebrovascular bed of seven unanesthetized newborn lambs was studied as the hematocrit and arterial PO2 (PaO2) were varied. Each subject was studied at a high hematocrit [44 +/- 3% (SD)] and a low hematocrit [24 +/- 3%]. At each hematocrit level the PaO2 was changed over a range of 30-150 mmHg. The relationship between cerebral blood flow and PO2 depended on hematocrit and vice versa. To the contrary, the relationship of blood flow to CaO2 was independent of hematocrit and/or PO/. As CaO2 fell, regardless of whether this was due to a fall in PO2 hematocrit or both, there was a reciprocal increase in cerebral blood flow such that cerebral O2 delivery (cerebral blood flow x CaO2) was constant. These data show that CaO2 is a variable of fundamental importance to the regulation of cerebral blood flow. Changes in CaO2 are accompanied by reciprocal changes in cerebral blood flow to maintain constant cerebral O2 delivery. Data among species with differing cerebral O2 consumption show that cerebral O2 delivery, in turn, is regulated according to cerebral O2 consumption.
Excitation-contraction coupling in mammalian cardiac muscle during Ba2+-induced contracture
Authors: Saeki Y. , Shibata T. , Shiozawa K.
Published: December 2017

The membrane potential and tension were recorded during contracture of mammalian ventricular muscles bathed in Tyrode solution with Ba2+ in the place of Ca2+. Strength of contracture increased with increasing Ba2+ concentration from 0.1 to 4 mM and reached a plateau above 4 mM. The membrane potential was depolarized to about -35 mV with 0.1 mM Ba2+ and to -20 mV with 5 mM Ba2+. When 0.5 mM Mn2+ was added to Ba2+-Tyrode solution, in which the muscle had been in a state of steady contracture, the muscle immediately started to relax to the resting level. In contrast, addition of 2 micrograms/ml epinephrine to Ba2+-Tyrode solution increased the strength of the contracture. Neither epinephrine nor Mn2+ caused any noticeable changes of the depolarized membrane potential. The results suggest that Ba2+ not only activates the contractile system but also depolarizes the membrane potential independently of activating the contractile system. These two remarkable actions of Ba2+ seem to be responsible for the long-lasting contracture.
Rabbit cardiac immunoreactive cathepsin D content during starvation-induced atrophy
Authors: Samarel A. M. , Ogunro E. A. , Ferguson A. G. , Allenby P. , Lesch M.
Published: December 2017

To determine whether the increased activity of cathepsin D observed during starvation-induced cardiac atrophy results from activation of preexisting enzyme or synthesis of new enzyme, a solid phase double-antibody radioimmunoassay was developed for measurement of immunoreactive cathepsin D in extracts of rabbit myocardium. Cathepsin D activity was significantly increased in the hearts of animals starved for 3, 7, and 14 days (82.6 +/- 0.8, 87.2 +/- 3.8, and 95.3 +/- 3.5 U/g wet wt, respectively) compared to controls (65.5 +/- 1.4 U/g wet wt; P less than 0.001). Immunoreactive cathepsin D was increased to a greater extent (168 +/- 7, 179 +/- 16, 200 +/- 17, and 104 +/- 5 micrograms/g wet wt for 3-, 7-, and 14-day starvation and controls, respectively; P less than 0.001) than that expected on the basis of the observed increase in enzyme activity. Sephadex G100 gel filtration of cardiac lysosomal extracts from starved and control animals revealed no evidence of high or low molecular weight forms of cathepsin D. The results suggest the observed increase in cathepsin D activity during starvation-induced cardiac atrophy is accompanied by an increased synthesis and/or decreased degradation of cathepsin D protein, rather than activation of preexisting enzyme. The lower activity levels observed during starvation possibly result from alterations in the concentrations of endogenous inhibitors or activators of cathepsin D.
Preload changes modify systolic pressure-diameter relations in the conscious dog
Authors: Crozatier B. , Caillet D. , Thuillez C. , Chevrier J. L. , Peronneau P. , Hatt P. Y.
Published: December 2017

The behavior of the end-systolic ventricular diameter was examined during control state, atrial pacing, and acute volume loading (VL) followed by methoxamine infusion in conscious dogs instrumented with a left ventricular micromanometer and ultrasonic crystals measuring internal diameter and wall thickness. Heart rate and systolic pressure were markedly increased by maximal VL but for moderate VL were minimally modified. Moderate VL increased end-diastolic diameter by 5% and end-systolic diameter by 2.9% with a significant increase of systolic stress. There was no common final pathway of shortening in the force-velocity-length diagram for different preloads. During methoxamine infusion, the end-systolic pressure-diameter points described a linear regression but points obtained during atrial pacing before VL were significantly shorter. We conclude that VL increases the total loading of the heart producing a lengthening of the end-systolic diameter when end-diastolic diameter is increased. This reduces the expression of the Starling mechanism and suggests caution when interpreting end-systolic pressure-diameter relations and derived indices for significantly different end-diastolic diameters.
Reversal of cardiac hypertrophy in renal hypertensive rats: medical vs. surgical therapy
Authors: Sen S. , Tarazi R. C. , Bumpus F. M.
Published: December 2017

Cardiac hypertrophy consequent to renovascular hypertension was investigated in two-kidney one-clip Goldblatt rats. Ventricular weight in renal hypertensive rats correlated closely with level of arterial pressure (r = 0.93, P less than 0.001). DNA, RNA and hydroxyproline contents of the hypertrophied hearts were higher than sham control, but there was no significant change in myocardial concentration of any of them. Surgical treatment (removal of clipped kidney) as well as medical therapy (inhibition of converting enzyme with orally administered captopril, 150 mg/l drinking water) led to reduction of ventricular weight (2.70 +/- 0.01 and 2.78 +/- 0.06, respectively, vs. 3.4 +/- 0.05 mg/g in controls, P less than 0.01 for both). Reduction of cardiac weight was associated with increase in both myocardial concentration and content of hydroxyproline in surgically treated rats and in medically treated animals. Ventricular catecholamine concentration was increased after nephrectomy but was unchanged by captopril treatment.
Effects of indomethacin in dogs with acute and chronic renovascular hypertension
Authors: Dietz J. R. , Davis J. O. , DeForrest J. M. , Freeman R. H. , Echtenkamp S. F. , Seymour A. A.
Published: December 2017

This study examines the role that prostaglandins play in both the developmental and chronic phases of renovascular hypertension. Two 5-mg/kg doses of indomethacin were given to conscious dogs with renal denervation and receiving propranolol during the acute and chronic phases of one-kidney (1-KHT) and the acute phase of two-kidney (2-KHT) renovascular hypertension. Indomethacin produced striking reductions in plasma renin activity from the high level observed during the acute phase of both 1-KHT and 2-KHT. However, plasma renin activity failed to return to normal, and the hypertensive level of pressure decreased only slightly. In the chronic 1-KHT dogs, indomethacin did not lower plasma renin activity or mean arterial blood pressure unless plasma renin activity was elevated above the normal level. Also, indomethacin failed to alter renal function during the acute phase of 1-KHT but effective renal plasma flow fell during chronic 1-KHT. These results suggest that, in the dog, renal prostaglandins are involved in the pathogenesis of both acute 1-KHT and 2-KHT, whereas the role of renal prostaglandins in the regulation of arterial pressure appears to be negligible in chronic 1-KHT except during superimposed sodium depletion or severe hypertension. The data indicate that prostaglandins are involved in renovascular hypertension in the dog only under conditions where plasma renin activity is elevated. It is suggested that the release of renin after renal artery constriction is mediated by the vascular receptor that is at least partially independent of renal prostaglandin synthesis.
Role of calcium and sodium in strophanthidin inotropy in cardiac Purkinje fibers
Authors: Bhattacharyya M. L. , Vassalle M.
Published: December 2017

The effects of strophanthidin on electrical and mechanical events in canine cardiac Purkinje fibers were studied in vitro in the absence and presence of tetrodotoxin (TTX), norepinephrine, and high calcium. In Tyrode solution, strophanthidin (1-3 X 10(-7) M), norepinephrine (3-5 X 10(-7) M), and high calcium 8.1 mM) increased the force of contraction, and TTX markedly reduced it. In the presence of TTX, strophanthidin had little or no inotropic effect, whereas that of norepinephrine and high calcium was less than in Tyrode solution. In the presence of TTX, strophanthidin increased force markedly if (and as long as) either norepinephrine or high calcium were also present. A higher dose of strophanthidin (10(-6) M) induced a markedly delayed increase in force in presence of TTX. The results suggest that, in the presence of TTX, in a low concentration strophanthidin has little effect on force, because cellular calcium is low; however, it becomes effective when the calcium is increased by norepinephrine or high calcium. In toxic doses, strophanthidin increases force even in the presence of TTX as the inhibition of the pump should increase intracellular sodium and therefore calcium.
Absence of active cutaneous vasodilation associated with congenital absence of sweat glands in humans
Authors: Brengelmann G. L. , Freund P. R. , Rowell L. B. , Olerud J. E. , Kraning K. K.
Published: December 2017

In the rare syndrome, hereditary anhidrotic ectodermal dysplasia (AED), sweat glands are congenitally absent. Assuming normal vasculature and normal central mechanisms, presence or absence of active cutaneous vasodilation (AVD) in hyperthermic subjects with AED critically tests the hypothesis that AVD is a consequence of sudomotor activity. Three men with full expression of the syndrome and a woman who is mosaic were heated in water-perfused suits until oral temperature was 1.4-1.7 degrees C above control. The men showed no sweat gland imprints on iodine-treated paper nor significant elevation in forearm blood flow (FBF, determined plethysmographically). In the woman, we observed sweat gland activity, approximately 9 and 22 glands/cm2, on the right and left side, respectively, and vasodilation, slight on the right and more on the left. Cutaneous vasoconstriction in response to negative pressure applied to the lower body was observed (3 subjects) and local FBF increased in response to local heating (2 subjects). Therefore, in AED, with apparently normal cutaneous vasculature and sympathetic innervation, AVD is absent as well as sweat glands.
Sympathetic neural effects on regional atrial recovery properties and cardiac rhythm
Authors: Kralios F. A. , Millar C. K.
Published: December 2017

The functional distribution of the cardiac sympathetic nerves to the atria and their arrhythmiogenic effects were determined in 16 open-chest pentobarbital-anesthetized dogs. Shortening of refractory periods at four right and two left atrial sites during stimulation of the nerves was taken as a criterion of their distribution. Stimulation of right stellate ganglion, craniovagal, and right stellate cardiac nerves produced localized shortening on the right atrium, particularly at the sinus node area, and invariably induced sinus tachycardia. The recurrent cardiac nerve produced little shortening at all sites and less arrhythmiogenic effect. The left stellate ganglion and ventrolateral cardiac nerve affected only left atrial sites and induced atrioventricular junctional rhythm. The ventromedial cardiac nerve affected all sites and had no consistent arrhythmiogenic effect. The innominate nerve had no substantial effect. We concluded that the functional distribution of the cardiac sympathetic nerves is localized, and that rate, rhythm, and refractory period changes induced by stimulation of these nerves are characteristic of the area of distribution.
Maximal negative dP/dt as an indicator of end of systole
Authors: Abel F. L.
Published: December 2017

The maximal negative peak of the first derivative of left ventricular pressure was examined as an index of the end of ventricular ejection by comparing it with the end of aortic flow. Under varying heart rate and afterload situations in anesthetized dogs, a correlation coefficient of 0.982 was obtained with a mean error of less than 0.4 ms. This may be a useful end point for determining systolic time where only ventricular pressure is available.
Ca2+ sensitivity change and troponin loss in cardiac natural actomyosin after coronary occlusion
Authors: Toyo-Oka T. , Ross J.
Published: December 2017

Ca2+ sensitivity of natural actomyosin (NAM) isolated from both the intact left ventricular free wall and an area of myocardial infarction (MI) was analyzed by use of superprecipitation response from 2 to 48 h after left anterior descending coronary artery ligation in the dog. NAM from the intact tissue showed normal superprecipitation and normal Ca2+ sensitivity. Four hours after coronary ligation, Ca2+ sensitivity was lowered only in the endocardial half of MI region; it was markedly decreased both in the epicardial and endocardial halves at 6 h and completely lost at 24 and 48 h. A superprecipitation response was, however, demonstrated in all samples, indicating that both myosin and actin preserved their functions in the course of MI. With polyacrylamide gel electrophoresis in sodium dodecyl sulfate, NAM from the MI region revealed moderate decrease of the tropomyosin-binding subunit of troponin(TN-T) and the Ca2+-binding subunit of troponin(TN-C) and drastic decrease of the inhibitory subunit of troponin(TN-I). This resulted in the formation of extra bands of low molecular weights. These results suggest that degradation of troponin subunits occurs relatively early (4 h after coronary artery occlusion) and from the endocardial half of MI region. This degradation may be caused by one or several proteases that preferentially degrade the regulatory proteins among myofibrillar proteins.
Pharmacologic- vs. ischemia-induced coronary artery vasodilation
Authors: Warltier D. C. , Gross G. J. , Brooks H. L.
Published: December 2017

Responses of total coronary and regional myocardial blood flow to ischemia- or drug-induced coronary artery vasodilation were studied in open-chest anesthetized dogs. Systolic, diastolic, and mean coronary blood flow after addition of chromonar (8 mg/kg iv), adenosine triphosphate (400 micrograms/min intracoronary), or adenosine (500 micrograms/min intracoronary) exceeded the respective flow at the peak of reactive hyperemia (90-s occlusion period). Whereas the regional distribution of total coronary flow favored the subendocardium of the left ventricle during reactive hyperemia, flow was preferentially distributed to subepicardium during drug-induced maximal coronary artery vasodilation. These results were independent of type of anesthesia, vasodilator agent, or degree of autonomic innervation. These data indicate that total coronary vasodilator reserve is greater than that observed at the peak of reactive hyperemia and that there is a transmural gradient of vasodilator reserve within the left ventricle. A greater regional vasodilator reserve is present in subepicardial than in subendocardial layers.
Blood flow and high-energy phosphates in microregions of left ventricular subendocardium
Authors: Kleinert H. D. , Weiss H. R.
Published: December 2017

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.
Effect of various degrees of systemic arterial hypertension on acute canine myocrdial ischemia
Authors: Hillis L. D. , Izquierdo C. , Davis C. , Brotherton S. , Eberhart R. , Roan P. G. , Willerson J. T.
Published: December 2017

There is continuing uncertainty about the effects of various degrees of systemic arterial hypertension on myocardial ischemia. In 46 open-chest anesthetized dogs, intramural carbon dioxide tension (PmCO2) was measured directly with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow. During each occlusion, transmural regional myocardial blood flow (RMBF) in the ischemic area was quantitated with the injection of radioactive microspheres (7-10 micrometers diam). In all dogs the increase in PmCO2 from before to 10 min after the first occlusion (delta PmCO2) exceeded that during subsequent occlusions. In those dogs in which systemic arterial hypertension was not produced (controls), delta PmCO2 during the third occlusion was similar to that during the second occlusion. When phenylephrine was administered during the third occlusion to increase systemic arterial pressure mildly (diastolic pressure 95-115 mmHg), RMBF to the ischemic myocardium was unchanged, and the severity of myocardial ischemia was reduced, as reflected by a fall in delta PmCO2. When diastolic pressure was elevated moderately (116-140 mmHg), RMBF was augmented, but the extent of myocardial ischemia was neither diminished nor worsened. In contrast, when diastolic pressure was increased markedly (greater than 140 mmHg), myocardial ischemic injury was intensified (as reflected by an increase in delta PmCO2) even though RMBF rose significantly. Thus, in the dog with acute coronary artery occlusion, an increase of systemic arterial pressure exerts an influence on the severity of myocardial ischemic injury that is related directly to the magnitude of systemic arterial hypertension: a mild increase of pressure reduces ischemic injury, a moderate increase exerts no consistent effect on ischemia, and a marked increase worsens ischemic injury.
Pressor responses to vasopressin in rabbits with 3-day renal artery stenosis
Authors: Johnson J. A. , Ichikawa S. , Kurz K. D. , Fowler W. L. , Payne C. G.
Published: December 2017

One-kidney rabbits were subjected to renal artery stenosis, and acute experiments were performed 3 days later on conscious animals; one-kidney rabbits without renal artery stenosis served as controls. Rabbits with 3-day renal artery stenosis were normotensive and had normal values for plasma renin activity. Intravenous infusion of arginine vasopressin at 5 mU.min-1.kg body wt-1 for 5 min resulted in a significantly (P less than 0.01) greater increase in mean arterial pressure and total peripheral resistance (TPR) in the renal artery stenosis rabbits than in the controls. Infusion of the angiotensin II (AII) competitive antagonist, [Sar1, Ile8]AII, before the vasopressin infusion abolished the hyperresponsiveness to vasopressin in the renal artery stenosis rabbits and resulted in changes in mean arterial pressure and TPR that were approximately of the same magnitude as the controls. Infusion of [SAr1, Ile8]AII before vasopressin infusion in control rabbits did not alter the cardiovascular responses to vasopressin. Because previous studies have shown that 3-day renal artery stenosis rabbits have exaggerated pressor responses to norepinephrine and that this hyperresponsiveness to norepinephrine is blocked by [Sar1, Ile8]-AII, the present study with vasopressin provided evidence that the increased responsiveness in this model is not specific for a single pressor agent. These studies also demonstrated that AII plays an important role in mediating the exaggerated pressor responses to vasopressin in this prehypertensive model.
Cutaneous and skeletal muscle vascular responses to hypothermia
Authors: Major T. C. , Schwinghamer J. M. , Winston S.
Published: December 2017

Vascular resistance and capacitance were studied in innervated or denervated canine forelimbs. Hypothermia (38-28 degrees C) was induced systemically, by external cooling of blood which returned to the right heart, or locally, by cooling blood perfusing the forelimb. Systemic cooling to 33 and then to 28 degrees C elicited significant decreases in limb weight with substantial increases in both skin and skeletal muscle vascular resistances. Acute denervation of the forelimbs attenuated both the fall in limb weight and increase in skin vascular resistance associated with cooling. These data support the contention that cutaneous vasoconstriction during systemic cooling is mediated primarily by sympathetic nerves, whereas skeletal muscle vasoconstriction is mediated primarily by circulating hormones. Local cooling elicited skin and skeletal muscle vascular dilation at 33 degrees C in both innervated and denervated forelimbs whereas either no change or a slight increase in skin and skeletal muscle vascular resistance resulted upon local cooling to 28 degrees C, perhaps due to the inhibition of Na+ - K+ - ATPase activity and/or a rise in blood viscosity. The locally induced vasodilation was found to override the powerful vasoconstrictor response caused by systemic cooling. The vasodilation is considered active rather than passive, because the increase in forelimb weight and decreases in forelimb vascular resistances occurred in the denervated as well as innervated limbs.