bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrotonic interactions in delayed propagation and block within the guinea pig SA node
Authors: Lipsius S. L.
Published: December 2017

The influence of electrotonic interactions on propagation within the SA node was studied by recording transmembrane potentials simultaneously from two neighboring (less than 1 mm apart) subsidiary pacemaker cells within the sinoatrial (SA) node of the guinea pig. As single premature stimuli were delivered progressively earlier in diastole, retrograde propagation between cells was delayed progressively. Cells activated earlier displayed secondary depolarizations that were coincident with the depolarization of neighboring cells activated later. The secondary depolarizations increased action potential duration markedly. Rapid pacing elicited secondary depolarizations that resulted in a progressive increase in action potential duration and decrease in upstroke amplitude. These changes were associated with a progressive delay in retrograde propagation that led to intermittent block with Wenckebach periodicity. Exposure to tetrodotoxin (10(-5) g/ml) delayed antegrade propagation, resulting in electrotonically mediated secondary depolarizations and exit block with Wenckebach periodicity. It is concluded that delayed activation and electrotonically mediated interactions between cells can increase action potential duration and refractoriness. These changes contribute to progressive delays in propagation that may result in intermittent block with Wenckebach periodicity within the SA node.
Impaired baroreflex control of vascular resistance in prehypertensive Dahl S rats
Authors: Gordon F. J. , Mark A. L.
Published: December 2017

The purpose of this study was to examine baroreflex control of vascular resistance and heart rate in prehypertensive Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Urethan-anesthetized normotensive DS rats demonstrated significantly impaired baroreflex control of both hindlimb vascular resistance and heart rate. This impairment was not secondary to elevated arterial pressure since blood pressure did not differ between DR and DS rats fed a low sodium diet. Vascular baroreflex responses were shown to depend on the integrity of efferent sympathetic innervation and to be mediated by the sinoaortic afferent arterial baroreceptors. No strain difference was observed for hindlimb vasodilation produced by papaverine or graded doses of nitroprusside, indicating that differences in resistance vessel vasodilator capacity or responsiveness could not account for differences in baroreflex responses. Since impaired baroreflex control was evident in DS rats prior to any elevation in arterial pressure, this abnormality may contribute to the DS rat's genetic propensity to develop hypertension.
Decreased myocardial Na+-K+-ATPase activity in one-kidney, one-clip hypertensive rats
Authors: Clough D. L. , Pamnani M. B. , Haddy F. J.
Published: December 2017

We have previously shown that Na+-K+ pump activity (ouabain-sensitive 86Rb uptake) is decreased in vascular tissue of animals with various forms of low renin hypertension. In the present study we measured Na+-K+-ATPase activity, the energy source for Na+-K+ pumping, in membrane fractions prepared from myocardial tissue of rats with chronic one-kidney, one-clip hypertension and their one-kidney normotensive controls. Membranes were prepared by two independent methods: microsomal fractions (method 1) and fractions prepared by the hypotonic LiBr method of Dhalla et al. (method 2). In membranes prepared from left ventricles of the hypertensive rats (by method 1) Na+-K+-ATPase activity was decreased, Mg2+-ATPase activity was increased, and the sialic acid content and 5'-nucleotidase activity (two putative membrane markers) were unchanged relative to the control rats. The sensitivity of cardiac Na+-K+-ATPase to inhibition by ouabain was also unchanged. Na+-K+-ATPase activity was also decreased in the right ventricles (method 1) of these hypertensive rats, suggesting that this defect is probably not pressure related. In membranes prepared from the left ventricles of the hypertensive rats by method 2, Na+-K+-ATPase activity was again reduced, whereas the Mg2+-ATPase and 5'-nucleotidase activities were unchanged relative to the controls. These studies suggest that myocardial Na+-K+-ATPase activity is suppressed in rats with this low renin form of hypertension and the possible effect of this suppression on myocardial contractile activity is discussed.
Kinetics of rouleaux formation using TV image analyzer. II. Rat erythrocytes
Authors: Shiga T. , Imaizumi K. , Maeda N. , Kon K.
Published: December 2017

With the use of a rheoscope combined with a TV image analyzer, the kinetics of specific pathogen-free rat erythrocyte aggregation was studied. Under certain conditions (gamma 7.5 s-1, hematocrit 0.36%, in own plasma, at 25 degrees C) one-dimensional aggregates (rouleaux) were formed without the development of three-dimensional aggregates, perhaps because of very low concentration of gamma-globulin. The observed phenomena could be explained by 1) the erythrocyte sedimentation and 2) the rouleaux formation. The time courses, of the biphasic change in erythrocyte count and of the increments in total area and in the area/count, were successfully simulated by a kinetic model of linear polymerization, assuming a sedimentation rate constant and an association rate constant. Further, a Poissonlike distribution of the length of rouleaux was shown, as predicted theoretically on the basis of the same kinetic model.
Blood flow to different skeletal muscle fiber types during contraction
Authors: Mackie B. G. , Terjung R. L.
Published: December 2017

Blood flow to fast-twitch red (FTR), fast-twitch white (FTW), and slow-twitch red (STR) muscle fiber sections of the gastrocnemius-plantaris-soleus muscle group was determined using 15 +/- 3-microns microspheres during in situ stimulation in pentobarbital-anesthetized rats. Steady-state blood flows were assessed during the 10th min of contraction using twitch (0.1, 0.5, 1, 3, and 5 Hz) and tetanic (7.5, 15, 30, 60, and 120/min) stimulation conditions. In addition, an earlier blood flow determination was begun at 3 min (twitch series) or at 30 s (tetanic series) of stimulation. Blood flow was highest in the FTR (220-240 ml X min-1 X 100 g-1), intermediate in the STR (140), and lowest in the FTW (70-80) section during tetanic contraction conditions estimated to coincide with the peak aerobic function of each fiber type. These blood flows are fairly proportional to the differences in oxidative capacity among fiber types. Further, their absolute values are similar to those predicted from the relationship between blood flow and oxidative capacity found by others for dog and cat muscles. During low-frequency contraction conditions, initial blood flow to the FTR and STR sections were excessively high and not dependent on contraction frequency. However, blood flows subsequently decreased to values in keeping with the relative energy demands. In contrast, FTW muscle did not exhibit this time-dependent relative hyperemia. Thus, besides the obvious quantitative differences between skeletal muscle fiber types, there are qualitative differences in blood flow response during contractions. Our findings establish that, based on fiber type composition, a heterogeneity in blood flow distribution can occur within a whole muscle during contraction.
Cardiac and splenic norepinephrine turnovers in endotoxic rats
Authors: Pardini B. J. , Jones S. B. , Filkins J. P.
Published: December 2017

Although sympathetic hyperactivity has been implicated in the pathogenesis of endotoxin shock, methodologies employed to assess the activity have been indirect in nature and results have been equivocal. The present experiments quantitated postganglionic sympathetic activity by measuring norepinephrine (NE) turnovers in hearts and spleens of fasted male Holtzman rats injected intravenously with Salmonella enteritidis lipopolysaccharide (2 mg/300 g rat; 5.7-6.7 mg/kg). NE turnovers were measured over 12 h by the [3H]NE decay method. Cardiac NE turnovers were increased in endotoxic rats (0.075 micrograms X g-1 X h-1) compared with controls (0.009). Similarly, NE turnovers in spleens of endotoxic rats (0.099 micrograms X g-1 X h-1) were increased compared with control rats (0.033). Because NE reuptake is depressed in spleens of severely shocked endotoxic rats, the singular effect of reduced reuptake (desmethylimipramine treatment, 20 mg/kg) on NE turnovers was evaluated in spleens of a separate group of control rats. Desmethylimipramine had no effect on the slopes of the NE decay lines compared with untreated rats (-0.015 +/- 0.008 vs. -0.015 +/- 0.029, respectively). Thus these experiments support the concept of heightened sympathetic activation during endotoxicosis as assessed quantitatively in a noninvasive, unanesthetized rat model.
Adrenergic control in three artery segments of diminishing diameter in rabbit ear
Authors: Owen M. P. , Walmsley J. G. , Mason M. F. , Bevan R. D. , Bevan J. A.
Published: December 2017

The adrenergic neuroeffector mechanism has been assessed in three different-sized vessels of the rabbit ear, i.e., the central ear artery (CEA), which has an unstretched lumen diameter (ULD) of approximately 300 micron; a main side branch (MSB) that comes off the CEA immediately distal to the crossover position of the central vein (ULD approx 150 micron); and a terminal branch (TB) that originates from the MSB (ULD approximately 75 micron). The vessels receive adrenergic innervation limited to the adventitia as assessed by fluorescence histochemistry. Density of innervation, as indexed by neuronal uptake of tritiated norepinephrine (NE) and NE content expressed in terms of surface area of the vascular segment, appears greater in the larger vessel than in the small vessels. The neurogenic contractile response of isolated segments in relation to the maximum response to iota-NE was significantly greater in CEA than in the smaller vessels; this paralleled the neuronal density. Phentolamine (10(-6) M) blocked neurally evoked contractions of ear vessels at 2 Hz and depressed the contraction at least 90% at 4 and 8 Hz. All arterial segments constricted in response to histamine and NE with equal maximal effects. Sensitivity to NE appeared equal, whereas that to histamine appeared greater in the smaller vessels. Only the two smaller vessels possessed intrinsic tone. On the basis of the substantial innervation and neurogenic response of the vessels studied, (substantive) sympathetic control of vascular tone occurs in the three different-sized vessels of the rabbit ear, a fact that may be related to the temperature regulation role of that vascular bed.
Direct measurement of left ventricular interstitial adenosine
Authors: Hanley F. , Messina L. M. , Baer R. W. , Uhlig P. N. , Hoffman J. I.
Published: December 2017

Characterization of adenosine's role as a regulator of coronary blood flow requires accurate measurement of endogenous adenosine concentration in the left ventricular (LV) interstitial compartment. Existing techniques for determining adenosine in this compartment are indirect, requiring the acceptance of major assumptions before conclusions can be drawn. We describe a new technique utilizing a LV epicardial diffusion well that allows us to make rapid, direct measurement of LV interstitial adenosine concentration, avoiding many problems inherent in existing techniques. Our results show adenosine concentrations of 555 pmol/ml in resting anesthetized dogs, indicating a resting adenosine level well within the vasoactive range. Further experiments using intramyocardial bolus injections of methylene blue dye and [8-14C]adenosine indicate that the epicardial well receives adenosine from a transmural distribution of LV interstitium and not from epicardial sources only. The transmural interstitial adenosine is transported via small lymphatics to the epicardial surface of the heart where diffusion occurs into the epicardial well. We also examined diffusion characteristics of the parietal pericardial membrane and found that the rate constant of adenosine diffusion for this and the visceral pericardium are of the same order of magnitude, indicating that the extensively used standard pericardial superperfusate method probably underestimates cardiac interstitial adenosine concentration by 50% or more. The influence of the parietal pericardium adequately explains why our resting adenosine concentrations using the epicardial well are higher than those recently reported using the standard pericardial superperfusate method.
Ca depletion and repletion in rat heart: age-dependent changes in the sarcolemma
Authors: Frank J. S. , Rich T. L.
Published: December 2017

It has been shown by Chizzonite and Zak (Science 213:1508-1511, 1981) that rat hearts perfused with calcium (Ca)-free medium exhibit an age-dependent response to the Ca paradox. Below 6 days the hearts were insensitive to Ca depletion. By 15 days the hearts developed a sensitivity to Ca depletion monitored by the development of contracture and release of intracellular enzymes on return to Ca. The present study compared the structure of the cell surface in the neonatal rat and the adult rat after Ca depletion and repletion. Our aim was to see if separation of the layers of the glycocalyx (surface coat-external lamina) correlated with the age dependence of the Ca paradox. Langendorff-perfused 3-day hearts exposed for 20 min to less than 10(-8) M Ca had an intact glycocalyx in 95% of their cells. By 20 days the hearts had separation between layers of glycocalyx over 38.5 +/- 1.6% of their surface in all cells (40) examined. Adult hearts had separation of external lamina in 65.9 +/- 4.6% of their surface. Lanthanum (La) used as a cytochemical probe for intact membrane permeability was excluded from the cytoplasm of 3-day hearts after both Ca depletion and repletion. Twenty- to 26-day-old hearts on the other hand had La deposits throughout the cytoplasm. In addition, intracellular enzyme release (creatine kinase) after Ca depletion and repletion was negligible at 3 days but rose to 1,152 +/- 163 IU/g dry wt for 22-day-old hearts. The parallelism between the development of ultrastructural changes in the cell surface and the pattern of increasing functional sensitivity to Ca loss in the neonate supports the idea of a role for the glycocalyx in the regulation of Ca permeability.
The cardiac cycle: regulation and energy oscillations
Authors: Wikman-Coffelt J. , Sievers R. , Coffelt R. J. , Parmley W. W.
Published: December 2017

Cyclical changes in energy-related metabolites were observed in glucose-perfused but not pyruvate-perfused isolated working rat hearts. A chronological study of various phases of the cardiac cycle indicated maximum changes in metabolites occurred at half time to peak pressure (dF/dtmax). The high-energy phosphates ATP and phosphocreatine, as well as the glycolytic metabolites, glucose 6-phosphate and pyruvate, reached minimum values immediately prior to peak systole and maximum values during late diastole. The products of high-energy phosphate hydrolysis, ADP, inorganic phosphate, and creatine, as well as the regulator, adenosine 3',5'-cyclic monophosphate, showed the phase alternate. It was necessary to study cyclical changes in a maximally stressed glucose-perfused heart because the cyclical changes were small and appeared to be the result of rate-limiting steps in glycolysis and the slow transport of NADH into the mitochondria. For stressing the heart, thereby increasing ATP utilization and augmenting cyclical changes, the afterload chamber was set at 110 mmHg, and the perfusate contained high concentrations of calcium (3.5 mM, free) and isoproterenol (5 X 10(-9) M). When correction was made for binding and compartmentation of metabolites, data indicated that the free energy of ATP hydrolysis was preserved during the contraction process by a continuous binding and recycling of ADP.
Transfer function through regional cerebral cortex evaluated by a photoelectric method
Authors: Tomita M. , Gotoh F. , Amano T. , Tanahashi N. , Kobari M. , Shinohara T. , Mihara B.
Published: December 2017

A new technique is reported for obtaining the transfer function through the regional cerebral cortex. Tissue carbon-black (CB) dilution curves were recorded with a photoelectric apparatus used as a densitometer head in cat cortex in situ following intracarotid injection of 0.2 ml of 1/40 diluted CB solution. The linearity and stationarity of the vascular system, reproducibility of the curve, and recirculation were tested. The tissue CB dilution curve, a cumulative distribution function, was first differentiated yielding two curves comprising the inlet and outlet curves. The error due to "overlapping" was corrected for by extrapolation using the gamma-density function. The transfer function through the cortex was then calculated by numerical deconvolution of the inlet and outlet curves. The validity of the calculated transfer function was verified by comparison with that obtained from actual CB dilution curves recorded simultaneously from the pial artery and superior sagittal sinus. The transfer function was further subjected to moment analysis for determining the intraparenchymal circulatory parameters of the cerebral cortex. Some examples demonstrating the applicability of technique are given.
Protection of ischemic rabbit myocardium by glutamic acid
Authors: Bittl J. A. , Shine K. I.
Published: December 2017

Glutamic acid may protect the ischemic myocardium by increasing the flux through anaerobic pathways for ATP production. We tested this in isolated rabbit hearts that were treated with 0 or 2 mM glutamate. Hearts were stabilized for 30 min, subjected to ischemia for 30 min, and then reperfused for 30 min. Cardiac performance was defined by measuring peak left ventricular pressure (PLVDP) at the apex of a Starling curve and expressed as the %PLVDP attained during the preischemia period. Glutamate improved cardiac performance (%PLVDP, treated vs. untreated) after moderate ischemia (92 vs. 67), severe ischemia (79 vs. 65), and total ischemia (61 vs. 41). During severe ischemia, improved performance was associated with enhanced release (nmol X g wet wt -1 X min -1, treated vs. untreated) of alpha-ketoglutarate (2.3 vs. 1.3), succinate (21.7 vs. 12.3), and lactate (478 vs. 386). The ischemic myocardial content (nmol/mg myocardial protein, treated vs. untreated) of alpha-ketoglutarate (1.7 vs. 1.2) was increased by glutamate. The ischemic content of ATP (25.4 vs. 21.9) and succinate (15.7 vs. 12.1) showed a slight trend toward improvement under glutamate treatment. The study shows an association between improved postischemic cardiac performance and increased production of alpha-ketoglutarate and succinate during glutamate treatment.
Interaction between adenosine and inotropic interventions in guinea pig atria
Authors: Dobson J. G.
Published: December 2017

Isolated guinea pig atria stimulated to contract isometrically were used to determine whether adenosine at a concentration that does not cause a direct depressant effect on peak contractile force, rate of force development, and rate of relaxation was capable of influencing the elevation in these contractile parameters caused by an increase in preload, paired electrical stimulation, an increase in contraction frequency, and catecholamine stimulation in K+-depolarized and nondepolarized atrial muscle. Adenosine had no effect on the contractile parameters that were enhanced by an increase in preload or paired electrical stimulation. The nucleoside reduced the increases in the contractile parameters produced by isoproterenol stimulation, an increase in contraction frequency, and isoproterenol-induced contractions in depolarized atria. All adenosine reductions were inhibited by theophylline, an antagonist of adenosine actions. The adenosine reduction of the elevated contractile parameters caused by increasing contraction frequency was not prevented by atropine (a muscarinic antagonist) or propranolol (a beta-adrenergic blocking agent). These results suggest that adenosine at a concentration that does not produce direct negative inotropic responses is capable of attenuating the elevation in contractility elicited by catecholamine stimulation, an increase in contraction frequency, and catecholamine-induced contractions in depolarized atria. However, the reduction by adenosine of the contractile responses elicited by an increase in contraction frequency appears to be independent of catecholamines.
Caffeine-induced current in embryonic heart cells: time course and voltage dependence
Authors: Clusin W. T. , Fischmeister R. , DeHaan R. L.
Published: December 2017

Abrupt exposure of 90- to 130-micron diameter chick embryonic myocardial cell aggregates to 10 mM caffeine has been shown to induce a transient inward current. In the present study, we recorded a similar current in small cell clusters (less than 10 cells) in which access of caffeine to each of the cells was rapid. The resulting inward current consisted of a single peak, which decayed exponentially (predominant time constant 335 +/- 130 ms at -40 mV) and had a peak amplitude of up to 15.5 microA/cm2. The caffeine-induced current persisted when the slow inward current was abolished by a 30-s pretreatment with 2 microM D 600 and could be observed at potentials where the fast sodium channels were fully inactivated. The current-voltage relation of the caffeine response was linear between -110 and -40 mV, giving an extrapolated voltage intercept of +12 mV. However, the inward current did not diminish or reverse with further depolarization. A substantial inward current occurred at potentials up to +60 mV, which is more positive than the reversal potential of the tetrodotoxin-sensitive inward current. We conclude that the caffeine-induced current is mediated in part by electrogenic Na+-Ca2+ exchange.
Effect of caval occlusion on the magnitude of unipolar atrial electrograms in dogs
Authors: Bedont R. A. , Abildskov J. A. , Lux R. L. , Green L. S.
Published: December 2017

Studies were done on eight mongrel dogs anesthetized with pentobarbital sodium to assess the effects of acute changes in heart volume on the magnitude of electrocardiographic potentials recorded from the right atrium. Following midsternotomy, acute changes in heart volume were produced by occlusion of the superior vena cava (SVC), inferior vena cava (IVC), or both vena cavae while heart rate was controlled by pacing the right atrium. P-wave area, defined by integrating absolute value of the P wave over time, increased by 8.2 +/- 7.4% during SVC occlusion, 13.3 +/- 8.5% during IVC occlusion, and 23.6 +/- 16.2% during occlusion of both vena cavae. Areas of ventricular complexes appearing in atrial electrograms decreased by 6.6 +/- 6.2% during SVC occlusion, 11.1 +/- 6.7% during IVC occlusion, and 15.2 +/- 9.2% during occlusion of both vena cavae. These results are compatible with predominately tangential activation of the atrium and radial excitation of the ventricle and provide experimental confirmation of the "Brody effect."
Secondary AV conduction responses during tonic vagal stimulation
Authors: Martin P.
Published: December 2017

We gave trains of supramaximal stimuli at frequencies of 2, 4, or 8 Hz to both vagi of anesthetized, open-chest dogs and studied the AV conduction and atrial contractility responses while the atria were paced at different frequencies. The vagal stimulation quickly induced a maximum negative inotropic effect on the atrium. This "initial" response was followed by a "secondary" fading back toward the control level. The negative dromotropic responses to vagal stimulation also rapidly reached an initial value. When this initial response was large, there was then a secondary, relatively rapid fading back toward control. However, when the initial dromotropic response was small, the secondary response instead consisted of a gradual increase in conduction time. At intermediate levels of the initial dromotropic response, there was no appreciable secondary change in AV response. We hypothesize that two opposing mechanisms account for the variable secondary changes in AV conduction time and that the stimulus intensity determines which mechanism will be prepotent. The mechanism responsible for the secondary decline appears to be related to that which causes the fade of the inotropic response; muscarinic receptor desensitization probably plays an important role. The secondary augmentation of the dromotropic response may be related either to a slow diffusion of acetylcholine from the surrounding tissue or to a slow cumulative change in AV nodal refractoriness.
Onset of relaxation in cardiac muscle segments
Authors: Rondinone J. F. , Martyn D. A. , Huntsman L. L.
Published: December 2017

The onset of relaxation has been studied in undamaged central segments of isolated ferret papillary muscles at 27 degrees C, 12 beats/min. A technique that provides a signal proportional to the length of a chosen segment was used to assess segment velocity and length. Feedback control was employed to obtain segment isometric contractions. At a variety of times during segment isometric twitches, rapid load clamps were imposed using a range of loads from resting force to greater than half peak developed force. For the purposes of this study, the onset of relaxation was defined as occurring when active segment shortening ceased and elongation began (i.e., Vseg = 0). Early load clamps to low loads resulted in V = 0 at comparatively short segment lengths and early times. Later load clamps caused zero velocity to occur at longer segment lengths and later times. The V = 0 points in fact formed a line in the segment length-time plane. Contractions clamped to higher loads exhibited reduced shortening and a prolonged time course so that the V = 0 points showed the same dependence on length and time. Remarkably, all the variations of load-clamp load, time, and initial length yielded V = 0 points that were intermixed along a single line. Increasing or decreasing extracellular Ca2+ caused the V equal to O points to shift to later times and shorter segment lengths or earlier times and longer segment lengths, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Avian renal portal valve: a reexamination of its innervation
Authors: Burrows M. E. , Braun E. J. , Duckles S. P.
Published: December 2017

The renal portal circulation of the avian kidney contains a unique smooth muscle valve that can direct blood flow from the posterior extremities to the central circulation or through the kidney. The neural control of the valve and adjacent venous tissue from Rhode Island Red roosters was characterized by measuring the isometric force developed following transmural nerve stimulation (TNS). During TNS, the valve relaxed while the iliac vein contracted. In the valve, a poststimulus contraction followed the relaxation. Propranolol and guanethidine abolished the TNS-induced relaxation of the valve, leaving a contraction that was increased by physostigmine and partially blocked by atropine or prazosin. In contrast, the TNS-induced contraction of the vein was blocked by guanethidine or prazosin. Measurement of choline acetyltransferase activity and norepinephrine content confirms that the valve is densely innervated with both cholinergic and adrenergic nerves. Thus the vein shows a predominantly adrenergic contractile response typical of most vascular smooth muscle, but the valve demonstrates a dual control, i.e., adrenergic nerves producing relaxation and cholinergic nerves causing contraction. Knowledge of the nature of neuronal control of the valve should aid in the design of experiments to determine its functional role.
Hyperreactivity of coronary vasculature in platelet-perfused hearts from diabetic rats
Authors: Reibel D. K. , Roth D. M. , Lefer B. L. , Lefer A. M.
Published: December 2017

Coronary vascular responsiveness to platelet-produced eicosanoids was examined in isolated perfused hearts of alloxan-diabetic rats. Coronary perfusion pressure was increased in isolated hearts of control and diabetic rats on perfusion with platelets and arachidonic acid (AA). However, the increase in perfusion pressure was approximately twofold higher in hearts of diabetic rats when compared with those isolated from control rats. This was associated with increased thromboxane B2 (TxB2) and prostaglandin F2 alpha (PGF2 alpha) production that was comparable in platelet-perfused hearts of control and diabetic animals. Ibuprofen, a cyclooxygenase inhibitor, blocked the increase in perfusion pressure and TxB2 and PGF2 alpha production by greater than 90% in both control and diabetic hearts perfused with platelets and AA. Dazoxiben, a thromboxane synthetase inhibitor, blocked the increase in perfusion pressure by 50%, totally inhibited TxB2 production, but increased PGF2 alpha production by 60% in both groups of platelet-perfused hearts. Increased levels of PGF2 alpha and possibly other constrictor eicosanoids (e.g., leukotriene D4) may account for the partial constriction observed in platelet-perfused hearts with dazoxiben. Results of the present study suggest that vascular reactivity to vasoconstrictor eicosanoids is increased in hearts of diabetic animals.
Angiotensin causes vasoconstriction during hemorrhage in baroreceptor-denervated dogs
Authors: Averill D. B. , Scher A. M. , Feigl E. O.
Published: December 2017

The participation of angiotensin II (ANG II) in the maintenance of arterial blood pressure during hypotensive hemorrhage was examined in unanesthetized, baroreceptor-denervated dogs. When mean aortic blood pressure was reduced to 69.0 +/- 2.2 mmHg, plasma renin activity increased from 0.6 +/- 0.3 ng ANG I X ml-1 X h-1 during the prehemorrhage control period to 4.5 +/- 1.6. Twenty minutes after the hemorrhage, mean aortic blood pressure rose to 78.9 +/- 3.1 mmHg. Subsequent infusion of the angiotensin II antagonist saralasin (5.2-14.0 micrograms X kg-1 X min-1) decreased mean aortic pressure to 59.6 +/- 3.3 mmHg. When 5% dextrose was infused in place of saralasin, mean aortic pressure was 79.3 +/- 4.3 mmHg. The lower aortic blood pressure caused by saralasin infusion was the result of a significant decrease in total peripheral resistance. Resistance was 10.3 +/- 3.2 mmHg X l-1 X min lower during saralasin infusion than during dextrose infusion. We conclude that baroreceptor reflexes are not essential for the elevation of plasma renin activity during hemorrhage. In baroreceptor-denervated dogs subjected to hypotensive hemorrhage, the increased formation of ANG II has a vasoconstrictor action that contributes to the maintenance of arterial blood pressure.
Swimming exercise, thyroid state, and the distribution of myosin isoenzymes in rat heart
Authors: Pagani E. D. , Solaro R. J.
Published: December 2017

We tested whether changes in cardiac myosin ATPase activity induced by swimming exercise in male rats are due to a redistribution of existing isoenzymic forms of ventricular myosin. The isoenzymic profiles were analyzed by nondissociating gel electrophoresis of ventricular samples and compared with ATPase activities of myofibrils prepared from the same ventricle. Myofibrils prepared from hearts of rats in the control sedentary group or from hearts of rats in the groups of 8- or 12-wk swimmers had the same actomyosin Mg2+-ATPase activities measured between pCa 8 and 5. However, the myosin Ca2+-ATPase activity of myofibrils prepared from hearts of 8- or 12-wk swimmers was 20% higher than the activity of control preparations. This increase in activity was in proportion to an increase in the relative amount of V1, the myosin isoenzyme with the highest Ca2+-ATPase activity. Thyroidectomized rats, whose hearts had no detectable V1, were also subjected to the swimming program. In the case of the hypothyroid rats, myofibrillar preparations from controls and 8- or 12-wk swimmers had the same actomyosin Mg2+-ATPase activity, myosin Ca2+-ATPase activity, and the same isoenzyme profiles. Co-electrophoresis of ventricular samples from the euthyroid and hypothyroid controls and swimmers showed no evidence for new variants of myosin. We conclude that the increase in myosin Ca2+-ATPase activity in the ventricles of euthyroid swimmers is due to a redistribution of existing isoforms of myosin and that the redistribution process may require thyroid hormone for its expression.
Hemodynamic changes induced by reversal of early and late renovascular hypertension
Authors: Russell G. I. , Bing R. F. , Swales J. D. , Thurston H.
Published: December 2017

The hemodynamic changes associated with reversal of Goldblatt two-kidney, one-clip hypertension in conscious rats were studied using radioactive microspheres. In both the early phase (less than 6 wk from clipping) when plasma renin was elevated and the chronic phase (greater than 4 mo) when plasma renin was normal, hypertension was maintained by elevated peripheral resistance. Unclipping or removal of the ischemic kidney normalized blood pressure within 24 h by reduction in peripheral resistance. In early-phase hypertension blood pressure remained normal at 60 days after nephrectomy or unclipping, but in chronic-phase hypertension blood pressure was significantly elevated at 60 days after nephrectomy despite a similar fall in peripheral resistance. Plasma renin fell to normal or subnormal values after reversal in both early and chronic hypertension. Thus reversal of hypertension is associated with a rapid reduction in peripheral resistance even in longstanding hypertension. Since removal of the ischemic kidney and unclipping were equally effective, reversal must depend on either inhibition of a pressor system derived from the ischemic kidney or activation of a peripheral vasodepressor system not dependent on a revascularized kidney.
Circulatory and humoral responses of sympathectomized fetal sheep to hypoxemia
Authors: Iwamoto H. S. , Rudolph A. M. , Mirkin B. L. , Keil L. C.
Published: December 2017

In fetal sheep, hypoxemia causes arterial hypertension, bradycardia, a redistribution of blood flow, and an increase in plasma vasopressin and catecholamine concentrations. To assess the role of the sympathetic nervous system in mediating these responses, we administered 6-hydroxydopamine to 11 chronically catheterized fetal sheep. Some of the responses to acute hypoxemia, achieved by administration of a low-O2 gas mixture to the ewe, were similar to those in intact fetal sheep. Fetal arterial O2 tension decreased from 22 +/- 3 to 12 +/- 3 (SD) Torr; fetal heart rate decreased transiently; combined ventricular output and umbilical-placental blood flow, as measured by the radionuclide-labeled microsphere technique, were maintained; cerebral, myocardial, and adrenal blood flow increased, and pulmonary blood flow decreased. However, there was no significant change in arterial pressure or blood flow to the peripheral, renal, and splanchnic circulations in the chemically sympathectomized fetuses in response to hypoxemia. The sympathetic nervous system is important in certain fetal vascular responses to hypoxemia but is not necessary for vascular responses in certain critical organs and thus is not crucial for fetal survival during hypoxia.
Left ventricular interaction with arterial load studied in isolated canine ventricle
Authors: Sunagawa K. , Maughan W. L. , Burkhoff D. , Sagawa K.
Published: December 2017

We developed a framework of analysis to predict the stroke volume (SV) resulting from the complex mechanical interaction between the ventricle and its arterial system. In this analysis, we characterized both the left ventricle and the arterial system by their end systolic pressure (Ps)-SV relationships and predicted SV from the intersection of the two relationship lines. The final output of the analysis was a formula that gives the SV for a given preload as a function of the ventricular properties (Ees, V0, and ejection time) and the arterial impedance properties (modeled in terms of a 3-element Windkessel). To test the validity of this framework for analyzing the ventriculoarterial interaction, we first determined the ventricular properties under a specific set of control arterial impedance conditions. With the ventricular properties thus obtained, we used the analytical formula to predict SVs under various combinations of noncontrol arterial impedance conditions and four preloads. The predicted SVs were compared with those measured while actually imposing the identical set of arterial impedance conditions and preload in eight isolated canine ventricles. The predicted SV was highly correlated (P less than 0.0001) with the measured one in all ventricles. The average correlation coefficient was 0.985 +/- 0.004 (SE), the slope 1.00 +/- 0.04, and the gamma-axis intercept 1.0 +/- 0.2 ml, indicating the accuracy of the prediction. We conclude that the representations of ventricle and arterial system by their Ps-SV relationships are useful in understanding how these two systems determine SV when they are coupled and interact.
Quantitative relation between sites of atrial impulse origin and cycle length
Authors: Boineau J. P. , Schuessler R. B. , Roeske W. R. , Autry L. J. , Miller C. B. , Wylds A. C.
Published: December 2017

Having previously described the multicentric origin of the atrial impulse from sites widely distributed over the right atrium as well as an intrinsic link between these sites of origin and cycle length (CL), we undertook a quantitative study of this relationship. In 132 dogs anesthetized with pentobarbital sodium or fentanyl citrate, we recorded atrial activation sequence maps from 360 closely positioned electrodes and determined locations of impulse origin at heart rates between 80 and 240 (CL between 750 and 250). We used cardiac nerve stimulation and agonist-antagonist infusion to produce changes in CL and impulse origin. Results demonstrate a significant correlation between site of impulse origin and CL. These sites, associated with both the sinus node (SN) and extranodal sites, function predictably and consistently controlling impulse initiation at heart rates above and below rates at which the SN predominates. This relationship can be used to specify an anatomic-functional model of atrial pacemaker hierarchy and to quantitate the response of different atrial regions to specific pharmacological and physiological interventions.
Vasodilator capacity of contralateral kidney in Goldblatt hypertensive dog
Authors: Zimmerman B. G. , Largent R. D.
Published: December 2017

Because of previous suggestions of impaired renal blood flow in the contralateral kidney of Goldblatt hypertensive animals, we examined the maximal vasodilator capacity of the contralateral kidney in 13 instrumented dogs during progression of Goldblatt hypertension. Constriction of a single renal artery (RAC) followed a week or more later by total renal artery occlusion (RAO) increased mean arterial blood pressure (BP) from a control level of 102 +/- 3 to 135 +/- 7 mmHg (P less than 0.001) and increased plasma renin activity (PRA) from 0.69 +/- 0.16 to 10.2 +/- 3.9 ng angiotensin I X ml-1 X h-1 (P less than 0.05) at 2 wk after RAO. The hypertension was accompanied by an increase in basal renal blood flow (RBF) from 224 +/- 21 to 300 +/- 27 ml/min (P less than 0.01) and RBF at maximal vasodilatation from 505 +/- 24 to 673 +/- 52 ml/min (P less than 0.05). Hypertension and the increase in PRA waned, but BP remained higher than control at 4 wk after RAO (117 +/- 6 mmHg, P less than 0.005). Basal and maximal RBF were sustained at the higher levels throughout the 4-wk period after RAO. When RBF was expressed on a per gram basis, basal and maximal flow before (3.72 +/- 0.40 and 8.26 +/- 0.62 ml X min-1 X g-1, respectively) did not differ from that in the final experiment after RAO (3.85 +/- 0.34 and 8.19 +/- 0.78 ml X min-1 X g-1). The basal and minimal vascular resistances based on flow per gram were increased by 24 +/- 8 and 41 +/- 16% (P less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional venous return: nitroprusside effect in normal and chronically congested dogs
Authors: Engler R. L. , Freeman G. L. , Covell J. W.
Published: December 2017

The venous circulation is a key determinant of cardiac loading conditions. Although it may be altered by chronic congestive heart failure and vasodilating drugs, the mechanisms of these alterations have not been thoroughly studied, and their exact nature is unclear. We used venous return curves characterized by the pressure at zero flow (PZF) and resistance to venous return (RVR) to study the effect of nitroprusside and chronic congestion on regional venous return from the splanchnic and superior vena cava (systemic) venous beds in dogs. Chronic venous congestion was induced by prior creation of tricuspid insufficiency and pulmonic stenosis (TIPS). Nitroprusside lowered splanchnic PZF but not systemic PZF in both normal and TIPS animals. In normal animals systemic RVR increased during nitroprusside infusion but was unchanged in the congested animals. Resting values of PZF and RVR were different in the splanchnic and systemic venous beds in both normal and TIPS animals. We conclude that 1) nitroprusside works to selectively lower PZF in the splanchnic venous bed, 2) the regionally specific site of action of nitroprusside is not altered by TIPS, and 3) the independent behavior of the venous parameters of the two beds represents an important mechanism for the control of cardiac output.
Medial morphometry and mechanics of sequential rabbit ear arteries and myograph ring segments
Authors: Walmsley J. G. , Owen M. P. , Bevan J. A.
Published: December 2017

The medial structure of three different branching orders of arteries in the rabbit ear was studied to assess the possible significance with regard to mechanical behavior determined with the in vitro myograph. The central ear artery, its main side branch, and a terminal branch were fixed while dilated in situ at 100 mmHg; this resulted in internal diameters of 960, 456, and 251 micron, respectively. The average ratio of medial thickness to internal diameter was 0.0293 for arteries in situ and 0.0487 for arterial rings in vitro. Measurements undertaken for the determination of smooth muscle (SM) stress included the percentage of SM in the media (74%) and the pitch of SM (0.89 degrees). These parameters were not significantly different in the three various-sized arteries or for the two myographs. Stereological estimates of SM cell volume, length, and diameter were based on counts of SM nuclei and their length. In evaluating the ring preparation of the vessel myographs, the damage due to the wires (20%) and cut edges (6.4%) was considered. The maximum active SM stress was approximately the same in the different-sized vessels with an average value of 3.14 X 10(5) N/m2. Since this stress is comparable to measurements made by others on different mechanical apparatus and consistent for the three arterial orders, these in vitro myographs should allow for valid comparison of arterial mechanical properties over the size range studied.
Kinase II-dependent formation of angiotensins II and III in the hepatic circulation
Authors: Britton S. L. , Thomas G. , Daniel C. , Ronau T. F.
Published: December 2017

Experiments were performed in 14 pentobarbital-anesthetized dogs to 1) determine if the hepatic arterial vasoconstrictor effects of [des-Asp1]angiotensin I [( des-Asp1]ANG I) were due to its local conversion to angiotensin III (ANG III) and 2) to evaluate the magnitude of conversion of ANG I to angiotensin II (ANG II) and of [des-Asp1]ANG I to ANG III in the hepatic arterial vascular bed. Graded doses of these peptide agonists were administered as bolus injections directly into the hepatic artery; hepatic arterial blood flow was measured with an electromagnetic flow probe. Dose-response relationships were determined before and during the inhibition of kinase II activity with captopril (2-D-methyl-3-mercaptopropanoyl-L-proline) and antagonism of angiotensin receptor sites with [Ile7]angiotensin III [( Ile7]ANG III). ANG I and [des-Asp1]ANG I were equipotent at all doses tested, as were ANG II and III. At all doses tested, ANG II and III were approximately three times more potent than ANG I and [des-Asp1]-ANG I. Captopril attenuated the vasoconstrictor responses to ANG I and [des-Asp1]ANG I only, whereas [Ile7]ANG III inhibited the responses to all four angiotensin peptides. These data indicate that the hepatic arterial vasoconstrictor responses to [des-Asp1]ANG I were due to the intrahepatic formation of ANG III. The extent of intrahepatic conversion of [des-Asp1]-ANG I to ANG III that occurred in one transit through the hepatic arterial vascular bed was estimated to be 33%, which was similar to the estimated 38% conversion of ANG I to ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
Unbalanced plasma control of TxA2 and PGI2 synthesis in vitamin E-deficient rats
Authors: Falanga A. , Doni M. G. , Delaini F. , De Bellis Vitti G. , Imberti L. , Donati M. B. , de Gaetano G.
Published: December 2017

Factors contributing to the antioxidant power of plasma may play a role in the control of arachidonic acid (AA) metabolism. The purpose of this study was to evaluate the possible effects of vitamin E deficiency on platelet and vascular prostaglandin synthesis. CD-COBS male rats were fed for 7 mo a diet containing either 1 or 75 mg/kg vitamin E. At the end of this period, serum levels of vitamin E were 0.4 +/- 0.1 and 10 +/- 0.6 micrograms/ml in the two groups, respectively. Malondialdehyde (MDA) generation by AA was significantly higher in platelet-rich plasma from vitamin E-deficient rats. Thromboxane B2 (TxB2) in serum from vitamin E-deficient rats increased about 16 times compared with controls, whereas 6-keto-PGF1 alpha levels increased only 3 times. The ratio between TxB2 and 6-keto-PGF1 alpha, increased therefore manyfold in vitamin E-deficient animals. MDA formation and [14C]AA metabolism in washed platelets were similar in the two groups of animals. No significant difference was found in the PGI2 (prostacyclin) antiaggregating activity released from the aortic rings resuspended in buffer. In contrast, the capacity of plasma to stimulate PGI2 activity from "exhausted" aortic rings (prostacyclin-stimulating factor) was significantly reduced in vitamin E-deficient animals. In conclusion, vitamin E deficiency induces an unbalanced plasma regulation of AA metabolism. This results in an excessive production of platelet TxA2 compared with vascular PGI2 generation. On the other hand, vitamin E deficiency does not seem to affect directly the enzymatic pathways of AA metabolism.