bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of thoracic spinothalamic neurons to intracardiac injection of bradykinin in the monkey.
Authors: Blair R W , Weber R N , Foreman R D
Published: June 2012

Bradykinin stimulates afferent fibers arising in the heart and may be involved in the mediation of anginal pain and the pain associated with myocardial infarction. The sensation of pain requires that noxious information reach the brain. The purpose of the present study was to determine whether the spinothalamic tract is involved in transmitting noxious information from the heart to the brain. Bradykinin was injected (0.3-3.5 micrograms/kg) into the heart via a catheter in the left atrium while we recorded from single spinothalamic cells in the C8 to T5 spinal segments. Thirty-one of 41 cells responded to bradykinin. The responses of 12 cells were characterized by both an increase in discharge rate and entrainment of cell activity with the cardiac cycle. Eighteen cells responded with only an increased rate, and one cell exhibited only entrainment of cell activity with the cardiac cycle. The mean onset of increased cell activity occurred 15 seconds following drug injection, and the average duration of the response was 54 seconds. Thirty cells increased their mean discharge rate from 11 +/- 2.5 to 29 +/- 4.4 spikes/second. Thus, some spinothalamic cells probably received input from both mechanosensitive and chemosensitive afferents. Tachyphylaxis to repeated doses of bradykinin was observed in 41% of cells. Cells responding to bradykinin had a spontaneous discharge rate that was significantly greater than that of nonresponding cells. Cells did not require input from C-fiber afferents to respond to bradykinin. No statistically significant relationships were found among anatomical locations (laminae and segments) and responses to bradykinin, although cells in lamina I seemed to be less responsive than more ventrally located cells. We conclude that the spinothalamic tract may be involved in the sensation of cardiac pain.
The effects of atrial fibrillation on atrial pressure-volume and flow relationships.
Authors: White C W , Kerber R E , Weiss H R , Marcus M L
Published: June 2012

To study whether atrial fibrillation might produce local changes in the atrium which could facilitate the tendency of this arrhythmia to become chronic and self-perpetuating, we compared the effect of atrial fibrillation, atrial pacing, and acute volume loading on the perfusion and oxygen consumption of the atrium in anesthetized dogs. Measurement of atrial perfusion with microspheres indicates that during atrial fibrillation, atrial blood flow increases 2- to 3-fold. Right atrial pacing is a significantly less potent metabolic stimulus for atrial vasodilation. Using Doppler velocity recordings of sinus node artery blood flow velocity, a marked increase in velocity is observed within 5 seconds after the initiation of atrial fibrillation. During atrial fibrillation, the sinus node artery reactive hyperemia response is markedly attenuated. Atrial fibrillation acutely decreases atrial distensibility; atrial pressure increased 81 +/- 19% with only a small increase (9.7 +/- 3%) in atrial diameter measured by echocardiography. During sinus rhythm, volume expansion to equivalent levels of atrial pressure as seen during atrial fibrillation increased atrial diameter 21 +/- 5% P less than 0.05. Atrial oxygen consumption determined by the microspectrophotometric method markedly increases during atrial fibrillation, compared to control conditions (12.3 +/- 2.8 vs. 3.9 +/- 0.6 ml O2/min per 100 g, respectively) P less than 0.05. Atrial O2 extraction was 5.5 +/- 0.4 ml O2/ml blood in the control state, and did not change with interventions. There was a linear relationship between left atrial O2 consumption and blood flow in all experimental conditions. Atrial fibrillation therefore alters atrial hemodynamics and metabolism by increasing atrial blood flow and oxygen consumption and decreasing atrial distensibility. Since atrial perfusion during atrial fibrillation is high and atrial flow reserve is limited, it is possible that additional atrial metabolic requirements might lead to atrial ischemia, fibrosis, and, thereby, perpetuation of the arrhythmia.
Release of enzymes from adult rat heart myocytes.
Authors: Murphy M P , Hohl C , Brierley G P , Altschuld R A
Published: June 2012

The release of lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase from initially viable, metabolically competent adult rat heart myocytes has been examined. Freshly isolated cells contain levels of total lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase, as well as lactic dehydrogenase and creatine phosphokinase isoenzyme profiles that are quite comparable to those of intact heart tissue. When the cells are lysed with digitonin, 89% of total lactic dehydrogenase, but only 58% of creatine phosphokinase and 27% of aspartate aminotransferase are released. The retention of creatine phosphokinase by the digitonin-lysed cells is accounted for by complete retention of mitochondrial creatine phosphokinase and 20% of MM-creatine phosphokinase. When intact myocytes are incubated under anoxic, substrate-deprived conditions, there is a gradual loss of the three enzymes to the suspending medium and a parallel increase in the fraction of the cells permeable to trypan blue. The fraction of freely soluble cytoplasmic enzymes lost was equivalent to the fraction of the cells permeable to the dye over a wide range of viability (17-95% viable by dye exclusion criteria), but permeable cells retained mitochondrial creatine phosphokinase and particulate aspartate aminotransferase. These results suggest that simultaneous and complete release of soluble cytoplasmic enzymes occurs as each individual cell sustains sarcolemmal damage.
Neurogenic electrical responses of single smooth muscle cells of the dog middle cerebral artery.
Authors: Suzuki H , Fujiwara S
Published: June 2012

Electrical responses induced by perivasascular nerve stimulation were recorded intracellularly from the smooth muscle of dog middle cerebral artery. With nerve stimulation, the muscle membrane produced excitatory junction potential and then a slow hyperpolarization. The excitatory junction potential showed facilitation and the slow hyperpolarization showed depression phenomena, when the nerves were stimulated with twin pulses. Generation of the slow hyperpolarization was associated with an increase in the potassium conductance of the membrane and was suppressed by tetraethylammonium, which depolarized the membrane, reduced the membrane conductance, and increased the amplitude of the excitatory junction potential. Treatment with 6-hydroxydopamine abolished the excitatory junction potential, but not the slow hyperpolarization; the latter was suppressed by tetrodotoxin. The amplitude of slow hyperpolarization was decreased by application of tetraethylammonium or ATP, but was not affected by application of atropine, neostigmine, theophylline, apamin, ouabain, norepinephrine, propranolol, or guanethidine. ATP produced transient depolarization of the membrane with associated decrease in the membrane resistance. The excitatory junction potential was attributed to activation of the noradrenergic nerves, whereas the slow hyperpolarization was not generated by activation of adrenergic, cholinergic, or purinergic receptors. Inasmuch as the electrogenic Na-K pump, cAMP, and ATP were not involved in the generation of slow hyperpolarization, the possibility of an unidentified chemical transmitter should be given attention.
Developmental hemodynamic changes in the chick embryo from stage 18 to 27.
Authors: Clark E B , Hu N
Published: June 2012

We report the hemodynamic parameters of stage 18, 21, 24, and 27 chick embryos (from 3 to 5 days of incubation). Dorsal aortic blood velocity and mean vitelline artery blood pressure are measured with a 20 MHz pulsed-Doppler meter and servo-null pressure system respectively. We also measure heart rate, dorsal aortic diameter and embryo weight of each developmental stage. From these data, we calculate mean dorsal aortic blood flow, mean dorsal aortic blood flow per cardiac cycle, mean dorsal aortic blood flow per milligram embryo weight, vascular resistance and cardiac work. Blood flow increases geometrically with each embryo stage but remains constant when normalized for embryo weight. Mean arterial pressure increases linearly and vascular resistance decreases geometrically. Cardiac work increases in proportion to embryo weight. These results define the parameters of normal hemodynamic function during early embryonic development.
Inhibition by carotid baroreflex of exercise-induced increases in arterial pressure.
Authors: Walgenbach S C , Donald D E
Published: June 2012

Mean arterial blood pressure, heart rate, and cardiac output were measured during continuous graded exercise (5.5 km/hr; 0, 7, 14, and 21% grades) in conscious dogs, under each of the following four conditions: (1) baroreceptors intact, (2) chronic aortic arch denervation, (3) chronic aortic arch denervation and surgical preparation of the carotid sinuses for later reversible vascular isolation, and (4) chronic aortic arch denervation and carotid sinuses vascularly isolated at a fixed pressure. Arterial blood pressure increased with increasing work load to a maximum of 12 +/- 3, 18 +/- 5, and 14 +/- 5 mm Hg above control in conditions 1, 2, and 3, respectively. In condition 4, the maximum increase in pressure during graded exercise was 51 +/- 7 mm Hg above control. Upon cessation of graded exercise, the increase in arterial pressure persisted through the 5-minute recovery period. Heart rate and cardiac output increased similarly in proportion to work load under all four conditions. In contrast to dogs in condition 4, three dogs with chronic sinoaortic denervation showed no work load-related increase in arterial pressure during exercise. Thus, during exercise, the carotid baroreflex acts to balance finely the opposing effects of sympathetic vasoconstriction and metabolic vasodilation.
Metabolic cost of the stimulated beating of isolated adult rat heart cells in suspension.
Authors: Haworth R A , Hunter D R , Berkoff H A , Moss R L
Published: June 2012

Heart cells from adult rats were induced to beat in suspension by electric field stimulation. We have gained evidence that all the rod-shaped cells in suspension were indeed beating, and that the beat had dynamic characteristics similar to those of intact heart muscle contracting under zero load. The cells were undamaged in the process, as judged by maintenance of ATP levels, morphology, and ability to beat. In gaining such evidence, we also measured the metabolic cost to the cells of beating under zero load. In cells with oxidative phosphorylation inhibited by rotenone plus oligomycin (termed anaerobic), the rate of beat-dependent lactate production suggested an equivalent rate of ATP utilization of 0.126 +/- 0.013 nmol ATP/beat per mg protein (plus isoproterenol), and 0.058 +/- 0.005 nmol ATP/beat per mg protein (minus isoproterenol). In respiring cells, the rate of beat-dependent oligomycin-sensitive oxygen consumption gave an equivalent rate of ATP utilization of 0.198 +/- 0.009 nmol ATP/beat per mg protein (plus isoproterenol), and 0.126 +/- 0.013 nmol ATP/beat per mg protein (minus isoproterenol). The cells beat with the same approximate maximum velocity whether isoproterenol was present or not. We calculate that--in the case of anaerobic cells without isoproterenol--this rate of ATP utilization can account for only about a 15% degree of activation of the contractile proteins. In addition, we have found an oligomycin-insensitive beat-dependent mitochondrial respiration of 0.023 +/- 0.006 nanoatom O/beat per mg. The cause of this respiration is not known. The total rate of oxygen consumption of cells and also the rate per beat was comparable to that measured in nonworking whole hearts.
Nonlinear summation of depressor effects of carotid sinus pressure changes and aortic nerve stimulation in the rabbit.
Authors: Ishikawa N , Sagawa K
Published: June 2012

We studied the interaction between the carotid sinus and aortic arch baroreflexes' control of arterial pressure in 13 rabbits anesthetized with urethane. The carotid sinus baroreceptor region was isolated to control carotid sinus pressure. The aortic nerve was transected cervically and stimulated with 4-V electrical pulses at 5 Hz and 0.5-msec duration, which caused a 20-30 mm Hg decrease in arterial pressure. Several protocols were used to analyze the interaction. In the first, we compared the combined effect of the stimulation of a unilateral aortic nerve and a simultaneous increase of bilateral carotid sinus pressures from 40 to 70-80 mm Hg to the sum of these effects measured separately. The combined effect was always larger than the sum of the separate effects. In the second protocol, we varied carotid sinus pressures between 40 and 140 mm Hg and, at each carotid sinus pressure, measured the decrease in arterial pressure caused by unilateral aortic nerve stimulation. The fall in arterial pressure was always greater in the middle range of carotid sinus pressure (70-90 mm Hg) than in the lower or higher range. In the third protocol, we increased the intensity of aortic nerve stimulation from 2 to 4 V while raising carotid sinus pressure from 90 to 110 mm Hg. At this increased tonic input level, the combined effect was always smaller than the sum of the separate effects. Thus, we observed a facilitatory summation when the input variables changed from subthreshold to physiological level, but an inhibitory summation when the input stimulus intensity increased from a physiological to a supraphysiological level. We conclude that interaction between the two reflexes depends in part upon the initial level of the input intensity to the receptors.
Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts.
Authors: Kléber A G
Published: June 2012

Transmembrane potentials, extracellular potassium activity, and intracellular sodium activity were determined during acute global ischemia in Langendorff perfused guinea pig ventricles by microelectrode techniques. Resting membrane potential decreased with a sigmoidal time course from -82 mV to -49.5 +/- 2.7 mV (SD, n = 6) and extracellular potassium activity increased from 4 to 5 mM to 14.7 +/- 1.3 mM (n = 8) during 15 minutes of ischemia. The estimated potassium equilibrium potential was 7 mV more negative than resting membrane potential prior to occlusion, but approached resting membrane potential during ischemia. An increase in extracellular potassium accumulation occurred when heart rate was increased abruptly from 60 to 170 beats/min. After rapid stimulation, a transient decrease of extracellular potassium activity occurred which was abolished in the presence of 10(-6) M strophanthidin. If the preparations were paced before and after aortic occlusion at a constant rate, potassium accumulation was independent of heart rate within a range of 50-170 beats/min. Intracellular sodium activity was 8.8 +/- 2.8 mM (n = 8) prior to occlusion and decreased slightly to values between 4.7 and 7.6 mM after 10-15 minutes of ischemia. The results suggest that relative potassium permeability largely predominates over relative sodium permeability during the decrease of resting membrane potential after interruption of aortic flow. Furthermore, active sodium-potassium exchange compensates for the rate-dependent fraction of potassium efflux and maintains a low intracellular sodium activity. For reasons of electroneutrality, the potassium efflux underlying extracellular potassium accumulation must be balanced by an equivalent charge movement which is not carried by sodium. The most probable hypothesis regarding the charge carriers is that net potassium efflux occurs secondary to efflux of phosphate and lactate generated during ischemia.
Relation between intracellular sodium and twitch tension in sheep cardiac Purkinje strands exposed to cardiac glycosides.
Authors: Wasserstrom J A , Schwartz D J , Fozzard H A
Published: June 2012

Changes in intracellular sodium ion activity (aiNa) produced by several cardiac glycosides were correlated with twitch tension in sheep cardiac Purkinje strands. Simultaneous measurements of aiNa and twitch tension were obtained through the use of Na-sensitive intracellular microelectrodes (ETH 227) in Purkinje preparations stimulated at a frequency of 1 Hz. All concentrations of ouabain, acetylstrophanthidin, and actodigin that were tested caused an increase in aiNa immediately before, or coincident with, a positive inotropic effect. No fall in aiNa was observed at any positive inotropic concentration of digitalis in these beating fibers. In all cases, the onset and washout of the positive inotropic effect were paralleled by the rise and fall in aiNa, respectively. No dissociation between changes in aiNa and twitch tension occurred at any concentration of any of the agents used. The relation between changes in aiNa and twitch tension was linear with 1 mM increase in aiNa producing about a 100% increase in the twitch magnitude. Propranolol did not significantly alter this relationship. The increase in aiNa with digitalis was also associated with a reduction in the maximum depolarization rate of the action potential, presumably as a consequence of a reduction in the transmembrane Na electrochemical gradient. These results indicate that the positive inotropic action of digitalis in sheep Purkinje strands is always associated with a rise in aiNa secondary to inhibition of the Na pump. This increase in aiNa could increase calcium available for contraction via the Na-Ca equilibrium exchange process. In addition, the increase in aiNa reduces Vmax, as a consequence of decreasing the electrochemical gradient for Na.
Toxic effects of silver-silver chloride electrodes on vascular smooth muscle.
Authors: Jackson W F , Duling B R
Published: June 2012

We found that silver, either as silver metal or silver chloride, exerted toxic effects on the smooth muscle of isolated cannulated hamster cheek pouch arterioles. Silver initially stimulated the smooth muscle, producing a marked vasoconstriction. The vessels then dilated back to control diameters. Once the arterioles began to dilate, they became refractory to norepinephrine or potassium stimulation. We caution the use of silver in the presence of smooth muscle, especially when tissue mass is small or free protein concentration is low.
Modification of the cardiac action potential by intracellular injection of adenosine triphosphate and related substances in guinea pig single ventricular cells.
Authors: Taniguchi J , Noma A , Irisawa H
Published: June 2012

Effects of varying the intracellular adenosine triphosphate level on both the action potential and the membrane current were studied in single ventricular cells isolated from the guinea pig heart, using collagenase. Intracellular injection of adenosine triphosphate elevated the plateau potential level and prolonged the action potential duration. Similar results were obtained by injecting adenosine diphosphate, adenosine monophosphate, or creatine phosphate, i.e., substances considered to increase the intracellular concentration of adenosine triphosphate. In contrast, the action potential was depressed by procedures which could reduce the intracellular adenosine triphosphate level, such as an injection of creatine, superfusion of glucose-free Tyrode's solution containing 5.4 mM cyanide ion, or an injection of adenosine monophosphate into the cyanide-superfused cell. When the membrane current was recorded under the voltage clamp, it was found that the injection of adenosine triphosphate increased the amplitude of the slow inward current, whereas the superfusion of cyanide ion did not significantly decrease the slow inward current, although the action potential became considerably shorter. It was also found that the adenosine monophosphate injection decreased the amplitude of the net outward membrane current at the plateau level and increased it at around -40 mV, and thus intensified the N-shape of the isochronal 0.3-second current-voltage curve. The cyanide ion superfusion produced the opposite effect; in response to depolarizing clamp pulses more positive to the plateau level, the membrane current increased significantly with cyanide ion, but increased only slightly with adenosine triphosphate. These results suggest that intracellular adenosine triphosphate modifies the membrane currents at the plateau potential range, thus altering the action potential duration.
Vanadate effect on the Na,K-ATPase and the Na-K pump in in vitro-grown rat vascular smooth muscle cells.
Authors: Searle B M , Higashino H , Khalil F , Bogden J D , Tokushige A , Tamura H , Kino M , Aviv A
Published: June 2012

The impact of vanadate on the Na,K-ATPase system in the vascular smooth muscle cell is poorly understood. The present study describes the kinetics of the effect of vanadate on Na,K-ATPase and the Na-K pump in in vitro grown rat VSMC's. Vanadate interaction with the Na,K-ATPase system in vascular smooth muscle cells was examined by observing its influence on ouabain-sensitive adenosine triphosphate hydrolysis in disrupted cells rendered permeable by osmotic shock, and the uptake of rubidium by intact cells. The I50 for vanadate inhibition of ouabain-sensitive hydrolysis of adenosine triphosphate occurred at vanadate concentrations of 10(-6) to 10(-7) M. This inhibition was potassium dependent. The maximal inhibitory effect of vanadate occurred at potassium concentrations of 10-20 mEq/liter. Sodium exerted a moderate antagonistic influence on vanadate inhibition of ouabain-sensitive adenosine triphosphate hydrolysis. Rubidium uptake by vascular smooth muscle cells was not altered within 120 minutes when 10(-5) M vanadate was added to the medium containing intact vascular smooth muscle cells. Yet, vanadium concentrations in the vascular smooth muscle cells within this incubation period reached levels 1.48-fold higher than the extracellular vanadate concentrations of 10(-5) M. These observations indicate that vanadate is a potent inhibitor of the VSMC Na,K-ATPase in disrupted vascular smooth muscle cells. However, in intact vascular smooth muscle cells vanadium gaining access into the vascular smooth muscle cell's interior does not inhibit the Na-K pump, probably because of its binding to intracellular proteins and/or conversion from the vanadate to the vanadyl ion.
Direct determination of vasa recta blood flow in the rat renal papilla.
Authors: Holliger C , Lemley K V , Schmitt S L , Thomas F C , Robertson C R , Jamison R L
Published: June 2012

Blood flow in vasa recta capillaries of the exposed renal papilla of young antidiuretic rats (n = 18) was determined by an adaptation of the video-photometric technique of Intaglietta. The erythrocyte velocity and capillary diameter in vasa recta (n = 97) were measured at the same location by means of fluorescence video microscopy, with fluorescein-labeled bovine gamma-globulin as a plasma marker. A factor relating erythrocyte velocity to mean cross-sectional blood velocity was determined in vitro to permit the calculation of single vasa recta blood flows from the measured indices, erythrocyte velocity and capillary diameter. Mean blood flow in descending vasa recta was 8.83 +/- 0.96 (SE) nl/min, significantly greater than that in ascending vasa recta, 4.82 +/- 0.34 nl/min. The total numbers of ascending and descending vasa recta at the base of the exposed papilla were also determined. Over 1500 vasa recta were identified as ascending vasa recta or descending vasa recta in electron micrographs of three papillas. At this level in the papilla (2 mm from the tip), there were four ascending vasa recta for each descending vas rectum. From the total numbers of ascending vasa recta and descending vas rectum, single vessel blood flows were converted to total blood flow. Total blood outflow in all ascending vasa recta, 11.3 microliter/min, substantially exceeded total blood inflow in all descending vasa recta, 5.2 microliter/min. The difference between outflow and inflow (6.1 microliter/min) represents an estimate of water by the papillary microcirculation, and is more than adequate to accommodate the known rate of water reabsorption from the collecting ducts of the exposed papilla.
Vasoactive intestinal peptide inhibitory innervation in bovine mesenteric lymphatics. A histochemical and pharmacological study.
Authors: Ohhashi T , Olschowka J A , Jacobowitz D M
Published: June 2012

The localization of vasoactive intestinal peptide-immunoreactive nerves innervating bovine lymphatic vessels was studied by an immunohistochemical technique. Nerve fibers containing vasoactive intestinal peptide immunoreactivity were present in the smooth muscle layers as well as in the adventitia of all mesenteric lymphatics that were examined. The effect of vasoactive intestinal peptide on isolated lymphatic vessels in vitro was studied. Vasoactive intestinal peptide caused a concentration-dependent relaxation of bradykinin-induced contractions of lymphatic vessels. The threshold and maximum relaxations were achieved with vasoactive intestinal peptide at concentrations less than 6 X 10(-9) M and 3 X 10(-7) M, respectively. The relaxant response to vasoactive intestinal peptide was not modified by atropine, propranolol, bretylium, or tetrodotoxin. These results suggest that vasoactive intestinal peptide may be a possible inhibitory neurotransmitter that causes relaxation of lymphatic vessels.
Factors modifying the early nondiuretic vascular effects of furosemide in man. The possible role of renal prostaglandins.
Authors: Johnston G D , Hiatt W R , Nies A S , Payne N A , Murphy R C , Gerber J G
Published: June 2012

Animal experiments have suggested that salt-balance, prostaglandin synthesis, and renal function are important determinants of the nondiuretic vascular effects of furosemide. To investigate the influence of these factors in humans, we studied 10 normal volunteers and five anephric patients. The volunteers were studied on three occasions: when on a 10 mEq/day sodium diet, on a 250 mEq/day sodium diet, and on a 10 mEq/day sodium diet with indomethacin, 200 mg/day. The anephric patients were studied immediately after dialysis. Plethysmographic methods were used to measure venous capacitance and blood flow in the calf before, and at 5, 10, and 15 minutes after furosemide, 80 mg, iv. Blood was obtained before and 15 minutes after furosemide for determination of plasma renin activity by radioimmunoassay and of plasma 6-keto-prostaglandin F1 alpha by chromatography-mass spectrometry. We found that furosemide significantly increased venous capacitance in the calf of the normal volunteers on a low salt diet. Indomethacin, high salt intake, or lack of renal function was sufficient to inhibit this effect. Plasma renin activity increased only in the group that had the increase in venous capacitance. Limb blood flow decreased gradually in the 15 minutes following administration of furosemide in the normal volunteers, regardless of salt balance or indomethacin, but remained unchanged in the anephric patients. Plasma 6-keto-prostaglandin F1 alpha was less than 30 pg/ml in all samples. Indomethacin concentration averaged 1.3 micrograms/ml in volunteers on the drug. To determine whether indomethacin, salt intake or renal function affected another venodilator, we studied an additional group of normal and uremic volunteers who received 0.6 mg nitroglycerin sublingually.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of gonadectomy on left ventricular function and cardiac contractile proteins in male and female rats.
Authors: Schaible T F , Malhotra A , Ciambrone G , Scheuer J
Published: June 2012

To examine the influence of the sex hormones on mechanical properties and biochemistry of the adult heart, we studied left ventricular function and cardiac contractile proteins in hearts from 20-week-old male and female rats that had been gonadectomized at 18 days of age, compared with hearts from sham-operated animals. Testosterone and estradiol were not detectable in serum from male and female gonadectomized rats, respectively. The male rats had lower body and heart weights than male sham operated rats, whereas these values were higher in female gonadectomized than in female sham-operated rats. Left ventricular function was studied in a working heart apparatus at similar heart rate and at controlled levels of aortic diastolic pressure and left atrial pressure. At moderate left atrial pressure, end-diastolic pressure and volume per gram dry left ventricle were the same in all groups, but at high left atrial pressure, end-diastolic pressure, and volume per gram dry left ventricle were lower in male and female gonadectomized than in the respective sham-operated rats. Further increases in left atrial pressure were associated with mechanical alternans in male and female gonadectomized rats. Significantly (P less than 0.05) lower values for cardiac output, peak systolic pressure, ejection fraction, and myocardial oxygen consumption occurred in male gonadectomized compared with sham-operated rats at moderate and high left atrial pressure at higher levels of aortic diastolic pressure. Decreases in these values for female gonadectomized compared with sham-operated rats occurred only at high left atrial pressure. A significant downward shift in the mean force-velocity relationship was observed in all gonadectomized rats at both moderate and high left atrial pressure. In a follow-up study, when end-diastolic pressure was kept the same at both moderate and high left atrial pressure in female sham-operated and gonadectomized rats by reducing heart rate, decreases in contractile function in gonadectomized rats were observed at all preloads. Ca++-myosin ATPase activity was significantly reduced by 34% in male and by 19% in female gonadectomized rats when compared to respective sham-operated control hearts. These alterations in myosin ATPase activity were associated with a reduction in the V1 myosin isoenzyme and an increase in the V3 isoenzyme. Thus, left ventricular filling and left ventricular function were impaired in hearts of gonadectomized rats. Alterations in function were associated with depressed cardiac myosin ATPase activity in male and female gonadectomized rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Increase in collateral blood flow following repeated coronary artery occlusion and nitroglycerin administration.
Authors: Brazzamano S , Mays A E , Rembert J C , Greenfield J C
Published: June 2012

The effects of occlusion, reperfusion, reocclusion (n = 13), and nitroglycerin (n = 10) on regional transmural myocardial collateral blood flow was tested in conscious dogs in which collateral development was stimulated by partial stenosis of the left circumflex coronary artery. Hemodynamics and collateral blood flow were measured during the awake state using 9-micron radioactive microspheres. Regional transmural flow was measured during transient occlusion of the circumflex artery at 7 and at 14 days postoperatively. On the 14th postoperative day, two sets of circumflex occlusions and blood flow measurements were carried out. The first set consisted of two occlusions separated by 15 minutes. The second set performed 2 hours later included two occlusions, separated by 15 minutes, and nitroglycerin administration. Mean collateral blood flow increased significantly (P = 0.002) from 0.10 +/- 0.07 ml/min per g on day 7 to 0.25 +/- 0.18 ml/min per g on day 14. A significant increase in mean collateral blood flow from occlusion one to two was observed (0.28 +/- 0.17 to 0.37 +/- 0.22 ml/min per g, P = 0.005). Mean collateral flow increased significantly (P = 0.01) between pre- to post-nitroglycerin occlusions, 0.28 +/- 0.20 to 0.46 +/- 0.32 ml/min per g. Although this increase appeared to be greater than during the first set of occlusions, it did not reach statistical significance (P = 0.08). These data indicate that when immature collaterals are present, occlusions, reperfusion, and reocclusions of a major coronary artery produce augmentation in collateral flow. This must be considered in evaluating interventions which may alter collateral flow.
Identification and characterization of the rabbit angiotensin II myocardial receptor.
Authors: Baker K M , Campanile C P , Trachte G J , Peach M J
Published: June 2012

The octapeptide, angiotensin II, elicits a positive inotropic response in myocardial tissue by activating slow calcium channels. Pharmacological studies suggest that the inotropic action of angiotensin II is receptor mediated. The current investigation was performed to characterize the binding of 125I-angiotensin II to the putative receptor in a plasma membrane-sarcoplasmic reticulum preparation of the rabbit left ventricle. In experiments performed at 18 degrees C, steady state binding occurred at 45 minutes and saturable binding was 80-85% of the total binding. Analysis of the binding data indicated that the 125I-angiotensin II interacted with a single class of sites with a Kd = 4.5 +/- 0.8 nM and exhibited a binding capacity of 53.5 +/- 8 fmol/mg protein. The potency order for the competitive binding of analogues and antagonists of angiotensin II paralleled that observed for in vitro contractile force development in bioassay systems utilizing left atrial tissue. The binding of 125I-angiotensin II was stimulated 2-fold in the presence of the divalent cations of calcium and magnesium (10 mM). Guanine nucleotides modified the binding of 125I-angiotensin II to the rabbit myocardial particulate fraction. Guanine triphosphate and nonhydrolyzable analogues of guanine triphosphate increased the dissociation rate of the bound 125I-angiotensin II and decreased hormone binding to the receptor at equilibrium. In the absence of magnesium, guanine nucleotides had no effect on the dissociation rate of 125I-angiotensin II. 125I-Angiotensin II binding to a rabbit myocardial particulate fraction was found to have high affinity, to be saturable, reversible, specific, and modulated by guanine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
Pericardial adaptations during chronic cardiac dilation in dogs.
Authors: Freeman G L , LeWinter M M
Published: June 2012

The manner in which the pericardium adapts to chronic cardiac dilation is not known. Recent work from our laboratory indirectly suggested that the size of the pericardium and/or its pressure-volume relation was altered by chronic cardiac enlargement. To examine this question further, we compared pericardial pressure-volume and stress-strain relations, surface area, mass, and average thickness in seven normal dogs and seven with chronic volume overload hypertrophy due to a systemic arteriovenous fistula. Dogs with significant cardiac hypertrophy had an increased pericardial volume at any pressure and a proportionality constant for the slope of the entire curve as determined by nonlinear regression analysis. This was associated with parallel increases in pericardial surface area and mass such that average thickness was unchanged. Stress-strain analysis of the data revealed that the mechanical properties of the pericardium were not significantly different in dogs with chronic cardiac dilation. These results indicate that during chronic cardiac dilation the pericardium enlarges in size and mass. The pericardial chamber is more compliant, although the intrinsic stiffness of the pericardium appears to be unchanged. Further, since pericardial mass is increased, the response to chronic dilation appears to also involve the addition of new pericardial tissue.
Effects of tonicity on tension and intracellular sodium and calcium activities in sheep heart.
Authors: Lado M G , Sheu S S , Fozzard H A
Published: June 2012

We have measured the effects of changing tonicity of the bathing solution on intracellular sodium and calcium activities and tension of sheep cardiac Purkinje strands and ventricular muscle. For Purkinje strands in solutions of normal tonicity, resting membrane potential was -77.4 +/- 0.4 mV (mean +/- SE), sodium activity was 7.9 +/- 0.4 mM, and calcium activity was 98 +/- 9 nM. For ventricular muscle in solutions of normal tonicity, resting membrane potential was -86.4 +/- 1.2 mV, sodium activity was 6.9 +/- 0.5 mM, and calcium activity was 70 +/- 4 nM. Reduction of tonicity to 75% of normal in both tissues produced depolarization of a few millivolts, and sodium activity fell almost to the level predicted for simple osmotic dilution. In Purkinje strands, calcium activity fell much more than that predicted for simple osmotic dilution. Twitch contraction was reduced in the hypotonic solution. Increase of tonicity to 150% and 200% caused the resting membrane potential to become more negative. In both tissues, sodium activity increased somewhat less than predicted from simple water movement, and calcium activity increased proportionately much more than sodium activity. The much larger change of calcium activity in both hypo- and hypertonic solutions could be explained by water movement plus the effect of sodium-calcium exchange. In hypertonic solutions, tonic tension was increased, along with the rise in calcium activity; however, the twitch tension was reduced. This reduction of twitch tension may be due to a direct effect of hypertonicity on cross-bridge behavior, as has been reported for skeletal muscle.
Effect of arterial impedance changes on the end-systolic pressure-volume relation.
Authors: Maughan W L , Sunagawa K , Burkhoff D , Sagawa K
Published: June 2012

To study the end-systolic pressure-volume relationship of left ventricle ejection against physiological afterload, we imposed seven simulated arterial impedances on excised canine left ventricles connected to a newly developed servo-pump system. We set each of the impedance parameters (resistance, capacitance, and characteristic impedance) to 50, 100, and 200% of normal value (resistance: 3 mm Hg sec/ml; capacitance: 0.4 ml/mm Hg; characteristic impedance: 0.2 mm Hg sec/ml), while leaving the other parameters normal. Under a given impedance, the end-systolic pressure-volume relationship was determined by preloading the ventricle at four different end-diastolic volumes. There was no significant change in the slope of the end-systolic pressure-volume relationship with changes in any of the afterloading impedance parameters. However, the volume intercept of the end-systolic pressure-volume relationship decreased significantly with resistance from 5.5 +/- 1.0 (SE) ml at resistance equal to 1.5 mm Hg sec/ml to 0.6 +/- 1.8 ml at resistance equal to 6 mm Hg sec/ml (P less than 0.01). The volume axis intercept also decreased with characteristic impedance, from 5.9 +/- 2.0 ml at a characteristic impedance of 0.1 mm Hg sec/ml to 5.4 +/- 2.1 ml at a characteristic impedance of 0.4 mm Hg sec/ml, (P less than 0.05). We conclude that the slope of the end-systolic pressure-volume relationship is insensitive to a wide range of changes in afterload impedance, but its volume intercept is dependent on resistance and characteristic impedance.
Intracellular sodium, membrane potential, and contractility of rat mesenteric small arteries.
Authors: Mulvany M J , Aalkjaer C , Petersen T T
Published: June 2012

We have investigated effects of altered extracellular sodium, intracellular sodium concentration, and membrane potential on the contractile responses of rat isolated mesenteric small arteries (internal diameter ca. 200 microns), when mounted as ring preparations on an isometric myograph. To avoid possible neural effects, all vessels were denervated in vitro using 6-hydroxydopamine. In unstimulated vessels, exposure to low-Na+ solutions (25 mM sodium, sucrose, or choline-substituted) did not cause any response nor did exposure to ouabain (1 mM) for 1 hour [when intracellular sodium concentration increased to 64 mmol/(liter-cell)]. However, a response was obtained if ouabain-exposed vessels were subjected to low-sodium solutions (ca. 15% of maximal response). The magnitude of the response was dependent on the ratio of intracellular to extracellular sodium and was not inhibitable by the calcium blockers, felodipine (1 nM) or D600 (10 microM). This response could therefore be explained in terms of Na-Ca exchange mechanism. The responses of activated vessels to ouabain and to low-sodium solutions were also investigated. The responses of vessels to submaximal doses of noradrenaline or potassium were potentiated acutely by ouabain (by 10-30% of the maximal response), even if the extracellular sodium was reduced to 25 mM. In all cases, the potentiation by ouabain was accompanied by a depolarization (3-12 mV). However, only in the case of noradrenaline-activated vessels with normal extracellular sodium was the potentiation accompanied by an increase in intracellular sodium [by ca. 7 mmol/(liter-cell)]. Moreover, the latter response was inhibited by felodipine and D600. The results suggest that Na-Ca exchange mechanisms may be present in these vessels but that they only play a role under extreme conditions; under normal conditions the effect of ouabain on activated vessels seems to be primarily due to its depolarizing effect, and not to its effect on intracellular sodium.
In vitro adrenergic and cholinergic innervation of the developing rat myocyte.
Authors: Marvin W J , Atkins D L , Chittick V L , Lund D D , Hermsmeyer K
Published: June 2012

We studied the development of selective adrenergic and cholinergic neuroeffector transmission in primary cultures of isolated ventricular muscle cells. Explants of either thoracolumbar sympathetic ganglia or sacrococcygeal spinal cord were added to newborn rat ventricular cultures harvested prior to the onset of in vivo autonomic innervation. Neuronal growth, migration, and the formation of neuromuscular junctions were observed with light and scanning electron microscopy. Glyoxylic acid histofluorescence, reflecting catecholamine synthesis, was found in only the sympathetic neuromuscular cultures. Choline acetyltransferase activity was detected in both spinal cord and sympathetic neuromuscular cultures, but was significantly higher in the spinal cord neuromuscular cultures. The isolated ventricular muscle cells remained at a constant spontaneous contraction frequency, regardless of the type of culture preparation. Guanethidine sulfate application produced a positive chronotropic response, blocked by propranolol, in the sympathetic neuromuscular cultures, but not in the spinal cord neuromuscular cultures. Bethanechol sulfate produced a negative chronotropic response, blocked by atropine, in the spinal cord neuromuscular cultures, but not in the sympathetic neuromuscular cultures. Isolated ventricular muscle cells in the absence of neurons failed to respond to either agent. Direct microelectrode stimulation of adrenergic or cholinergic neurons likewise respectively produced either a positive or negative ventricular muscle cell chronotropic response. These studies are the first to establish the selective production of functional cholinergic and adrenergic innervation of isolated cardiac muscle cells in vitro.
Increased venous pressure causes myogenic constriction of cerebral arterioles during local hyperoxia.
Authors: Wei E P , Kontos H A
Published: June 2012

The responses of cerebral (pial) arterioles to increased venous pressure were examined in anesthetized cats equipped with cranial windows for the observation of the cerebral microcirculation. Increased venous pressure was induced by occlusion of the superior vena cava. Intracranial pressure was kept constant. Increased venous pressure when the window was filled with stationary cerebrospinal fluid caused 9-12% arteriolar dilation. Cerebral arteriolar dilation of equal magnitude (8-12%) was also seen when the space under the cranial window was perfused with fluorocarbon FC-80 equilibrated with 100% nitrogen. Increased venous pressure when the cranial window space was perfused with fluorocarbon equilibrated with 100% oxygen caused a small (5%) but significant arteriolar constriction. These results show that the dominant mechanism of autoregulation in the cerebral arterioles is metabolic, and that it involves an oxygen-sensitive mechanism. Myogenic vasoconstriction is unmasked during venous hypertension when the dominant metabolic mechanism is eliminated by increased local supply of oxygen.
Oxygen radicals mediate the cerebral arteriolar dilation from arachidonate and bradykinin in cats.
Authors: Kontos H A , Wei E P , Povlishock J T , Christman C W
Published: June 2012

Topical application of sodium arachidonate (50-200 micrograms/ml) or bradykinin (0.1-10 micrograms/ml) on the brain surface of anesthetized cats caused dose-dependent cerebral arteriolar dilation. This dilation was blocked by 67-100% in the presence of superoxide dismutase and catalase. These enzymes did not affect the changes in arteriolar diameter caused by alterations in arterial blood PCO2, or the arteriolar dilation from topical acetylcholine. Enzymes inactivated by heat had no effect on the vasodilation from arachidonate or bradykinin. Superoxide dismutase alone or catalase alone reduced the dilation during application of 200 micrograms/ml of arachidonate for 15 minutes; they also completely prevented the residual dilation seen 1 hour after washout, as well as the reduction in the vasoconstrictive effects of arterial hypocapnia observed at this time. The results show that superoxide anion radical and hydrogen peroxide, or radicals derived from them, such as the hydroxyl radical, are mediators of the cerebral arteriolar dilation from sodium arachidonate or bradykinin. These radicals are not the endothelium-derived relaxant factor released by acetylcholine. The presence of both superoxide anion radical and hydrogen peroxide is required for the production of the vascular damage seen during prolonged application of high concentrations of sodium arachidonate.
Ionic basis for the antagonism between adenosine and isoproterenol on isolated mammalian ventricular myocytes.
Authors: Isenberg G , Belardinelli L
Published: June 2012

We studied the effects of adenosine and isoproterenol on membrane currents of isolated bovine and guinea pig ventricular myocytes with a two-microelectrode voltage clamp technique. Adenosine (50 microM to 0.2 mM) alone had no effect on any of the membrane currents measured, but it antagonized the effects induced by 10 nM isoproterenol. Peak calcium membrane current was augmented by isoproterenol from a control of 4.8 +/- 0.6 to 8.6 +/- 0.8 nA and adenosine reduced it to 5.7 +/- 0.7 nA (mean +/- SEM of six cells). The inactivation time constant was not altered by isoproterenol alone or isoproterenol plus adenosine, and neither was the voltage dependence of peak calcium membrane current. Thus, the changes caused by isoproterenol could be described as an increase in maximal calcium conductance from 0.86 +/- 0.7 to 1.55 +/- 0.04 mS/cm2 and partially antagonized by adenosine to 0.97 +/- 0.04 mS/cm2. Isoproterenol also increased the non-inactivating component of calcium membrane current from 17 +/- 1 to 24 +/- 4%, and adenosine reduced it to 18 +/- 2% (n = 4). The steady state activation and inactivation variables remained unchanged. Consistent with these effects on calcium membrane current, adenosine completely antagonized the isoproterenol-induced increase of the slow action potentials obtained in sodium-free medium. Isoproterenol increased the steady state outward currents at potentials between -90 and -30 mV (i.e., probable iK1). Adenosine alone had no effect on potassium membrane current, but it antagonized the effects of isoproterenol. Slow action potentials in 25 mM potassium were enhanced by isoproterenol, but were only moderately attenuated by adenosine. Accordingly, in 25 mM potassium the isoproterenol-induced changes in membrane currents were not antagonized by adenosine. This lack of inhibition by adenosine of the isoproterenol effects in 25 mM potassium could not be mimicked by 1-minute-long conditioning prepulses to -45 mV. The results indicate that adenosine by itself (absence of isoproterenol) has no effect on maximal calcium conductance, that the isoproterenol-induced increase in cyclic adenosine 3',5'-monophosphate, which leads to an increase in maximal calcium conductance, is antagonized by adenosine, and that such action can account for the ability of adenosine to attenuate the stimulatory effects of isoproterenol.