bluuebunny/crossref_metadata_2025 huggingface dataset:
O2 radicals in arachidonate-induced increased blood-brain barrier permeability to proteins
Authors: Wei E. P. , Ellison M. D. , Kontos H. A. , Povlishock J. T.
Published: December 2017

We studied the effect of topical application of arachidonate on the brain surface on blood-brain barrier permeability to either 125I-labeled human albumin or to horseradish peroxidase administered intravenously. Arachidonate was applied under a cranial window, and the concentration of albumin was measured in brain after elimination of the blood by perfusion-fixation. Permeability to 125I-labeled albumin was increased in the superficial 4 mm of the cortex but not in the deeper cortical layer 4-6 mm from the surface. This increased permeability to albumin was prevented by simultaneous topical application of superoxide dismutase (60 U/ml) and catalase (40 U/ml). Alterations in vascular permeability to horseradish peroxidase were evaluated in semiquantitative fashion, and they behaved similarly. Extravasated horseradish peroxidase was found in the wall of penetrating arterioles, and to a lesser extent in the wall of intraparenchymal vessels and capillaries, but not in the wall of pial arterioles or veins, although these latter vessels displayed focal endothelial lesions. We conclude that arachidonate increases the blood-brain barrier permeability to proteins. This increase in permeability is mediated by O2 radicals. The increased permeability occurs primarily in penetrating arterioles and not in pial arterioles or veins.
Pulmonary injury depresses cardiac systolic function through Starling mechanism
Authors: Calvin J. E. , Baer R. W. , Glantz S. A.
Published: December 2017

To determine whether pulmonary microvascular injury or lung hyperinflation changes left ventricular (LV) performance and whether ventricular interaction plays a role in mediating such changes, we studied seven open-chest, closed-pericardium, anesthetized dogs before and after right ventricular (RV) injections of 150- to 200-micron glass beads. Because people with pulmonary disease are often treated with positive end-expiratory pressure, we also hyperinflated the lungs before and after creating the pulmonary microvascular injury. Measurements of LV and RV pressures and dimensions were taken at end expiration during the basal state, during lung hyperinflation, and after microvascular injury at RV end-diastolic pressures of 5, 10, and 15 mmHg produced by volume loading. Acute volume loading produced upward shifts in the LV diastolic pressure-size curve both before and after microvascular injury. Neither microvascular injury nor lung hyperinflation substantially affected the LV diastolic pressure-size relationship. LV end-diastolic size determined LV stroke work with no consistent independent influence of microvascular injury or lung hyperinflation. Neither microvascular injury nor lung hyperinflation depressed systolic performance beyond that associated with changes in end-diastolic heart size.
Origin of atrial coving in canine phasic coronary artery blood flow
Authors: McHale P. A. , Greenfield J. C.
Published: December 2017

The transient decrease in left circumflex coronary artery blood flow during atrial contraction (atrial coves) was examined in open-chest, heart-blocked dogs. Prominent atrial coves were observed in left circumflex flow during both diastole and systole as a result of the asynchrony of atrial and ventricular contractions. In eight open-chest dogs, atrial contractions decreased diastolic circumflex coronary flow by 0.016 +/- 0.002 ml and systolic flow by 0.014 +/- 0.001 ml compared with diastolic and systolic intervals during which no atrial contractions occurred. The diastolic and systolic flow reductions in this vessel were not significantly different (P greater than 0.14). In five of the eight dogs no diastolic atrial coves were observed in left anterior descending coronary flow, and only minimal diastolic coving was present in the remaining three dogs; no systolic coves were present in this vessel in any of the eight dogs. In five additional open-chest dogs, brief inflation of a balloon in the left atrium produced elevations of left ventricular diastolic pressure comparable to those produced by atrial contraction. Only minimal atrial coves were associated with these balloon inflations. These data are consistent with the hypothesis that atrial contraction limits flow through the atrial blood vessels and results in a transient decrease in flow in the atrial arteries that arise from the left circumflex coronary artery. Although increases in ventricular diastolic pressure may be partially responsible for the appearance of atrial coves in the left circumflex coronary artery, mechanical contraction of the atrial musculature appears to be of significant importance.
Microvascular distribution of coronary vascular resistance in beating left ventricle
Authors: Chilian W. M. , Eastham C. L. , Marcus M. L.
Published: December 2017

To determine the distribution of resistance in the coronary vasculature, measurements of microvascular pressure and diameter were obtained with vasomotor tone intact and during coronary dilation produced by papaverine. We studied anesthetized, open-chest cats and used jet ventilation synchronized to the cardiac cycle to eliminate respiratory-induced cardiac motion. The system for measuring microvascular pressure compensated for cardiac motion with stroboscopic illumination of the microvessels and a computer-controlled electromechanical micromanipulator that moved a micropipette in synchrony with the heart. Pressures were measured with the servonull technique, and diameters were measured via a video system. Resistance was estimated from the pressure gradient from the aorta to a particular class (size) of coronary microvessel. During control conditions, with coronary vasomotor tone intact, myocardial perfusion was 139 +/- 9 ml X min-1 X 100 g-1 and was increased to 339 +/- 52 during papaverine infusion (P less than 0.05). During control conditions (mean arterial pressure 70-80 mmHg), approximately 25% of total coronary resistance was proximal to 200-microns diameter arterioles and approximately 20% was produced by arterioles between 100 and 200 microns diameter; there was approximately 20-mmHg pressure gradient from the aorta to 200-microns arterioles and a 30- to 35-mmHg gradient from the aorta to 100-microns arterioles. Present results also indicate that 55% of total coronary resistance is distal to the 100-microns arterioles under control conditions. Coronary vasodilation with papaverine (mean arterial pressure maintained at 70-75 mmHg with an aortic snare) produced a redistribution of resistance; only 10% of total resistance was proximal to the 200-microns arterioles, and the pressure gradient from the aorta to these vessels was only 5-10 mmHg. Thus, under these experimental conditions with vasomotor tone intact, a substantial portion (45%) of coronary resistance resides in relatively large (greater than 100-microns) coronary arterioles, and the distribution of resistance and microvascular pressures can be shifted with coronary vasodilation.
Mean circulatory filling pressure: potential problems with measurement
Authors: Gaddis M. L. , Rothe C. F. , Tunin R. S. , Moran M. , MacAnespie C. L.
Published: December 2017

Three experimental series using 22 acutely splenectomized mongrel dogs were completed to 1) compare fibrillation (Fib) and acetylcholine (ACh) injection as methods to stop the heart for the mean circulatory filling pressure (Pmcf) maneuver, and 2) test whether Pmcf equals portal venous pressure 7 s after heart stoppage (Pportal7s). Blood volume changes of -10, -20, +10, or +20 ml/kg were imposed and Pmcf and Pportal measurements were obtained. Pportal7s and Pmcf were significantly different with volume depletion but were similar under control conditions. Pmcf with ACh and Pmcf with Fib were significantly different only after a volume change of -20 ml/kg. However, severe pulmonary congestion and atelectasis were detected in animals where Ach was used to stop the heart. In some cases (with injection directly into the pulmonary artery) the damage was severe enough to cause irreversible arterial hypoxia. Thus we conclude that the repeated use of ACh may exert a detrimental influence on pulmonary function, changing the physiological status of the experimental animal. Also, the central venous pressure at 7 s of heart stoppage (Pcv7s) is not a fully accurate estimate of the true mean circulatory filling pressure during the Pmcf maneuver, because Pcv7s did not equal the Pportal7s under all experimental conditions.
Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C
Authors: Franson R. , Gamache D. , Blackwell W. , Eisen D. , Hess M. L.
Published: December 2017

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac vasculature and flow during pressure-overload hypertrophy
Authors: Breisch E. A. , White F. C. , Nimmo L. E. , Bloor C. M.
Published: December 2017

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.
Depolarizing effects of catecholamines in quiescent sheep cardiac Purkinje fibers
Authors: Terris S. , Wasserstrom J. A. , Fozzard H. A.
Published: December 2017

Isoproterenol reversibly depolarizes quiescent sheep cardiac Purkinje fibers, in contrast to its reported hyperpolarizing effect in many excitable tissues. The depolarization is inhibited by drugs that block beta 1-adrenergic receptors. Tetrodotoxin and verapamil have no effect on the isoproterenol-induced depolarization. Cesium reduced the isoproterenol-induced depolarization by 74%. The voltage dependency of activation of a current component called If, measured under voltage clamp, was shifted in the depolarizing direction by isoproterenol. No evidence was found to support the suggestion made for other tissues that the Na+-K+ pump is stimulated by isoproterenol. These data suggest that in quiescent sheep Purkinje fibers the isoproterenol-induced depolarization reflects activation of a pacemaker current.
Hemodynamic changes during onset of high-sodium one-kidney figure-8 renal hypertension
Authors: Hinojosa C. , Haywood J. R.
Published: December 2017

The hemodynamic changes associated with the onset of one-kidney, figure-8, renal-wrap hypertension were monitored in rats fed a high-sodium diet. In addition, the hemodynamic contributions of the sympathetic nervous system (SNS) and arginine vasopressin (AVP) were assessed during the 1st week of hypertension. Renal wrapping caused mean arterial pressure (MAP) to increase significantly from 108 +/- 4 to 140 +/- 4 mmHg on day 5 after renal surgery. The hypertension was associated with a significant bradycardia and no significant change in cardiac output (CO), as measured with an electromagnetic flow probe. Total peripheral resistance (TPR) was significantly elevated to 140% above control value on day 5 after renal surgery. Ganglionic blockade caused similar decreases in MAP and TPR in normotensive and hypertensive animals. Sympathetic blockade after pretreatment with a specific vascular antagonist of AVP, [1-beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin ([d(CH2)5Tyr(Me)]AVP), caused a greater depressor response in the renal-wrapped animals as compared with the effect of ganglionic blockade alone in these animals. The effect of [d(CH2)5Tyr(Me)]AVP alone on the hemodynamics was not different between the two groups of rats. After ganglionic blockade pretreatment, [d(CH2)5Tyr(Me)]AVP caused a significant decrease in MAP and TPR in the renal-wrapped animals. In addition, the difference in MAP and TPR between the two groups of rats was eliminated after combined blockade of AVP and the SNS. The results of this study indicated that the onset of hypertension was a result of an activation of neurohumoral mechanisms to increase TPR.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial blood flow in left ventricular hypertrophy developing in young and adult dogs
Authors: Bache R. J. , Alyono D. , Sublett E. , Dai X. Z.
Published: December 2017

This study was performed to test the hypothesis that growth of coronary vasculature would be facilitated if myocardial hypertrophy occurred during the period of normal body growth rather than in mature adult animals. Left ventricular hypertrophy was produced by banding the ascending aorta in eight young dogs 7 wk of age and in nine adult dogs. Adult dogs were studied 2 mo after aortic banding, whereas young dogs were allowed to grow to adulthood before study. Left ventricular weight-to-body weight ratios were increased to 6.88 +/- 0.36 g/kg in the young dogs and 6.64 +/- 0.47 in adult dogs; both were significantly greater than seven normal control animals (4.32 +/- 0.05; each P less than 0.01). Myocardial blood flow per gram measured with microspheres during quiet resting conditions was significantly higher in young dogs with left ventricular hypertrophy than in normal dogs. Myocardial blood flow rates during maximum coronary vasodilation with adenosine (4 mumol X kg-1 X min-1 iv) were similar in all three groups. However, since mean coronary perfusion pressure was higher in the dogs with aortic banding, minimum coronary vascular resistance per gram of myocardium was significantly higher in both young (21.1 +/- 3.1 mmHg X ml-1 X min X g) and adult dogs with left ventricular hypertrophy (21.8 +/- 2.2) than in the normal dogs (16.8 +/- 3.1; each P less than 0.01). Mean coronary vascular resistance for the total left ventricle was similar in all three groups of animals, suggesting that growth of coronary vasculature did not occur as the myocardium underwent hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Maturational differences in the isolated isovolumic rabbit heart
Authors: Parrish M. D. , Ayres N. A. , Kendrick B. T. , Fixler D. E.
Published: December 2017

To determine maturational differences in myocardial pressure work, oxygen consumption, and stability, we evaluated an isolated retrogradely perfused isovolumic rabbit heart model in newborns (0–6 days of age, mean 3.3 +/- 1.9 days), immatures (4–6 wk) and adults (5–7 mo). To reduce ischemic time and cardiac trauma, the hearts were isolated and instrumented within the chest cavity. By design, there were no significant age-related differences in coronary flow per gram, heart rate, or resting pressure. Left ventricular developed pressure was similar at all ages, but myocardial oxygen consumption was much lower in newborns and immatures than in adults. Coronary resistance was lower in the younger hearts. There were no significant age-related differences in contractility, left ventricular stiffness, or myocardial pH. All hearts were stable for 120 min, but thereafter immatures and adults deteriorated more rapidly than newborns. The study demonstrates that this model is technically suitable for the study of age-related differences in cardiac physiology. Furthermore, newborn and immature hearts are able to more efficiently use oxygen to develop left ventricular pressures, possibly due to a lower wall tension.
Attenuation of reactive and active hyperemia by sympathetic stimulation in dog gracilis muscle
Authors: Klabunde R. E.
Published: December 2017

The effects of sympathetic stimulation (SS) on reactive hyperemia (RH) and active hyperemia (AH) were evaluated in dog gracilis muscles. Sympathetic nerves to the muscle vasculature were activated by electrical stimulation of the obturator nerve during neuromuscular blockade. The frequency of stimulation was adjusted to decrease control conductance by 50%. RH responses to 1 and 5 min of arterial occlusion and AH after 1, 4, 7, and 10 s of tetanic contraction (direct muscle stimulation) at 30% maximal tensions were recorded in the absence and presence of SS. RH peak conductance (Cp), recovery half-time (T0.5), and excess flow (EQ) were significantly attenuated by SS at both occlusion durations. The change in conductance (delta C) during RH was not altered by SS, since the absolute reductions in control and peak conductances were not different. The Cp of AH was reduced at each contraction duration while the delta C was reduced only with 1-s contractions. The T0.5 and EQ of AH were not affected by SS. The data demonstrate that low frequency SS limits the degree of vasodilation associated with both muscle ischemia and tetanic contraction. Furthermore, the more pronounced effects of SS on RH suggest that there is greater inhibition of sympathetic vasoconstrictor influences associated with muscle contraction than muscle ischemia possibly due to the production of a substance during contraction, but not ischemia, that antagonizes sympathetic vasoconstrictor mechanisms.
Time sequential prediction of ventricular-vascular interactions
Authors: Latson T. W. , Hunter W. C. , Burkhoff D. , Sagawa K.
Published: December 2017

A new analytical method (sequential convolution) for describing ventricular-vascular interactions was used to predict instantaneous pressure and flow in four isolated canine left ventricles ejecting into a computer-simulated arterial system. Ventricular pumping ability was described by a load-independent elastance, [E*(t)] combined with a ventricular internal resistance. “Arterial” properties were characterized using a time-based impulse response function that is derived from impedance measurements. Sequential convolution was then used to couple these independent descriptions of ventricular and vascular properties. Predicted pressure-volume trajectories, as well as instantaneous pressures and flows, closely matched the experimental data. Stroke volume, peak pressure, and peak flow were typically within 5% of measured values. This method provides a powerful analytical technique for examining ventricular-vascular interactions and has potential application in evaluating the ventricular-loading effects of more complex in vivo vascular properties.
Increased aortic PGI2 and plasma lyso-PAF in the unclipped one-kidney hypertensive rat
Authors: McGowan H. M. , Vandongen R. , Codde J. P. , Croft K. D.
Published: December 2017

Previous studies have implicated vasodilatory prostaglandins (PGs) in the reversal of hypertension following unclipping in the one-kidney, one-clip (1K,1C) hypertensive rat. The capacity of the aorta to synthesize prostacyclin (PGI2) was compared in clipped (group A, n = 9), unclipped (group B, n = 8 and group D, n = 9), and sham-unclipped (group C, n = 9) 1K,1C hypertensive rats. The involvement of platelet-activating factor (PAF), a potent renal antihypertensive phospholipid, in the reversal of renal clip hypertension was also examined. Hypertensive rats [systolic blood pressure (BP) greater than 180 mmHg] were fed a synthetic diet for 4 wk, after which group A was killed immediately, group C was sham-unclipped, and groups B and D unclipped and killed 24 h later. Blood was drawn for the measurement of plasma lyso-PAF (the precursor of PAF) and the aorta removed for determination of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of PGI2). BP fell substantially in the unclipped rats (groups B and D) but did not change in the sham-unclipped rats (group C). Mean aortic 6-keto-PGF1 alpha was increased in the unclipped groups [group B, 15.4 +/- 2.4 (SE) ng/mg; group D, 10.8 +/- 2 ng/mg] compared with group A (7.7 +/- 1 ng/mg) and group C (7.1 +/- 1 ng/mg) (H = 13.74, P less than 0.01). Plasma lyso-PAF was also significantly increased in the unclipped (group D, 261 +/- 26 ng/ml) vs. the sham-unclipped group (group C, 211 +/- 23 ng/ml, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Cerebral vascular responsiveness in deoxycorticosterone acetate-salt hypertensive rats
Authors: Soltis E. E. , Bohr D. F.
Published: December 2017

Alterations in cerebral vascular responsiveness were investigated in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Initial studies on the passive-force response characteristics of strips of basilar artery revealed no difference between control and DOCA-salt rats. No difference in acetylcholine-induced relaxation was seen between the two groups. The contractile response to KCl was similar in control and DOCA-salt rats. An increase in both threshold and midrange sensitivities to serotonin (5-HT) was seen in basilar artery from DOCA-salt rats. However, extracellular Ca sensitivity in the presence of 10(-6) M 5-HT was not altered. Intracellular Ca release (phasic contraction in response to 10(-6) M 5-HT) was similar in control and DOCA-salt rats. Relaxation in response to Ca (membrane stabilization) was also not different. Whereas sodium nitroprusside (SNP)-induced relaxation was not altered in basilar artery from DOCA-salt rats, a significant decrease in isoproterenol (ISO)-induced relaxation was observed. Relaxation following washout of maximal contractions to KCl and 5-HT was similar in the two groups. These results demonstrate specific alterations in cerebral vascular responsiveness of DOCA-salt rats. Whereas KCl contractile and SNP relaxation responses were not affected, responses to 5-HT and ISO were significantly altered. These changes do not appear to be related to alterations in the endothelium or in the Ca responsiveness of the vascular smooth muscle.
Cell-to-cell diffusion of fluorescent dyes in paired ventricular cells
Authors: Imanaga I. , Kameyama M. , Irisawa H.
Published: December 2017

The intracellular and cell-to-cell diffusion of fluorescent dyes of various molecular sizes were studied in enzymatically isolated paired ventricular cells of the guinea pig heart. Fluorescein sodium (mol wt 332), 6-carboxyfluorescein (mol wt 376), Lucifer yellow CH (mol wt 457), lissamine rhodamine B-200 (mol wt 559), and tetraglycine-conjugated lissamine rhodamine B-200 (mol wt 859) were all diffused into the single ventricular cell through the patch-clamp pipette. All these dyes were able to diffuse through the gap junction of the paired cells. The diffusion coefficient of 6-carboxyfluorescein in the cytoplasm was 5.8 X 10(-6) cm2/s, Lucifer yellow CH was 3.0 X 10(-6) cm2/s, and lissamine rhodamine B-200 was 8.6 X 10(-7) cm2/s. Permeability of the gap-junctional membrane was 6.8 X 10(-4) cm/s for 6-carboxyfluorescein, 2.8 X 10(-4) cm/s for Lucifer yellow CH and 7.4 X 10(-5) cm/s for lissamine rhodamine B-200. Thus lissamine rhodamine B-200 diffused in the cytoplasm and through the gap junction approximately 10 times slower than 6-carboxyfluorescein. Tetraglycine-conjugated lissamine rhodamine B-200 (mol wt 859) passed through the gap junction, suggesting that the critical pore size of the ventricular gap junction may be somewhat larger than that of the conjugated tetraglycine rhodamine.
Rat cardiac myocyte adenosine transport and metabolism
Authors: Ford D. A. , Rovetto M. J.
Published: December 2017

Based on the importance of myocardial adenosine and adenine nucleotide metabolism, the adenosine salvage pathway in ventricular myocytes was studied. Accurate estimates of transport rates, separate from metabolic flux, were determined. Adenosine influx was constant between 3 and 60 s. Adenosine metabolism maintained intracellular adenosine concentrations less than 10% of the extracellular adenosine concentrations and thus unidirectional influx could be measured. Myocytes transported adenosine via saturable [Michaelis constant = 6.2 +/- 2.1 microM and maximal velocity (Vmax) = 9.58 +/- 0.98 X 10(-1) pmol X mg protein-1 X s-1] and nonsaturable (rate constant = 1.8 X 10(-3)/s) processes. A minimum estimate of the Vmax of myocytic adenosine kinase (2 pmol X mg protein-1 X s-1) indicated the saturable component of adenosine influx was independent of adenosine kinase activity. Saturable transport was inhibited by nitrobenzylthioinosine and verapamil (inhibitor constant = 17 +/- 5 microM). Extracellular adenosine taken up by myocytes was rapidly phosphorylated to adenine nucleotides. Not all extracellular adenosine, though, was phosphorylated on entering myocytes, since free, as opposed to protein-bound, intracellular adenosine was detected after digitonin extraction of cells in the presence of 1 mM ethylene-diaminetetraacetic acid.
Effect of inflation on microvascular pressures in lungs of young rabbits
Authors: Raj J. U. , Chen P. , Navazo L.
Published: December 2017

We have examined the effect of positive pressure inflation on the longitudinal distribution of vascular resistance and intravascular pressures in isolated blood-perfused lungs of 3- to 4-wk-old rabbits. Lungs were perfused in zone 3 at airway inflation pressures (P airway) of 6, 14, and 19 cmH2O (pleural pressure, atmospheric) corresponding to 60, 80, and 90% of total lung capacity. We measured microvascular pressures by the micropipette servo-nulling technique in 20- to 50-microns diameter subpleural arterioles and venules. Pulmonary arterial and left atrial pressures were also measured. Lung blood flow was kept constant at 145 +/- 18 ml X kg body wt-1 X min-1. We found that at P airway of 6 cmH2O, approximately 55% of the total pressure drop was in arteries, approximately 23% in microvessels, and approximately 22% in veins. With increasing P airway and lung volume, there was a significant decrease in arterial and venous resistance, but an increase in resistance in microvessels. We conclude that lung inflation significantly alters the distribution of segmental vascular resistance, and therefore lung volume is an important variable that should be considered during estimation of capillary filtration pressure.
Nonosmotic influences on osmotic stimulation of vasopressin in humans
Authors: Goldsmith S. R. , Dodge D. , Cowley A. W.
Published: December 2017

To study the influence of cardiopulmonary baroreceptor loading and unloading on the osmotic stimulation of arginine vasopressin (AVP) in normal humans, we gave 105-min 5% saline infusions (0.06 ml X kg-1 X min-1) to three groups of subjects under different cardiopulmonary baroreceptor loading conditions. Group A received only the infusion, with a consequent increase in central venous pressure (CVP) of 2.6 +/- 1.7 mmHg; group B had CVP held constant by continuous lower body negative pressure; and group C had CVP decreased by -3.3 +/- 1.4 mmHg, also with lower body negative pressure, for the duration of the infusion. Mean arterial pressure increased in group A by 6.6 +/- 3.7 mmHg, but did not change in groups B and C. On average, osmolality increased by the same amount in each of the three groups (11.6 +/- 3.3, 13.7 +/- 3.2, and 10.9 +/- 2.5 mosmol/kg, P = NS). The changes in AVP in the three groups were 3.6 +/- 2.0, 2.7 +/- 1.9, and 6.2 +/- 3.5 pg/ml, P less than 0.03, with group C different from group B and groups A and B not different by individual pairs testing. An independent effect of prolonged CVP reduction on AVP levels in group C was made unlikely by studies in four additional subjects in whom AVP did not change at constant osmolality during 105 min of CVP reduction comparable with that in group C. Thus modest loading of both cardiopulmonary and sinoaortic baroreceptors does not alter the osmotic stimulation of AVP in normal humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased myocardial beta-receptors and adrenergic responses in hyperthyroid pigs
Authors: Hammond H. K. , White F. C. , Buxton I. L. , Saltzstein P. , Brunton L. L. , Longhurst J. C.
Published: December 2017

Controversy exists presently as to whether thyroid hormone potentiates the action of catecholamines on the heart. Therefore, the relationships between adrenergic sensitivity, myocardial beta-receptor number, and the cardiovascular responses associated with excess thyroid hormone were investigated in pigs (Sus scrofa). A hyperthyroid state was induced by the administration of triiodothyronine (T3; 1 mg/kg iv). After 7 days there was a significant increase in resting heart rate, systolic blood pressure, rate-pressure product, and O2 consumption in the hyperthyroid state. At this time echocardiography showed a substantial increase in myocardial cross-sectional size. Pharmacological tests showed an increased intrinsic heart rate (127 +/- 29 to 205 +/- 25 beats/min; P less than 0.001) and an increased chronotropic sensitivity to isoproterenol. The concentration of isoproterenol required for a 50% of maximal response (ED50) was reduced by 33 +/- 30% (2.1 +/- 1.0 to 1.2 +/- 0.3 micrograms/l; P less than 0.025). The slope of the line relating isoproterenol concentration and change in heart rate was increased by 29 +/- 33% (61 +/- 10 to 78 +/- 10; P less than 0.025). Radioligand studies demonstrated an increase in the number of beta-receptors in right atrial membranes from hyperthyroid animals (41 +/- 7 vs. 75 +/- 18 fmol/mg; P less than 0.02). The apparent dissociation constant (KD) of the receptor for l-isoproterenol was similar in membranes from euthyroid and hyperthyroid animals (157 +/- 57 vs. 219 +/- 59 nM, respectively; P = NS). This study demonstrates that hyperthyroidism is associated with an increased chronotropic sensitivity to isoproterenol, consequent to an up-regulation of beta-adrenergic receptors in the right atrium.
Effect of vasopressors on organ blood flow during endotoxin shock in pigs
Authors: Breslow M. J. , Miller C. F. , Parker S. D. , Walman A. T. , Traystman R. J.
Published: December 2017

A volume-resuscitated porcine endotoxin shock model was used to evaluate the effect on organ blood flow of increasing systemic arterial blood pressure with vasopressors. Administration of 0.05–0.2 mg/kg of Escherichia coli endotoxin (E) reduced mean arterial blood pressure (MAP) to 50 mmHg, decreased systemic vascular resistance to 50% of control, and did not change cardiac output or heart rate. Blood flow to brain, kidney, spleen, and skeletal muscle was reduced during endotoxin shock, but blood flow to left ventricle, small and large intestine, and stomach remained at pre-endotoxin levels throughout the study period. Four groups of animals were used to evaluate the effect of vasopressor therapy. A control group received E and no vasopressor, whereas the other three groups received either norepinephrine, dopamine, or phenylephrine. Vasopressors were administered starting 60 min after E exposure, and the dose of each was titrated to increase MAP to 75 mmHg. Despite the increase in MAP, brain blood flow did not increase in any group. Norepinephrine alone increased blood flow to the left ventricle. Kidney, splanchnic, and skeletal muscle blood flow did not change with vasopressor administration. The dose of norepinephrine required to increase MAP by 20–25 mmHg during E shock was 30 times the dose required for a similar increase in MAP in animals not receiving E. We conclude that hypotension in the fluid resuscitated porcine E shock model is primarily the result of peripheral vasodilatation, that the vascular response to vasoconstrictors in this model is markedly attenuated following E administration, that blood pressure elevation with norepinephrine, dopamine, and phenylephrine neither decreases blood flow to any organ nor increases blood flow to organs with reduced flow, and that norepinephrine, dopamine, and phenylephrine affect regional blood flow similarly in this model.
Alterations in substance P binding in brain nuclei of spontaneously hypertensive rats
Authors: Shigematsu K. , Niwa M. , Kurihara M. , Castren E. , Saavedra J. M.
Published: December 2017

Substance P binding sites were characterized in brain nuclei of young (4-wk-old) and adult (16-wk-old) spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Young SHR presented higher affinity constants (KA) than young WKY. The changes were restricted to the locus coeruleus, the area postrema, the dorsal motor nucleus of the vagus, and to discrete areas located in lobes 9 and 10 of the vermis cerebelli of SHR. There were no differences in the maximal binding capacity (Bmax) except in the nucleus ambiguus where the Bmax was lower than in WKY. Conversely, the number of substance P binding sites was higher in the locus coeruleus, the nucleus tegmentalis dorsalis, the nucleus ambiguus, the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the inferior olivary nucleus, and lobes 9 and 10 of the vermis cerebelli of adult SHR when compared with adult WKY. Our results support the hypothesis of a role for brain substance P in blood pressure regulation and in genetic hypertension in rats.
Endothelium-derived relaxant factor inhibits effects of nitrocompounds in isolated arteries
Authors: Pohl U. , Busse R.
Published: December 2017

We investigated the influence of endothelial cells on the smooth muscle vasodilator effects to sodium nitroprusside (SNP) or Teopranitol (an organic mononitrate) in isolated segments of rabbit aorta and femoral artery. In the femoral artery, the vasodilator responses to both nitrocompounds were significantly higher in the absence of endothelial cells or after pretreatment with the endothelium-derived relaxant factor (EDRF) inhibitor nordihydroguaiaretic acid (NDGA; 10 microM). Moreover, under conditions of stimulated EDRF release (induced by acetylcholine; 30–100 nM) the vasodilator responses to SNP were further attenuated in vessels with intact endothelium. By contrast, in the rabbit aorta, the vasodilator responses to the nitrocompounds were not significantly altered by either endothelium removal or treatment with NDGA. However, in the presence of the EDRF stimulator acetylcholine, the dose-response curve to SNP was shifted to right in the aorta as well. The role of EDRF in the endothelium-mediated attenuation of the dilator potency of SNP was further investigated by using EDRF released from cultured (bovine aortic) endothelial cells. The dilator effects of SNP were compared in endothelium denuded femoral or aortic segments in the presence or absence of EDRF. The vasodilator effects of SNP in both types of arteries were significantly reduced in the presence of EDRF. We conclude that EDRF attenuates the arterial vasodilation induced by SNP and Teopranitol. The results further suggest that endothelial cells exhibit a greater basal release of EDRF in the femoral artery than in the aorta, since under unstimulated conditions an EDRF-induced attenuation was seen only in femoral and not in aortic segments.
Maps of optical action potentials and NADH fluorescence in intact working hearts
Authors: Salama G. , Lombardi R. , Elson J.
Published: December 2017

Voltage-sensitive dyes were used to stain intact perfused hearts and to simultaneously measure optical action potentials (APs) from 124 sites on the epicardium. Patterns of electrical depolarization (activation) and repolarization (recovery) along the surface of the heart were determined from the upstrokes and repolarization phases of optical APs. Standard surface extracellular techniques can detect electrical activation but not the recovery or the duration of APs. The optical recordings were previously shown to be equivalent to intracellular electrode measurements (Salama and Morad, Science Wash. DC 191: 485–487, 1976) and now reveal that AP durations are heterogeneous throughout the epicardium, with durations increasing from the base to the apex of the ventricles. In hearts beating under normal sinus rhythm, the direction and conduction velocity of the activation waves could be altered by electrical stimulation. The normal heterogeneities in AP durations became more pronounced in the presence of the Ca2+-entry blocker, verapamil. The local metabolic state of the tissue was also monitored optically through its intrinsic NADH fluorescence measured from 124 separate regions on the heart. The time course and extent of metabolic injury caused by general anoxia or by a local ischemia induced by a coronary ligation was monitored through maps of NADH fluorescence. The present technique makes it possible to correlate changes in the metabolic state of the muscle with detailed changes in patterns of electrical activity and thus provides a powerful new tool to study fundamental aspects of normal and abnormal cardiac rhythm.
Effect of superfusate albumin on single capillary hydraulic conductivity
Authors: Huxley V. H. , Curry F. E.
Published: December 2017

It has been proposed that albumin interacts with the endothelial cell surface to form part of the molecular filter at the capillary wall. Previous investigations of the “protein effect” have been limited to sites accessible to albumin from the capillary lumen. We tested for a specific interaction of albumin with the ablumenal surface of the capillary wall. The hydraulic conductivity (Lp) of single capillaries in frog mesentery, perfused initially with albumin-free Ringer, was reduced when albumin (concentration greater than 1 mg/ml) was added to the superfusate (mean fractional reduction 0.56 +/- 0.05 SE, n = 15). A similar reduction was measured when the mesothelial barrier to water and solute flows between the superfusate and the albuminal surface of the capillary was destroyed. When the albumin was extensively dialyzed against Ringer to remove small vasoactive molecules, no change in the fractional reduction of Lp was observed. Lp was reduced to a minimum value in any capillary when the albumin concentration on both sides of the capillary wall was greater than 1 mg/ml. Our data conform to the hypothesis that albumin modifies structures throughout the capillary wall to maintain normal permeability. We predict that extravascular albumin reduces the ability of a Ringer perfusate to increase permeability in many isolated perfused organs.
Myocardial temperature variation: effect on regional function and coronary flow in dogs
Authors: D'Ambra M. N. , Magrassi P. , Lowenstein E. , Kyo S. , Austen W. G. , Buckley M. J. , LaRaia P. J.
Published: December 2017

Incremental changes in the temperature (28–42.5 degrees C) of the anterior left ventricular wall in a canine, working, beating right heart bypass preparation (constant preload, afterload, and heart rate) were produced to measure the effect of regional temperature on myocardial function and blood flow. Circumferential-axis segment lengths were measured with sonomicrometry in both the temperature-varied, left-anterior descending coronary artery (LAD)-supplied myocardium and the normothermic (38 degrees C) circumflex-supplied myocardium. Fast thermistors (time constant less than 0.25 s) continuously monitored midmyocardial temperature in both areas. A Silastic loop with heat exchanger, thermistors, strain gauge, and flow probe was inserted into the LAD and allowed precise control of regional myocardial temperature. Nine-micron microspheres injected into left atrium were used to evaluate coronary flow and distribution. In six anesthetized dogs, relative to normothermic control (38 degrees C), regional systolic shortening decreased 42.2 +/- 10% at 41 degrees C and increased 23.3 +/- 6% at 31 degrees C. There was no significant change in coronary blood flow or distribution at the three temperatures. Pressure-length areas varied inversely with myocardial temperature. These data demonstrate that there is a reversible inverse relationship between midwall T and ventricular function when heart rate, preload, and after-load are controlled.
Red cell perfusion in skeletal muscle at rest and after mild and severe contractions
Authors: Tyml K.
Published: December 2017

The aim of this study was to evaluate the distribution of red cell perfusion in sartorius muscle of anesthetized frogs by analyzing simultaneously red cell velocity (VRBC), number of cells per unit capillary length (NRBC), and density of perfused capillaries (CD) in a 2.07 X 2.71-mm region of the muscle visualized microscopically at very low magnification. In the 16 muscles studied, a severe 1-min electrical stimulation induced statistically significant increases in the mean values, VRBC, NRBC, and CD, as well as significant decreases in heterogeneities (SD/mean) of these three parameters when going from rest to postcontraction hyperemia. A mild 3-s stimulation caused significant increases only in VRBC and NRBC. Red cell perfusion, computed as a product of the three parameters divided by the mean capillary length, increased significantly from 87.4 +/- 81.9 to 417.9 +/- 118.2 (SD) and from 96.9 +/- 75.7 to 192.5 +/- 190.2 (SD) cells X s-1 X mm-3, respectively. In both stimulations, the postcontraction increase of red cell supply to the muscle, expressed in cells per second per cubic millimeter, was larger than any individual increase in the three parameters. Based on pooled data from all muscles, both NRBC and CD were determined to be dependent on VRBC. The present study supports the view that VRBC, NRBC, CD, and heterogeneity of red cell distribution depend on vascular tone and demonstrates for the first time that these four dependencies can operate both concurrently and synergistically to increase O2 supply to muscle after contraction.
Neural control of adrenal medullary and cortical blood flow during hemorrhage
Authors: Breslow M. J. , Jordan D. A. , Thellman S. T. , Traystman R. J.
Published: December 2017

Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, we compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz (n = 4 each group) for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. We conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.
Evidence for a pathogenetic role of xanthine oxidase in the "stunned" myocardium
Authors: Charlat M. I. , O'Neill P. G. , Egan J. M. , Abernethy D. R. , Michael L. H. , Myers M. L. , Roberts R. , Bolli R.
Published: December 2017

Recent evidence suggests that postischemic myocardial dysfunction (or myocardial “stunning”) may be mediated by oxygen free radicals, but the mechanism for their production remains unknown. To explore the role of xanthine oxidase as a potential source of free radicals, open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received intravenously either allopurinol (50 mg/kg 48 h, 20 h, and 30 min before occlusion, 10 mg/kg 1 min before REP, and 6.25 mg X kg-1 X h-1 throughout REP, n = 13) or saline (n = 14). The two groups were similar with respect to occluded bed size (postmortem perfusion) and collateral flow (radioactive microspheres). In controls, the transcardiac difference in plasma uric acid (great cardiac vein - arterial concentration) increased 199 +/- 70% (means +/- SE) during ischemia (P less than 0.02) and remained elevated for 5 min after REP; no increase was observed in treated dogs. Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. Following REP, however, recovery of contractile function (expressed as percent of preocclusion values) was considerably greater in allopurinol-treated as compared with control dogs: 57 +/- 14 vs. -22 +/- 16 (P less than 0.01) at 1 h, 70 +/- 13 vs. -15 +/- 15 (P less than 0.001) at 2 h, 65 +/- 14 vs. -28 +/- 13 (P less than 0.001) at 3 h, and 68 +/- 13 vs. -17 +/- 14 (P less than 0.001) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that xanthine oxidase is a source of the oxygen free radicals responsible for myocardial stunning following a brief episode of reversible regional ischemia.