bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional ventricular segmental dynamics in normal conscious dogs
Authors: Hittinger L. , Crozatier B. , Belot J. P. , Pierrot M.
Published: December 2017

Left ventricular (LV) subendocardial segmental behavior was analyzed during the whole cardiac cycle for different loading and inotropic conditions in six conscious dogs that were instrumented with ultrasonic crystals in the basal (B) and apical (A) LV regions, a LV micromanometer, and an aortic cuff occluder. There were large variations of A and B segmental behavior during isovolumic contraction and relaxation. In contrast, a linear relationship between A and B was observed during ejection but segmental shortening was larger during control in A than in B, whether it was expressed as a percentage of systolic shortening (34.6 +/- 1.1 and 25.0 +/- 1.2%, respectively; P less than 0.005), or whether segments were normalized for passive resting length. This linear relationship during ejection with a slope of 1.49 was not significantly modified by alterations of loading conditions or inotropic state. The larger A than B shortening, independent of the normalization procedure, is attributed to the regional stress distribution in the LV. The absence of regional and cycle invariance particularly during isovolumic phases prevents the inference of ventricular volume from a limited number of dimensions.
Direct platelet-fibrin interaction that does not require platelet activation
Authors: Jen C. J. , Hu S. J.
Published: December 2017

Interactions between platelets and fibrin are important in hemostasis but often confused with platelet-fibrinogen interactions. Fibrin solubilized in NaBr-acetic acid formed polymers in neutral pH buffers. A stirred mixture of solubilized fibrin and washed human platelets at neutral pH range showed drastic reduction in turbidity and concomitant platelet adhesion onto newly formed fibrin strands. Optimally, more than 99% of platelets could be associated with fibrin, whereas only 3% of erythrocytes were trapped in the fibrin network under similar conditions. This platelet-fibrin interaction was fibrin concentration dependent and polymerization stage dependent. It preceded any detectable platelet release of serotonin. Gly-Pro-Arg-Pro (250 times in excess) retarded the kinetics of fibrin polymerization as well as that of platelet-fibrin interaction. However, factors affecting platelet activation showed little effect on platelet-fibrin interaction. Our results support the existence of a platelet-fibrin interaction that does not require platelet activation.
Hyperosmotic sodium salts reverse severe hemorrhagic shock: other solutes do not
Authors: Rocha e Silva M. , Velasco I. T. , Nogueira da Silva R. I. , Oliveira M. A. , Negraes G. A. , Oliveira M. A.
Published: December 2017

Severe hemorrhage in pentobarbital-anesthetized dogs (25 mg/kg) is reversed by intravenous NaCl (4 ml/kg, 2,400 mosmol/l, 98% long-term survival). This paper compares survival rates and hemodynamic and metabolic effects of hypertonic NaCl with sodium salts (acetate, bicarbonate, and nitrate), chlorides [lithium and tris(hydroxymethyl)aminomethane (Tris)], and nonelectrolytes (glucose, mannitol, and urea) after severe hemorrhage (44.5 +/- 2.3 ml/kg blood loss). Sodium salts had higher survival rates (chloride, 100%; acetate, 72%; bicarbonate, 61%; nitrate, 55%) with normal stable arterial pressure after chloride and nitrate; near normal cardiac output after sodium chloride; normal acid-base equilibrium after all sodium salts; and normal mean circulatory filling pressure after chloride, acetate, and bicarbonate. Chlorides and nonelectrolytes produced low survival rates (glucose and lithium, 5%; mannitol, 11%; Tris, 22%; urea, 33%) with low cardiac output, low mean circulatory filling pressure, and severe metabolic acidosis. Plasma sodium, plasma bicarbonate, mean circulatory filling pressure, cardiac output, and arterial pressure correlated significantly with survival; other parameters, including plasma volume expansion or plasma osmolarity, did not. It is proposed that high plasma sodium is essential for survival.
Myocardial potassium uptake during alpha- and beta-adrenoceptor stimulation
Authors: Ellingsen O. , Vengen O. A. , Ilebekk A.
Published: December 2017

The changes in myocardial K+ balance during alpha- and beta-adrenoceptor stimulation were compared in 10 anesthetized open-chest pigs by intracoronary isoproterenol and phenylephrine infusions. K+ concentration was continuously recorded by polyvinyl chloride catheter-valinomycin minielectrodes in arterial and coronary sinus blood. The arterial-coronary sinus difference and accumulated myocardial K+ uptake were calculated after computerized data sampling. Isoproterenol (2.5 nmol/min ic) reduced coronary sinus K+ transiently to a nadir of 0.37 (0.23-0.53) mM (median and 95% confidence interval) below control. The accumulated K+ uptake amounted to 139 (63-215) mumol/100 g. After beta-blockade by propranolol, phenylephrine (100 nmol/min ic) induced a transient coronary sinus K+ lowering of 0.16 (0.13-0.21) mM and an accumulated K+ uptake of 30 (20-41) mumol/100 g, both values less than those of isoproterenol (P less than 0.001). Myocardial contractility increased only during isoproterenol infusion, arterial blood pressure rose slightly by phenylephrine, but changes in myocardial O2 extraction and lactate uptake did not indicate cardiac ischemia. We conclude that both alpha- and beta-adrenoceptor stimulation induce a myocardial K+ uptake presumably due to increased Na-K pump activity, the latter more efficiently.
Role of sympathetic nerves during developing cardiac hypertrophy in Grollman hypertensive rats
Authors: Tomanek R. J. , Carlson D. W. , Palmer P. J. , Bhatnagar R. K.
Published: December 2017

Peak left ventricular (LV) function, during rapid volume expansion, and cardiocyte structure were studied in rats with developing cardiac hypertrophy in response to Grollman hypertension (1 kidney, 1 figure 8) after chemical sympathectomy with 6-hydroxydopamine. This form of renovascular hypertension led to the same magnitude of hypertrophy in rats with or without sympathectomy. Indices of peak LV function, measured during acute volume expansion, tended to be normal or slightly higher in hypertensive rats than in controls. Sympathectomy in rats with hypertension significantly improved cardiac and stroke indices while decreasing total peripheral resistance at peak cardiac output. Despite similar magnitudes of LV hypertrophy (LVH) in the two hypertensive groups, cardiocytes in sympathectomized rats had higher mitochondrial volume densities and slightly lower myofibrillar volume densities. After regional sympathectomy of the anterior portion of the LV with phenol, mitochondrial volume density increased by 21% in hypertensive rats with LVH. These data indicate that, during the development of LVH in response to renovascular hypertension, sympathetic nerves do not contribute to the magnitude of LVH but may limit improvement in peak LV performance in response to increased preload. However, sympathetic nerves do play a role in the regulation of mitochondrial and myofibril growth.
Determination of pyridine nucleotide fluorescence from the perfused heart using an internal standard
Authors: Koretsky A. P. , Katz L. A. , Balaban R. S.
Published: December 2017

Mitochondrial reduced nicotinamide adenine dinucleotide (NADH) is a key intermediate in energy metabolism in the heart, which can be qualitatively monitored using nondestructive surface fluorescence techniques. However, this optical technique is subject to artifacts from alterations in tissue absorbance, motion of the heart, and variations in excitation intensity. In this study rapid-scan fluorescence emission spectroscopy was used in conjunction with an internal fluorescence standard to compensate for these optical artifacts. The fluorescence spectra obtained from heart had a maximum at 460 nm and a shoulder at 415 nm. Dilution of heart homogenates resulted in a fluorescent spectrum characteristic of suspensions of mitochondria, indicating that absorption of fluorescence by tissue components produces an inner filter effect. This internal filter was characterized, and isobestic points with regard to O2 were found at 425 and 450 nm. Alterations in the inner filter effect due to changes in tissue oxygenation were eliminated by monitoring the NADH at 425 nm. Motion artifacts and excitation source fluctuations were corrected by loading heart cells with an internal fluorescent standard, 5(6)-carboxy-2',7'-dichlorofluorescein (ClCF). Motion of the heart and changes in excitation intensity altered the fluorescence detected from both NADH and ClCF. The use of the NADH-to-ClCF ratio detected at isobestic wavelengths (425 nm NADH and 520 nm ClCF) gives a relative measure of NADH fluorescence, which adequately compensates for both internal absorbance and motion artifacts.
Acetylcholine release by a stimulus train lowers atrial fibrillation threshold
Authors: Euler D. E. , Scanlon P. J.
Published: December 2017

This study was designed to evaluate the importance of local release of autonomic neuromediators when electrical stimuli are applied to the right atrium to measure the atrial fibrillation threshold (AFT). Experiments were performed in 16 open-chest dogs anesthetized with alpha-chloralose. The dogs were denervated by bilateral transection of the stellates and cervical vagi. The AFT was determined in 11 dogs by delivering either a train of stimuli (14 pulses, 4 ms, 100 Hz) or a single stimulus (10 ms) to the right atrium during its vulnerable period. In eight dogs, beta-adrenergic blockade with timolol (0.1 mg/kg) had no effect on the AFT determined with either method. Atropine (0.2 mg/kg), given after timolol, significantly increased the train-of-pulses AFT from 4.7 +/- 0.4 to 32.3 +/- 4.6 mA (P less than 0.001). The single-pulse AFT increased from 16.5 +/- 1.5 to 17.8 +/- 1.5 mA (P less than 0.05). Atropine had a similar effect on the AFT when it was given in the absence of timolol (n = 3). In five additional dogs, a monophasic action potential was recorded while a 10-mA train was delivered to the atrium during its absolute refractory period. There was marked shortening of the monophasic action potential duration (55 +/- 6 ms) in the first beat after the train. The shortening was totally abolished by atropine (0.2 mg/kg). The results suggest that a train of stimuli liberates local stores of acetylcholine, which cause a shortening of atrial repolarization time and a profound decrease in the current necessary to evoke fibrillation.
Effect of ambient oxygen on cultured endothelial cells from different vascular beds
Authors: Farber H. W. , Center D. M. , Rounds S.
Published: December 2017

By the use of production of neutrophil chemoattractant activity as a marker, we investigated the responsiveness of endothelial cells of four different anatomic origins to altered ambient oxygen tension to determine whether genetic or conditioned variation existed. The ability of bovine aortic, bovine pulmonary arterial, bovine coronary arterial, and human umbilical vein endothelial cells incubated in decreased oxygen concentrations to release neutrophil chemoattractant activity was assessed. Bovine aortic, human umbilical vein, and bovine coronary arterial endothelial cells produce neutrophil chemoattractant activity in response to 10 or 3% ambient oxygen in vitro. In contrast, 0% ambient oxygen is required for appearance of neutrophil chemoattractant activity from pulmonary artery endothelial cells. These studies suggest that there may be genetic or conditioned variations in the response of endothelium from different vascular beds to decreased oxygen tensions. Furthermore, endothelial cells may play a role in neutrophil-mediated tissue injury during ischemia.
Altered intracellular adrenoceptor distribution in myocardium of spontaneously hypertensive rats
Authors: Limas C. J. , Limas C.
Published: December 2017

The number of membrane-bound beta-adrenoceptors is reduced in the myocardium of spontaneously hypertensive rats, and this decline may account for the decreased inotropic responsiveness to beta-agonists. It is not known, however, whether the total complement of cellular beta-receptors is lower in hypertensive animals. This issue was examined using two different approaches: acid elution of cell surface-bound beta-receptor ligands and comparison of the number of receptors in the plasma membrane and a postcytosolic vesicular fraction. Approximately 30% of the total beta-receptors were located intracellularly in Wistar-Kyoto rats compared with 42% for spontaneously hypertensive rats. Similarly, a decline in membrane-bound beta-receptors in hypertensive rats was balanced by a rise in receptors associated with the vesicular fraction. In contrast, alpha 1-adrenoceptors were higher in the membrane and lower in the vesicular fraction of hypertensive rats without a significant difference in total alpha-receptors compared with normotensive animals. Differences in adrenergic responsiveness in this, and perhaps other, models of cardiac hypertrophy reflect altered intracellular distribution of adrenoceptors, which may be under the control of the sympathetic nervous system.
Role of catecholamines in mediating fetal blood volume decrease during acute hypoxia
Authors: Brace R. A. , Cheung C. Y.
Published: December 2017

Hypoxia was induced in chronically catheterized sheep fetuses at 133 days gestation (term = 145-150 days) by lowering the O2 content of air inspired by the ewe while supplementing with 1-3% CO2. Control fetal arterial oxygen tension (PO2) averaged 22.5 +/- 0.4 (SE) mmHg. During 30 min of mild hypoxia (PO2 decrease less than 6 mmHg) in normal fetuses, fetoplacental blood volume decreased by 4.7 +/- 0.4% and fetal PO2 by 4.3 +/- 0.7 mmHg. In fetuses with alpha- plus beta-receptor blockade, no change in blood volume occurred during mild hypoxia even though PO2 decreased by 3.4 +/- 0.5 mmHg. During severe hypoxia (PO2 decrease greater than or equal to 6 mmHg), fetal blood volume decreased by 9.2 +/- 1.4% and PO2 by 10.4 +/- 0.4 mmHg in normal fetuses. After adrenergic receptor blockade, blood volume decreased by 7.6 +/- 2.5% when PO2 decreased by 8.0 +/- 0.8 mmHg. Fetal arterial and venous pressure were unchanged during mild hypoxia. Vascular pressures increased significantly during severe hypoxia in normal and blocked fetuses, but these were significantly delayed following adrenergic blockade. Thus, although the catecholamines appear to mediate the decrease in fetal blood volume during mild hypoxia, they appear to have little effect on the blood volume decrease that occurs during severe hypoxia. In addition, the changes in blood volume are not directly correlated with the changes in arterial and venous pressures.
Role of hypotension in decreasing cerebral blood flow in porcine endotoxemia
Authors: Miller C. F. , Breslow M. J. , Shapiro R. M. , Traystman R. J.
Published: December 2017

The role of reduced arterial blood pressure (MAP) in decreasing cerebral blood flow (CBF) during endotoxemia was studied in pentobarbital-anesthetized pigs. Microspheres (15 microns diam) were used to measure regional CBF changes during MAP manipulations in animals with and without endotoxin. Endotoxin (0.2 mg/kg iv) decreased MAP to 50 mmHg and decreased blood flow to the cortex and cerebellum without affecting cerebral cortical oxygen consumption (CMRO2). Elevating MAP from 50 to 70 mmHg during endotoxemia with norepinephrine (1.82 +/- 0.58 micrograms . kg-1 . min-1, iv) did not change cortical blood flow or CMRO2 but increased cerebellar blood flow. Brain stem blood flow was not affected by endotoxin or norepinephrine. When MAP was decreased to 50 mmHg by hemorrhage without endotoxin, no change in blood flow to cortex, cerebellum, or brain stem was observed from base-line levels. These results suggest that decreased MAP below a lower limit for cerebral autoregulation does not account for the decreased CBF observed after endotoxin.
Double-barrel pipette system for microinjection
Authors: Davis M. J. , Gore R. W.
Published: December 2017

A method for constructing double-barrel micropipettes is described. The pipettes are made from theta-tubing, which permits easy beveling of the tips. The two sides of the system operate independently and are suitable for simultaneous microinjection, microperfusion, or servo-null micropressure measurements.
Canine AV nodal artery: anatomical variations and a detailed description of cannulation technique
Authors: Mitsuoka T. , Pelleg A. , Michelson E. L. , Dreifus L. S.
Published: December 2017

Cannulation of the atrioventricular (AV) nodal artery for selective perfusion of the AV node is a useful physiological method for evaluating the direct effects of pharmacological agents on the AV node. However, previous reports have not included a detailed description of the technique for AV nodal artery cannulation. Furthermore, successful cannulation is dependent on familiarity with the anatomical variations of the AV nodal artery [i.e., the most superior posterior septal artery (PSA)], which supplies blood to the AV nodal region and the posterior descending artery (PDA). The purpose of this report is to describe in detail the technique for cannulation of the AV nodal artery as well as the common anatomical variations of this artery. The anatomy of the PDA and PSA was studied at postmortem examination with ink injection in 30 dogs. Verification of the anatomical location of the AV nodal artery was aided by the induction of transient AV nodal conduction block following intracoronary administration of acetylcholine in the beating heart, as was done in previous studies. Two main variations and two subtypes of PDA anatomy and three main variations of AV nodal artery were found. Based on the present findings, an improved technique for cannulation of the AV nodal artery was established. Using this technique, we achieved a high rate of successful cannulation.
Hypertension in SHR rats: contribution of maternal environment
Authors: Cierpial M. A. , McCarty R.
Published: December 2017

The role of the maternal environment in the development of hypertension in spontaneously hypertensive (SHR) rats was evaluated using the technique of reciprocal cross fostering. Litters of SHR and Wistar-Kyoto (WKY) normotensive pups were either reared by their natural mothers, in fostered to mothers of the same strain, or cross fostered to mothers of the opposite strain shortly after birth. Litters were weaned at 21 days of age, at which time all pups were weighed. At 18-20 wk of age, resting mean arterial blood pressures (MAP) and heart rates were determined for male subjects from the six groups (2 strains X 3 rearing conditions) via an indwelling tail artery catheter. At weaning, SHR animals weighed less than WKY animals. SHRs fostered to WKY mothers were significantly heavier than control SHRs, and WKYs fostered to SHR mothers were significantly lighter than WKY controls at weaning. These body weight differences were also evident in adulthood. Cross fostering SHR pups to normotensive WKY mothers resulted in a dramatic reduction in resting MAP measured in adulthood. Conversely, cross fostering WKY pups to SHR mothers had no measurable effect on adult resting MAP. We propose that an interaction between characteristics of the SHR maternal environment and a genetic susceptibility in SHR pups is essential in triggering the full expression of the hypertensive phenotype in this animal model of human essential hypertension.
Electrical restitution process in dispersed canine cardiac Purkinje and ventricular cells
Authors: Robinson R. B. , Boyden P. A. , Hoffman B. F. , Hewett K. W.
Published: December 2017

Rate-dependent changes in cardiac action potential duration (APD) have been related to ion accumulation and depletion in restricted extracellular spaces. Isolated cardiac cells lack intercellular clefts and thus are less likely than intact tissue to experience ionic transients immediately outside the plasma membrane. Furthermore, isolated Purkinje cells lack the T tubules found in ventricular tissue and cells, which also can be a site of ion accumulation and depletion. We therefore employed single canine ventricular and Purkinje cells to investigate the contribution of restricted spaces to the electrical restitution process. In both cell types, abrupt changes in cycle length do not alter resting potential, but APD alters with a time constant of approximately 1 min. In addition, both preparations exhibit two components to the electrical restitution process of the APD. The rapid component has a time constant of 66 +/- 17 ms in the ventricle cells and 186 +/- 43 ms in the Purkinje cells. The slower component is both smaller and more variable. These values are similar to those reported in intact canine ventricular and Purkinje tissue. Thus the restitution process of APD, as measured in these isolated cardiac cells, is not markedly dependent on the presence or absence of restricted extracellular spaces.
Receptor-mediated effects of a PGH2 analogue (U 46619) on human platelets
Authors: Morinelli T. A. , Niewiarowski S. , Daniel J. L. , Smith J. B.
Published: December 2017

The specific effects of U 46619 (9,11-dideoxy,9 alpha-11 alpha-methanoepoxyprostaglandin F2 alpha), thromboxane A2-prostaglandin H2 (TxA2/PGH2) analogue, on human platelet shape change, myosin light-chain phosphorylation, serotonin release, fibrinogen receptor exposure, and platelet aggregation were measured and compared with binding of [3H]U 46619 to platelets. Shape change and myosin light-chain phosphorylation were found to be saturable and dose dependent, having effective concentration producing 50% of the maximum response (EC50) values of 0.035 +/- 0.005 and 0.057 +/- 0.021 microM, respectively (mean +/- SE). These two effects were competitively inhibited by specific antagonists of TxA2/PGH2 receptors (BM 13177, PTA-OH, and 1.PTA-OH) indicating that they are receptor mediated. Binding of [3H]U 46619 showed two components. Occupancy of high-affinity binding sites [dissociation constant (Kd) = 0.041 +/- 0.009 microM, maximum binding site (Bmax) = 19.4 +/- 5.3 fmol/10(7) platelets, with 1,166 +/- 310 sites/platelet; n = 12] correlated with platelet shape change and myosin light-chain phosphorylation. We propose that a second component with an apparent Kd of 1.46 +/- 0.47 microM (n = 12) represents a second, low-affinity site. Mean EC50 values for U 46619-induced serotonin release, platelet aggregation, and fibrinogen receptor exposure were 0.54 +/- 0.13. 1.31 +/- 0.34 and 0.53 +/- 0.21 microM, respectively. Therefore, the platelet release reaction was not directly correlated with occupancy of high-affinity receptors but could be related to the second binding component of U 46619. Fibrinogen receptor exposure and platelet aggregation caused by U 46619 appeared to be events mediated by the release of adenosine diphosphate from platelet-dense granules.
Participation of adrenoceptors in liver blood flow regulation in anesthetized dogs
Authors: Terada N. , Koyama S. , Horiuchi J. , Takeuchi T.
Published: December 2017

We evaluated involvement of adrenergic receptors in the responses of the hepatic vasculature to reduction either of portal venous flow or hepatic arterial inflow. Portal vein occlusion caused an increase in hepatic arterial blood flow (HAF) and decreases in hepatic arterial pressure (HAP) and hepatic arterial vascular resistance (HAR) in the intact group. After pretreatment with either yohimbine or prazosin, but not propranolol, occlusion of the portal vein produced a greater decrease in HAP as compared with that in the intact group. No significant changes in HAF, HAR, or hepatic tissue blood flow (HTF) occurred after the treatment. These results indicate that the compensatory response of the hepatic arterial vasculature to altered portal blood flow (PVF) is regulated independently of the intrahepatic adrenergic receptors. Hepatic arterial occlusion caused a significant decrease in portal venous pressure, PVF, and HTF. Portal venous vascular resistance (PVR) was reduced slightly, but not significantly. After pretreatment with either yohimbine or prazosin, but not propranolol, occlusion of the hepatic artery produced an opposite effect: to increase PVF and significantly decrease PVR. These results indicate that intrahepatic alpha-adrenoceptors participate in the regulation of portal vascular tone to maintain portal vein pressure at a steady level, when inflow from the hepatic artery is reduced.
Sympathetic modulation of rabbit aortic baroreceptors in vitro
Authors: Munch P. A. , Brown A. M.
Published: December 2017

Previous studies indicate that sympathetic efferent nerves to the carotid sinus can modulate carotid sinus baroreceptor (BR) activity. There are, however, no studies that demonstrate this in the aortic arch. Since application of exogenous norepinephrine to the aortic arch can alter BR activity, we examined whether electrically stimulating the efferent innervation would likewise be effective. We used an in vitro preparation from anesthetized rabbits. This consisted of the aortic arch and sections of the aortic afferent and sympathetic efferent nerves. The aorta was perfused at a constant pulseless pressure set 10-15 mmHg above BR pressure threshold, and aortic diameter was measured with a photoelectric device. We electrically stimulated the efferent innervation with 1-ms duration constant-voltage pulses, while simultaneously recording aortic pressure, diameter, and BR discharge. In 12 of 18 BRs, discharge decreased with vasoconstriction and subsequently recovered with vasorelaxation. This BR inhibition was blocked when constriction was prevented with the alpha-adrenergic antagonist prazosin (10(-6) M). In the remaining six BRs, discharge increased in five units and remained constant in one unit; however, the excitation occurred only during and a few seconds after the stimulus period. Discharge then fell below control while aortic constriction persisted and subsequently increased back to control with aortic relaxation. In this second group of fibers, treatment with the smooth muscle relaxant sodium nitroprusside (10(-6) M) prevented BR inhibition but not excitation. Lastly, BR responses were eliminated if the efferent nerve was crushed but not cut, indicating that the sensory endings were not activated directly by electrotonic current spread.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriolar oxygen reactivity: where is the sensor?
Authors: Jackson W. F.
Published: December 2017

The hypothesis that arterioles are intrinsically sensitive to oxygen was tested by comparing arteriolar diameter responses with local and global PO2 changes in superfused hamster cheek pouch preparations. Local PO2 changes were produced by microapplication of fluid onto the surface of occluded or unoccluded aparenchymal arterioles or by cannulation and perfusion of arterioles in situ. Global changes refer to PO2 changes in the superfusate flowing over the entire preparation. Local, effective PO2 changes had no significant effect on arteriolar diameters. In contrast, global PO2 changes produced significant, reproducible changes in diameter. These observations do not support the hypothesis that arterioles are intrinsically oxygen sensitive, unless the oxygen-sensitive sites are distributed sparsely along the arteriolar tree. The data are consistent with oxygen sensors located either in vessels downstream from 15-micron arterioles (in terminal arterioles, capillaries, or venules) or in the parenchyma. The data also suggest that these sensors detect changes in PO2 and then initiate responses that can be conducted along the vasculature to an arteriole distant from the sensor.
Adenosine and hypoxia effects on atrioventricular node of adult and neonatal rabbit hearts
Authors: Young M. L. , Ramza B. M. , Tan R. C. , Joyner R. W.
Published: December 2017

An isolated perfused heart model was used to assess the effects of hypoxia and adenosine on the adult and neonatal (1-5 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by the A-H interval at a constant atrial pacing cycle length and by the longest pacing cycle length resulting in Wenckebach periodicity. We defined the pacing cycle length at or below which the AV node demonstrated Wenckebach periodicity as the Wenckebach cycle length. Adenosine produced a smaller dose-dependent increase in A-H interval in neonates than in adults, but the increase in Wenckebach cycle length was similar in the two age groups. When the hearts were exposed to 5 min of hypoxia the increase of Wenckebach cycle length was greater for adults than for neonates. The change in Wenckebach cycle length in adults caused by hypoxia was significantly greater than that caused by 1 mM adenosine. In addition, in adults aminophylline could partially attenuate the increase in Wenckebach periodicity caused by adenosine, but aminophylline could not attenuate the increase in Wenckebach cycle length caused by hypoxia. We conclude that in the rabbit AV node 1) the adenosine effect in neonates is similar to that in adults; 2) neonates are relatively resistant to acute hypoxia compared with adults; and 3) the response to acute hypoxia in adults cannot be totally explained by the adenosine release theory.
Does inadequate oxygen delivery trigger pressor response to muscle hypoperfusion during exercise?
Authors: Sheriff D. D. , Wyss C. R. , Rowell L. B. , Scher A. M.
Published: December 2017

In dogs running on a treadmill at 2 or 4 mph or 4 mph plus 10% incline, graded reductions in hindlimb perfusion reflexly elicited pressor responses. To test the idea that systemic arterial pressure (SAP) is raised by accumulation in muscle of a nerve-activating "pressor substance" release when O2 delivery becomes inadequate, arterial O2 content (CaO2) was reduced 29.1% by carbon monoxide (CO) inhalation before repeating exercise at 2 mph. We reasoned that the pressor substance, or related substances, should appear in femoral venous blood and be correlated to SAP. [K+] behaved inappropriately as a signal to raise SAP, i.e., when flow was reduced, SAP rose markedly with little or no change in [K+]. SAP was well correlated to pH and [lactate] over the three work loads. Compared with the same work load with normal CaO2, CO shifted the relation between SAP and terminal aortic flow rightward 0.30 l/min (34.5%) and the relation between SAP and PO2 leftward 7.7 mmHg. CO did not affect the relation of SAP to terminal aortic O2 delivery, hindlimb O2 uptake index, pH, or [lactate]. Thus pressor responses are apparently generated when O2 delivery falls below some critical level causing accumulation of a pressor substance the release of which is linked to a metabolic event that precipitates lactate accumulation.
Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts
Authors: Miller W. P. , Shimamoto N. , Nellis S. H. , Liedtke A. J.
Published: December 2017

We determined the independent influence of coronary hyperperfusion on myocardial metabolism in isolated and intact hearts. In an isovolumic blood-perfused rat heart preparation working against a left ventricular (LV) balloon, the effect of increasing coronary perfusion pressure from 100 to 150 mmHg was assessed. In three groups of rat hearts LV volume was fixed to obtain LV peak pressures of 42 +/- 3, 101 +/- 5, and 130 +/- 6 mmHg. With coronary hyperperfusion, LV pressure increased 27, 18, and 16%, LV maximum time derivative of pressure (dP/dt) increased 39, 20, and 22%, and myocardial O2 consumption (VO2) increased 16, 17, and 33%, respectively. In a fourth group, LV peak pressure was held constant at 92 +/- 4 mmHg during coronary hyperperfusion by decreasing LV volume. In this group, despite an increase in coronary blood flow of 48%, there was no significant difference in LV maximum dP/dt or myocardial VO2. Thus, in isolated rat hearts, coronary hyperperfusion was not an independent stimulus to myocardial VO2. To further test this, the effect of coronary hyperperfusion on myocardial metabolism was studied in an intact working swine heart preparation where the cardiac output was fixed with a right heart bypass circuit. Fatty acid oxidation in the left anterior descending bed was assessed by production of 14CO2 from [14C(U)]palmitate. A comparison of coronary perfusion 106 +/- 5 vs. 197 +/- 5 mmHg resulted in no significant change in global LV function, including LV internal diameter. Despite a 70% increase in coronary blood flow, there was no significant change in myocardial VO2 or fatty acid utilization.(ABSTRACT TRUNCATED AT 250 WORDS)
[14C]iodoantipyrine and microsphere blood flow estimates in cat brain
Authors: Schuier F. J. , Jones S. C. , Fedora T. , Reivich M.
Published: December 2017

A comparison of local cerebral blood flow estimates with the microsphere and the 4-[N-methyl-14C]iodoantipyrine ([14C]IAP) techniques has been performed in cats. Good correlation of [14C]IAP with microsphere flow estimates in the gray matter was found. In the white matter, however, [14C]IAP flow estimates were consistently lower than microsphere flow estimates. Error analysis of both techniques and comparison with previous studies suggest that peculiarities of white matter arterial vasculature with preferential microsphere accumulation may lead to this discrepancy. Microspheres did not interfere with flow as shown by the normal appearance of subsequent [14C]IAP autoradiograms. The number of microspheres seen on autoradiograms was used for an estimate of microvessels blocked by spheres and found to be negligible. The study also demonstrates that [14C]IAP is not diffusion limited up to the observed flow values of 2 ml.g-1.min-1. Both techniques might be used together for a combination of their respective advantages, which are temporal and spatial resolution for microsphere and [14C]IAP, respectively.
Modifications of electrode design for recording monophasic action potentials in animals and humans
Authors: Runnalls M. E. , Sutton P. M. , Taggart P. , Treasure T.
Published: December 2017

An Ag-AgCl electrode for recording monophasic action potentials by pressure contact is described. The electrode is mounted in a hand-held support designed for epicardial recordings during open-heart surgery from both the anterior and lateral walls of the left ventricle with minimal displacement of the heart. The support allows the electrode to be manipulated without the need for direct vision by the surgeon to any desired position while ensuring perpendicular apposition of the electrode without risk of damage to the myocardium. The permanently mounted electrode is also suitable for animal experiments. The electrode may be used for endocardial recordings in animals by direct puncture. Either a straight or curved electrode may be chosen as dictated by the recording site. The monophasic action potentials recorded by this electrode are of a high quality in terms of configuration, lack of drift, and amplitude.
Separation of Na-Ca exchange and transient inward currents in heart cells
Authors: Shimoni Y. , Giles W.
Published: December 2017

Enzymatically dispersed single cells from rabbit ventricle were voltage clamped using the suction pipette method to investigate whether in isolated cardiac cells a recently described slow inward current (IEX) due to the electrogenic Na+-dependent Ca2+ extrusion also underlies a transient inward current (ITI), which can trigger certain cardiac arrhythmias. The cells were held at -40 mV to inactivate the fast sodium current. After depolarizing pulses (to 0 or +10 mV for 50 to 200 ms), slow inward "tail" currents were consistently recorded. Previous results indicate that this tail current IEX is generated by the Na+-Ca2+ exchanger. After loading the cells with Ca2+ by blocking the Na+-K+ pump [either with strophanthidin (10(-5) M) treatment or by reducing external K+ to 1 mM or less], ITIS appeared. These were usually spontaneous but occasionally were time locked to the clamp pulses. It was possible to separate IEX and ITI by a variety of methods. These include the following. 1) Different stimulation protocols; repolarizing to more negative potentials augmented IEX and decreased or eliminated ITI. Increasing the rate of stimulation diminished IEX and increased ITI. 2) Pharmacological methods; adding BaCl2 (0.5-2.0 mM) or caffeine (5-10 mM) decreased IEX but abolished ITI. The findings suggest that different mechanisms regulate these two currents.
Effects of transplantation on atrioventricular nodal accommodation and hysteresis
Authors: Tuna I. C. , Barragry T. P. , Walker M. , Lillehei T. , Blatchford J. W. , Gornick C. , Ring W. S. , Bolman R. M. , Benditt D. G.
Published: December 2017

In the present study, atrioventricular nodal accommodation and hysteresis characteristics were evaluated in awake, unsedated dogs, before (n = 10) and after cardiac transplantation (n = 10). Chronically instrumented animals were atrially paced at a cycle length (CL) of 400 ms, followed by an abrupt decrease in pacing CL to 300 ms, followed by an abrupt return in pacing CL to 400 ms (with pacing sustained for 60 s at each CL). Atrioventricular nodal conduction characteristics (assessed by AH intervals) were simultaneously monitored. Under control conditions, AH intervals lengthened rapidly after an abrupt decrease in pacing CL [mean time for AH interval lengthening to stabilize (Tonset) = 2 +/- 1 s], whereas AH intervals lengthened more slowly (P less than 0.05) after transplantation (Tonset = 41 +/- 4 s). Similarly, after an abrupt increase in pacing CL, control AH intervals shortened rapidly [mean time for AH interval to return to base line (Tonset) = 5 +/- 1 s], whereas AH intervals shortened more slowly (P less than 0.05) after transplantation (Tonset = 42 +/- 5 s). Thus accommodation appears to be an intrinsic atrioventricular nodal response (present after cardiac denervation by transplantation) to abrupt, sustained atrial CL changes. Furthermore equivalence (P = NS) in atrioventricular nodal accommodation responses to symmetric CL decreases and increases after transplantation suggests that hysteresis [i.e., nonequivalence (P less than 0.05) in atrioventricular nodal accommodation responses], as seen under control conditions, results primarily from extrinsic (neural) modification of intrinsic atrioventricular nodal responses to symmetric CL changes.
Endogenous prostaglandins selectively mask large arteriole constriction to angiotensin II
Authors: Fleming J. T. , Harris P. D. , Joshua I. G.
Published: December 2017

Television microscopy was used to observe the responses of in vivo arterioles and venules of the rat cremaster muscle to the topical application of angiotensin II (10(-8) and 10(-6) M). Neither the first- (A1) or second-order arterioles (A2) nor the first- (V1) or second-order venules (V2) constricted significantly to angiotensin II. However, after the inhibition of local prostaglandin synthesis with either mefenamic acid or indomethacin, both A1 and A2, but not the venules, gave a significant constrictor response to angiotensin II (10(-6) M). Arterioles and venules, which were preconstricted with norepinephrine, dilated to their initial baseline diameters after angiotensin II (10(-6) M), a response not observed when the microvessels were pretreated with either an angiotensin antagonist or a prostaglandin synthesis inhibitor. These observations indicate that endogenous prostaglandins exert a significant dilator influence on the larger arterioles, that this dilator influence appears to oppose the constrictor effect of angiotensin II, and that angiotensin II acts on specific receptors to induce synthesis and/or release of dilator prostaglandins in large arterioles. However, prostaglandins cannot account for the absence of a venular constriction to angiotensin.
Use of acetylcholine to measure total vascular pressure-volume relationship in dogs
Authors: Lee R. W. , Lancaster L. D. , Gay R. G. , Paquin M. , Goldman S.
Published: December 2017

To define total vascular capacitance, we used acetylcholine to arrest the heart and measured mean circulatory filling pressure (MCFP) during controlled hemorrhage and volume loading in 12 splenectomized dogs after ganglion blockade with hexamethonium. We also examined the gross pathological and histological changes in the lungs. Controlled hemorrhage (n = 12) of 5 and 10 ml/kg decreased MCFP from 6.8 +/- 0.1 to 4.9 +/- 0.3 and 3.6 +/- 0.2 mmHg, respectively. Volume loading of 5 (n = 8) and 10 ml/kg (n = 4) increased MCFP to 9.3 +/- 0.2 and 12.1 +/- 0.1 mmHg, respectively. At MCFPs below 5 mmHg, the pressure (P)-volume (V) relationship was not linear [(P = P0ekV, where k is slope of ln (MCFP) vs. V, k = 0.061, R2 = 0.998]. At MCFPs between 5 and 12 mmHg, the pressure-volume relationship was linear (slope = 0.479 mmHg.ml-1.kg-1, R2 = 0.992) and total vascular compliance was 2.09 ml.mmHg-1.kg-1. There were no changes in heart rate, cardiac output, right atrial, pulmonary artery, and pulmonary artery wedge pressures when values at base line were compared with those measured 15 min after each arrest. There were no changes in arterial gas measurements or acid-base balance, and there was no evidence of atelectasis or interstitial or intra-alveolar edema. We conclude that the total body pressure-volume relationship in the presence of ganglion blockade had a nonlinear configuration. The use of acetylcholine to arrest the heart, four times with hexamethonium in reflex-blocked animals, did not result in changes in hemodynamics or pulmonary function.
Effect of sciatic nerve stimulation on pial arterioles in rats
Authors: Ngai A. C. , Ko K. R. , Morii S. , Winn H. R.
Published: December 2017

The present study documents the microvascular response of the pial circulation in sensory hindlimb cortex to sciatic nerve stimulation. Rats, anesthetized with alpha-chloralose and urethan, were equipped with closed cranial windows, and pial arteriolar diameter was measured during stimulation of the contralateral sciatic nerve. The effects of varying stimulus frequency, intensity, and duration were examined. Optimal stimulus frequency was 5 Hz, but response diminished significantly beyond 10 Hz. Optimal stimulus intensity was 0.2 V. At higher stimulus strength, arteriolar dilation was reduced, but systemic blood pressure rose significantly. At low stimulus frequency and intensities, pial arterioles responded to stimulation with a consistent pattern: initial delay of 1.4 s followed by abrupt dilation to a peak magnitude, subsequent decline to a lesser but still dilated state, and recovery to a resting diameter after the cessation of stimulation. No consistent response profile was discernible at high stimulus intensity and/or frequency. This vasodilatory response was discretely restricted to a limited number of arterioles, confined to the hindlimb somatosensory cortex as confirmed by sensory evoked response. The response of the pial circulation provides a well-characterized model for analysis of brain microcirculation, which presumably is linked to cerebral metabolism.
Base-line O2 extraction influences cerebral blood flow response to hematocrit
Authors: Hudak M. L. , Tang Y. L. , Massik J. , Koehler R. C. , Traystman R. J. , Jones M. D.
Published: December 2017

We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Delayed rectifier K+ current in embryonic chick heart ventricle
Authors: Clapham D. E. , Logothetis D. E.
Published: December 2017

Single ventricular cells from 7- to 10-day-old embryonic chicks were studied with the use of whole cell, outside-out, and cell-attached patch-clamp techniques. The macroscopic delayed rectifier current, IK, activated at membrane potentials above -25 mV. Peak IK at +40 mV was 103 +/- 20 pA (5.7 +/- 1 microA/cm2). IK was selective for K ions with reversal potentials close to the Nernst equilibrium potentials. The onset of current during a voltage step was sigmoidal and was fit by the function IK = IKoo (1-e-t/tau)2. The peak time constant of activation was greater than 6 s at -25 mV (22 degrees C). Significant inactivation was not observed. IK was blocked by intracellular cesium, extracellular 1 mM 4-aminopyridine, 20 mM tetraethylammonium chloride, and 1 mM barium chloride. Single-channel recordings revealed a K+-selective channel with a slope conductance of 15 pS (extracellular [K+] = 4 mM, intracellular [K+] = 145 mM). An ensemble average of consecutive single-channel traces reproduced the whole cell current. The single-channel density was approximately 0.04/micron 2 based on frequency of patches containing the 15-pS single conductance. Approximately 100 channels/cell would sum to account for the net IK. We have described for the first time a channel underlying the main delayed rectifier current and, as such, a main repolarization current in chick ventricle.
Pressor and intestinal vascular bed responses to vasopressin after cholinergic blockade
Authors: Martin D. S. , McNeill J. R.
Published: December 2017

Superior mesenteric arterial flow, aortic blood pressure, and heart rate were recorded, and plasma arginine vasopressin (AVP) concentrations were measured in conscious unrestrained cats during intravenous infusions of AVP (0.1–8.1 mU.kg-1. min-1). Responses to AVP were studied when autonomic nervous system (ANS) function remained intact and when the cholinergic limb of the system had been antagonized by methscopolamine nitrate (0.5 mg/kg) or by pirenzepine (60 micrograms/kg). Elevations in the circulating levels of AVP to approximately 30 and 600 fmol/ml in cats with intact ANS function were associated with decreases in superior mesenteric arterial conductance (SMAC, ml.min-1.kg-1.mmHg-1) of approximately 9 and 50%. The relationship between the dose of AVP and the decreases in SMAC for methscopolamine-treated cats was displaced slightly but significantly to the left of that for intact cats. The relationship between the dose of AVP and the increases in arterial pressure for methscopolamine-treated cats was also significantly displaced to the left of that for intact cats; however, the magnitude of the displacement was much greater than that for the dose-conductance relationship. In contrast to the findings with methscopolamine, pirenzepine did not significantly influence either the dose-conductance or dose-blood pressure response curves. These results are consistent with three conclusions. First, physiologically (less than 30 fmol/ml) and pathophysiologically (less than 600 fmol/ml) relevant concentrations of AVP are capable of inducing intestinal vasoconstriction, even in the presence of intact autonomic function. Second, the cholinergic limb of the autonomic nervous system plays a major role in buffering the vasopressor effects of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)