bluuebunny/crossref_metadata_2025 huggingface dataset:
Local cerebral circulatory and metabolic effects of indomethacin
Authors: McCulloch J. , Kelly P. A. , Grome J. J. , Pickard J. D.
Published: December 2017

The effects of indomethacin, a prostaglandin synthesis inhibitor, upon local cerebral glucose utilization and local cerebral blood flow have been examined in 36 conscious, lightly restrained rats. Cerebral glucose utilization and cerebral blood flow were determined by means of the quantitative autoradiographic techniques that utilize, respectively, 2-deoxy-D-[1-14C]glucose and iodo[14C]antipyrine as tracer molecules. The administration of indomethacin (0.3-30 mg/kg iv) did not alter significantly the rate of glucose utilization in any of the 38 discrete regions of the central nervous system that were examined. In contrast, cerebral blood flow in every region was significantly reduced by between 30 and 50% from vehicle-injected control levels after the administration of 10 mg/kg iv indomethacin and by 5-31% after 1 mg/kg iv indomethacin. These results provide further evidence that prostaglandins may play a major role in cerebrovascular regulation, but they provide no positive evidence for a role in neuronal activity, as reflected in local cerebral glucose utilization.
Responses of cerebral arterioles to increased venous pressure
Authors: Wei E. P. , Kontos H. A.
Published: December 2017

The responses of pial arterioles to increased venous pressure were studied in anesthetized cats equipped with cranial windows for the observation of the pial microcirculation. Stable increases in venous pressure consistently induced arteriolar vasodilation, which averaged 6-12% of the control diameter. The vasodilation occurred when arterial blood pressure was normal and during arterial hypotension induced by bleeding; it also occurred irrespective of whether intracranial pressure was kept constant or was allowed to increase venous hypertension. The results are consistent with the view that autoregulatory adjustments in caliber of pial arterioles are mediated predominantly by metabolic rather than myogenic mechanisms.
Sympathetic nerve discharge in chronic spinal cat
Authors: Ardell J. L. , Barman S. M. , Gebber G. L.
Published: December 2017

A study was made of external carotid, renal, and splanchnic sympathetic nerve discharge (SND) in chloralose-anesthetized cats subjected to transection of the sixth cervical spinal segment 2-37 days earlier. Minimal activity was observed under normocapnic conditions 2 days after spinal transection, and ganglionic blockade failed to lower blood pressure. Moderate hypercapnia increased SND and led to synchronization of activity into 1-6 cycle/s slow waves. Such slow-wave activity was present under normocapnic conditions in cats 9-37 days after spinal transection. Ganglionic blockade significantly reduced blood pressure in these preparations. The interval between successive 1-6 cycle/s slow waves was variable. Thus, unlike the case in baroreceptor-denervated cats with an intact neuraxis [Barman and Gebber, Am. J. Physiol. 239 (Regulatory Integrative Comp. Physiol. 8): R42-R47, 1980], chronic spinal cats are incapable of rhythm generation in the 1-6 cycle/s frequency range. Crosscorrelation analysis revealed that the discharges of pairs of segmental (but not intersegmental) sympathetic nerves were related in the chronic spinal cat. This situation differs from that in the baroreceptor-denervated cat in which the discharges of pairs of intersegmental as well as segmental sympathetic nerves are related. Thus coordination of activity in sympathetic nerves that arise from different spinal segments requires the integrity of bulbospinal connections. Finally, no evidence was obtained for the existence of a baroreceptor-like reflex mechanism acting to control SND in the chronic spinal cat.
Coherence of cardiac output with rate changes
Authors: Melbin J. , Detweiler D. K. , Riffle R. A. , Noordergraaf A.
Published: December 2017

In awake or lightly anesthetized dogs increases in heart rate (HR) induced by atrial pacing affect cardiac output (CO) and stroke volume (SV) in a predictable way that is represented by a SV-HR relationship (dSV/dHR). Under our experimental conditions where normal regulation of atrial rate was bypassed, atrial rate was the independent variable and CO and SV were dependent variables. As HR is increased, CO and SV are modified by reflex and other circulatory regulators. The dSV/dHR relation characterized the circulatory response to increasing HR. A single dSV/dHR curve consistently predicted responses under a number of different conditions (standing, recumbent, awake, various anesthetics, beta-adrenergic stimulation, or depression) and thus appeared as an expression of cardiac function. Alterations of the circulation by stellate ganglion or vagal stimulation, volume loading, aortic compression, and ventricular pacing were not represented by the same dSV/dHR function. The dSV/dHR function (including its linear version as reported by others for anesthetized dogs) showed that, when SVs were larger at low rates, maximum CO occurred at a higher HR. Recognition of this arithmetic-based feature resolves apparent contradictory findings reported in the literature.
Nonischemic myocardial hypoxia: coronary dilation without increased tissue adenosine
Authors: Downey H. F. , Crystal G. J. , Bockman E. L. , Bashour F. A.
Published: December 2017

Experiments were performed in 23 open-chest, anesthetized dogs to evaluate 1) the extent of coronary vasodilation during nonischemic hypoxia and 2) whether this dilation is associated with changes in cardiac concentrations of adenosine, inosine, and hypoxanthine. Three minutes of nonischemic myocardial hypoxia caused by selective perfusion of the left anterior descending coronary artery (LAD) with hypoxic blood (PO2 = 11.7 Torr) increased coronary flow 623%, an increase that was not significantly different from that at the peak hyperemic response following 3 min of ischemic hypoxia secondary to LAD occlusion (+534%). Concentrations for adenosine and inosine (nmol/g) in myocardium sampled during nonischemic hypoxia [0.8 +/- 0.2 (SE) and 0.8 +/- 0.2, respectively] were significantly less than values during control conditions (1.7 +/- 0.3 and 1.4 +/- 0.2). Hypoxanthine concentrations did not differ for nonischemic hypoxia and control conditions. During ischemic hypoxia concentrations for adenosine (31.2 +/- 4.9), inosine (91.0 +/- 13.6), and hypoxanthine (44.0 +/- 15.3) were considerably greater than values during nonischemic hypoxia and during control conditions. The results indicate that nonischemic hypoxia induced pronounced coronary vasodilation similar to that during ischemic hypoxia, with reduced rather than with increased tissue concentrations of adenosine and inosine. These findings suggest that reduced myocardial oxygen tension may cause dilation of coronary resistance vessels by a direct relaxant effect on arteriolar vascular smooth muscle.
Phospholipid phosphorylation in erythrocyte of spontaneously hypertensive rats
Authors: Koutouzov S. , Marche P. , Cloix J. F. , Meyer P.
Published: December 2017

The rapid turnover of phosphoinositides within membranes suggests that these lipids play an important role in membrane function. Since various abnormalities have been described in the erythrocyte membrane of the spontaneously hypertensive rat (SHR) we have studied the turnover of phosphoinositides in the erythrocyte of SHR and age-matched normotensive Wistar-Kyoto rat (WKY). This was achieved by measuring the incorporation of 32P into inositol lipids after incubation of 1) intact erythrocytes with [32P]orthophosphate and 2) isolated ghost membranes with [gamma-32P]ATP. In both series of experiments more than 99% of the radioactivity incorporated into lipids was into the polyphosphoinositides diphosphoinositide (DPI) and triphosphoinositide (TPI). In both intact erythrocytes and ghost membranes, the levels of 32P incorporated into DPI and TPI were significantly different in SHR than in WKY. Further analysis of factors known to influence the labeling of DPI and TPI indicated that this could be ascribed to decreased activities of phosphatidylinositol kinase and/or DPI kinase, with respect to ATP as substrate. Moreover comparison of data obtained in intact cells with those obtained with ghost membranes suggests that within the SHR erythrocyte, membrane-cytosol interactions may occur that could also be responsible for the alteration of phosphoinositide labeling observed in hypertensive animals. Since phosphoinositides have been reported to be involved in the Ca2+-gating system of membrane, our findings could be associated with the abnormal Ca2+ binding and transport recently described in SHR erythrocyte.
A study of rat intracerebral arterioles: methods, morphology, and reactivity
Authors: Dacey R. G. , Duling B. R.
Published: December 2017

Penetrating, intracerebral arterioles from rat were isolated, cannulated, and studied in vitro. Vessel wall elements were found to consist of an endothelial cell layer, one smooth muscle cell layer, and a thin adventitial layer or leptomeningeal sheath. Smooth muscle cell nuclei were oriented perpendicular to the vessel's longitudinal axis; endothelial cell nuclei were parallel to the axis. Mean vessel diameter with the smooth muscle inactivated (passive diameter) was 36.7 +/- 1.6 (SE) micrometer. Spontaneous smooth muscle tone developed at 37 degrees C and reduced vessel diameter to 70 +/- 4% of passive diameter. Vessels were activated by the extraluminal application of 140 mM KCl solution at pH 8.00, which produced a transient contraction that decayed within 30 s to a steady contraction of somewhat less intensity. Changes in intravascular pressure were used to alter wall tension of the vessels. Tension in the vessel wall was computed, and length-tension curves for the arteriolar smooth muscle were approximated. Length-tension relationships similar to those seen in other smooth-muscle preparations were found with maximal estimated force development of 1.29 x 10(-5) N . m-2. Alterations of bath pH caused changes in vessel diameter that were inversely related to extraluminal pH and varied by approximately 77% in the range from pH 6.85 to 8.00. Adenosine dilated vessels to 140 +/- 6% of control diameter at a concentration of 10(-5) M. The mechanical characteristics and the reactivity to H+, K+, and adenosine of these vessels were quantitatively consistent with in vitro data from larger cerebral vessels and in vivo data from pial arteries.
A digital sonomicrometer for two-point length and velocity measurements
Authors: Goodman C. A. , Castellana F. S.
Published: December 2017

We have designed, fabricated, and tested an improved digital sonomicrometer for two-point ultrasound measurements in the experimental cardiology laboratory. The system design incorporates state-of-the-art analog and digital circuitry and demonstrates 1) capability for either analog or digital output; 2) a resolution of +/- 0.15 mm, readily adjustable to +/- 0.03 mm as required; 3) excellent stability; 4) low cost; and 5) ease of operation by untrained personnel. The device was calibrated in vitro and successfully evaluated by making measurements of contractile motion in the myocardium of the open-chest dog.
Catecholamine effects on intracellular sodium activity and tension in dog heart
Authors: Wasserstrom J. A. , Schwartz D. J. , Fozzard H. A.
Published: December 2017

Because catecholamines have been reported to stimulate the sodium pump and Na+-K+-ATPase in skeletal and cardiac muscle, we examined the effects of isoproterenol (0.2-1.0 X 10(-6) M) and norepinephrine (2-4 X 10(-7) M) on intracellular sodium activity (aiNa) and twitch tension in dog Purkinje strands and ventricular muscles, aiNa was measured with Na+-sensitive microelectrodes. During the initial rapid increase in tension induced by catecholamines in Purkinje strands, no changes in aiNa were found. After 5-10 min aiNa decreased by about 2 mM, coincident with a small decline in twitch tension. When the catecholamine was removed, tension declined rapidly to a level less than control. Recovery of tension to its control level less than control. Recovery of tension to its control level occurred simultaneously with recovery of aiNa. Comparable changes in aiNa occurred in ventricular muscle, but the biphasic effect of catecholamines on tension was not seen. These results are consistent with sodium pump stimulation in cardiac muscle. In Purkinje strands the resulting changes in aiNa may alter the direct positive inotropic effect of catecholamines, probably by influencing Na+-Ca2+ exchange.
Movement of necrotic wavefront after coronary artery occlusion in rabbit
Authors: Connelly C. , Vogel W. M. , Hernandez Y. M. , Apstein C. S.
Published: December 2017

Movement of the necrotic wavefront after coronary artery occlusion (CAO) was defined in rabbits by comparing transient CAO (15, 30, or 60 min) and reperfusion to permanent CAO (n = 5-9/group). At 24 h after CAO the area of necrosis was determined by nitro-blue tetrazolium staining, and the transmural and circumferential extent of necrosis was evaluated at four levels from ligation to apex. Infarct size after permanent CAO for 24 h was 27 +/- 2 (SE) % of the left ventricle. Reperfusion at 60, 30, or 15 min after CAO reduced the infarct size to 24 +/- 3 (P = NS vs. 24 h), 14 +/- 2, and 8 +/- 1% (P less than 0.05 vs. 60 min), respectively. Reperfusion at 15 and 30 min after CAO decreased transmural extent by 49 and 38% (P less than 0.001 vs. 24 h), whereas the circumferential extent was reduced by only 10 and 12%, respectively (P = NS). After 60 min of CAO, reperfusion did not significantly reduce either transmural or circumferential necrosis. Thus early reperfusion reduced infarct size by converting potentially transmural infarcts into subendocardial infarcts but did not significantly reduce the lateral or circumferential extent of necrosis.
Metabolism of norepinephrine in vitro by dog pulmonary arterial endothelium
Authors: Rorie D. K.
Published: December 2017

The importance of endothelial cells in the removal of norepinephrine from synaptic clefts in dog pulmonary artery was studied. Strips of artery cut helically were denuded of endothelium by gently stroking the intimal surface with a wooden applicator stick or were studied with endothelium intact. All strips were prelabeled in L-[3H]norepinephrine (2 X 10(-7) M) and mounted for superfusion. Superfusate was collected continuously before, during, and after electrical stimulation (10 V, 2 ms, 2 Hz). Measurements were made of the amounts of [3H]norepinephrine and its metabolites in superfusate and in tissue. These studies have established that 3,4-dihydroxyphenylglycol is of neuronal origin and O-methylated metabolites are of extraneuronal origin. The formation of extraneuronal metabolites in smooth muscle and endothelium was examined by either blocking uptake of norepinephrine into each, in turn, or by combining blockade of uptakes with the elimination of access of norepinephrine to endothelial tissue by completely removing it. Electrical stimulation elicited the overflow of large amounts of norepinephrine, 3,4-dihydroxyphenylglycol, and O-methylated metabolites into superfusate in strips with intact endothelium; in strips denuded of endothelium there were striking decreases in the amounts of O-methylated metabolites produced. These studies show that pulmonary arterial endothelium participates in the extraneuronal metabolism of norepinephrine released by sympathetic nerve stimulation.
Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time
Authors: Sarelius I. H. , Duling B. R.
Published: December 2017

A method is presented for the in vivo study of red cell flow dynamics. The method permits direct measurement of the red cell volume fraction in microvessel blood without resort to in vitro calibration curves. Furthermore, the method does not require extensive mathematical manipulation and can be applied to any microvascular network in any tissue. The method also enables direct measurement of red cell velocity, flux, and capillary transit time. Fluorescently labeled erythrocytes in tracer quantities, but known concentrations, are used as indicators of the behavior of the total cell population. Erythrocyte transit time across vascular networks and erythrocyte velocity are determined directly by following the behavior of the labeled cells. Hematocrit and red cell flux are measured by standard microcirculatory methods using labeled cells instead of the total cell population. Data are then converted to absolute values from the measured fraction of labeled cells. The method is thus absolutely dependent on the labeled cells being rheologically normal, and the conditions under which this requirement is satisfied are defined. Microvascular data obtained by the use of this method are presented for hamster cheek pouch and cremaster muscle.
Myocardial pH during regional ischemia: evaluation of a fiber-optic photometric probe
Authors: Tait G. A. , Young R. B. , Wilson G. J. , Steward D. J. , MacGregor D. C.
Published: December 2017

The relationship between the decrease in intramyocardial extracellular pH and the degree of stenosis of the left anterior descending (LAD) coronary artery was studied in eight dogs pretreated with propranolol. Intramyocardial pH was measured with a miniature glass pH electrode and with a new photometric pH probe that uses fiber-optic filaments to measure the color change of an indicator substance in a small permeable chamber. The LAD was cannulated and perfused from the axillary artery. Cannula flow was measured with an electromagnetic flow probe, and regional myocardial blood flow (RMBF) was measured with radioactive microspheres before and at the end of a period of critical stenosis, 2/3 reduction of flow, or total occlusion of the LAD cannula. In the region of the glass electrode, the mean RMBF (+/-SE) decreased by 16.3 +/- 3.3, 52.7 +/- 7.3, and 84.8 +/- 6.5% during the three levels of stenosis, and the pH correspondingly decreased by 0.05 +/- 0.01, 0.29 +/- 0.10, and 0.94 +/- 0.17 units. In the region of the photometric probe, the RMBF decreased 19.1 +/- 1.3, 47.2 +/- 6.7, and 84.3 +/- 6.0%, and the pH decreased by 0.05 +/- 0.02, 0.14 +/- 0.04, and 0.76 +/- 0.18 units. There was no statistically significant difference between the two types of pH sensor.
Renin-angiotensin and development of collateral circulation after renal ischemia
Authors: Fernandez L. A. , Caride V. J. , Twickler J. , Galardy R. E.
Published: December 2017

Aortic ligation between the origins of the renal arteries in the rat produces a left renal ischemia, renin-dependent hypertension, and a transitory hindlimb paralysis of less than 2 h. Removal of the left ischemic kidney at the time of aortic ligation curtails the rise of blood pressure, plasma renin activity is normal, and paralysis is still present 24 h after surgery. Administration of an angiotensin-converting enzyme inhibitor or saralasin also prevents recuperation from paralysis after aortic ligation. Independent manipulation of the mean arterial pressure or plasma renin activity by pretreatment with reserpine or deoxycorticosterone before surgery shows that the presence or absence of paralysis is dependent on the plasma renin activity and not on the high blood pressure. Blood flow measurements show that paralysis is due to a persistent impairment of blood supply to the hindlimb muscle and not to ischemia of the spinal cord. Infusion of angiotensin II to aortic-ligated, left-renoprival animals tends to restore blood flow to muscle. It is concluded that after renal ischemia the renin-angiotensin system, independent of its hypertensive effect, restores blood flow by stimulating the development of collateral circulation.
Altered arterial ion transport and its reversal in aldosterone hypertensive rat
Authors: Garwitz E. T. , Jones A. W.
Published: December 2017

Alterations in vascular ionic metabolism preceded the onset of elevated blood pressure in the aldosterone-treated rat. Increases in 42K+ and 36Cl- turnover in the aorta and femoral artery were detected as early as 1 wk after the start of aldosterone infusion. These vascular changes were completely reversed after a 3-wk recovery period. An increased sensitivity to the effect of norepinephrine (NE) on aortic 42K+ turnover was also observed prior to a significant rise in systolic blood pressure. Enhanced sodium transport was also found in vessels from hypertensive rats infused with aldosterone for 4 wk. The potassium-sensitive component of the 24Na+ efflux was significantly elevated in vessels from hypertensives. This increase in sodium pump activity appeared to compensate for an increase in passive membrane permeability to sodium in that cell sodium levels were not altered by aldosterone treatment. A more rapid increase in 42K+ turnover occurred in aorta from aldosterone-treated rats when extracellular calcium was removed. Therefore, an impaired ability of calcium-dependent processes to adequately stabilize the vascular smooth muscle membrane may contribute to altered vascular ion transport. It is concluded that altered vascular electrolyte metabolism is an important pathogenic mechanism in the development of aldosterone-induced hypertension in the rat.
Arterial wall oxygen consumption rate varies spatially
Authors: Buerk D. G. , Goldstick T. K.
Published: December 2017

The ratio of the O2 consumption rate (Q) to the O2 transmissibility (diffusivity-solubility product, Dk) was estimated by curve-fitting O2 tension profiles measured in vascular strips in vitro and in blood vessels in vivo. For rabbit aortic tissue in vitro, Q/Dk was 2.51 +/- 0.28 (SE) X 10(5) Torr/cm2 (n = 9). For various dog vessels in vivo, Q/Dk ranged from 0.15 to 47 X 10(5) Torr/cm2. In most cases, Q/Dk was higher near the endothelium than in the outer wall. This difference appears to be caused by a higher Q. Computer simulations using a two-layer O2 transport model with estimated Q/Dk indicate that the O2 supply from the vasa vasorum is essential to prevent medial wall hypoxia.
Maximum fluid concentrations of materials released from platelets at a surface
Authors: Adams G. A. , Feuerstein I. A.
Published: December 2017

We examine the estimation of local concentrations of materials that are released from the dense and alpha-granules of platelets during accumulation of platelets upon collagen-coated glass. Platelet/red blood cell suspensions were perfused through a 1.3-mm-ID tube. Empirical data were used in a calculation procedure, based on diffusion and convection, designed to yield an upper bound on the interfacial fluid concentration (IFC) for each substance considered. The necessary empirical data are the rate of platelet accumulation and the maximum amount of material in the platelet capable of secretion. It was found that the IFC is dependent on the shear rate at the surface (G) and is proportional to G0.27. This means that an eightfold increase in flow rate would increase the IFCs approximately twofold. Serotonin, pyrophosphate, adenosine 5'-monophosphate (AMP), and adenosine 5'-triphosphate (ATP) were found not to be present in sufficient quantities to produce IFCs that could influence platelet aggregation if used alone at the IFC. A second set of materials, fibrinogen, fibronectin von Willebrand factor, and calcium, had IFCs less than their concentrations normally found in plasma. A third category, containing adenosine 5'-diphosphate (ADP) alone, had an IFC close to those known to affect platelet aggregation. The role of metabolites of arachidonic acid, which may promote or inhibit platelet aggregation, awaits further description.
Distribution of internal carotid artery blood flow in the pony
Authors: Orr J. A. , Wagerle L. C. , Kiorpes A. L. , Shirer H. W. , Friesen B. S.
Published: December 2017

This study determined whether blood flow through the internal carotid artery (ICA) could be used to sample total cerebral blood flow in the pony. To answer this question we considered both the anatomic arrangement of the ICA in cadavers and the relative distribution of ICA blood flow to cerebral and extracerebral tissue using radioactive microspheres. Acrylic corrosion casts of the ICA indicated that this vessel traveled directly to the base of the brain, contributing to the formation of the circle of Willis, and did not send any significant branches to other tissues. Two vessels (internal ethmoidal artery and internal ophthalamic artery) did arise anteriorly from the circle of Willis and were, therefore, indirectly supplied by the ICA. Injection of radioactive microspheres of 15 microns diameter indicated that blood flow to extracerebral structures supplied by the internal ethmoidal and internal ophthalamic arteries was less than 5% of total ICA blood flow. Increases in ICA blood flow as measured with an electromagnetic flowmeter during isocapnic hypoxia (arterial PO2 near 40 Torr) in the awake pony (n = 6) were compared with increases in total brain flow as measured with radioactive microspheres (n = 6). ICA blood flow increased 40% compared with a 38% increase in total brain blood flow as measured with microspheres. We conclude that the ICA supplies predominantly brain tissue (approximately 95%) and that changes in ICA blood flow are representative of changes in total brain blood flow in the awake pony.
The nature of electrical propagation in cardiac muscle
Authors: Spach M. S. , Kootsey J. M.
Published: December 2017

It has long been appreciated that cardiac muscle is composed of individual cells connected by low-resistance connections, but most concepts of cardiac impulse conduction have been based on a simplified model of propagation assuming continuously uniform intracellular resistivity in the direction of propagation. In this article we describe the development of the application of the theory of continuous media to propagation in cardiac muscle and review some of the successes achieved with this theory. New evidence is cited that propagation in cardiac muscle often displays a discontinuous nature. We consider the hypothesis that this previously unrecognized aspect of propagation can be explained by discontinuities in axial resistance related to known structural complexities of cardiac muscle. A major implication is that the combination of discontinuities of effective axial resistivity at several size levels can produce a wide variety of complex abnormalities of propagation, including most currently known cardiac conduction disturbances that have been considered to require spatial nonuniformity of membrane properties.
Effect of intrarenal administration of dopamine on renin release in conscious dogs
Authors: Mizoguchi H. , Dzau V. J. , Siwek L. G. , Barger A. C.
Published: December 2017

We investigated the effect of intrarenal administration of dopamine on renin release in conscious dogs. Dopamine in doses ranging from 0.28 to 3.0 micrograms . kg(-1) . min(-1) produced a significant increase in systemic plasma renin activity (PRA) and renin secretion rate without altering systemic blood pressure. Dopamine also induced renal vasodilatation and natriuresis within this dose range. To determine if the dopamine-induced renin release is related to its vasodilatory action, two other vasodilators, papaverine and acetylcholine, were infused into the renal artery, but neither, in doses that produced a rise in renal blood flow similar to that of dopamine, had any effect on PRA. As dopamine can activate alpha- and beta-adrenergic receptors in addition to dopaminergic receptors, experiments were also performed to characterize the type of receptors involved in dopamine-induced renin release. Intrarenal infusion of sulpiride and haloperidol, dopamine antagonists, significantly inhibited dopamine-induced renin release and renal vasodilatation. In contrast, intrarenal infusion of propranolol failed to alter dopamine-induced rise in PRA or renal blood flow. Simultaneous infusion of phentolamine and dopamine, on the other hand, produced a significant potentiation of dopamine-induced renin release and renal vasodilatation. In conclusion, our studies demonstrate that dopamine is capable of inducing renin release and renal vasodilatation in conscious dogs. Moreover, such actions of dopamine are mediated through activation of specific dopamine receptors in the kidney. Finally, we present evidence for the existence of the intrarenal alpha-adrenergic mechanism that is inhibitory to renin release.
Intravascular receptors and renal responses of monkey to volume expansion
Authors: Peterson T. V. , Felts F. T. , Chase N. L.
Published: December 2017

Experiments were performed in anesthetized Macaca fascicularis monkeys to determine the effects of combined thoracic dorsal rhizotomy (C8-T7) and vagotomy-sinoaortic denervation on the renal responses to acute intravascular volume expansion. Expansion of the estimated blood volume by 15% with 6% dextran in isotonic saline produced attenuated diuretic and natriuretic responses in the denervated animals when compared with sham-operated controls. The times to peak diuresis and natriuresis after volume expansion also were significantly earlier in the denervated group. Although central venous pressure increased similarly in both groups, mean arterial pressure increased to a greater extent after volume expansion in the denervated group. As opposed to the previously reported failure of either denervation alone to attenuate the renal responses to hypervolemia in the monkey, our results suggest that these neural pathways may play a role in maintaining salt and water balance in this species. However, because of the possibility of functionally redundant afferent mechanisms, blunted renal responses to volume expansion in the primate can only be demonstrated after an extensive denervation.
Differential effect of verapamil isomers on sinus node and AV junctional region
Authors: Gloor H. O. , Urthaler F.
Published: December 2017

The l- and d-isomers of verapamil were selectively perfused into the sinus node artery and atrioventricular (AV) node artery of 48 dogs. Injection of l-verapamil into the sinus node artery during sinus rhythm and into the AV node artery during AV junctional rhythm depresses both sinus rhythm and AV junctional rhythm significantly more than does the d-isomer. l-Verapamil is three to four times more powerful than d-verapamil. Injection of the isomers into the AV node artery during sinus rhythm rapidly impairs AV conduction. Increments in conduction time are measured exclusively at the level of the A-H interval of the His bundle electrogram, and l-verapamil is six times more powerful than d-verapamil. Neither d- nor l-verapamil in concentrations that exert a profound negative chronotropic effect or cause AV block, has any significant effect on transatrial or His bundle conduction. Thus these concentrations of d-verapamil have little or no significant effect on the fast sodium channel, but both verapamil isomers affect the slow channel. The main difference in action between l- and d-verapamil appears to be only quantitative in nature. The sinus node is significantly more sensitive to the negative chronotropic action of verapamil than is the AV junctional pacemaker, and this differential responsiveness appears to be related to the different intrinsic rates of the two pacemakers. During sinus rhythm (either in the presence or absence of atropine) sinus node automaticity is less affected than AV conduction when verapamil is given parenterally. We propose that this greater negative dromotropic effect of verapamil is also in part due to a rate-dependent process, since during sinus rhythm AV junctional cells have to be depolarized at frequencies significantly higher than their intrinsic rates.
Cardiac muscle function: results from skinned fiber preparations
Authors: Best P. M.
Published: December 2017

During the last decade cardiac muscle preparations with disrupted surface membranes (skinned fibers) have been used with increasing frequency to study cardiac muscle function. Removal of the surface membrane as an effective permeability barrier allows the experimenter to control the ionic conditions surrounding the contractile proteins and intracellular organelles. Several different techniques are used to disrupt or remove the surface membranes of cardiac muscle. The resulting preparations differ significantly in size, in the extent of membrane removal, and in some cases in their physiological response. Skinned cardiac fibers have been used to study the physiological properties of the contractile proteins and sarcoplasmic reticulum. The influences of disease and pharmacologic agents on normal muscle function have also been investigated.
Role of adrenals on development of pressure-induced myocardial hypertrophy
Authors: Nichols J. R. , Clancy R. L. , Gonzalez N. C.
Published: December 2017

The effect of coarctation of the abdominal aorta (AC) and of sham operation (SO) on the development of myocardial hypertrophy was studied in three groups of male rats, i.e., a group without treatment prior to AC or SO (untreated), a group with bilateral adrenalectomy (ADX) 5-7 days before AC or SO, and a group in which the adrenal medulla was removed (MDX) 5-7 days before AC or SO. MDX resulted in functional elimination of the adrenal medulla without apparent effect on cortical function. The animals were killed 7-10 days after AC or SO. AC produced carotid blood pressure (CBP) increases of 33, 31, and 25 mmHg in the untreated, ADX, and MDX groups, respectively. Ventricular weight (HW), ventricular RNA concentration, and RNA-to-DNA ratio increased significantly after AC only in the untreated and MDX groups. In the ADX group, hypertension was followed by an increase in HW that could be detected only after normalization for body weight. It is concluded that absence of the adrenal gland significantly reduces the development of pressure-induced myocardial hypertrophy. Apparently, this is due to the absence of the adrenal cortex and not absence of the adrenal medulla.
Tricarboxylic acid cycle metabolites during ischemia in isolated perfused rat heart
Authors: Peuhkurinen K. J. , Takala T. E. , Nuutinen E. M. , Hassinen I. E.
Published: December 2017

Isolated rat hearts were, after a retrograde perfusion by the Langendorff procedure, rendered ischemic by lowering the aortic pressure to zero. The rate of proteolysis and temporal patterns of the changes in the concentrations of the metabolites of the tricarboxylic acid cycle, related amino acids, ammonia, and breakdown products of the adenine nucleotides were determined. The most significant change in the amino acid metabolism was a decrease of the proteolysis to one-tenth and a large accumulation of alanine, which was almost stoichiometric to the degradation of aspartate plus asparagine. The accumulation of malate and succinate was small compared with the metabolic net fluxes of aspartate and alanine. The metabolic balance sheet suggests that aspartate was converted to alanine. A prerequisite for this would be a feed in of carbon of aspartate to the tricarboxylic acid cycle as oxalacetate, reversal of the malate dehydrogenase, and production of pyruvate by the malic enzyme reaction. Alanine accumulating during ischemia is not glycolytic in origin but occurs through a concerted operation of anaplerotic reactions and tricarboxylic acid cycle metabolite disposal. The data also suggest that the potentially energy-yielding reduction of fumarate to succinate is not significant in the ischemic myocardium.
Comparison of arterial wall mechanics using ring and cylindrical segments
Authors: Cox R. H.
Published: December 2017

Thin rings and intact cylindrical segments of canine carotid and iliac arteries were used to determine wall mechanics. Measurements of force and length were obtained from the ring segments, whereas measurements of pressure and diameter were obtained from the cylindrical segments under conditions of active (147 mM K+) and passive smooth muscle (Ca2+ free and 2 mM ethyleneglycolbis (beta-aminoethylether)-N,N'-tetraacetic acid). These measurements were normalized to values of segment stress and strain. Under passive conditions stress-strain relations for the rings appeared to be stiffer than those obtained using cylindrical segments. Pressure-diameter curves computed using force-length data from the rings were shifted to higher values of diameter compared with values from the intact segments at all pressure levels. Passive mechanics derived from measurements on ring segments yielded poor estimates of mechanics derived from intact segments. Despite this finding, values of active force development from the two sample geometries were similar. No statistically significant differences were found in values of maximum force development expressed in terms of sample cross-sectional area. Some differences in values of active force development at low values of muscle length were found. The latter were probably related to the differences in passive mechanics and the procedure used to normalize muscle length. Reasonable values of active force development can be obtained from ring segments.
Phenothiazine protection in calcium overload-induced heart failure: a possible role for calmodulin
Authors: Schaffer S. W. , Burton K. P. , Jones H. P. , Oei H. H.
Published: December 2017

The effect of several phenothiazines on the extent of cellular damage resulting from the calcium paradox was examined. Hearts treated with trifluoperazine, a potent calmodulin inhibitor, exhibited less cellular damage than untreated myocardium as reflected by light microscopy, high-energy phosphate content and the loss of protein and creatine phosphokinase into the perfusate. A dose response of this effect revealed a maximal response at about 1 microM trifluoperazine, a concentration which lies well within the range generally attributed to calmodulin inhibition. Several other lines of evidence were also obtained suggesting a possible role for calmodulin in calcium-overload induced necrosis. First, the phenothiazines had little influence on membrane changes believed responsible for altered calcium permeability. Second, trifluoperazine was without major effect unless included in the reperfusion buffer, indicating that the drug is only effective during the phase associated with calcium overload. Finally, less protection was afforded hearts exposed to phenothiazines such as chlorpromazine and promethazine, which are weaker inhibitors of calmodulin, than those treated with the potent inhibitor trifluoperazine. While other interpretations are possible, these studies are consistent with a role for calmodulin in calcium overload-induced heart failure.
Pericardial superfusion to measure cardiac interstitial adenosine concentration
Authors: Kusachi S. , Olsson R. A.
Published: December 2017

The steady-state concentration of adenosine in pericardial superfusates, [Ado]SS, may estimate the concentration in the cardiac interstitium. As reaching a steady state may sometimes require many minutes, the concentration at an earlier time is often used as an index of [Ado]SS. The latter assumes that the rate of approach to [Ado]SS is uniform and insensitive to perturbations of cardiac oxygen usage (MVO2). In 11 open-chest dogs superfusate adenosine rose at a rate (+/- SD) of 0.53 +/- 0.99/min to an [Ado]SS of 68 +/- 32. The mean rate of equilibration has a very large coefficient of variation, indicating substantial dog-to-dog variation. In five dogs the rate of equilibration during the second of successive superfusions was significantly lower than the first. Raising MVO2 by cardiac pacing or isoproterenol infusion changed neither the rate of equilibration nor [Ado]SS. Aortic constriction or propranolol slowed equilibration but had no effect on [Ado]SS. Thus superfusate adenosine concentration early in the course of equilibration seems an unreliable index of [Ado]SS. That interventions that change MVO2 do not change [Ado]SS from control means either that [Ado]SS fails to reflect the concentration in the vicinity of the coronary resistance vessels or, alternatively, that adenosine does not regulate coronary blood flow.
Early transient depletion of extracellular Ca during individual cardiac muscle contractions
Authors: Bers D. M.
Published: December 2017

Extracellular free [Ca] in rabbit papillary muscles was monitored using double-barreled Ca microelectrodes. These electrodes had tip diameters of 4-12 microns, electrical time constants of 2-5 ms, and electrochemical time constants of less than 30 ms. During individual beats a transient depletion of extracellular Ca (CaO) was recorded. This decrease of [Ca]O begins very early during the action potential, before significant tension development, and reaches a maximum much before the peak of developed tension (T). The depletion of CaO is blocked by CoCl2 or verapamil and enhanced by 10(-8) M isoproterenol or reduction of extracellular Na concentration to 35 mM. The magnitude of this early depletion of CaO increases in parallel with tension as a function of [Ca]O (8.46 +/- 0.98 microM at 0.2 mM CaO, 16.9 +/- 1.6 microM at 0.5 mM CaO, and 44.7 +/- 3.7 microM at 2.0 mM CaO). However the magnitude (in mV) of the recorded signal decreases with increasing [Ca]O and T, suggestive of saturation. The magnitude of this early transient CaO depletion also increases in parallel with the increase of T produced by initiating stimulation from rest (except for the first beat, which may be more dependent on stored Ca). It is probable that the depletions recorded represent Ca influx into cardiac cells from the extracellular space. The magnitude of Ca influx represented by the CaO depletions is difficult to quantitate but may be roughly in the range of Ca entry that would be required for direct activation of the myofilaments.
Freeze-fractured cardiac gap junctions: structural analysis by three methods
Authors: Page E. , Karrison T. , Upshaw-Earley J.
Published: December 2017

In isolated rat left ventricles perfused at 37 degrees C with control, Ca2+-loading, and Ca2+-depleting solutions (pH 7.3-7.4), we have investigated freeze-fractured gap junctional membrane by three quantitative techniques designed to correlate changes in junctional permeability with changes in membrane ultrastructure, i.e., 1) optical diffraction, 2) direct measurement of center-to-center spacings and particle diameters, and 3) statistical analysis of the spatial distribution of P-face particles based on analysis of nearest neighbor center-to-center distances. Junctions fixed either with glutaraldehyde or by quick freezing were compact, with closely packed rather than dispersed membrane particles even in the permeable state. Analysis of variance for all three methods indicated that replication was a major variability source limiting structural discrimination. Discrimination between random, regular, and clustered distributions depended critically on particle diameter and particle density. The results differ from published data of others on mammalian ventricular gap junctions and from measurements by our laboratory on sheep cardiac Purkinje fibers (J. Ultrastruct. Res. 75: 195-204, 1981).
Tissue adenosine content in active soleus and gracilis muscles of cats
Authors: Bockman E. L. , McKenzie J. E.
Published: December 2017

Vascularly isolated cat soleus and gracilis muscles were stimulated to contract isometrically and were then frozen in situ. Adenosine, inosine, and hypoxanthine (nucleosides), and lactate were measured in neutralized, perchloric acid extracts of muscle. During contraction, nucleoside content increased in soleus muscle but changed little in gracilis muscle. However, adenosine content did not correlate with vascular conductance or oxygen consumption in either soleus or gracilis muscle. Adenosine content did correlate with lactate content in soleus but not gracilis muscle. The activity of AMP deaminase was highest in cat gracilis muscle and lowest in dog cardiac muscle. The activity of 5'-nucleotidase was lowest in cat gracilis muscle and highest in dog cardiac muscle. Cat soleus and dog gracilis muscles had intermediate activities of both enzymes. The findings of the present study do not support a role for adenosine in mediating prolonged active hyperemia in fast-twitch gracilis muscle of cats and cast doubt on such a role in slow-twitch soleus muscle of cats. Differences in the activities of AMP deaminase and 5'-nucleotidase provide a qualitative, biochemical explanation for apparent differences in net adenosine production among muscles composed of different fiber types and between skeletal and cardiac muscle.
Selective denervation of the heart
Authors: Randall W. C. , Thomas J. X. , Barber M. J. , Rinkema L. E.
Published: December 2017

Total denervation of the canine heart consisted of intrapericardial neural dissection of the left atrium, left superior pulmonary vein, and main pulmonary artery and cutting of the ventrolateral cardiac nerve (stage I). The fat pad and all nerves were removed from between the pulmonary artery and aorta (stage II). Dissection proceeded from the pericardial reflection along the superior vena cava to the azygos vein, which was cleared, double tied, and cut. The right pulmonary artery was cleaned, and the superior right atrium was dissected to its intersection with the left atrium (stage III). Denervation was tested by electrical stimulation of both vagi and stellate ganglia, while recording inotropic, chronotropic, and dromotropic events, before and after each stage. Stage I deleted most left autonomic input to the heart without interrupting right sympathetics. Stage II completed left autonomic denervation but preserved much of the right sympathetic input. Large nerves along the dorsal surface of the pulmonary artery carried inputs from both left and right sympathetics. Stage III completed the denervation of atrioventricular and sinoatrial nodal structures and removed all remaining ventricular inotropic influences. Selective denervation of atrioventricular and sinoatrial nodal regions appears feasible for preparation of chronic canine models.
Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat
Authors: Pfeffer M. A. , Pfeffer J. M. , Lewis R. A. , Braunwald E. , Corey E. J. , Austen K. F.
Published: December 2017

Although local administration of the sulfidopeptide leukotrienes into cutaneous and coronary vascular beds indicates that these naturally occurring metabolites of arachidonic acid are vasoconstrictors, their systemic administration has produced both pressor and depressor responses. The systemic hemodynamic effects of intravenous leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were assessed in ether-anesthetized rats and compared with the effects produced by equimolar doses (2 X 10(-10) to 4 X 10(-8) mol/kg) of norepinephrine and angiotensin. Mean arterial pressure, right atrial pressure, and cardiac output (electromagnetic flowmetry) were recorded during bolus administrations of these vasoactive compounds. LTC4 and LTD4 had similar hemodynamic effects that were characterized by moderate pressure elevations produced by dose-dependent increases in total peripheral resistance, since cardiac output declined. Although the peak mean arterial pressure levels produced by LTC4 and LTD4 (135 +/- 7 and 129 +/- 5 mmHg, respectively) were less than those by norepinephrine (157 +/- 3 mmHg) and angiotensin (174 +/- 5 mmHg), the peak total peripheral resistance values of LTC4 and LTD4 (2.23 +/- 0.32 and 1.86 +/- 0.17 mmHg X ml-1 X min-1, respectively) were between those of the well-known vasopressors, norepinephrine (1.50 +/- 0.09) and angiotensin (2.72 +/- 0.41). The pressor response to LTC4 and LTD4 was less marked than that to norepinephrine and to angiotensin because of the concomitant reduction in cardiac output. These results indicate that LTC4 and LTD4 are systemic vasoconstrictors with potencies similar to those of norepinephrine and angiotensin.