bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsaturated fatty acids and cyclooxygenase inhibitors: effects on pial arterioles
Authors: Rosenblum W. I.
Published: December 2017

Cerebral surface arterioles of the mouse were constricted in a dose-dependent manner by three different unsaturated fatty acids each with one of its double bonds in the n-6 position: arachidonate, linoleic, and 11,14,17-eicosatrienoic acid (ETA) in doses of 10-200 micrograms/ml. The constriction was transient, and its magnitude was significantly reduced by pretreatment of the mice with intraperitoneal injections of indomethacin (5 mg/kg), aspirin (100 mg/kg), or sodium 2-amino-3-(4 chlorobenzyl)-phenylacetate (AHR-6293, 100 mg/kg). The inhibitory effect of these cyclooxygenase inhibitors suggests that this enzyme is involved in the response to these fatty acids and is in keeping with suggestions in the literature stating that such unsaturated fatty acids may interact with cyclooxygenase even when they cannot form prostaglandin (PG) endoperoxides, The PG endoperoxide formed by arachidonate or the analogous hydroperoxy compounds formed by linoleic or 11,14,17 ETA, may then alter cerebrovascular tone by production of reactive, O2-containing species. Alternate explanations for the data are also proposed.
Fetal myocardial oxygen and carbohydrate consumption during acutely induced hypoxemia
Authors: Fisher D. J. , Heymann M. A. , Rudolph A. M.
Published: December 2017

Two days after catheter placement we measured the heart rate, arterial blood pressure, myocardial blood flow, and the myocardial consumption of oxygen, glucose, lactate, and pyruvate in 11 fetal sheep in utero. We then administered 8-10% oxygen to the ewe, producing a 50% decrease in oxygen content in the fetal ascending aortic blood. After 15 min of hypoxemia we repeated the measurements. Oxygen content in the fetal coronary sinus blood decreased significantly, but the arteriovenous difference of oxygen across the left ventricle also decreased during hypoxemia. Fetal myocardial blood flow increased 160% above the control level, and the myocardial oxygen consumption did not change. The systolic arterial blood pressure increased and the heart rate decreased, but cardiac work, as estimated by the rate-pressure product, was unchanged. As both fetal myocardial oxygen consumption and cardiac work did not change, myocardial oxygenation, the relationship between oxygen consumption and cardiac work, appears to be unchanged during this degree of hypoxemia. Although arterial blood glucose, lactate, and pyruvate concentrations increased significantly during hypoxemia, only the myocardial consumption of pyruvate increased; the arteriovenous difference of glucose and lactate decreased in proportion to the increase in myocardial blood flow. During hypoxemia, glucose consumption did not change, and lactate continued to be consumed rather than produced; thus it is apparent that fetal myocardial metabolism continued to be aerobic during this degree of hypoxemia. Complete oxidative combustion of the quantities of carbohydrates that were consumed would supply all of the substrate necessary to meet fetal myocardial energy demands both at rest and during hypoxemia.
Determination of safety factor for defibrillator waveforms in cultured heart cells
Authors: Jones J. L. , Jones R. E.
Published: December 2017

We studied excitation thresholds and arrhythmias produced in cultured chick embryo myocardial cells subjected to electric shocks using rectangular, untruncated resistor-capacitor (RC), and critically damped resistor-inductor-capacitor (RLC) waveforms with variable intensities while photocell mechanograms were recorded. Strength-duration curves for excitation and production of a specific postshock arrhythmia (4-s arrest) were constructed. Excitation curves closely resembled those for in situ defibrillation threshold (or specific % success). The ratio between the shock intensity producing a 4-s arrest and that producing excitation at each duration (termed the "safety factor") was determined. Waveforms with a large safety factor in vitro defibrillated most effectively in situ with little postshock dysfunction. Waveforms with low safety factors had a low rate of success in situ and produced much postshock dysfunction. Safety factor of monophasic clinical waveforms were lower than that of the 5-ms rectangular wave. The close correspondence between in vitro safety factor and in situ defibrillating effectiveness, as reported in the literature, suggests that the cell culture system is an effective screening system for determining waveforms that will improve the efficacy and safety of defibrillation procedures.
Synthesis and use of radio cobaltic EDTA as an extracellular marker in rabbit heart
Authors: Bridge J. H. , Bersohn M. M. , Gonzalez F. , Bassingthwaighte J. B.
Published: December 2017

A new gamma-labeled marker for extracellular space is the cobaltic form of 58Co-ethylenediaminetetraacetic acid (58Co-EDTA). The cobaltic ion has a much higher affinity for EDTA than the cobaltous ion; it is prepared as a potassium salt, K+(58Co3+-EDTA4-), and is apparently biologically inert. Testing by equilibration in intact rabbits and comparing the myocardial content with that of [14C]sucrose give values of the volume of distribution in the myocardium of 0.294 +/- 0.052 ml/g for 58Co-EDTA and 0.303 +/- 0.051 ml/g for [14C]sucrose (SD, n = 130, for two hearts), with the ratios of 58Co-EDTA/sucrose averaging 0.973 +/- 0.043 (n = 130). The average value of the extracellular fluid measured in isolated rabbit interventricular septum using Co-EDTA was 0.51 +/- 0.05 ml/g (SD, n = 16) and 0.46 +/- 0.04 ml/g using [14C]sucrose as an extracellular fluid space (ECF) marker. Flushing with a high concentration of nontracer Co-EDTA does not reveal any release from binding sites. The gamma-energy (811 KeV), long half-life (71.4 days), stability, and lack of binding to tissue components make 58Co-EDTA a useful marker for ECF.
alpha- and beta-Adrenergic effects of epinephrine on ventricular pacemakers in dogs
Authors: Hordof A. J. , Rose E. , Danilo P. , Rosen M. R.
Published: December 2017

We studied the effects of epinephrine on idioventricular rhythm in 15 adult dogs with chronic complete heart block induced by the injection of formalin into the His bundle. Atropine (0.1 mg/kg) was given intravenously to attenuate any potential vagal effects, and epinephrine was infused in graded doses of 0.01-10.0 micrograms.kg-1.min-1. Two different responses were seen. In 12 dogs there was a concentration-dependent increase in ventricular rate following epinephrine infusion. These animals then were given the beta-blocker propranolol (0.5 mg/kg iv), and the epinephrine infusions were repeated. In this situation epinephrine concentrations less than 0.1 micrograms.kg-1.min-1 induced a decrease in ventricular rate with no associated change in arterial pressure. In four additional dogs this decrease in ventricular rate was prevented by alpha-blockade with phentolamine. In three dogs epinephrine less than 0.1 micrograms.kg-1.min-1 induced a decrease in ventricular rate without an associated change in arterial blood pressure. This decrease in rate was abolished by the alpha-blocker phentolamine. It therefore appears that an alpha-adrenergic effect on ventricular automaticity can occur in the intact animals. When this does not occur initially, it can be unmasked by propranolol and results in a slowing of ventricular rate unrelated to changes in blood pressure.
Calcium-dependent contractile activation of cerebral artery produced by quick stretch
Authors: Nakayama K.
Published: December 2017

Quick stretch of helical strips of rabbit basilar artery at a rate of 4-50 cm/s to 140% of the initial muscle length evoked phasic contraction. The contraction was potentiated by cardiac glycosides, tetraethylammonium, and high K+, all of which augment transmembrane influx of Ca2+, and the enhanced response was suppressed by Ca2+-antagonists such as verapamil and nifedipine. The stretch-induced contraction in Ca2+-free medium was progressively reduced depending on the number of stretches during the observation period of 90 min. The response to quick stretch in Ca2+-free solution was enhanced by norepinephrine or histamine but was not affected by high K+ (40-100 mM), verapamil, or nifedipine. These results suggest that contraction of rabbit basilar artery produced by quick stretch depends not only on transmembrane supply of Ca2+ but also on release of Ca2% bound to the membrane or in internal depots. It also seems possible that, in addition to depolarization of the membrane, mechanical deformation itself triggers the release of Ca2+.
Cardiovascular responses to unilateral and bilateral stimulation of rabbit aortic nerves
Authors: Stinnett H. O. , Sepe F. J. , Magnusson M. R.
Published: December 2017

Reflex heart and mean arterial pressure (MAP) responses during unilateral and bilateral electrical stimulation of the central end of the cut aortic nerves were studied in 14 anesthetized closed-thorax rabbits. During control of carotid intrasinus pressure (ISP), with ISP = MAP, heart rate was 248 +/- 12 beats/min and fell -79 +/- 14, -61 +/- 16, and -117 +/- 16 beats/min during left (LAN), right (RAN), and bilateral (BAN) nerve stimulation. MAP was 79 +/- 5 mmHg and fell -57 +/- 4 (LAN), -46 +/- 6 (RAN), and -65 +/- 4 mmHg (BAN). Responses were also determined following blockade of cardiac vagal efferents (atropine) and then vagotomy (n = 4) or vagotomy alone (n = 10). Results indicated that cardiac parasympathetic effects of LAN and RAN stimulation were additive, whereas the respective summation of cardiac and arterial vascular sympathetic effects were mutually inhibitory. BAN stimulation at low (25 mmHg) and high (greater than or equal to 125 mmHg) ISP levels resulted in different magnitudes of MAP and heart rate responses before and after vagotomy and beta-receptor blockade. These results indicated that summation was mutually inhibitory for cardiac and vasomotor sympathetics when maximal stimulation of opposite influence was applied to aortic and carotid afferents. However, arterial baroreceptor afferents may summate differently at more normal blood pressure conditions.
Effect of adenosine on calcium uptake by intact and cultured vascular smooth muscle
Authors: Fenton R. A. , Bruttig S. P. , Rubio R. , Berne R. M.
Published: December 2017

The effect of adenosine (ADO), a potent vasodilator, on the cellular calcium uptake by vascular smooth muscle (VSM) was studied. In addition, similar experiments were conducted with other vasoactive agents to ensure the validity of results obtained with the cultured VSM cell model. Primary VSM monolayers from rat aorta were incubated for 30 min in 45Ca-enriched physiological salt solution (PSS) (37 degrees C) and washed with 20 mM Ca-EGTA (4 degrees C) to remove extracellular 45Ca. Calcium uptake with 4.6 mM K+ was 65.3 +/- 2.4 pmol Ca/10(5) cells. Verapamil (10(-6) M) or 4 degrees C incubation decreased this value 27 and 65%, respectively, whereas ADO (10(-7) M) and isoproterenol (10(-6) M) elevated calcium uptake 21 and 9%, respectively. Elevation of extracellular K+ (25 mM) increased calcium uptake to 87.8 +/- 5.0 pmol Ca/10(5) cells. ADO (10(-7) M), isoproterenol (10(-6) M), and 4 degrees C incubation significantly attenuated this K+-induced increase 25, 19, and 64%, respectively. The calcium uptake of nondepolarized cells was not changed by norepinephrine (10(-6) M) in the presence of either alpha- or beta-adrenergic blockade. Experiments were performed in a similar manner with porcine carotid artery strips in the presence of alpha- and beta-adrenergic blockade. Calcium uptake increased from 2.3 +/- 0.2 X 10(-7) to 3.0 +/- 0.1 X 10(-7) mol Ca/g wet wt after elevation of the medium K+ to 25 mM. This increase was inhibited by 10(-6) M ADO. ADO (10(-6) M) was found to have no effect on the 45Ca efflux from cultured VSM. It is concluded that ADO relaxes VSM by reducing the inward movement of calcium during stimulation. The significant ADO-induced elevation of cellular calcium under conditions when cultured cells were not partially depolarized suggests the existence of an enhanced calcium sequestration within these cells.
Load dependence of mammalian heart relaxation during cardiac hypertrophy and heart failure
Authors: Lecarpentier Y. , Martin J. L. , Gastineau P. , Hatt P. Y.
Published: December 2017

Mechanical properties of relaxation were studied in left ventricular rat papillary muscle during cardiac hypertrophy induced by chronic pressure and/or volume overload. Maximum velocity of isotonic lengthening was linearly related to total extent of isotonic shortening and to maximum velocity of isotonic contraction and depended on the type of chronic overloading without correlation with the degree of cardiac hypertrophy. Time to peak shortening was significantly increased in each group of hypertrophied heart muscles as compared to controls. The sensitivity of cardiac relaxation to the loading conditions was determined by the time course of relaxation. To quantify the degree of load sensitivity, we measured the ratio of isotonic area to isometric area, which was the area limited by the afterloaded force vs. time at 50% of the isometric peak tension divided by the area of the force vs. time trace in the isometric twitch below the same level of load. The value of this ratio was about 0.81 in normal rat and did not show any significant differences in hypertrophied heart muscles even at the terminal stage of congestive heart failure. During acute hypoxia the load sensitivity of relaxation disappeared both in normal and in hypertrophied hearts. Thus inadequacy in oxygen supply has more drastic effects, as compared with those induced by chronic overload, probably by affecting the sarcoplasmic reticulum uptake of activating calcium.
The bloodless rat: a new model for macromolecular transport studies across lung endothelium
Authors: Schneeberger E. E. , Neary B. A.
Published: December 2017

To examine the effect of circulating proteins on the passage of intravenously injected native ferritin across pulmonary capillary endothelium, rats were exchange transfused with FC-43 fluorocarbon emulsion (FCE) under ether anesthesia. Protein concentration was reduced to less than 1.1 mg/ml by exchange transfusion, followed by FCE containing 15, 30, or 60 mg/ml of lyophilized rat serum protein (LRSP). Two minutes after ferritin injection lungs were prepared for ultrastructural morphometry. The diameter and numerical density of vesicles remained unchanged under all experimental conditions; however, at 0.6 mg/ml of circulating protein there was a 5- and 10-fold increase, respectively in percent vesicle (%VL) and basement membrane labeling (BML) by ferritin. This was reversible; at 60 mg/ml of circulating protein %VL and BML was indistinguishable from controls. Following a reduction of circulating protein to less than 1.1 mg/ml, the addition of 15 mg/ml LRSP reduced %VL but had no effect on BML. This suggests that in addition to shuttling vesicles there may be a second mechanism for the transport of ferritin, possibly involving transendothelial chains of vesicles.
Membrane properties of smooth muscle cells in pulmonary arteries of the rat
Authors: Suzuki H. , Twarog B. M.
Published: December 2017

Electrical properties of the membrane of smooth muscle cells in the rat main pulmonary artery (MPA) and a small pulmonary artery (SPA) were compared. MPA and SPA differed in several important respects, suggesting characteristic quantitative and qualitative differences in membrane properties. 1) Resting membrane potentials were similar in both (MPA 52.2 +/- 1.3 mV; SPA 51.5 +/- 1.7 mV). The cells displayed no spontaneous electrical activity. The muscle layers in both MPA and SPA showed cablelike properties; a graded local response to outward current pulses was observed, but no action potentials were evoked. 2) Tetraethylammonium chloride (TEA, 1-5 mM) depolarized, increased membrane resistance, and suppressed rectification in MPA. TEA strongly depolarized SPA and contraction ensued. 3) The maximum membrane depolarization produced by a 10-fold increase in extracellular [K+] was 48 mV in MPA and 47 mV in SPA. In K+-free solution gradual depolarization was observed in SPA, but the membrane potential in MPA was not modified. Restoration of K+-containing solution produced equivalent hyperpolarization in both tissues, indicating a similar degree of stimulation of electrogenic Na+-K+ pumping. 4) A Na+-deficient solution did not affect the membrane potential in MPA but depolarized SPA.
A planimetric technique for measuring deformation of the carotid sinus region
Authors: Koushanpour E.
Published: December 2017

This paper describes a planimetric technique for measuring the volume of the carotid sinus region from still photographs taken during pressure and volume forcings. The method consists of first digitizing the curves defining the boundary of the carotid sinus and then calculating its volume by assuming that the carotid sinus region is made up of a finite number of circular "pancake" slices. Plots of the calculated volume (Vc) vs. applied pressure forcings (P) were compared with plots of injected volume (Vi) vs. recorded pressure to assess the sensitivity of the method used to calculate volume changes from still photographs. The plots of Vc vs. P were remarkably similar to the plots of Vi vs. recorded pressure, and a plot of Vc vs. Vi was linear, suggesting that this method provides a good estimate of volume changes. Application of this method can yield useful data on mechanisms of the baroreceptor process.
Contracture of isolated rat heart cells on anaerobic to aerobic transition
Authors: Hohl C. , Ansel A. , Altschuld R. , Brierley G. P.
Published: December 2017

Adult rat heart myocytes prepared by collagenase perfusion show a progressive loss of adenylate energy charge and total adenine nucleotide as a function of time of anaerobic incubation in the absence of glucose. Re-aeration of the rod-shaped anaerobic cells produces a population of viable rounded cells in hypercontracture. The round cells show extensive morphological dislocations but remain metabolically competent in that they 1) restore adenosine 5'-triphosphate levels to the extent permitted by the depleted adenine nucleotide pool: 2) reestablish a low Na+-K+ ratio; and 3) restore creatine phosphate to 73% of control. The hypercontracture on re-aeration of anaerobic myocytes closely resembles an analogous contracture of heart cells in situ produced when hypoxic perfused hearts are reoxygenated, the so-called "oxygen paradox." Both processes are eliminated by inclusion of glucose during the anaerobic phase and by inhibitors of respiration and uncouplers of oxidative phosphorylation added before reoxygenation. Mitochondria in the hypercontracted myocytes retain high acceptor control ratios. Contracture on re-aeration occurs to nearly the same extent in the presence of either mM Ca2+ or 0.1 mM EGTA. Contracture appears related to dislocations in intracellular Ca metabolism that result from the declining energy charge and depleted nucleotide pool produced during anoxic incubation.
Effects of left atrial stretch in cardiac-denervated and intact conscious dogs
Authors: Fater D. C. , Schultz H. D. , Sundet W. D. , Mapes J. S. , Goetz K. L.
Published: December 2017

We monitored cardiovascular and renal function in conscious dogs with surgically denervated hearts during two experimental procedures: 1) inflation of a balloon in the left atrium and 2) intravascular volume expansion. The results obtained were compared with results from identical experiments on sham-operated control dogs. Left atrial balloon inflation in the sham-operated dogs produced an increase in left atrial pressure, heart rate, urine flow, and sodium excretion; central venous pressure decreased. These changes were absent in the cardiac-denervated dogs. Infusion of 6% dextran in isotonic saline (16% of estimated blood volume) increased the heart rate significantly in the control dogs but not in the cardiac-denervated dogs; other hemodynamic measurements were comparable in the two groups. Urine flow and sodium excretion increased significantly in both the cardiac-denervated and control dogs; the responses did not differ significantly between the two groups. These experiments demonstrate that inflation of a balloon in the left atrium of a conscious dog elicits diuretic and natriuretic responses that are dependent on intact cardiac neural pathways, presumably specifically dependent on afferent neural impulses from left atrial receptors. On the other hand, an increase in circulating blood volume induced by the intravenous infusion of an isotonic, isoncotic solution elicits diuretic and natriuretic responses in the cardiac-denervated dog that are similar to the renal responses produced in a control dog. Thus, although cardiac receptors are capable of eliciting reflex changes in both hemodynamics and renal function, it is not clear what role they play in mediating the renal responses evoked by increases in blood volume.
Endogenous triacylglycerol metabolism in diabetic heart
Authors: Paulson D. J. , Crass M. F.
Published: December 2017

The metabolism of endogenous triacylglycerols (TG) was studied in perfused working hearts of control and 12-day-old streptozotocin-treated diabetic rats. TG synthesis was assessed by the incorporation of exogenous [9,10(-3)H]palmitate. TG lipolysis was assessed by the following two methods: 1) measurement of the decrease in [14C]TG after prior in vivo isotopic prelabeling with [1-14C]palmitate and 2) calculation of the change in TG content as TG synthesis minus TG lipolysis. Control and diabetic hearts were perfused with buffer containing substrate concentrations characteristic of the in vivo state [normal: 9 mM glucose, 0.5 mM free fatty acid (FFA); diabetic: 27 mM glucose, 1.2 mM FFA]. Diabetic hearts were also perfused under normal substrate conditions. In diabetic hearts perfused under diabetic conditions elevated TG levels were maintained, lipolysis was reduced or unchanged (depending on the method of determination), and synthesis was enhanced. Oxidation of TG fatty acids (TGFA) was not impaired. Control hearts showed net lipolysis coupled with lower rates of exogenous FFA uptake and TG synthesis. In diabetic hearts perfused under normal substrate conditions lipolysis and TGFA oxidation were markedly enhanced. Thus we suggest that the basis of TG accumulation seen in the diabetic heart is due to both inhibition of lipolysis and enhancement of synthesis resulting from high levels of exogenous FFA and glucose.
Segmental renal vascular resistance in the spontaneously hypertensive rat
Authors: Hsu C. H. , Slavicek J. H. , Kurtz T. W.
Published: December 2017

Renal hemodynamics were studied during different stages of development of hypertension in unanesthetized spontaneously hypertensive rats (SHR). In SHR at 4 wks of age mean arterial pressure (MAP) was higher than in age-matched Wistar Kyoto rats (WKY); however, renal blood flow (RBF) and renal vascular resistance (RVR) were not different between these two groups. Mean values of RVR and MAP in 8- and 12-wk-old SHR were significantly greater than those of age-matched WKY. Both RBF of 8- and 12-wk-old SHR were significantly lower than the corresponding values of WKY. Afferent arteriolar diameter (AAD) was measured with a microsphere method. AAD was not different between 4-wk-old SHR and WKY; however, the AAD of 8-wk-old (16.3 +/- 0.23 micrometers, n = 5) and 12-wk-old (17.4 +/- 0.48, n = 5) SHR were significantly smaller than those of respective control WKY (17.3 +/- 0.34, n = 4, P less than 0.05; 19.3 +/- 0.12, n = 5, P less than 0.01). Calculated preglomerular (Rpre) and postglomerular resistances (Rpost) of 12-wk-old SHR were increased 96 and 129% when compared with respective segmental resistances of the control WKY. The decrease in AAD of 12-wk-old SHR was sufficient to account for a 33% increase in Rpre. After the rats were treated with hydralazine (0.5 mg/kg iv), MAP, RBF, and RVR of SHR were not different from the control WKY values. Rpre and Rpost of SHR were substantially decreased; however, vasodilation occurred at vessels proximal and distal to the afferent arteriole because AAD was not altered. Our results indicate that increased RVR in SHR involves increases in Rpre and Rpost.
Effect of tetrodotoxin on membrane potentials and active tone in vascular smooth muscle
Authors: Lombard J. H. , Burke M. J. , Contney S. J. , Willems W. J. , Stekiel W. J.
Published: December 2017

The suitability of tetrodotoxin (TTX) for studies of the neural control of vascular smooth muscle (VSM) tone in the microcirculation was evaluated by determining 1) whether TTX blockade of neural input to adrenergically innervated VSM is reversible and 2) whether TTX depresses active VSM tone directly. Diameters of rat mesenteric veins and third- and fourth-order arterioles of the hamster cheek pouch were measured by image splitting. VSM transmembrane potentials (Em) were measured with microelectrodes in rat mesenteric veins. In the veins TTX suffusion (10(-6) g/ml) resulted in dilation and reversible Em hyperpolarization. TTX also reversibly blocked the venoconstrictor response to perivascular nerve stimulation. TTX had no effect on the resting tone of hamster arterioles or on arteriolar constriction in response to increased oxygen availability. TTX did not affect the response to norepinephrine in either preparation. This study indicates that TTX specifically and reversibly blocks VSM responses to neural activation but that it has no direct depressant effect on resting VSM tone or active constriction in response to nonneural activation.
Nonsympathetic increased inotropic state early after aortic insufficiency
Authors: Crozatier B. , Caillet D. , Chevrier J. L. , Hatt P. Y.
Published: December 2017

The very early left ventricular response to chronic volume overload induced by aortic insufficiency (AI) was examined in conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring internal diameter, segmental length, and parietal wall thickness. Acute volume loading with dextran (AVL) was compared with that 24 and 48 h after AI induced by a perforation of the aortic valve. beta-Blockade was also produced before and after AI. For a similar increase in preload in AVL and after AI, the percent change in systolic shortening of diameters and segments (% delta L) increased from 30.4 to 34.1% after AI (P less than 0.01). For matched calculated wall stress during AVL and AI, % delta L and peak velocity of shortening were significantly increased after AI, and the same results were reproduced after beta-blockade. We conclude that, at the early phase of chronic volume overload before hypertrophy appears, left ventricular hyperfunction is mainly due to a nonsympathetic increased contractility and that, in the conscious dog, the inotropic state appears to be modified by a sustained increased preload.
Arteriolar vasoconstriction in rat cremaster muscle induced by local heat stress
Authors: Hogan R. D. , Franklin T. D. , Avery K. S. , Burke K. M.
Published: December 2017

The effect of moderate local heat stress on arteriolar tone in the cremaster muscle of anesthetized rats was investigated by direct microscopic observation. Muscle temperature was raised from the in vivo temperature of 34.5 to 38 degrees C, over a 5-min period, by elevating bath temperature. Muscle temperature, arteriolar lumen diameter, and arteriolar red blood cell velocity were continuously recorded. A number of the smallest arterioles studied (approximately 30 micrometers lumen diam) underwent a rapid and significant vasoconstriction near 36 degrees C. Denervation of the muscle eliminated the constrictor response. Addition of an alpha-blocking agent (dibenzyline to the denervated muscle unmasked the constriction, but the percent of arterioles demonstrating thermal reactivity remained decreased. We conclude that in some skeletal muscle beds a local thermoregulatory mechanism may exist whereby blood is shunted away from the tissue during heat stress at rest.
Helical fibers in myocardium of dogs change their pitch as they contract
Authors: Meier G. D. , Ziskin M. C. , Bove A. A.
Published: December 2017

We have investigated the dynamic relationship between fiber structure and deformation of the epicardium in the canine right ventricle. We have reconstructed this deformation as the motion undergone by groups of three radiopaque markers implanted close together in small epicardial regions. As reported earlier, this motion has a stretch and a rotation component. The stretch relates to shortening in the epicardial segment, whereas the rotation describes how this segment changes orientation during the heart cycle. If one postulates this segment as attached to a myocardial spiral, then one can interpret the systolic shortening of the ventricular axis as a compression of the spiral with decrease in pitch and the diastolic lengthening as an extension with increase in pitch. If one further postulates that the epicardial segment is attached to a right-hand spiral, then decreases in pitch imply local clockwise segment rotations, and increases, local counterclockwise rotations. From the motion of the implanted markers, we have found that a small segment ion the midfree wall of the right ventricle twists first locally clockwise as the ventricular axis shortens and later counterclockwise as the axis lengthens. We conclude that deformation of the epicardium is the result of a helical fiber arrangement that is characteristic of the endocardial half of the wall. Near the apex we observed the segment rotation to be reversed: counterclockwise during systole and clockwise during diastole. This observation implies a left-hand helix, which is the path of the apical epicardial fibers, suggesting that the endocardial half of the wall is no longer predominant here.
Vasodilation or altered perfusion pressure moves 15-micrometers spheres trapped in the gut wall
Authors: Maxwell L. C. , Shepherd A. P. , Riedel G. L.
Published: December 2017

To determine whether the microsphere method for measuring the intramural distribution of intestinal blood flow is affected by perfusion pressure or vasodilation, we infused radioactive 9- and 15-micrometers spheres into adjacent segments of isolated canine small bowel. After sphere infusion the blood supply of the control loop was occluded, and the vasculature of the experimental loop was either dilated by infusing isoproterenol or was subjected to increased perfusion pressure. Intestinal segments were dissected into mucosal, submucosal, and muscularis samples. Venous blood was collected during sphere infusions and experimental perturbations. Accumulations of spheres in tissue samples and venous blood were assessed in a gamma radioactivity counter. Isoproterenol caused previously infused spheres to leave submucosa and redistributed them primarily to mucosa with few additional spheres reaching venous blood. An increase in perfusion pressure also dislodged spheres from submucosa, but these did reach venous blood. The combined estimate of mucosal plus submucosal blood flow was relatively unaffected by isoproterenol infusion but was significantly altered by increased perfusion pressure. These results have the following implications for microsphere studies of the intramural distribution of intestinal blood flow: 1) tissue must be sampled after each sphere infusion unless the possibility of sphere migration has been experimentally eliminated and 2) even a two-compartment fractionation of blood flow into muscularis and mucosal-plus-submucosal compartments is not valid under some experimental conditions.
Cerebral circulatory response to carbon monoxide and hypoxic hypoxia in the lamb
Authors: Koehler R. C. , Jones M. D. , Traystman R. J.
Published: December 2017

In 14 unanesthetized newborn lambs the relationship between cerebral blood flow (measured by radiolabeled microspheres) and arterial O2 saturation (SaO2) was compared during two types of hypoxia: hypoxic hypoxia and carbon monoxide (CO) hypoxia. Cerebral venous samples were obtained from the sagittal sinus. The Increase in blood flow was 47% greater during CO than during hypoxic hypoxia. Cerebral O2 consumption and O2 delivery were constant during hypoxic hypoxia. Thus fractional O2 extraction, which equals O2 consumption/O2 delivery, remained constant with hypoxic hypoxia. During CO hypoxia, although O2 consumption remained constant, O2 delivery increased and fractional O2 extraction decreased. This decline in fractional O2 extraction was correlated with the leftward shift of the oxyhemoglobin dissociation curve that accompanied CO hypoxia. We suggest that cerebral blood flow depends on both SaO2 and the position of the oxyhemoglobin dissociation curve in the newborn lamb. However, this correlation does not exclude other potential histotoxic effects contributing to the relative overperfusion with CO hypoxia.
Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs
Authors: Macho P. , Hintze T. H. , Vatner S. F.
Published: December 2017

The effects of three alpha-adrenergic-receptor blocking agents (phentolamine, prazosin, and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 20%) and in the presence of beta-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the three drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 +/- 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 +/- 2 and 11 +/- 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 +/- 4%. The three drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 +/- 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 +/- 2%, which was significantly more than reductions in LDCR induced by prazosin (22 +/- 2%) and by phentolamine (11 +/- 3%). A test dose of phenylephrine (5.0 micrograms/kg) increased mean arterial pressure by 53 +/- 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 +/- 2.1, 14 +/- 1.6, and 1.9 +/- 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.
Role of mitochondrial oxidative phosphorylation in regulation of coronary blood flow
Authors: Nuutinen E. M. , Nishiki K. , Erecinska M. , Wilson D. F.
Published: December 2017

Regulation of coronary blood flow was studied in isolated rat hearts perfused under various metabolic conditions. Alterations in coronary flow were induced by hypoxia, amobarbital (Amytal) infusion, increase in work load of the heart, and adenosine infusion. Hypoxia induced, on the average, a 92.5% rise in coronary flow; 0.88 mM Amytal, a 85.7% increase; 12 microM adenosine, a 49.5% rise; and increased work load (elevation of the perfusion pressure from 6.9 kPa to 12.8 kPa), a 53.4% increase. In normoxia, adenosine, inosine, and hypoxanthine were present in the effluent in very low concentrations, and these greatly increased in response to hypoxia. In contrast, increased coronary flow caused by Amytal infusion or by elevated perfusion pressure was not accompanied by elevation in the effluent concentration of adenosine and its catabolites. Infusion of Amytal was followed by decrease in oxygen consumption of the heart and increase in oxygen tension in the effluent. This indicates that tissue oxygen tension per se can not be responsible for the regulation of coronary blood flow. Analysis of the data showed that under conditions in which there was a decrease in the tissue [ATP]free/[ADP]free[Pi] an increase in coronary flow was observed irrespective of the nature of the vasodilatory stimulus. It is concluded that mitochondrial oxidative phosphorylation provides a link between tissue oxygen metabolism and coronary blood flow. Mechanisms are discussed whereby changes in the cellular energy state ([ATP]free/[ADP]free[Pi]) are coupled to vasodilation, including possible direct effects on the vascular smooth muscle and/or generation of "second messengers."
Pericoronary nerve mediates inhibitory sympathetic response to coronary occlusion
Authors: Suehiro S. , Ninomiya I.
Published: December 2017

We determined the effect of pharmacological blood of the pericoronary nerve either along the experimentally occluded left circumflex (CX) or the nonoccluded left anterior descending coronary artery (LAD) on the reflex inhibition of renal nerve activity (RNA) during a brief CX occlusion. In 15 pentobarbital-anesthetized dogs with carotid sinuses denervated, CX was occluded under four different conditions of the pericoronary nerves. With intact pericoronary nerves, CX occlusion resulted in a significant decrease [-44 +/- 6.4 (SE) %] in RNA. The decrease in RNA remained basically the same (-34 +/- 10.0%) after block of the pericoronary nerve along LAD with local infiltration of 2% lidocaine. However, the reduction of RNA was abolished after block of the pericoronary nerve along CX (-6 +/- 4.9%) and after block of the pericoronary nerves along both LAD and CX (3 +/- 2.6%). These results indicate that the afferent input transmitted via the pericoronary nerve along the experimentally occluded coronary artery plays a dominant role in mediating the reflex inhibition of RNA during the coronary occlusion.
Selective sympathetic neural changes in hypertrophied right ventricle
Authors: Schmid P. G. , Lund D. D. , Davis J. A. , Whiteis C. A. , Bhatnagar R. K. , Roskoski R.
Published: December 2017

Selective pressure overload of the right ventricle in guinea pigs resulted in early and sustained reductions in tyrosine hydroxylase and dopamine-beta-hydroxylase activities in the right ventricle. No changes in tyrosine hydroxylase activity were detected in stellate ganglia sinoatrial (SA) nodal region, atrioventricular (AV) nodal region, or left ventricle. Reductions in tyrosine hydroxylase activity in stressed right ventricle were similar regardless of duration of pulmonary artery constriction, extent of hypertrophy, presence or absence of hepatic congestion, and preservation or depletion of catecholamines. The changes may represent localized loss of sympathetic nerve fibers; factors involved directly in the process of pressure-overload-induced hypertrophy may be responsible. However, sympathetic nerves remaining in hypertrophied ventricle respond normally to cold-induced sympathetic activation. The reduction in tyrosine hydroxylase activity and the maintenance of norepinephrine turnover in residual innervation to hypertrophied right ventricle support the concept that sympathetic neural regulation of hypertrophied cardiac tissue is altered but not lost.
Development of microvascular rarefaction in the spontaneously hypertensive rat
Authors: Prewitt R. L. , Chen I. I. , Dowell R.
Published: December 2017

Using stereological methods in vivo, we have investigated the rarefaction of arterioles and capillaries in male spontaneously hypertensive rats (SHR) and the Wistar-Kyoto controls (WKY) at 6-8, 12-14, and 16-18 wk of age. Under chloralose-urethan anesthesia, the gracilis muscle was isolated for microscopic observation. Vessel length and surface area per unit volume of tissue (density) were determined during three consecutive states: innervation, denervation, and vasodilation with nitroprusside. Arteriolar wall-to-lumen ratio was measured after vasodilation. At 6-8 wk capillary density was reduced in the SHR. At 12-14 wk there was a reduction of arteriole and capillary density under innervated and denervated conditions but not after vasodilation (a state of functional rarefaction). At 16-18 wk there was a reduction of arteriolar and capillary density under all three conditions (a state of anatomical rarefaction). At 12-14 and 16-18 wk there was an elevated level of arteriolar vasoconstriction in the SHR that was masked in any one state by the closure of the smaller arterioles. Arteriolar wall-to-lumen ratio was not elevated in the SHR at any time. Arteriolar closure was not reversed by acute denervation.
Role of carotid artery resistance to collapse during high-intrathoracic-pressure CPR
Authors: Yin F. C. , Cohen J. M. , Tsitlik J. , Zola B. , Weisfeldt M. L.
Published: December 2017

The driving force for carotid artery flow during high-intrathoracic-pressure cardiopulmonary resuscitation is a peripheral arteriovenous pressure gradient resulting from differential transmission of the high intrathoracic pressure to the carotid artery but not to the jugular vein. To study the role of carotid artery resistance to collapse in establishing this differential pressure transmission, we manipulated the upstream, downstream, and surrounding pressures and measured the resultant carotid artery flow in both intact dogs and in excised arteries. Stepwise reductions in downstream pressure produced a narrowing near the outlet from the high-pressure chamber (the thorax in vivo), but increments in flow continued despite the presence of a positive (outside--inside) transmural pressure gradient. Flow limitation occurred only when downstream pressure was further decreased. Resistance to collapse was indexed by the transmural pressure at the onset of flow limitation (Pcrit), which was 7.2 +/- 1.6 mmHg in eight intact dogs. After administration of norepinephrine Pcrit increased by 2.6 +/- 0.7 mmHg, P less than 0.001). Seven excised carotid arteries also demonstrated resistance to collapse which was enhanced somewhat with norepinephrine. Thus resistance of the carotid artery to collapse is a critical factor in maintaining forward flow during high intrathoracic pressure. This resistance to collapse is also seen in vitro and can be enhanced by vasoconstricting agents.
No effect of intrarenal converting enzyme inhibition on canine renal blood flow
Authors: Zimmerman B. G. , Wong P. C. , Kounenis G. K. , Kraft E. J.
Published: December 2017

Captopril and teprotide were administered intra-arterially to the kidney and intravenously to inhibit intrarenal and extrarenal converting enzyme (CE), respectively. Captopril was infused at 0.4, 0.8, and 1.6 micrograms . kg-1 . min-1 intra-arterially, and teprotide was given at 0.4 and 0.8 micrograms . kg-1 . min-1 intra-arterially in salt-replete dogs (group 1). Both agents were also given intravenously in the dose of 0.2 mg/kg, known to cause maximal extrarenal CE inhibition. The intra-arterial infusions of the inhibitors had no effect on renal hemodynamics but caused a graded degree of intrarenal CE inhibition. A lesser degree of extrarenal CE inhibition was seen after captopril in these doses. Intravenous administration of captopril and teprotide inhibited extrarenal CE, but only captopril increased renal blood flow (13%). When teprotide was given in a higher dose (group 3, 1.02 mg/kg), it too increased renal blood flow. In salt-deplete dogs (group 2), captopril infused intra-arterially caused a degree of intrarenal CE inhibition comparable with that in the salt-replete dogs but again produced little or no renal hemodynamic changes. When given intravenously in this group, captopril inhibited extrarenal EE and elicited a greater increase in renal blood flow (36%) than in the group 1 dogs. These results indicate that in conscious dogs renal vasodilatation is associated with extrarenal, but not intrarenal, CE inhibition.
[K+]o accumulation and electrophysiological alterations during early myocardial ischemia
Authors: Weiss J. , Shine K. I.
Published: December 2017

Double-barreled valinomycin K+-sensitive electrodes and floating microelectrodes were used to monitor extracellular K+ concentration ([K+]o) and intracellular potential, respectively, in the isolated arterially perfused rabbit interventricular septum, under conditions of global ischemia without collateral flow and hypoxia with maintained flow. During ischemia [K+]o reproducibly increased at rates of 0.5-1 mM/min, usually in a triphasic pattern, and was accompanied by shortening of the action potential duration (APD) and an increase in conduction time (CT). Hyperkalemia, equivalent to that occurring during ischemia, in combination with respiratory acidosis (pH 6.2-6.5) and catecholamines reproduced quantitatively the ischemia-induced changes in APD and CT. None of these factors alone produced quantitatively comparable electrophysiological changes. Faster heart rates increased [K+]o accumulation during ischemia and accentuated the changes in APD and CT during ischemia. These findings suggest that local hyperkalemia, intracellular acidosis, and catecholamines release during early ischemia may account for electrophysiological changes predisposing to the development of reentrant arrhythmias.
Comparative force-velocity relation and analyses of myosin of dog atria and ventricles
Authors: Wikman-Coffelt J. , Refsum H. , Hollosi G. , Rouleau L. , Chuck L. , Parmley W. W.
Published: December 2017

The isolated muscle and purified myofibrillar proteins of canine atria and ventricles were compared relative to force-velocity relations and rate of adenosine 5'-triphosphatase (ATPase) activity as a function of calcium concentrations. The maximal stress development of isolated trabeculae of canine atria was similar to that of canine right ventricular papillary muscles when analyzed at saturating calcium concentrations (7.5 mM); however, stress was less in the atria when studied at normal calcium concentrations (2.5 mM). The maximal velocity of shortening of atrial trabeculae was about 2.3 times higher than that of ventricular muscle. Regulated actomyosin characterized from the myofibrillar proteins of the two tissues gave directionally similar calcium sensitivity. The maximum velocity of shortening for actin-activated atrial myosin of the dog was approximately 1.8 times higher when the latter was analyzed as a function of actin concentration. Both maximal tension of isolated muscle and regulated actomyosin ATPase activity were dependent on calcium concentration.
Regional coronary vasoconstriction in response to stimulation of stellate ganglia
Authors: Rinkema L. E. , Thomas J. X. , Randall W. C.
Published: December 2017

Recent experiments have demonstrated that direct and reflex sympathetic stimulation elicit coronary vasoconstriction when the inotropic and chronotropic effects are blocked with beta-adrenergic blocking agents. This vasoconstriction can be blocked with alpha-adrenergic blocking agents. Regional variations in the flow reduction produced by right (RSS) vs. left (LSS) stellate stimulation were delineated in this study. Open-chest pentobarbital-anesthetized dogs were given propranolol (1 mg/kg iv). Hearts were neurally decentralized and paced just above the spontaneous heart rate. Radiolabeled microspheres (15 +/- 2 micrometers) were injected into the left atrium before and during RSS (n = 11) or LSS (n = 11). RSS produced relatively little vasoconstriction confined to anterior left ventricle. In contrast, LSS produced significant vasoconstriction in all areas of the right and left ventricles. In the endocardial half of the left ventricle the flow decrease was uniformly distributed among the regions studied. In the epicardial half of the flow decrease was more pronounced in posterior than in anterior regions. No significant change occurred in the endo-epi ratios with RSS, but with LSS there was a significant change in three areas. The changes were related to regional variations in the degree of epicardial constriction. Thus RSS and LSS have differential effects (quantitatively) on regional coronary blood flow.