bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of blood-free and protein-free perfusion on CFC in the isolated cat hindlimb
Authors: Watson P. D.
Published: December 2017

To investigate the effects of blood and protein on capillary filtration coefficient (CFC), isolated cat hindlimbs were perfused at constant flow from a reservoir containing one of three perfusates: 1) an electrolyte solution also used for dialyzing bovine serum albumin (BSA) and hence labeled dialysate, 2) dialyzed 6.5–7.0 g/100 ml BSA, labeled albumin, and 3) albumin plus cat blood, labeled control. CFC during control perfusion averaged 0.0137 +/- 0.003 (SD, n = 26) and increased slowly with time. CFCs with dialysate and albumin were 3.1 +/- 0.56 (n = 11) and 1.7 +/- 0.52 (n = 15) times control, respectively. However, the ratio in a particular experiment depended on control CFC, the ratio being low when the control CFC was low and high when control CFC was high. The data can be explained if water flow occurs through two types of transcapillary pathways, one having a hydraulic capacity constant from animal to animal and insensitive to blood and protein, the second varying in hydraulic capacity and requiring blood and protein for its normal values.
Hemodynamic disturbances in the rat as a function of the number of microspheres injected
Authors: Stanek K. A. , Smith T. L. , Murphy W. R. , Coleman T. G.
Published: December 2017

The purpose of this study was to reevaluate the radioactive microsphere technique used to measure blood flow distribution. The rats were conscious when studied. A dextrose solution with specific gravity of 1.3 was used as the suspension media instead of 10% dextran, which has previously been shown to cause hypotension. The microspheres were injected into the left atrium, which provided for maximal mixing with the blood before being ejected into the aortic arch. Ficoll-70 was given after each reference sample as a fluid replacement. With these modifications an injection of 360,000 microspheres or less caused no hemodynamic disturbances, as judged by electromagnetic flowmetry. After 1.4 X 10(6) microspheres had accumulated in the rat (several injections) the only significant hemodynamic disturbance was a decreased heart rate. This study establishes the limits in the rat regarding the number of microspheres that can be injected before hemodynamic disturbances result.
Acute hypoxemia and hypercapnia: increase in plasma catecholamines in conscious dogs
Authors: Rose C. E. , Althaus J. A. , Kaiser D. L. , Miller E. D. , Carey R. M.
Published: December 2017

To systemically evaluate the effects of acute hypoxemia and hypercapnic acidosis on the sympathetic nervous system, five unanesthetized mongrel dogs were studied during acute hypoxemia [arterial O2 tension (PaO2) 33 +/- 2 Torr], acute hypercapnic acidosis [arterial CO2 tension (PaCO2) 53 +/- 1 Torr; pH, 7.19 +/- 0.02], and combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 Torr; PaCO2, 52 +/- 1 Torr; pH, 7.18 +/- 0.02). Combined acute hypoxemia and hypercapnic acidosis resulted in increased mean arterial pressure, cardiac output, and heart rate. Moreover, combining acute hypoxemia and hypercapnic acidosis acted synergistically to increase circulating norepinephrine and epinephrine. Acute hypoxemia alone and acute hypercapnic acidosis alone resulted in reversible increases in mean arterial pressure, cardiac output, heart rate, and circulating norepinephrine. Although plasma epinephrine concentrations increased during acute hypoxemia, circulating epinephrine was unchanged during acute hypercapnic acidosis. These data indicate that acute hypoxemia and hypercapnic acidosis result in synergistic increase in circulating catecholamines.
Total body vascular capacitance changes during high intracranial pressure in dogs
Authors: Stein P. M. , MacAnespie C. L. , Rothe C. F.
Published: December 2017

The active capacitance response to increased intracranial pressure (Pic) was studied in nine chloralose-anesthetized dogs. The vena cavae were cannulated and drained into a reservoir as blood was pumped at a constant flow (Q) into the right atrium. Central blood volume was determined as Q times the mean transit time of dye from the right atrium to the aortic root. Arterial compliance (Ca) was determined from the monoexponential decay of systemic arterial pressure (SAP) during vagal cardiac arrest to compute changes in arterial volume (delta SAP X Ca). Atropine was administered to prevent bradycardia and dangerous, constant cardiac output-induced increases in pulmonary arterial (PAP) and right and left atrial pressures. Blood volume shifts indicative of active venoconstriction, included changes in reservoir, central, and arterial volumes during Pic of 100–200 mmHg. Raised Pic, after atropine, induced a tachycardia, increased systemic and pulmonary resistances, and increased SAP and PAP. Venoconstriction caused marked blood shifts between 125 and 200 mmHg Pic. The extrapolated response threshold was about 112 mmHg. In the most sensitive range, venoconstriction amounted to 3.9 ml X kg-1 per 25-mmHg change in Pic. These results indicate that intense active capacitance vessel constriction is an important part of cardiovascular hemostasis during rapidly increased intracranial pressure.
Mediation of pressor responses to cerebral ischemia by superficial ventral medullary areas
Authors: Rohlicek C. V. , Polosa C.
Published: December 2017

The effects on the pressor response to cerebral ischemia (CIR) of superfusion of the ventral medullary surface with artificial cerebrospinal fluid (CSF) containing local anesthetic was investigated in 10 sinoaortic-denervated, anesthetized cats. Prior to application of the local anesthetic, occlusion of the common carotid and vertebral arteries caused an increase in mean systemic arterial pressure (SAP) of 58 +/- 7 mmHg (+/- SE) from an initial level of 98 +/- 6 mmHg. Following 108 +/- 15 s of superfusion with artificial CSF containing 2% procaine, the CIR decreased to 19 +/- 3 mmHg. At this time phrenic nerve activity had been eliminated but basal SAP had only decreased by 14 +/- 2 mmHg, and significant neurogenic vasomotor tone remained. The residual CIR can be accounted for by the passive increase in systemic resistance due to occlusion of the cerebral vascular bed. The effects of procaine were reversible. On attenuation of the CIR, electrical stimulation of pressor points 2–4 mm from the ventral medullary surface was still effective. Autoradiographic analysis following application of 14C-labeled lidocaine showed that attenuation of the CIR occurred when estimated concentrations of the anesthetic sufficient to block nerve conduction extended 85 micron from the ventral medullary surface. These results indicate that the CIR is mediated by superficial structures in the ventral medulla that are not involved in the generation of a major fraction of basal vasomotor tone.
Cardiac sarcoplasmic reticulum function in insulin- or carnitine-treated diabetic rats
Authors: Lopaschuk G. D. , Tahiliani A. G. , Vadlamudi R. V. , Katz S. , McNeill J. H.
Published: December 2017

Cardiac sarcoplasmic reticulum (SR) function and SR levels of long-chain (LC) acylcarnitines were determined in streptozotocin-induced diabetic rats treated with insulin or D,L-carnitine. ATP-dependent calcium transport was significantly depressed in cardiac SR isolated from untreated diabetic rats compared with control rats. Diabetic rat cardiac SR levels of LC acylcarnitines were also significantly elevated. Various parameters of heart function (left ventricular developed pressure, +dP/dT, and -dP/dT), as determined on an isolated working heart apparatus, were found to be depressed in untreated diabetic rats. Cardiac SR isolated from diabetic rats treated throughout the study period with insulin or D,L-carnitine did not have elevated levels of LC acylcarnitines associated with SR membrane nor was SR calcium transport activity depressed. Heart function in the diabetic rats treated with insulin was similar to control rat hearts but heart function remained depressed in diabetic rats treated with D,L-carnitine. The data suggest that the LC acylcarnitines are involved in the observed impairment of cardiac SR function in diabetic rats. Other factors, however, must be contributing to the depression in heart function noted in these animals.
P-face particle density of freeze-fractured vertebrate cardiac plasma membrane
Authors: Kordylewski L. , Karrison T. , Page E.
Published: December 2017

P-face particle density of freeze-fractured cardiac plasmalemma provides an estimate of the total population of membrane channels, carriers, and receptors that insert into or traverse unit area of lipid bilayer. We have determined the size of this population of integral membrane protein assemblies by counting the number of P-face particles per square micron of plasmalemma in freeze-fractured hearts, using stereoimaged replicas tilted with a goniometer stage in the electron microscope. Particle numbers per square micron were 4,525 +/- 231, 4,799 +/- 235, 4,122 +/- 153, 4,281 +/- 218, and 5,848 +/- 300 for ventricular myocyte plasmalemmas of rat, rabbit, 8-day chick, adult chicken, and frog, respectively. These values are at least two times greater than published values, in which stereo imaging was not used. Published ligand-binding studies indicate that only the surface density of the Na+-K+ pump sites can account for a significant fraction of P-face particles; the rest so far lack functional correlates. Particle density of frog heart plasmalemma significantly exceeded particle densities of chicken and mammalian plasma membranes.
Changes in smooth muscle tone influence characteristic impedance of the aorta
Authors: Stone D. N. , Dujardin J. P.
Published: December 2017

Experiments were performed on anesthetized dogs to quantitate the effects of changes in aortic smooth muscle tone on the passive pressure dependence of the aortic characteristic impedance (Zc). Zc was calculated from the diastolic pressure-diameter relationship in a wide pressure range induced by forced slow oscillations in pressure. Changes in aortic smooth muscle activity were induced by hemorrhage (-15% of the estimated blood volume), by volume expansion (+15 and +30%), and by alpha-adrenergic blockade. Curves relating Zc to pressure showed a minimum in the physiological pressure range and were well described by parabolas under all conditions. Under control conditions, the minimum Zc pressure was located close to the mean arterial pressure. Both levels of volume expansion as well as alpha-blockade reduced Zc at all pressure levels. Hemorrhage increased Zc at each pressure level and caused the minimum in the Zc vs. pressure curves to shift to higher values. The observed changes in Zc may play an important role in the hemodynamic adjustments to hemorrhage and to volume expansion.
Lactate accumulation in fully aerobic, working, dog gracilis muscle
Authors: Connett R. J. , Gayeski T. E. , Honig C. R.
Published: December 2017

Tissue lactate was measured in dog gracilis muscles frozen at rest and during phasic twitch contractions, which evoked 10-100% of maximum O2 consumption (VO2 max). Myoglobin cryomicrospectroscopy was used to obtain the distribution of PO2 in subcellular volumes. Tissue sampling was designed to estimate lactate concentration in the population of cells used for spectroscopy. Covariates included vascular resistance, functional capillary density, VO2, tissue pyruvate, ATP, phosphocreatine, and creatine, as well as lactate efflux. Myoglobin saturation did not decrease in the first seconds of stimulation at 1 or 4/s. In the steady state, muscle lactate accumulation was linear with stimulation rate and VO2. At 1 and 4/s the minimum PO2 found was greater than 5 Torr during the rest-work transition and greater than 2 Torr in the steady state. VO2 did not increase when flow was increased during contraction at 1/s, although the minimum PO2 found rose to approximately 10 Torr. If flow was restricted during stimulation, PO2 was 0 at many loci, and lactate concentration was elevated above the value predicted by its linear relationship with twitch rate. We conclude that fully aerobic lactate accumulation occurs in this pure red muscle. This accumulation results from causes other than a simple O2 limit on mitochondrial ATP production.
Plasma pharmacokinetics and interstitial diffusion of macromolecules in a capillary bed
Authors: Nugent L. J. , Jain R. K.
Published: December 2017

Concentration-time profiles of fluorescein isothiocyanate (FITC)-conjugated bovine serum albumin and a graded series of FITC-dextrans of 20,000-70,000 molecular weight were measured within the erythrocyte-free plasma layer in individual vessels and at various positions within the interstitial tissue space of mature granulation tissue grown in a rabbit ear chamber. Sodium fluorescein was used as a representative small molecule. The plasma pharmacokinetic data were found to follow a biexponential decay in time. A one-dimensional model of diffusion adequately described interstitial transport. Interstitial diffusion coefficients decreased progressively with Stokes-Einstein radius with values for albumin being significantly reduced from that for a dextran of equivalent hydrodynamic radius. Interstitial diffusion of sodium fluorescein and albumin agreed with a fiber-matrix model, whereas the interstitial diffusion of dextrans more closely corresponded to a pore model.
Norepinephrine increases beta-receptors and adenylate cyclase in canine myocardium
Authors: Raum W. J. , Laks M. M. , Garner D. , Ikuhara M. H. , Swerdloff R. S.
Published: December 2017

Norepinephrine, a known inducer of myocardial hypertrophy, was found to have marked effects on the myocardial adrenergic system, which occurred prior to the development of a significant increase in heart weight. The chronic subhypertensive infusion (1.4 microgram/min) in free-roaming dogs produced a threefold increase in plasma norepinephrine (determined by radioimmunoassay). After 3 mo of infusion, right and left ventricular norepinephrine content (ng/mg protein) decreased significantly by twofold (right, 2.50 +/- 0.24; left, 2.08 +/- 0.36) compared with controls (right, 4.76 +/- 1.48; left, 4.65 +/- 1.49), and beta-receptor density (125I-pindolol) increased (right, 0.122 +/- 0.029; left, 0.153 +/- 0.021) over the controls (right, 0.082 +/- 0.015; left, 0.069 +/- 0.008 pmol/mg protein). Accompanying the beta-receptor changes, isoproterenol-stimulated adenylate cyclase activity also increased significantly [right, 29.2 +/- 2.1; left, 29.5 +/- 1.0 vs. controls, right, 13.8 +/- 1.1; left, 20.2 +/- 2.2 pmol adenosine 3',5'-cyclic monophosphate (cAMP) generated X min-1 X mg protein-1]. Because the above changes occurred in the absence of cardiac hypertrophy, it suggests that alterations in the myocardial adrenergic system are dependent on the stimulus (in this case norepinephrine) invoking the change and not the degree of hypertrophy. It also suggests that changes in the adrenergic system may not directly reflect the mechanism involved in the development of hypertrophy.
Oxygen consumption and pressure-volume area of abnormal contractions in canine heart
Authors: Suga H. , Yamada O. , Goto Y. , Igarashi Y.
Published: December 2017

Oxygen consumption rates (VO2) of isovolumic and normally ejecting contractions are closely correlated with their systolic pressure-volume areas (PVA) in a stable canine left ventricle. PVA is the area in the pressure-volume (PV) diagram that is circumscribed by the end-systolic and end-diastolic PV relation curves and the systolic segment of the PV loop trajectory. We studied whether VO2s of abnormally loaded ejecting contractions were similarly correlated with their PVAs. Various abnormally ejecting contractions were produced in the left ventricle of the cross-circulated canine heart. VO2 and PVA data of the various abnormal contractions and the isovolumic and normally ejecting contractions were pooled together, to which the correlation and regression analyses were applied. They could be fitted by a linear regression analyses were applied. They could be fitted by a linear regression line with a high correlation coefficient and a slight scatter in each heart. We therefore conclude that PVA is the primary correlate of VO2, not only in the isovolumic and normally ejecting contractions but also in various abnormally loaded contractions in a given canine left ventricle with a stable contractile state.
Effect of renin-angiotensin system on limb circulation in normal subjects
Authors: Creager M. A. , Faxon D. P. , Rockwell S. M. , Melby J. C. , Gavras H. , Coffman J. D.
Published: December 2017

It is not known whether the renin-angiotensin-aldosterone (RAA) system contributes to the regulation of the limb circulation in normal human beings. Accordingly, the effect of the angiotensin converting-enzyme inhibitor, captopril, on forearm vascular resistance (FVR) and forearm venous volume (FVV) was studied in nine normal subjects during states of both sodium loading and sodium depletion. All subjects were studied in the supine position and during 60 degrees head-up tilt. By analysis of variance, the combined intervention of sodium depletion and converting-enzyme inhibition was responsible for a decrease in both FVR and mean blood pressure (BP). In sodium-depleted subjects, converting-enzyme inhibition decreased supine mean BP 7.0% and supine FVR 22.8% but did not change FVV. Neither the fall in BP nor the fall in FVR, however, was significantly augmented by tilting from a supine to upright posture. In sodium-loaded subjects, captopril did not alter BP, FVR, or FVV in recumbent or upright positions. Therefore, the RAA system contributes to the maintenance of blood pressure and limb vascular resistance only in sodium-depleted subjects. Limb venous capacitance in normal subjects is not regulated by the RAA system.
Postextrasystolic pulsus alternans and heart rate
Authors: Carlson C. J. , Rapaport E.
Published: December 2017

Postextrasystolic (PES) pulsus alternans, an alternation in systolic blood pressure above and then below base line for several beats after a premature ventricular depolarization was noted many years ago in patients with heart failure. We noted in acute animals studies that the occurrence of PES alternans was related to heart rate. We studied five open-chest dogs suppressing intrinsic heart rate by vagal stimulation and pacing the right ventricle over a range of 100-200 beats/min introducing an extrastimulus at 50% of the paced rate. We found that the pressure of the second PES beat was augmented up to 120 beats/min and then began to decrease approximately 10 Torr for each 10-beats/min increase in rate. The physiological variables most closely related to the occurrence of PES alternans were the duration of systole of the first PES (strong) beat and the rate of rapid diastolic filling of the second PES (weak) beat. Postextrasystolic and possibly sustained pulsus alternans is an inevitable consequence of heart rate and of the relationship between ejection and diastolic filling. The details of that relationship and the effects of various diseases determine whether alternans is observed or not.
Fetal canine cardiac Purkinje fibers: electrophysiology and ultrastructure
Authors: Danilo P. , Reder R. F. , Binah O. , Legato M. J.
Published: December 2017

We studied the ontogenesis of the transmembrane action potential and the ultrastructure of fetal canine Purkinje fibers. Fetal hearts were obtained from fetuses just after implantation to end gestation. Using standard microelectrode recording techniques, we found that action potential characteristics varied linearly over this period of development. Maximum diastolic potential (MDP) ranged from -65 to -85 mV; action potential amplitude (AMP) varied from 100 to 120 mV; maximum upstroke velocity (Vmax) increased from 200 to 550 V/s. Action potential duration measured to 50% repolarization (APD50) increased from 15 to 156 ms while duration measured at full repolarization (APD100) similarly increased from 75 to 236 ms. The relationship between external potassium concentration and membrane potential was equivalent across all stages of fetal development. Tetrodotoxin (TTX, 7.7 X 10(-7) to 1.6 X 10(-5) M) caused concentration-dependent decreases in AMP, Vmax, and APD50. Verapamil (1 X 10(-7) to 1 X 10(-5) M) decreased Vmax and APD50 in a concentration-dependent manner. The effects of both TTX and verapamil were statistically equivalent across all stages of fetal development. Ultrastructural studies of fetal Purkinje fibers showed that myocytes at the earliest stages of development (Purkinje fibers were not visually distinct at this time) were arranged as a tightly packed mosaic with a rounded shape, with a large amount of glycogen, small sparse mitochondria, and relatively large nuclei. Mitotic cells were observed frequently. Purkinje fibers when first identified grossly had fewer myofilaments than working myocardial cells and sarcomeres without M lines. By late gestation, intercalated disks appeared with an increase in surface areas; desmosomes occurred more frequently. Myofilaments are organized around Z bands into rudimentary sarcomeres that still lack M lines. These data indicate that, although the fetal canine Purkinje fiber undergoes marked developmental changes in ultrastructure, cellular electrophysiological changes are more subtle. The action potential has a qualitative appearance similar to those of the neonatal or adult fiber. At no time during fetal development could we find slow-response action potentials.
Adenosine as a mediator of postcontraction hyperemia in dog gracilis muscle
Authors: Kille J. M. , Klabunde R. E.
Published: December 2017

The role of adenosine in postcontraction hyperemia (PCH) following sustained, maximal isometric contractions was studied in free-flowing dog gracilis muscles. The hemodynamic responses to contraction were examined in the presence and absence of dipyridamole (an adenosine transport inhibitor), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, an adenosine deaminase inhibitor), or alpha, beta-methyleneadenosine-5'-diphosphate (AOPCP, an inhibitor of 5'-nucleotidase). Each muscle was stimulated to contract for 1, 3, 5, and 10 s during saline and drug infusions. For each contraction, the tension-time integral (TT), excess flow (EQ), and excess oxygen consumption (EVo2) were computed. Linear regression analyses were then performed on EQ vs. TT, EVo2 vs. TT, and EQ vs. EVo2. An alteration of the PCH response by the drug was determined as any significant change from the saline control in the slope of the linear regression of EQ vs. EVo2. Dipyridamole and EHNA caused increases of 73 and 48%, respectively, in the slope of EQ vs. EVo2, whereas AOPCP decreased the slope by 41%. The changes in the PCH produced by these drugs are consistent with the hypothesis that an increase in interstitial adenosine during muscular contraction contributes to PCH.
Effect of beta-adrenergic blockade on in vivo norepinephrine release in canine heart
Authors: Cousineau D. , Goresky C. A. , Bach G. G. , Rose C. P.
Published: December 2017

The beta-adrenergic blockade-induced reduction in myocardial norepinephrine overflow during sympathetic stimulation was examined by use of the multiple indicator-dilution technique. A kinetic model incorporating the effects of flow, capillary permeability surface product for norepinephrine, the interstitial uptake rate constant for neurotransmitter, and plasma norepinephrine input and output values was used to estimate the rate of local release of norepinephrine into the interstitial space. The model was tested by first examining the effects of two drugs that increase myocardial norepinephrine overflow during sympathetic stimulation by differing mechanisms: desmethylimipramine, a norepinephrine uptake inhibitor, and phentolamine, an alpha-adrenergic blocker. The uptake inhibitor was demonstrated to reduce interstitial uptake and the alpha-blocker to increase local neurotransmitter release, without change in blood flow. The beta-adrenergic blocker, in contrast, reduced coronary blood flow and decreased the capillary norepinephrine permeability surface product but did not change the rate of local release. The decreased norepinephrine overflow after beta-blockade was deduced to result from the decrease in transcapillary flux and secondary increase in interstitial uptake.
Measurement of myocardial contractility in conscious rabbits
Authors: McRitchie R. J. , Blood R. , Chalmers J. P.
Published: December 2017

This paper describes modifications and adaptation of currently available techniques for the measurement of left ventricular diameter and pressure and their derivatives, dD/dt (the velocity of myocardial shortening) and dP/dt for the characterizing of the left ventricular contractile response of the conscious rabbit. It consists of an improved ultrasonic transit time dimension gauge together with an intraventricular catheter system. This system has been employed successfully to describe the left ventricular response to both physiological and pharmacologic interventions.
Effect of increased pulmonary vascular resistance on right ventricular systolic performance in dogs
Authors: Ghignone M. , Girling L. , Prewitt R. M.
Published: December 2017

We tested the possibility that for a given contractile state and right ventricular systolic pressure (RVSP), rate and extent of ventricular shortening would be reduced as resistance to ejection increased. In eight anesthetized, ventilated dogs, we measured RV and pulmonary artery pressure (Ppa), blood pressure, heart rate, cardiac output (CO), and RV dP/dt before (condition 1) and after (condition 2) pulmonary vascular resistance (PVR) was increased by injection of small (80 micron) glass beads. Glass beads caused a large increase (P less than 0.001) in Ppa and in RVSP and, despite increased RV end-diastolic pressure (EDP), CO and stroke volume (SV) were reduced. A third set of measurements was obtained following a further increase in resistance (condition 3). A comparison of condition 2 with condition 3, despite constant RVSP, constant mean Ppa, and increased EDP, showed a marked fall in CO and SV (P less than 0.001) when glass bead injection increased calculated resistance from 21 (condition 2) to 34 (condition 3) mmHg X 1(-1) X min. RV contractility, as assessed by Vmax and peak dP/dt was similar in both conditions. In five additional dogs, we measured the same parameters as before plus instantaneous pulmonary artery flow in all conditions. In a comparison of conditions 2 and 3, despite constant RVSP and increased EDP, peak and total flow (P less than 0.05) were reduced as resistance to RV ejection increased. We conclude that the right ventricle shortens more slowly and to a smaller extent against the same systolic pressure when its resistive afterload increases.
Cardiac receptor influences on the plasma osmolality-plasma vasopressin relationship
Authors: Wang B. C. , Sundet W. D. , Hakumaki M. O. , Geer P. G. , Goetz K. L.
Published: December 2017

Changes in blood volume are capable of altering the relationship between plasma osmolality (Posmol) and plasma arginine vasopressin (PAVP), presumably via a reflex elicited from cardiovascular receptors, but the precise location of the receptors involved in this response has not been established. Because cardiac receptors are capable of influencing AVP secretion, their specific effect was examined by producing volume changes in cardiac-denervated (CD) dogs and comparing the Posmol-PAVP relationship in these dogs with data from comparable experiments on sham-operated control dogs (cardiac-sham, CS). Posmol was increased by water deprivation for 96 h (volume depletion) and also by administration of hypertonic saline for 2 h (volume expansion). The slope of the regression line describing the Posmol-PAVP relationship in CS control dogs was steeper (P less than 0.01) during volume depletion (0.390) than it was during volume expansion (0.228), thus suggesting that volume depletion had enhanced and volume expansion had inhibited the secretion of AVP. In contrast, the slope of the regression line delineating the Posmol-PAVP relationship in CD dogs was essentially the same during volume depletion (0.288) as it was during volume expansion (0.291). It would seem that most, if not all, of the volume influences on the Posmol-PAVP relationship are mediated via reflex effects elicited by cardiac receptors.
Dietary manipulation of cardiac and aortic smooth muscle reactivity to isoproterenol
Authors: Herlihy J. T.
Published: December 2017

The responsiveness to isoproterenol of isolated atria and aortic strips was examined in two groups of male Fischer 344 rats. Group A (control) was composed of 5-mo-old rats fed ad libitum; group R (experimental) was composed of rats whose food intake had been restricted for 2 mo to 60% of that consumed by group A. Aortic strips obtained from group R and preconstricted with 30 mM K+ relaxed by 18% when challenged by a maximal concentration of isoproterenol (1 microM). This relaxation was significantly less than the 28% relaxation observed with strips from group A. No effect on the inotropic response of the left atria or on the chronotropic response of the right atria to maximal concentrations of isoproterenol was observed. A slight but statistically significant increase in sensitivity to isoproterenol was observed in the inotropic response of the left atria. The 50% effective concentration (EC50) for the isoproterenol-stimulated increase in force development observed with group R was 0.87 +/- 0.16 X 10(-8) M, which was significantly less than the value of 1.56 +/- 0.28 X 10(-8) M obtained with atria from group A. Food restriction exerted no significant effect on the EC50 for the chronotropic response of right atria to isoproterenol. Both the body weight and the heart weight of group A were greater than those of group R. However, the ratio of heart weight to body weight was significantly greater in group R than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of T4-induced cardiac hypertrophy on O2 supply-consumption balance during normoxia and hypoxia
Authors: Talafih K. , Grover G. J. , Weiss H. R.
Published: December 2017

The purpose of this study was to determine if thyroxine-induced hypertrophic hearts can maintain an adequate O2 supply-consumption balance both at rest and under hypoxic stress. New Zealand White rabbits were given 0.5 mg/kg L-thyroxine (T4) for 3 or 16 days, and a third group served as a control. Chests were opened under anesthesia, and myocardial blood flow was determined using microspheres. In half of these animals, microspectrophotometric determinations were made on left ventricular arterial and venous O2 saturation, and by combining this data with blood flows, O2 consumption was determined. The other animals were then subjected to hypoxia (8% O2 in N2), and flows and O2 consumption were again determined. T4 increased arterial pressure and heart rate in normoxic animals and also increased myocardial blood flow 65 and 210% for 3- and 16-day T4 groups, respectively, with no regional differences. O2 extraction was also increased in T4 animals. O2 consumption increased 134 and 280% in 3- and 16-day T4 groups. Only normoxic saline controls had a regional O2 consumption difference with subendocardial O2 consumption higher than subepicardial values. When compared with their respective normoxic groups, blood flow increased 49 and 101% for the hypoxic 3- and 16-day T4 groups. Hypoxia had no effect on saline control blood flow. Hypoxia decreased O2 extraction 29 and 41%, respectively, in the 3- and 16-day T4 groups and was unchanged in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Muscular blood flow distribution patterns in the hindlimb of swimming rats
Authors: Laughlin M. H. , Mohrman S. J. , Armstrong R. B.
Published: December 2017

We previously observed that muscle blood flow (MBF) is primarily directed to the active oxidative muscle fibers within muscles of rats during treadmill exercise. Since muscle fiber recruitment patterns and the relative level of activities of muscles are distinctly different in swimming and treadmill exercise, we hypothesized that the distribution of MBF would also be different. The purpose of this study was to measure the distribution of MBF in swimming rats for comparison with the patterns previously observed in treadmill exercise. MBF was measured with labeled microspheres in 25 hindlimb muscles before, during, and after 5 min of swimming. During swimming, MBFs ranged from 10 to 403 ml X min-1 X 100 g-1 in the white vastus lateralis and red tibialis anterior, respectively. MBFs were increased during swimming in most muscles with the flexor muscles generally showing larger increases than the extensor muscles. Comparison of swimming with treadmill exercise indicates that swimming produces greater increases in MBFs in flexor muscles than in extensor muscles, whereas treadmill exercise produces larger increases in extensor muscles. The increased MBF during swimming was directed to the fast-twitch oxidative fibers. Therefore regional hindlimb MBF distribution is different in swimming than in treadmill exercise, and it appears that MBF is matched to the fiber recruitment patterns during both types of locomotory exercise.
Preload-induced alterations in capacitance-free diastolic pressure-flow relationship
Authors: Aversano T. , Klocke F. J. , Mates R. E. , Canty J. M.
Published: December 2017

We have studied the influence of left ventricular diastolic pressure (LVDP) on diastolic coronary pressure-flow relationships independently of effects of capacitive flow in an open-chest heart-blocked canine preparation in which the left circumflex (LC) bed was vasodilated with adenosine and perfused with a programmable servo valve pressure source. At the onset of long diastoles produced by cessation of ventricular pacing, LVDP was adjusted to, and maintained at, a preselected level using a blood-filled reservoir. Right atrial pressure was kept constant at approximately 8 mmHg. LC pressure (PLC) was then made to decline and rise sequentially at a constant rate (2-40 mmHg/s), with LC inflow reaching zero at the nadir of the declining pressure ramp. The capacitance-free diastolic pressure-flow relationship was considered to lie midway between the instantaneous relationships derived from each down and up ramp pair. All capacitance-free relationships were curvilinear, and the degree of curvilinearity was accentuated with increasing preload. Pressure-axis intercepts (Pf = 0) increased from 14 +/- 1.1 (SE) to 23 +/- 1.4 mmHg as preload was raised from 6-10 to 31-35 mmHg. Coronary conductance, taken as the slope of the pressure-flow relationship at any given PLC, fell progressively as preload rose, with the fall being more marked at higher levels of preload and lower values of PLC. Diastolic coronary flow also decreased as a function of preload, reflecting the increases in Pf = 0 and decreases in conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
Divergent influences of leukotrienes C4, D4, and E4 on mesenteric and renal blood flow
Authors: Chapnick B. M.
Published: December 2017

Influences of leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) on mesenteric and renal blood flow were investigated in the anesthetized dog. Blood flow was measured with noncannulating electromagnetic flow probes, and all agonists were injected as a bolus close arterially. When injected into the superior mesenteric artery, LTC4 (0.1-3.0 ng), LTD4 (0.1-1.0 ng), and LTE4 (1-30 ng) produced dose-dependent decreases in blood flow in absence of a change in mean arterial pressure. When compared with intestinal vasoconstrictor responses caused by angiotension II, which was most active, and norepinephrine, which was least active, the leukotrienes were intermediate between these two well-known vasoactive hormones. LTD4 was more active than LTC4, and both were considerably more active than LTE4. In contrast to the intestine, injection of leukotrienes (1,000 ng) into the kidney resulted in little to no change in renal blood flow or mean arterial pressure, but mesenteric flow decreased 10-15 s later. Administration of indomethacin (5 mg/kg iv) did not alter mesenteric vasoconstrictor responses produced by LTD4. However, mesenteric vasoconstrictor responses to prostaglandin (PG)D2 were reduced after indomethacin, whereas renal vasodilation caused by PGD2 was unaffected. These results demonstrate that LTC4, LTD4, and LTE4 differentially affect blood flow in the intestine and kidney and suggest that if circulating levels of leukotrienes are increased, blood flow would be expected to be diverted away from the intestine. These data are thus compatible with the hypothesis that leukotrienes may participate in regulation of peripheral regional blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Cessation of arterial and venous flow at a finite driving pressure in porcine coronary circulation
Authors: Bellamy R. F. , O'Benar J. D.
Published: December 2017

We investigated the hypothesis that coronary capacitance is responsible for epicardial coronary artery flow stopping at arterial pressures greater than the coronary venous pressure. Using an in situ blood-perfused swine heart preparation, we compared the arterial pressures at which coronary artery inflow and coronary sinus outflow ceased. A pressure change was used that had the time course of aortic pressure during diastole. Data were obtained in hypocalcemic-arrested, adenosine-vasodilated preparations before and after pharmacologic interventions simulating the coronary circulation of the intact beating heart. The effect of extravascular compression was studied with barium contracture, while acetylcholine was infused to increase coronary vasomotor tone. The arterial pressure when arterial flow ceased was 13 +/- 5 mmHg in the arrested-vasodilated preparations, 37 +/- 10 mmHg after acetylcholine, and from 18 to 150 mmHg during barium contracture. Coronary sinus outflow ceased when arterial pressure was slightly less than the arterial pressure at which arterial flow had stopped. The differences between the arterial and venous zero flow arterial pressures were as follows: arrested-vasodilated 4 +/- 3 mmHg, acetylcholine 9 +/- 4, and barium contracture 0 +/- 3. The arteriovenous pressure gradients across the coronary bed at the instant venous flow ceased were as follows: arrested-vasodilated 5 +/- 6 mmHg, acetylcholine 23 +/- 6, and from 12 to 128 during barium contracture. These data do not support the suggestion that cessation of epicardial artery flow is solely a capacitance phenomenon.
Alpha 1-adrenoceptor blockade in renal hypertensive rats with low and high renin levels
Authors: Waeber B. , Nussberger J. , Brunner H. R.
Published: December 2017

A total of 75 male Wistar rats with one-kidney, one-clip renal hypertension was maintained on either a regular (RNa) or a low-salt (LNa) diet for 3 wk after clipping. Blood pressure in the unanesthetized rats was equally elevated independent of sodium intake. Plasma renin activity was higher in LNa animals, and blood pressure was renin dependent only in this group, as evidenced by the blood pressure response to 10 mg/kg captopril iv. There was no significant difference in plasma catecholamines between RNa and LNa rats, although in the former the sympathetic nervous system is believed to play a major role in sustaining high blood pressure. The acute intravenous administration of 0.5 mg/kg prazosin did not induce a more pronounced blood pressure fall in the RNa rats. Prazosin enhanced plasma norepinephrine levels similarly in both groups, but epinephrine levels only rose in the LNa animals. Prazosin also markedly stimulated plasma renin activity rendering blood pressure renin dependent even in RNa rats. Thus, using alpha 1-adrenoceptor blockade, it has not been possible to demonstrate that the blood pressure elevation of salt-repleted one-kidney, one-clip renal hypertensive rats is due to an enhanced sympathetic nerve activity. Data obtained with sympatholytic agents must be interpreted with great caution if renin activity cannot be kept unchanged.
High-speed eight-channel thermocouple amplifier
Authors: Carlson C. J. , Miller S. , Chilton G. C. , Rubenstein M. L. , Mickelson J. , Rapaport E.
Published: December 2017

An eight-channel thermocouple amplifier system was constructed to measure rapid changes in temperature of only 1 or 2 degrees C simultaneously from many sites within the heart. The system has a response time of less than 5 ms, a resolution of less than 0.025 degrees C, and a voltage gain of approximately 2,500.
Regional myocardial blood flow and necrosis in primates following coronary occlusion
Authors: Lavallee M. , Vatner S. F.
Published: December 2017

The effects of acute coronary artery occlusion on regional myocardial blood flow distribution in the remote nonischemic zone, the central ischemic zone, and the lateral border zone of the infarct were evaluated in conscious primates. Prior to coronary artery occlusion, blood flow was 1.51 +/- 0.11 in endocardial (Endo) and 1.36 +/- 0.11 ml X min-1g-1 in epicardial (Epi) layers with an Endo-to-Epi ratio of 1.17 +/- 0.05. Regional blood flow in the remote nonischemic zone increased by 28.0 +/- 4.7 and 31.7 +/- 3.6% for Endo and Epi layers, respectively, following coronary occlusion and remained elevated during the subsequent 24 h. At the center of infarct, Endo and Epi blood flows were depressed by 97.9 +/- 0.7 and by 97.9 +/- 0.8%, respectively, at 5 min after coronary occlusion and remained severely depressed throughout the 24-h observation period. Blood flow at the ischemic lateral border of the infarct was severely depressed and similar to the flow at the center of the infarct, whereas the nonischemic lateral border of the infarct had blood flow levels similar to the remote, nonischemic myocardium. Microsphere loss was not a feature of the primate infarct.
Effect of increased intracardiac and arterial pressure on plasma vasopressin in humans
Authors: Goldsmith S. R. , Cowley A. W. , Francis G. S. , Cohn J. N.
Published: December 2017

The effects of loading cardiopulmonary and sinoaortic baroreceptors on plasma arginine vasopressin (AVP) levels were examined in 18 healthy young adults after a mild water restriction. Cardiopulmonary receptors were acutely loaded by volume expansion which increased central venous pressure (CVP) from 4.7 +/- 1.9 to 7.3 +/- 2.2 mmHg but did not change mean arterial blood pressure (MAP). Both receptor groups were acutely loaded by applications of lower body positive pressure, which induced a comparable increase in CVP and, in addition, raised MAP from 85 +/- 6.7 to 93 +/- 6.8 mmHg (P less than 0.001). There was evidence of reflex activation as forearm blood flow and heart rate increased during volume expansion while the increase in heart rate was blocked during lower body positive pressure. Neither intervention significantly altered the control AVP level of 4.6 +/- 1.4 pg/ml. An investigation of more prolonged stimulation of cardiopulmonary receptors was carried out using 1 h of head-down tilt. Again, despite increases in CVP (5.1 +/- 1.3 to 9.0 +/- 1.4 mmHg, P less than 0.005), AVP (5.7 +/- 2.4 pg/ml) did not decrease. MAP did not change during head-down tilt. There were no changes in osmolality throughout any of the studies. AVP levels in humans are therefore not responsive to moderate isosmotic loading of the cardiopulmonary and sinoaortic baroreceptors under conditions of mild water restriction.
Decreased uptake of exogenous substrates following graded muscle stimulation
Authors: Walker P. M. , Mickle D. A. , Tanner W. R. , Harding R. , Romaschin A. D.
Published: December 2017

An exercising in vivo canine hindlimb model was used to assess the pattern of exogenous substrate delivery and uptake as a function of contraction frequency. The limb was stimulated to contract at 0, 4, 8, 12 8, 4, and 0 Hz for 10-min periods. Blood flow was proportional to stimulatory frequency. Oxygen consumption increased to a maximum at 12 Hz and subsequently declined. Glucose, free fatty acid, and lactate uptakes decreased despite increased deliveries and maintained arterial concentrations at 12 Hz. At this point there was a net release of glycerol and lactate from the muscle. Microvascular shunting was not the cause of decreased exogenous substrate uptake at 12 Hz. A switch from exogenous to endogenous muscle substrates occurred with the onset of decreased substrate uptake. The mechanism that facilitates this switch from exogenous to endogenous substrates remains unknown.
Measurement of cardiac output in adult and newborn animals by ascorbic acid dilution
Authors: Smallwood J. K. , Haselby K. A. , Paradise R. R.
Published: December 2017

We have developed an ascorbic acid-dilution method for measuring cardiac output which requires minimal blood withdrawal. Ascorbate is injected into a central venous catheter. The indicator-dilution curve is obtained by drawing blood from an arterial catheter through an amperometric cell at 0.96 ml/min for 35 s. The current is measured by a picoammeter . A calibration curve is obtained in 15 s prior to each indicator-dilution curve. An on-line digital computer measures the curve areas and calculates the cardiac output. Cardiac outputs of heparinized dogs anesthetized with pentobarbital and halothane measured by this method (AA) compared closely to cardiac outputs measured by the dye-dilution method (CG) (AA = 0.96 CG + 20 ml/min, r = 0.98). Both the cardiac output and the arterial blood pressure remained stable during replicate measurements of the cardiac output of 1-day-old piglets. This system allows cardiac output determinations of neonatal subjects without excessive blood removal and, with further development, should be practical in human neonates.
Effects of thrombocytopenia on monocrotaline pyrrole-induced pulmonary hypertension
Authors: Hilliker K. S. , Bell T. G. , Lorimer D. , Roth R. A.
Published: December 2017

Monocrotaline pyrrole (MCTP) causes lung injury, pulmonary hypertension, and right ventricular hypertrophy in rats. To determine if platelets are involved in the cardiopulmonary effects of MCTP, the response to MCTP was determined in thrombocytopenic rats. Blood platelet count was reduced to 10–20% of normal for 48 h by ip administration of an antirat platelet serum (PAS) prepared in the goat. Rats were treated iv with either MCTP 5 mg/kg or dimethylformamide vehicle and with either PAS or preimmune serum. Fourteen days after MCTP, right ventricular hypertrophy and several indexes of lung injury were measured. MCTP treatment produced right ventricular hypertrophy, increased lactate dehydrogenase activity and protein concentration in bronchopulmonary lavage fluid, increased perfusion pressure in isolated lungs, and decreased pulmonary clearance and metabolism of perfused 5-hydroxytryptamine. Thrombocytopenia did not influence the changes in these indexes of lung injury produced by MCTP in this protocol. When PAS was given 12 h before MCTP, it did not affect right ventricular hypertrophy, but when PAS treatment was begun 3 or 6 days after MCTP, right ventricular hypertrophy was decreased by 19 or 41%, respectively. These results suggest that platelets help to mediate the development of pulmonary hypertension and the hypertrophic response of the right heart following MCTP administration.