bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular responses to high-fat and high-carbohydrate meals in young subjects
Authors: Sidery M. B. , Macdonald I. A. , Cowley A. J. , Fullwood L. J.
Published: December 2017

We compared the cardiovascular, glucose, insulin, and catecholamine responses to high-fat (F) and high-carbohydrate (C) meals in healthy young subjects (mean age 23 yr, range 19-39). Cardiac output rose 30 min after C by 32% [95% confidence interval (CI) of the increase +0.32 to +1.64 l/min] and after F by 22% [95% CI +0.30 to +1.96 l/min; P = 0.03, analysis of variance (ANOVA)]. Superior mesenteric artery blood flow rose by 87% 15 min after C (95% CI +119 to +258 ml/min) and by 122% (95% CI +138 to +392 ml/min) 45 min after F, with significantly different patterns of response (interaction effect P less than 0.05, ANOVA). Calf blood flow fell and remained low for 60 min after F but only fell 15 min after C, with a return to fasting levels thereafter (interaction effect P less than 0.03, ANOVA). Thirty minutes postprandially the change of calf blood flow from baseline after C was significantly different than after F (95% CI of differences +0.1 to +2.04 ml.100 ml-1.min-1). Glucose, insulin, and norepinephrine levels increased more after C than after F. Thus there are different regional vascular responses to C and F despite similar cardiac output increases.
Effects of left ventricular volume overload produced by mitral regurgitation on diastolic function
Authors: Zile M. R. , Tomita M. , Nakano K. , Mirsky I. , Usher B. , Lindroth J. , Carabello B. A.
Published: December 2017

We hypothesized that the left ventricle's ability to compensate for the volume overload produced by mitral regurgitation (MR) depends, at least in part, on associated changes in left ventricular (LV) diastolic function. Indexes of the rate of LV pressure decline, the rate and extent of early diastolic filling, and LV diastolic stiffness were measured with simultaneous echocardiography and catheterization in the baseline state (baseline), immediately after creation of MR (acute MR), and 3 mo after creation of MR (chronic MR). Data are means +/- SD. MR caused LV dilation; end-diastolic dimension increased from 4.3 +/- 0.4 in baseline to 4.7 +/- 0.5 in acute MR and 5.8 +/- 0.1 cm in chronic MR (P less than 0.05 vs. baseline for both). Chronic MR caused eccentric LV hypertrophy; LV-to-body weight ratio increased from 3.6 +/- 0.3 in baseline to 4.5 +/- 0.2 g/kg in chronic MR (P less than 0.05 vs. baseline). Acute MR increased LV end-diastolic pressure from 8 +/- 4 in baseline to 15 +/- 3 mmHg (P less than 0.05 vs. baseline); chronic MR did not further increase LV end-diastolic pressure (14 +/- 4 mmHg). MR increased the transmitral pressure gradient from 5 +/- 1 in baseline to 14 +/- 3 in acute MR and 20 +/- 6 mmHg in chronic MR (P less than 0.05 vs. baseline for both). MR increased LV early diastolic filling rate; peak rate of increase in minor axis dimension increased from 11 +/- 2 baseline to 18 +/- 2 in acute MR and 19 +/- 2 cm/s in chronic MR (P less than 0.05 vs. baseline for both). Acute MR did not change LV stiffness constants. Chronic MR decreased LV stiffness; the modulus of chamber stiffness decreased from 7.1 +/- 2.8 in baseline to 2.9 +/- 1.6 in chronic MR (P less than 0.05 vs. baseline). Thus MR caused compensatory changes in LV diastolic function. These changes resulted from an increased transmitral pressure gradient and increased LV distensibility.
Effects of beta-adrenergic agonists on splanchnic vascular volume and cardiac output
Authors: Chang P. I. , Rutlen D. L.
Published: December 2017

The effect of beta-adrenergic agonists on splanchnic intravascular volume (SIV), measured with radionuclide imaging, and the subsequent influence of such volume changes on cardiac output (CO) were examined in 40 anesthetized dogs. Isoproterenol (6 micrograms/min) caused a decrease in total SIV of 12 +/- 1% (P less than 0.001). The decrease was due entirely to a decrease in splenic volume of 24 +/- 3% (P less than 0.001), since volume increased in the remainder of the splanchnic vasculature [hepatic and mesenteric volume increased 12 +/- 2% (P less than 0.001) and 11 +/- 3% (P less than 0.02), respectively]. CO increased from 1,724 +/- 187 to 3,138 +/- 321 ml/min (P less than 0.001); after subsequent splenectomy, isoproterenol caused a similar increment. Isoproterenol-associated SIV changes were not altered by carotid denervation and vagotomy or by beta 1-adrenergic inhibition with metoprolol but were abolished by nonselective beta-adrenergic inhibition with propranolol. With a larger dose of metoprolol and smaller dose of isoproterenol to minimize beta 1-adrenergic effects, the isoproterenol-associated CO increment was attenuated (P less than 0.01) by splenectomy. With the beta 2-agonist terbutaline (41 micrograms/min) after metoprolol, total SIV decreased 15 +/- 4% (P less than 0.001). After subsequent alpha-adrenergic inhibition with phenoxybenzamine, terbutaline caused no change in SIV and an attenuated (P less than 0.05) increase in CO. Thus beta-adrenergic agonist administration causes a decrease in total SIV due entirely to a decrease in splenic volume. The SIV decrement is dependent on beta 2- and alpha-adrenoceptor stimulation and appears to enhance CO only if beta 1-adrenergic effects are minimized.
Renal hemodynamic changes during serial seizures in rats
Authors: Zweifler R. M. , Slaven E. M. , Rihn L. L. , Magee J. C. , Kreisman N. R.
Published: December 2017

Renal blood flow (RBF) and mean arterial blood pressure (MABP) were measured during serially induced seizures in anesthetized paralyzed rats to investigate possible alterations in hemodynamic responses during experimental status epilepticus. During initial seizures, MABP increased from 143 to 193 mmHg, and RBF decreased from 4.8 to 1.5 ml/min. In contrast, MABP fell from 124 to 100 mmHg and RBF dropped from 3.6 to 2.8 ml/min during late seizures. The large decreases in RBF during initial seizures were blocked by renal denervation or bilateral adrenalectomy. During the period of late seizures, both the increase in MABP and the decrease in RBF in response to intravenous boluses of norepinephrine fell to 55% of the preseizure value. Our data indicate that the marked decreases in RBF during early seizures can be mediated by either the renal nerves or the adrenal glands. Furthermore, decreased sensitivity of the vasculature to norepinephrine likely contributes to the diminution of both MABP and RBF responses during later seizures.
Receptor mediation of microvascular responses to serotonin in striated muscle
Authors: Alsip N. L. , Harris P. D.
Published: December 2017

Serotonin constricts large arterioles and dilates small arterioles in striated muscle. Our study aimed to identify the receptors that mediate this differential response. Rats were anesthetized with pentobarbital sodium, and the cremaster muscle was prepared for videomicroscopy. Serotonin, applied topically, caused a constriction of large (A1) arterioles that was attenuated by cyproheptadine, methysergide, and LY 53857 but not by MDL 7222, phentolamine, propranolol, or diphenhydramine. The 5-hydroxytryptamine (5-HT)-induced constriction of A1 arterioles was mimicked by alpha-CH3-5-HT but not by 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) or 5-carboxamidotryptamine (5-CT). In addition, 5-HT caused a dilation of small (A3 or A4) arterioles that was blocked by cyproheptadine and methysergide but not by LY 53857, MDL 7222, phentolamine, or propranolol. Diphenhydramine caused a slight increase in the small arteriole mean effective concentration to serotonin but did not change the maximal response. The serotonin-induced dilation of small arterioles was mimicked by 5-CT but not by alpha-CH3-5-HT or 8-OH-DPAT. These data indicate that the 5-HT-induced constriction of large A1 arterioles is mediated via a 5-HT2 or 5-HT1C receptor, whereas 5-HT-induced dilation of smaller arterioles appears to be mediated by a 5-HT1-like receptor.
Role of ICAM-1 in neutrophil-mediated lung vascular injury after occlusion and reperfusion
Authors: Horgan M. J. , Ge M. , Gu J. , Rothlein R. , Malik A. B.
Published: December 2017

We examined the role of intracellular adhesion molecule 1 (ICAM-1 or CD54) in the development of pulmonary edema in rabbits after pulmonary artery occlusion and reperfusion using a monoclonal antibody (MAb) RR1/1 directed against ICAM-1, a ligand for the CD18 leukocyte adhesion glycoprotein complex. A vascular clamp was placed around the left pulmonary artery for 24 h and then released to allow reperfusion for 2 h. Lungs subjected to 24 h of unilateral pulmonary artery occlusion showed increased binding of 125I-labeled RR1/1 and immunocytochemical evidence of ICAM-1 expression in pulmonary vascular endothelial cells compared with the contralateral lung. MAbs RR1/1 (0.5 mg/kg) or IB4 (1.0 mg/kg) (MAb directed against an epitope on the CD18 adhesion glycoprotein) was infused 45-60 min before the start of reperfusion to assess the roles of ICAM-1 and CD18 in the response. After reperfusion, the lungs were removed, suspended from one end of a weighing balance, and perfused with Ringer-albumin (0.5 g/100 ml), and the changes in lung weight were monitored for 60 min. Lung tissue myeloperoxidase (MPO) content (a marker of neutrophil sequestration) was determined after reperfusion. The increases in lung weight gain in the RR1/1- and IB4-treated groups of 960 +/- 100 and 865 +/- 110 mg, respectively, were less (P less than 0.05) than in untreated controls (3,550 +/- 725 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
Force-interval relation in normal and cardiomyopathic hamster atria
Authors: Howlett S. E. , Bobet J. , Gordon T.
Published: December 2017

The purpose of this study was to determine how cardiomyopathy affects the beat-to-beat regulation of contractile force in cardiac muscle. Isometric force produced by left atria from 80- to 85-day-old normal and cardiomyopathic (CM) hamsters was measured in vitro at 29 degrees C in 2.5 and 6.0 mM Ca2+. During steady-state stimulation at 1 Hz, single test stimuli were interpolated at varying test intervals (0.3-600 s). The force-interval curves were fitted with an equation using five parameters to define the curve and were compared under different conditions; the recovery of force after long rest intervals was fitted with a single exponential curve. Results showed that the force-interval curves were similar in normal and CM atria except that force was depressed at all intervals in 2.5 mM external Ca2+ concentration ([Ca2+]e) and that the parameter U(0), reflecting force produced at short test intervals, tended to be lower in CM muscles. At high [Ca2+]e (6.0 mM) the force-interval curves were similar, but recovery of steady-state force after long test intervals was much slower in CM atria (tau = 77.3 +/- 8.5 s, n = 11) than in normal atria (tau = 30.5 +/- 3.9 s, n = 11). Recovery was also slower at 2.5 mM [Ca2+]e. These findings suggest that, on a beat-to-beat basis, there is less Ca2+ available in intracellular compartments in the CM heart.
Flash photolysis of intracellular caged GTP gamma S increases L-type Ca2+ currents in cardiac myocytes
Authors: Kozlowski R. Z. , Twist V. W. , Brown A. M. , Powell T.
Published: December 2017

L-type calcium currents were recorded from isolated ventricular myocytes using standard patch-clamp methods. Rapid release of photolabile guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), tetralithium salt, by flash photolysis of intracellular caged-GTP gamma S increased the magnitude of the L-type calcium current: an effect independent of the ultraviolet flash per se or the production of photolytic by-products. This increase in calcium current was markedly reduced by intracellularly applied guanosine 5-O-(thiodiphosphate), trilithium salt or by an excess of GTP gamma S. It is therefore likely that rapid release of GTP gamma S intracellularly in the absence of an agonist can, via a G protein-mediated mechanism, cause L-type calcium current activation. In the presence of Rp-adenosine 3,5-mono-thionophosphate (Rp-cAMP), photoreleased GTP gamma S results in a transient and much reduced increase in the amplitude of the L-type calcium current. We conclude that activation of Gs coupled to adenylate cyclase and ultimately cAMP-dependent phosphorylation may be primarily responsible for L-type channel activation, although a fast membrane-delimited (direct) pathway, not involving cytoplasmic second messengers, may also contribute to this effect.
Reciprocal regulation by putatively nitroxidergic and adrenergic nerves of monkey and dog temporal arterial tone
Authors: Toda N. , Okamura T.
Published: December 2017

In monkey and dog superficial temporal artery strips denuded of the endothelium, transmural electrical stimulation and nicotine produced a contraction that was abolished by phentolamine and potentiated by NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthesis inhibitor. The potentiation was reversed by L-arginine but not by its D-enantiomer. The arteries treated with phentolamine and contracted with prostaglandin F2 alpha responded to the electrical stimulation and nicotine with relaxations that were abolished by tetrodotoxin and hexamethonium, respectively, and were markedly inhibited by L-NNA but not by D-NNA, atropine, and timolol. The L-NNA-induced inhibition was reversed by L-arginine. Nicotine increased the level of guanosine 3',5'-cyclic monophosphate in the monkey arteries; the increment was prevented by L-NNA. It is concluded that the monkey and dog temporal arterial tone appears to be reciprocally regulated by adrenergic vasoconstrictor and nonadrenergic noncholinergic vasodilator nerves. The neurogenic relaxation would be mediated by NO that is possibly released from the vasodilator nerve and transmits information to smooth muscle; therefore the nerve may be called "nitroxidergic."
External mechanical work during relaxation period does not affect myocardial oxygen consumption
Authors: Hata K. , Goto Y. , Suga H.
Published: December 2017

We assessed the effect of external mechanical work (EW) during the relaxation period (RP) on myocardial oxygen consumption (VO2) and clarified the energetic significance of the potential energy (PE) portion of the pressure-volume area (PVA) in the cross-circulated dog left ventricle. We changed the course of the relaxation segment of the pressure-volume (P-V) trajectory by increasing or decreasing EW within a given PVA without changing the end-diastolic volume (EDV) and the systolic segment of the P-V trajectory while measuring VO2. Thus the ventricle underwent ejection or filling during RP. Although the percent fraction of EW in PVA (%EW/PVA) was markedly increased from 32 +/- 12 (SD) to 93 +/- 3% in ejecting contractions (8 hearts) and from 0 to 93 +/- 5% in isovolumic contractions (3 hearts), these marked changes in %EW/PVA did not significantly affect VO2. Moreover, the VO2-PVA data during these procedures fell on the reference VO2-PVA relation line obtained by changing EDV and PVA of isovolumic contractions. We conclude that EW during RP at a constant PVA does not affect VO2 and part of PE can be converted into EW in an energetically equivalent manner.
Regional circulatory contributions to increased systemic vascular conductance of pregnancy
Authors: Curran-Everett D. , Morris K. G. , Moore L. G.
Published: December 2017

In pregnancy, maternal systemic vascular conductance increases, a new vascular circuit grows, and the maternal systemic circulation develops a diminished pressor response to angiotensin II (ANG II). However, the quantitative contributions of the latter two circulatory changes to the increased systemic vascular conductance of pregnancy have not been explored. In this experiment, we examined regional circulatory contributions to the increased systemic vascular conductance in conscious, late-gestation guinea pigs. Systemic arterial pressure, cardiac output (dye dilution), and regional blood flows (radiolabeled microspheres) were measured during baseline conditions and progressive ANG II infusion. Systemic and regional conductances were calculated from arterial pressure and cardiac output or regional blood flows. In pregnancy, maternal systemic vascular conductance increased from 3.2 to 5.0 ml.min-1.mmHg-1 (P less than 0.001); increased nonuteroplacental conductance contributed 71% to the increase in whole body conductance. Pregnancy tended to decrease the nonuteroplacental conductance response (P = 0.072), but did not change the uteroplacental conductance response (P greater than or equal to 0.29), to ANG II. The increased uteroplacental blood flow of pregnancy was preserved during ANG II-induced vasoconstriction. We conclude that maternal systemic vascular conductance increased primarily because nonuteroplacental vascular conductance increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationships between lymphatic pump flow and total lymph flow in the small intestine
Authors: Benoit J. N.
Published: December 2017

Response of collecting lymphatics to acute elevations in lymph formation was studied in vivo. Mesentery of 33 rats was prepared for intravital microscopic study, and indexes of lymph propulsion (contraction frequency, stroke volume, and ejection fraction) were monitored. In 14 rats, total lymph flow was measured by cannulating the main intestinal lymph trunk. After a control period, lymph flow was increased by hemodilution with isotonic saline. Right atrial pressure did not significantly increase during the hemodilution period. Total lymph flow increased to approximately 25 times control. Lymph propulsion (the product of stroke volume and contraction frequency) decreased in five lymphangions (group I). In 22 lymphangions, lymph propulsion increased one to five times control (group II). The remaining six lymphangions increased lymph propulsion by greater than five times control (group III). Group I possessed the largest end-diastolic diameter, highest baseline contraction frequency, and did not dilate as lymphatic filling increased. Group III possessed the smallest initial end-diastolic diameter and lowest baseline contraction frequency, and end-diastolic diameter doubled as lymphatic filling increased. The characteristics of group II were between those of groups I and III. Total lymph flow and lymph propulsion by group III lymphangions tended to agree when lymph flow was less than five times control. In more edematous conditions, total lymph flow exceeded lymphatic pump flow. The characteristics of group II were between those of groups I and III. Analysis of the location of various sized lymphangions within the lymphatic network indicated that the smaller group III lymphangions were located nearer the intestinal wall, and the larger group I lymphangions were nearer the outflow from the mesentery.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoxia inhibits calcium influx in rabbit basilar and carotid arteries
Authors: Pearce W. J. , Ashwal S. , Long D. M. , Cuevas J.
Published: December 2017

We examined the hypothesis that hypoxia inhibits Ca2+ influx in isolated rabbit common carotid, internal carotid, and basilar arteries. In arteries mounted for measurement of isometric tension and exposed to 122 mM K+ in Ca(2+)-free Krebs, cumulative addition of Ca2+ produced Ca(2+)-force relations that were right-shifted by hypoxia (PO2 approximately 15 Torr) with no decrease in maximum force attained. In arteries precontracted with 122 mM K+, exposure to hypoxia produced relaxations whose rates and magnitudes were enhanced by reductions in bath Ca2+ from 8.0 to 0.8 mM. Using an ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid method for 3-min 45Ca influx measurements, modified for use in rabbit basilar and carotid arteries, we found that resting levels of Ca2+ influx (mumol.min-1.kg dry wt-1) were significantly higher in basilar (67 +/- 1, n = 10) than in internal carotid (27 +/- 1, n = 12) or common carotid (33 +/- 1, n = 12) arteries. K+ stimulation increased Ca2+ influx more than two-fold compared with control in all three artery types, and hypoxia inhibited this increase by 74% in basilar, 49% in internal carotid, and 33% in common carotid arteries. Exposure to 10 microM serotonin and 100 microM uridine 5'-triphosphate (UTP) also increased Ca2+ influx, but these increases were less than observed during K+ contractions and averaged 10 (basilar), 31 (internal carotid), and 82% (common carotid) above control. Hypoxia completely inhibited serotonin- and/or UTP-induced increases in Ca2+ influx in basilar and internal carotid segments and inhibited 47% of this increase in the common carotid segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Superoxide stimulates IP3-induced Ca2+ release from vascular smooth muscle sarcoplasmic reticulum
Authors: Suzuki Y. J. , Ford G. D.
Published: December 2017

Reactive oxygen intermediates (ROI) have been implicated in a variety of pathophysiological conditions, and vascular smooth muscle may be a site of damage in such oxygen toxicity. Mechanisms of the effects of these intermediates on vascular smooth muscle at the cellular level, however, have not been well studied. We have previously shown that xanthine oxidase (XO)-generated superoxide radicals (O2-.) inhibited the Ca(2+)-adenosine triphosphatase of vascular smooth muscle sarcoplasmic reticulum (SR) through mechanisms that do not involve H2O2 or hydroxyl radicals. In the present study, we report that the D-myo-inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release from bovine aortic SR was also affected by O2-(.). Hypoxanthine (100 microM) plus XO (10 mU/ml) in the presence of catalase (100 U/ml) stimulated the IP3-induced Ca2+ release from SR monitored using arsenazo III. At 10 microM IP3, the release was doubled by O2-. treatment. As a consequence of using the higher SR protein concentrations required to observe the Ca2+ release, this effect was independent of Ca2+ uptake inhibition induced by O2-(.). Since the effect of O2-. was not seen when a nonhydrolyzable analogue of IP3 was used to induce Ca2+ release, O-2. may be inhibiting the degradation processes of IP3.
Positive end-expiratory pressure potentiates the severity of canine right ventricular ischemia-reperfusion injury
Authors: Johnston W. E. , Vinten-Johansen J. , Shugart H. E. , Santamore W. P.
Published: December 2017

Positive end-expiratory pressure (PEEP) increases right ventricular (RV) afterload and oxygen demands. However, whether increased RV oxygen demands with high levels of PEEP can potentiate the severity of RV ischemic damage is unknown. In 20 anesthetized, closed-chest dogs randomly assigned to 0 cmH2O PEEP (ZEEP; n = 10) or 15 cmH2O PEEP (PEEP; n = 10), RV blood flow (radioactive microspheres) and segmental shortening (ultrasonic crystals) were determined during 90 min ischemia and 120 min reperfusion while mean aortic pressure was maintained above 90 mmHg. The in vivo RV area at risk (gentian violet) and area of necrosis (triphenyltetrazolium chloride) were assessed. After application of 15 cmH2O PEEP, pulmonary vascular resistance increased by 75% (P less than 0.05). During ischemia, the RV rate-pressure product remained greater with PEEP (2,403 +/- 174 mmHg.beat.min-1) than with ZEEP (1,909 +/- 94 mmHg.beat.min-1; P less than 0.05), indicating higher oxygen demands with PEEP. The area at risk from ischemia relative to RV free wall tended to be greater with PEEP (68.5 +/- 2.4%) than with ZEEP (60.0 +/- 3.9%; P = 0.08), and collateral blood flow in this risk zone was significantly lower during ischemia with PEEP (9.0 +/- 1.7 ml.min-1 x 100 g-1) than with ZEEP (18.3 +/- 3.6 ml.min-1 x 100 g-1; P less than 0.05). Accordingly, PEEP extended RV necrosis in the area at risk from 21.8 +/- 5.3% (ZEEP) to 58.1 +/- 8.4% (PEEP; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Transport parameter estimation from lymph measurements and the Patlak equation
Authors: Watson P. D. , Wolf M. B.
Published: December 2017

Two methods of estimating protein transport parameters for plasma-to-lymph transport data are presented. Both use IBM-compatible computers to obtain least-squares parameters for the solvent drag reflection coefficient and the permeability-surface area product using the Patlak equation. A matrix search approach is described, and the speed and convenience of this are compared with a commercially available gradient method. The results from both of these methods were different from those of a method reported by Reed, Townsley, and Taylor [Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1037-H1041, 1989]. It is shown that the Reed et al. method contains a systematic error. It is also shown that diffusion always plays an important role for transmembrane transport at the exit end of a membrane channel under all conditions of lymph flow rate and that the statement that diffusion becomes zero at high lymph flow rate depends on a mathematical definition of diffusion.
Distribution of blood flow in normal and arthritic joints. Role of arteriovenous shunting studied in growing dogs
Authors: Stender Hansen E. , He S. Z. , Hjortdal V. E. , Kjolseth D. , Soballe K.
Published: December 2017

Juvenile dog knee with chronic carrageenin-induced arthritis was studied under general anesthesia with 15-microns and 50-microns-sized microspheres (MS) to compare the distribution of absolute and weight-standardized blood flow in normal and arthritic limbs and to localize possible sites of arteriovenous (AV) shunting. Arthritic joints had severe synovial and capsular hyperemia. Absolute as well as standardized blood flow was increased in juxta-articular epiphyses and patella. Shafts were atrophic and had decreased absolute flow but normal standardized flow. However, redistribution of blood flow occurred among regions within the shafts, e.g., in metaphyses away from growth plates. The mean nonentrapment of 15-microns MS was 13.8% in arthritic limbs and 4.2% in control limbs. The uptake of 50-microns MS was lower than that of 15-microns MS in all bony flow compartments due to differences in their rheologic behavior in larger arteries. The relative distribution of 50-microns MS and 15-microns MS varied considerably among regions within bone. Arthritis caused a net shift in the uptake of 50-microns MS relative to that of 15-microns MS from central to subchondral epiphyseal bone, evidencing precapillary vasodilation, but the relationship was strictly unchanged when bones were examined in toto. This result militates against the hypothesis of AV shunting in arthritic bone.
Permeation of divalent cations through the Ca2+ channel of rabbit portal vein myocytes
Authors: Katzka D. A. , Cox R. , Davidoff A. J. , Morad M.
Published: December 2017

The divalent selectivity of the Ca2+ channel in the rabbit portal vein myocyte was examined by the whole cell clamp method. A concentration-dependent selectivity of divalent ion permeation was found such that when Ca2+ was replaced by Ba2+ or Sr2+, the order of maximum current was Ca2+ = Ba2+ greater than Sr2+ at 2 mM and Ba2+ greater than Sr2+ greater than or equal to Ca2+ at 5-10 mM. The possibility of block of the Ca2+ channel by micromolar concentrations of "contaminant" Ca2+ as a determinant of change in the order of selectivity of divalents was examined. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (500 microM) significantly increased maximum Ba2+ current (IBa) or ISr in solution containing 5 mM Ba2+ or Sr2+. Furthermore, at 5 mM extracellular Ba2+ concentration, addition of 10, 20, 50, and 100 microM Ca2+ caused a 6, 14, 22, and 33% decrease in IBa, respectively. These results suggest that the portal vein Ca2+ channel has three orders of magnitude higher selectivity for Ca2+ over Ba2+ and Sr2+ such that micromolar Ca2+ may block permeation of other divalents through the channel.
Capillary endothelial transport of uric acid in guinea pig heart
Authors: Kroll K. , Bukowski T. R. , Schwartz L. M. , Knoepfler D. , Bassingthwaighte J. B.
Published: December 2017

Much of the adenosine formed in the heart is degraded by endothelial enzymes to uric acid, which is exported across the coronary capillary endothelial cell membrane before renal excretion. Because previous experiments suggested that cell permeability for uric acid is either very high (similar to water) or very low, multiple indicator-dilution experiments were carried out to distinguish between the two possibilities. An intravascular reference tracer, 131I-labeled albumin, and an extracellular reference tracer, L-[3H]glucose, were injected together with [14C]uric acid as a bolus into the coronary inflow, while fractionating the venous outflow for 90 s. Recovery of injected uric acid averaged 99.0 +/- 2.9% (mean +/- SD, n = 12) that of L-glucose. Peak capillary extraction of L-glucose and uric acid averaged 0.38 +/- 0.032 and 0.42 +/- 0.035 (P less than 0.005) compared with albumin. Except at the peaks, the dilution curves for [14C]uric acid and L-[3H]glucose coincided closely, indicating that little uric acid was transported into cells. The dilution curves were analyzed using an axially distributed, multipathway, four region mathematical model, to estimate membrane permeability-surface area (PS) products. Since the endothelial cell PS for uric acid was low (0.12 +/- 0.09 ml.g-1.min-1), approximately 3% of the PS reported for adenosine, the possibility of flow-limited exchange for uric acid is ruled out. To estimate steady-state endothelial concentrations of uric acid in vivo, equations were developed describing electrochemical potential gradients for dissociated and undissociated forms of a weak acid. Despite endothelial production, intracellular concentrations that are lower than outside are expected because the negative membrane potential and lower cellular pH assist uric acid efflux.
Hyaluronan flux from cat intestine: changes with lymph flow
Authors: Reed R. K. , Townsley M. I. , Laurent T. C. , Taylor A. E.
Published: December 2017

Isolated and autoperfused ileal segments from pentobarbital-anesthetized cats were used to study turnover of hyaluronan in the intestine. A postnodal lymphatic was cannulated, and transcapillary and interstitial fluid fluxes were increased by raising venous pressure. Lymph hyaluronan concentration in control averaged 20.2 +/- 18.8 (SD) micrograms/ml (range 4.6-50) and increased with increasing lymph flow in all experiments to peak at concentrations two to three times above control values (at 15-20 mmHg increase in venous pressure). At higher lymph flows, hyaluronan concentration fell to below 5 micrograms/ml to an average of 21.3 +/- 19.5% of control value at the highest venous pressures used (30-40 mmHg). Tissue hyaluronan content fell from 349 +/- 191 micrograms/g dry wt in control to 148 +/- 78 micrograms/g dry wt (P less than 0.05) at the end of the experiment. In a second group, vasodilators were administered before elevation of venous pressure to prevent redistribution of blood flow between mucosal and muscular layers. The results were similar to those obtained above. In a third experimental group, venous pressure was elevated in one step to 30 mmHg and maintained at this level. Again, hyaluronan concentration initially increased and later fell well below control values. We conclude that a major part of the intestinal hyaluronan is easily mobilized by increased interstitial fluid flux.
Effects of kwashiorkor malnutrition on measured capillary filtration rate in forearm
Authors: Richardson D. , Iputo J.
Published: December 2017

This study investigated the effects of kwashiorkor malnutrition on blood tissue fluid exchange by measuring the rate of capillary filtration (CFR) in response to a 60-mmHg increment in venous pressure in the forearms of 1- to 3-yr-old native African children within the Transkei Homeland. They were divided into the following subject groups: kwashiorkor patients (K); kwashiorkor patients who were at various stages of recovery (RK); marasmus patients (M); patients with edema of nonkwashiorkor origin (E); and control children (C). Measurements of CFR were significantly lower in the K subjects compared with any of the other groups (P less than 0.05), whereas, the RK, M, E, and C subjects were not significantly different from each other. This latter finding indicates that the lower CFR of the K patients is reversible and is not due to malnutrition or edema per se. Measurements of forearm cutaneous blood flow by laser Doppler flowmetry (LDF) in C and K subjects showed only a slightly lower value for the K patients (P greater than 0.20), and there was no relationship between CFR and LDF for either group (r = 0.073). These results suggest that the lower CFR of the K patients is not secondary to peripheral vasoconstriction.
Capillary network geometry during postnatal growth in rat hearts
Authors: Batra S. , Rakusan K.
Published: December 2017

To determine the effects of postnatal growth on the coronary microcirculation, the geometry of capillary nets was studied in male rats at 21, 28, 60, and 240 days of age. Tissue sections were exposed to a histochemical technique that distinguished arteriolar (AC) and venular (VC) capillary regions by color. The tissue area (capillary domain) surrounding individual capillaries progressively increased with growth of the heart (P less than 0.01). In all groups, AC domain area was larger than VC domain area (P less than 0.01). The heterogeneity of capillary spacing, which is another important determinant of oxygen supply, demonstrated significant increases with age for AC regions (P less than 0.01). With increasing left ventricular mass, there was a lateral expansion of the arteriovenous capillary set, which was displayed by an increase in the number of and distance between adjacent capillaries that traversed the distance from arteriole to venule (P less than 0.01). Our data indicate that differences in the geometry of arteriolar and VC regions are present by 21 days of age. During postnatal growth, the results from both cross and longitudinal sections suggest that the geometrical conditions for oxygen supply are notably reduced.
Modulatory role of EDRF in hypoxic contraction of isolated porcine pulmonary arteries
Authors: Ogata M. , Ohe M. , Katayose D. , Takishima T.
Published: December 2017

To examine the hypothesis that suppression of basal release of endothelium-derived relaxing factor (EDRF) by hypoxia might be related to the mechanism of hypoxic pulmonary vasoconstriction, rings of porcine pulmonary artery (PA, 2 mm OD) were suspended in organ chambers and changes in isometric force were measured. Hypoxia significantly reduced endothelium-dependent relaxation induced by acetylcholine and augmented contractile response to phenylephrine. This augmentation by hypoxia was not seen in rings without endothelium. Contractile response to phenylephrine was also enhanced by removal of endothelium. With 15 min of hypoxia, PA contracted and guanosine 3',5'-cyclic monophosphate content decreased. Pretreatment with 10(-6) M methylene blue, 3 x 10(-7) M oxyhemoglobin, and 9.6 x 10(-5) M NG-monomethyl-L-arginine significantly enhanced hypoxic contraction. Furthermore, removal of endothelium also enhanced hypoxic contraction. These results suggest that suppression of basally released EDRF by hypoxia was not the cause of the contractile response to hypoxia and that EDRF modulates the hypoxic contraction of porcine PA in basal conditions at this diameter.
Use of blue dextran for measuring changes in perfused vascular surface area in lungs
Authors: Roerig D. L. , Dawson C. A. , Ahlf S. B. , Bongard R. D. , Linehan J. H. , Kampine J. P.
Published: December 2017

We investigated the uptake and efflux of Blue Dextran in the isolated perfused rabbit lung. Blue Dextran is a high-molecular-weight glucose polymer (original mol wt 2 x 10(6) g/mol) containing covalently bonded Reactive Blue 2 dye (approximately mmol/g dextran). This blue dye is known for its high binding affinity to a wide variety of proteins, with a particularly high affinity for serum albumin. In isolated rabbit lungs perfused with a protein-free perfusate, both bolus injection and recirculation of Blue Dextran revealed a rapid saturable uptake. Once the lungs were loaded with Blue Dextran, efflux of the Blue Dextran accumulated in the lungs could be induced by addition of bovine serum albumin (BSA) to the recirculating perfusate. The amount of BSA-induced efflux of Blue Dextran from the lung was independent of perfusate flow. When the left pulmonary artery was ligated after the lungs had been loaded with Blue Dextran, the dye-induced BSA efflux was only about 50% of normal. Release of the ligature so that both lungs were perfused resulted in efflux of the remaining Blue Dextran. The combination of high airway pressure and low flow also reduced the dye efflux, and the effect was reversed by reducing the airway pressure. With the assumption that the high average molecular weight of Blue Dextran confines this molecule to interaction with proteins on the vascular surface, the results of this study suggest that Blue Dextran uptake and its BSA-induced efflux are proportional to the perfused vascular surface area in the lung.
Ischemically sensitive visceral afferents: importance of H+ derived from lactic acid and hypercapnia
Authors: Stahl G. L. , Longhurst J. C.
Published: December 2017

Ischemically sensitive abdominal visceral afferents reflexly stimulate the cardiovascular system. To explore the role of H+ contribution by lactic acid and hypercapnia, we recorded single-unit activity of ischemically sensitive abdominal afferents in anesthetized cats. The individual responses to sodium lactate, lactic acid, and hypercapnia then were examined. Abdominal ischemia significantly decreased organ tissue pH from an average of 7.21 +/- 0.03-7.05 +/- 0.03 (P less than 0.05), during which impulse activity of 13 A delta- and 32 C-fibers significantly increased. Although hypercapnia (12% CO2) induced a similar decrease in tissue pH, impulse frequency increased in 0 of 4 A delta- and only 2 of 13 C-fibers. In contrast, lactic acid decreased tissue pH significantly less than ischemia or hypercapnia but increased impulse activity in 7 of 10 A delta- and 11 of 12 C-fibers. Conversely, only 1 of 3 A delta- and 0 of 10 C-fibers responded to sodium lactate. Thus ischemically sensitive visceral afferents respond to the H+ derived from lactic acid rather than hypercapnia. However, these afferents do not respond to sodium lactate. These data suggest that ischemically sensitive abdominal visceral afferents are responsive specifically to lactic acid rather than to the dissociated ions lactate or H+ or to changes in PCO2.
Comparison of responses to sarafotoxins 6a and 6c in pulmonary and systemic vascular beds
Authors: Minkes R. K. , Bellan J. A. , Higuera T. R. , Kadowitz P. J.
Published: December 2017

Cardiovascular and pulmonary responses to sarafotoxin (S) 6a and S6c were investigated in the anesthetized cat. Intravenous injections of the peptides in doses of 0.1-1.0 nmol/kg caused decreases or biphasic changes in arterial pressure (AP) and increases in central venous pressure, pulmonary arterial pressure (PAP), and cardiac output (CO). Secondary decreases in CO were observed in response to higher doses, and biphasic changes in systemic (SVR) and pulmonary (PVR) vascular resistances were observed. Under constant-flow conditions, the peptides only increased pulmonary lobar arterial perfusion pressure and lobar vascular resistance. AP responses to S6a, S6c, endothelin (ET)-1, ET-2, vasoactive intestinal contractor (VIC), and Lys7-ET-1 were similar, whereas AP responses to S6b and ET-3 were similar. S6a, S6b, S6c, ET-1, ET-2, ET-3, VIC, Lys7-ET-1, and big ET-1 increased PAP. S6a and S6c increased distal aortic and superior mesenteric arterial (SMA) blood flow and caused biphasic changes at the highest doses. Under constant-flow conditions, S6a and S6c produced dose-dependent biphasic changes in hindquarters perfusion pressure. Changes in SVR and PVR in response to the peptide were not affected by hexamethonium, glyburide, or meclofenamate, indicating that responses are independent of autonomic reflexes, activation of ATP-regulated K+ channels, or release of cyclooxygenase products. In contrast, N-nitro-L-arginine methyl ester decreased hindquarters vasodilator response to S6a and S6c. The present data show that S6a and S6c produce both vasodilation and vasoconstriction in the systemic vascular bed and increase lobar vascular resistance and that hindquarters vasodilator responses are mediated, in part, by the release of endothelium-derived relaxing factor.
Minimal compartmental model of circulatory mixing of indocyanine green
Authors: Henthorn T. K. , Avram M. J. , Krejcie T. C. , Shanks C. A. , Asada A. , Kaczynski D. A.
Published: December 2017

A model of indocyanine green (ICG) disposition from the moment of its injection in blood was developed. ICG disposition was characterized in five dogs deeply anesthetized with halothane, which decreased cardiac output and prolonged intravascular mixing. After ICG injection into the right atrium, femoral arterial blood samples were collected every 3 s for the 1st min and less frequently to 20 min. ICG concentrations were measured by high-performance liquid chromatography and modeled with SAAM 30.1. A fully identifiable recirculatory compartmental model with time delays was used to describe ICG disposition. The central blood volume averaged 23.4 ml/kg, and total blood volume averaged 78.9 ml/kg. Fifty-three percent of the cardiac output flowed through 14% of the peripheral blood volume while the remaining 47% flowed through 86% of the peripheral volume. This new model is isomorphic with a parallel channel, lumped-parameter circulation model and provides more information than stochastic, noncompartmental recirculatory pharmacokinetic techniques. This intravascular mixing model can be applied to determine the contribution of the circulation to drug distribution.
Effect of perfusion pressure at reoxygenation on reflow and function in isolated rat hearts
Authors: Seiler K. S. , Kehrer J. P. , Starnes J. W.
Published: December 2017

The effect of coronary perfusion pressure during reoxygenation on recovery of endocardial flow, arrhythmogenesis, and mechanical function was investigated in the isolated rat heart. Hearts were subjected to 30 min of substrate-free hypoxia followed by 30 min reoxygenation at either 80 or 150 cmH2O perfusion pressure. No flow areas were quantified by 0.3% phthalocyanine blue injection after 30 min of hypoxia, 30 min reoxygenation at 80 cmH2O, or 30 min reoxygenation at 150 cmH2O. After hypoxia, 31 +/- 2% of the myocardium was unperfused. After 80 cmH2O reoxygenation, 13 +/- 4% of the heart remained unperfused. Ten of 12 (83%) 80-cmH2O hearts were in sustained fibrillation after 10 min of reoxygenation. Reoxygenation at 150 cmH2O resulted in complete reperfusion of the myocardium. Fibrillation was absent in all hearts reoxygenated at this higher pressure. Functional recovery after 30 min reoxygenation (% of normoxic heart rate x left ventricular developed pressure) was significantly (P less than 0.05) higher in 150 cmH2O vs. 80 cmH2O (60 +/- 5 vs. 42 +/- 8%). Elevating perfusion pressure upon reoxygenation appears to counter the vascular compression caused by contracture and leads to a more rapid and homogeneous restoration of coronary flow during the transition from the hypoxic to the normoxic state.
Adenosine formation and energy status in isolated guinea pig hearts perfused with erythrocytes
Authors: Ning X. H. , He M. X. , Gorman M. W. , Romig G. D. , Sparks H. V.
Published: December 2017

The purpose of this study was to examine adenosine release and high-energy phosphate concentrations during norepinephrine (NE) infusion in isolated guinea pig hearts perfused with a physiological salt solution (PSS) containing erythrocytes (RBC). Phosphate concentrations were monitored using 31P-nuclear magnetic resonance spectroscopy while NE was infused at 6 x 10(-10) mol/min. Compared with perfusion with PSS alone, RBC-perfused hearts consumed more oxygen and developed higher left ventricular pressure and first time derivative of left ventricular pressure at lower coronary flow rates. Adenosine release rates were very similar with both perfusates. NE infusion did not produce a decline in ATP concentration ([ATP]) or an increase in calculated [ADP] and [AMP] in RBC-perfused hearts. However, phosphorylation potential ([ATP]/[ADP][Pi]) declined because of increased [Pi]. We conclude that NE infusion does not change adenine nucleotide concentrations in well-oxygenated guinea pig hearts and that changes in nucleotide concentrations are not necessary for increased adenosine release. Phosphorylation potential is a better predictor of adenosine release than any individual nucleotide or phosphate concentration.
Perceived vessel lumen and cell-blood velocity ratio: impact on in vivo blood flow rate determination
Authors: Cokelet G. R. , Sarelius I. H.
Published: December 2017

Microscopic images of blood flow through individual capillary segments and divergent capillary bifurcations in cremaster muscle of golden hamster were videotaped, and the data from the videotapes (projected vessel image width and individual red cell velocities) were used in two ways to evaluate blood flow rate. The first method assumes 1) that the vessel lumen is circular with a diameter equal to the projected image width and 2) that the blood average velocity is proportional to the average red cell velocity. The second method makes neither of these assumptions but relies only on the principle of mass conservation. It is demonstrated that the two assumptions of the first method can lead to significant errors in hemodynamic relationships deduced from in vivo data. Although the second method cannot independently give absolute values of average velocity at one vessel location, it can give absolute values of the ratio of blood flow rates through two (or more) vascular lumina.
Cardiac instability amplified by use-dependent Na channel blockade
Authors: Starmer C. F. , Lancaster A. R. , Lastra A. A. , Grant A. O.
Published: December 2017

Drugs that exhibit use-dependent Na channel blockade, including antiarrhythmic agents, tricyclic antidepressants, opiate-like analgesics, and cocaine, are linked with an increased susceptibility to cardiac arrhythmias and sudden death. Computer simulations indicate that Na channel blockade retards recovery of excitability, thereby increasing the spatial dispersion of refractoriness, a precursor of many cardiac arrhythmias. In isolated rabbit left atria, stimuli timed to occur at increasing intervals following conditioning stimuli reveal an unstable interval (vulnerable period) during which single stimuli initiate trains of responses. The vulnerable period is extended by use-dependent Na channel blockade and provides a model for assaying proarrhythmic potential and probing cardiac instability.