bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental changes in regional cerebral blood flow in fetal and newborn lambs
Authors: Szymonowicz W. , Walker A. M. , Cussen L. , Cannata J. , Yu V. Y.
Published: December 2017

Developmental changes in regional cerebral blood flow (CBF) were determined using radioactively labeled microspheres to measure flow to the cortex, brain stem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs under physiological conditions: 90- to 100-day preterm fetal lambs (n = 14), 125- to 136-day near-term fetal lambs (n = 11), and newborn lambs 5-44 days old (n = 10). We continually monitored heart rate, central venous pressure, and mean arterial blood pressure (MAP) and periodically measured arterial blood O2 and CO2 tensions (PaO2, PaCO2, respectively), pH, hemoglobin, and oxygen saturation (SaO2). The regional CBF measurements (ml.100 g-1.min-1) revealed that in all three age groups the high flow areas are the choroid plexus and caudate nucleus, whereas the lowest flow area is the white matter. There is, however, a different hierarchy of regional CBF in utero (cortex less than cerebellum and brain stem) compared with extrauterine life in the newborn lamb (cortex and cerebellum greater than brain stem). Analysis of regional cerebral oxygen delivery [CBF times arterial oxygen content (CaO2)] demonstrated a progressively increasing oxygen transport to the cortex with increasing gestational maturity and after birth. Oxygen transport to the brain stem, cerebellum, and white matter increased with gestational age, but did not increase after birth. Relationships between regional CBF and natural physiological variations of cardiorespiratory parameters (PaO2, SaO2, CaO2, pH, PaCO2, and MAP) were assessed using regression analysis. Correlations of regional CBF with PaO2 and SaO2 suggest that cerebral perfusion is not primarily determined by CaO2 when variations occur within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS)
Contractile properties of single isolated feline ventriculocytes
Authors: Duthinh V. , Houser S. R.
Published: December 2017

Isolated single cardiac myocytes are becoming an increasingly popular experimental preparation. To date, however, the mechanical properties of these isolated adult mammalian cardiac myocyte preparations have not been thoroughly evaluated. The aims of this research were to 1) define the basic contractile properties of externally unloaded single feline ventriculocytes, 2) determine their response to standard inotropic stimuli, and 3) determine whether contractile properties vary as a function of cell size. Cell contractions were elicited by field stimulation (1 Hz) and recorded with the use of a photodiode array technique. In the 121 myocytes studied (2 mM Ca2+; 37 degrees C) the maximum extent of shortening averaged 7.5 +/- 0.2% resting cell length (L). The maximum rates of shortening and relengthening were 92 +/- 2.7 and 103 +/- 2.0% L/s, respectively. Elevating the extracellular Ca2+ and paired pulse stimulation increased the magnitude of twitch contractions as well as the rates of shortening and relengthening. The relationship between cell size and contractile performance was assessed in this research either by comparing the contractile properties of large and small myocytes or by plotting specific contractile parameters as a function of myocyte surface area. The results of this research support the idea that single feline ventricular myocytes retain normal contractile capabilities following isolation and respond to inotropic maneuvers in a similar fashion to that observed in multicellular preparations. In addition the present experiments showed that the contractile properties of the myocytes isolated from normal feline hearts are not cell size dependent.
Vasomotion in cerebral microcirculation of awake rabbits
Authors: Hundley W. G. , Renaldo G. J. , Levasseur J. E. , Kontos H. A.
Published: December 2017

Cerebral arterioles of unanesthetized rabbits equipped with chronically implanted cranial windows exhibited spontaneous rhythmic variation in vessel caliber characteristic of vasomotion. This variation was noted in all examined vessels. The vasomotion was independent of arterial blood pressure or respiration. The average frequency was 0.74 cycles/min and was independent of vessel size. The mean amplitude of the oscillations had a statistically significant inverse relationship to vessel diameter (r = 0.69). Vasodilation induced by arterial hypercapnia, topical adenosine, or topical acetylcholine had no significant effect on the frequency or amplitude of vasomotion. Anesthesia significantly reduced the frequency in arterioles of all sizes and markedly reduced amplitude in large arterioles. Topical verapamil resulted in a statistically significant reduction in frequency and in peak amplitude. Variations in vessel diameter occurred simultaneously in arterioles and their companion venules. We conclude that the cerebral microcirculation displays active vasomotion, which is significantly depressed by anesthesia or topical verapamil. The results also suggest that vasomotion is probably controlled by local factors.
Estimates of left ventricular interstitial fluid adenosine during catecholamine stimulation
Authors: Gidday J. M. , Hill H. E. , Rubio R. , Berne R. M.
Published: December 2017

The hypothesis that changes in myocardial interstitial fluid (ISF) adenosine (Ado) concentrations couple coronary blood flow (CBF) with myocardial oxygen need is still controversial. Measurements of Ado in cardiac tissue, coronary sinus plasma, and pericardial infusates have commonly been used as indexes of ISF Ado, but recent studies have highlighted the potential invalidity of many of the assumptions underlying these sampling methods. With the use of an epicardial chamber (EC) to contain a small volume of buffer on the undisturbed left ventricular epicardium of anesthetized open-chest dogs, estimates of ISF Ado can be obtained without invoking these assumptions. In experiments designed to validate our method and investigate the role of Ado in the regulation of CBF during myocardial catecholamine stimulation, we found that endogenous Ado accumulated in the EC exponentially and attained constant steady-state concentrations, ranging from 75 to 125 nM, within 4 min. Intravenous infusions of two catecholamines increased steady-state EC Ado concentrations twofold, but did not affect Ado influx kinetics. We conclude that the EC technique yields more direct estimates of steady-state ISF Ado concentrations than previously available and that ISF Ado is involved in the mediation of the hyperemia accompanying myocardial catecholamine stimulation.
Release of adenosine from pig aortic endothelial cells during hypoxia and metabolic inhibition
Authors: Shryock J. C. , Rubio R. , Berne R. M.
Published: December 2017

The purpose of this study was to determine the effects of acute hypoxia on the ATP content of, and release of adenosine from, cultured endothelial cells. Pig aortic endothelial cells grown on plastic dishes or on microcarrier beads were incubated in physiological saline and gassed to achieve normoxia (media PO2 = 80-85 mmHg) or hypoxia (media PO2 = 2-12 mmHg) in the presence and absence of glucose and dipyridamole. Acute hypoxia did not significantly augment adenosine release from cells but did appear to decrease the reuptake of adenosine by cells. Hypoxia of a longer duration (3 h) led to ATP degradation and increased adenosine release when glucose was absent from the incubating medium, but not otherwise. Similarly, incubation of cells with NaCN in a glucose-free medium led to an increase in extracellular adenosine accumulation, whereas NaCN in the presence of glucose did not increase the accumulation of adenosine above the control level. The results suggest that the adenine nucleotide metabolism of cultured endothelial cells is not acutely sensitive to hypoxia or to inhibition of oxidative metabolism and can be maintained by glycolysis.
Osmolality-mediated Fahraeus and Fahraeus-Lindqvist effects for human RBC suspensions
Authors: McKay C. B. , Meiselman H. J.
Published: December 2017

The effects of suspending medium osmolality (166 to 836 mosm/kg) on flow in narrow bore tubes (33- to 146-microns diameter) were studied for 40% hematocrit suspensions of human red blood cells (RBC) in buffer; concurrent measurements of viscosity (eta r) and tube hematocrit (HT) allowed evaluation of the Fahraeus-Lindqvist effect (FLE) and Fahraeus effect (FE). The FLE and FE were present for all suspensions regardless of osmolality. Viscosity increased markedly for the hypertonic media, and the FLE was more pronounced for the hypertonic region; changes in eta r from 146 to 33 microns were -22% (220 mosm/kg), -34% (290 mosm/kg), and -45% (460 mosm/kg). In contrast, HT and hence the FE were relatively insensitive to osmolality (14% change over entire range of osmolality and diameter). Suspension viscosities in 33- and 146-microns tubes could not, in general, be accurately calculated using experimental HT values combined with eta r -HT data from 340-microns tubes; however, a semiempirical model indicated that 1) RBC number concentration in the tube and tube diameter per RBC volume are primary determinants of eta r, and 2) eta r can be predicted over a wide range of osmolalities and tube diameters. RBC transport efficiency was a function of both tube diameter and osmolality (maximum for 33 micron at approximately equal to 400 mosm/kg). Our results appear applicable to blood flow in nonisotonic regions of the circulation and to estimation of blood viscosity in microcirculatory vessels.
Complement is not involved in monocrotaline pyrrole-induced pulmonary injury
Authors: Bruner L. H. , Johnson K. J. , Till G. O. , Roth R. A.
Published: December 2017

Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury, pulmonary hypertension, and right ventricular hypertrophy in rats. The mechanisms by which MCTP causes lung injury are not known. After treatment with a moderate dose of MCTP, several days pass before major lung injury is detected, thus suggesting that the damage is caused indirectly. Since activation of the complement system can cause lung injury, it was of interest to test whether complement activation may be important in lung injury due to MCTP. Accordingly, rats were given a single dose of MCTP (3.5 mg/kg iv), and serum hemolytic complement activity was measured at several times after rats were treated. Neutrophil aggregometry also was used to determine whether complement activation products could be detected in serum after MCTP was given in vivo. The effect of complement depletion on MCTP-induced pulmonary injury was tested by cotreating rats with purified cobra venom factor and MCTP. MCTP treatment did not cause detectable complement activation in vivo, and complement depletion did not protect rats from lung injury. The direct effect of MCTP on serum complement also was tested by exposing fresh rat serum to MCTP in vitro and measuring serum complement activity. MCTP decreased serum hemolytic complement activity in vitro, but it did not interfere with subsequent zymosan-induced activation of complement. These results suggest that complement does not play a role in the development of major lung injury that occurs several days after treatment of rats with MCTP.
Matching between feline left ventricle and arterial load: optimal external power or efficiency
Authors: Toorop G. P. , Van den Horn G. J. , Elzinga G. , Westerhof N.
Published: December 2017

We tested the hypothesis that the feline left ventricle normally works at optimal external power as opposed to optimal efficiency by (re)analyzing data from five isolated, blood-perfused cat hearts and 39 open-thorax cats. In the isolated hearts, we measured pump function, external steady power, myocardial oxygen consumption, and efficiency. Optimal external power and optimal efficiency were found at different left ventricular outputs (6.94 +/- 0.33 and 8.35 +/- 0.37 ml/s, respectively; P less than 0.001). In the in situ cat hearts the working point was found at an output of 4.72 +/- 0.32 ml/s, whereas optimal external power was found at 4.84 +/- 0.26 ml/s. These values were not significantly different. Assuming that the point of optimal efficiency was located at the same fraction of the maximal unloaded left ventricular output (Fmax) as in the isolated hearts, i.e., 0.7, we found the point of optimal efficiency for the in situ heart at a flow of 5.83 +/- 0.32 ml/s, which was significantly different (P less than 0.001) from the flow in the working point. Our data therefore indicate that the left ventricle in the open-thorax cat is matched to the arterial load such that its external power output rather than efficiency is optimized.
Single capillary permeability to proteins having similar size but different charge
Authors: Adamson R. H. , Huxley V. H. , Curry F. E.
Published: December 2017

We investigated the hypothesis that solute charge modulates transcapillary exchange in microvessels with continuous endothelium. Two globular proteins, alpha-lactalbumin and ribonuclease, having approximately the same size (mol wt 14,176 and 13,683, respectively) but different net charge (-10 and +4, respectively) were test solutes. Each solute was labeled with the fluorescent probe tetramethylrhodamine isothiocyanate. Labeling did not significantly change solute size, but increased negative charge on each solute by one valency unit. An in vivo fluorescent microscope technique [Huxley et. al., Am. J. Physiol. 252 (Heart Circ. Physiol. 21): H188-H197, 1987] was used to measure solute permeability coefficients (P) in single microvessels of frog mesentery at 14-16 degrees C. The mean P for alpha-lactalbumin, measured when capillary pressure was 10 cmH2O, was 2.1 X 10(-6) cm/s and the mean P for ribonuclease was 4.3 X 10(-6) cm/s. Our results conform to the hypothesis that the transcapillary pathways of frog mesenteric microvessels are negatively charged. With the use of a Donnan-type model for electrostatic partitioning, charge density in the pathway is estimated as 11.4 meq/l. Comparison of measured Ps with those for small solutes in frog mesenteric microvessels indicates that molecular size is a proportionally more significant determinant of solute permeability in continuous capillaries than is solute charge.
O2 modulation of single-vessel hydraulic conductance
Authors: Tucker V. L. , Huxley V. H.
Published: December 2017

To investigate the response of the microvascular endothelial barrier to O2 lack, hydraulic conductivities (Lp) were compared under control and hypoxic conditions. In 29 decerebrate frogs (Rana pipiens) the mesentery was exposed and continuously superfused with room air-equilibrated frog Ringer (14 degrees C, pH 7.4). Single mesenteric microvessels (15- to 50-microm diam) were cannulated and perfused with frog Ringer containing 5-40 mg/ml bovine serum albumin and 5-10% (vol/vol) human erythrocytes. The modified Landis technique was used to measure transmural water flux per unit area (Jv/S) from marker red cell movement at pressures ranging from 15 to 45 cmH2O. In 21 vessels, a 10-min superfusion with 100% N2-equilibrated Ringer increased Lp 2.4-fold (+/- 0.72 SD) over control (P less than or equal to 0.05). In an additional six vessels, simultaneous exposure to 100% N2-equilibrated perfusate and superfusate resulted in a 10-fold (+/- 3.0) increase in Lp (P less than or equal to 0.05). In 15 of the vessels, a 10- to 75-min reexposure to control conditions decreased Lp, averaging a 77% recovery toward base line. These data support an active role for O2 in the regulation of microvascular membrane permeability, which appears to be sensitive to the severity of O2 lack. The rapid increase in capillary water conductivity following exposure to hypoxic conditions may be the initial process in the events leading to edema formation.
Aortic pressure reduction redistributes transmural blood flow in dog left ventricle
Authors: Smolich J. J. , Weissberg P. L. , Broughton A. , Korner P. I.
Published: December 2017

We studied the effect of graded aortic blood pressure reduction on left ventricular (LV) blood flow in anesthetized, autonomically blocked, open-chest dogs at constant heart rate and mean left atrial pressure. Aortic diastolic pressure (ADP) was lowered from rest (average 116 mmHg) to 90, 75, and 60 mmHg with an arteriovenous fistula. Global and regional LV blood flow was measured with radioactive microspheres. Mean LV blood flow fell stepwise from 145 ml.min-1.100 g-1 at rest to 116 ml.min-1.100 g-1 at ADP of 60 mmHg, whereas the endocardial-to-epicardial flow ratio decreased from 1.20 to 0.84. The transmural redistribution of LV blood flow was not accompanied by increases in LV oxygen extraction, depression of LV contractility, LV dilatation or LV electrical dysfunction and also occurred in the presence of considerable coronary vasodilator flow reserve. Electrical evidence of subendocardial ischemia appeared at ADP of 32 mmHg and an endocardial-to-epicardial flow ratio of 0.41 in a subgroup of animals. We conclude that the redistribution of LV flow during moderate aortic pressure reduction was an appropriate physiological adjustment to uneven transmural alterations in regional LV wall stress and that it preceded a more pronounced redistribution evident with myocardial ischemia.
Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats
Authors: Bertinieri G. , Di Rienzo M. , Cavallazzi A. , Ferrari A. U. , Pedotti A. , Mancia G.
Published: December 2017

The arterial baroreceptor control of the sinus node operating in unanesthetized conditions was evaluated in 10 cats in which blood pressure was recorded intra-arterially and scanned by a computer to identify the "spontaneous" sequences of three or more consecutive beats in which systolic blood pressure (SBP) progressively rose and pulse interval (PI) progressively lengthened (type 1 sequences) or SBP progressively fell and PI progressively shortened (type 2 sequences). Many type 1 and 2 three-beat sequences were found; four-, five-, and six-beat sequences of either type were progressively less common, and sequences longer than six beats were almost never identified. The regression coefficient was 30% greater for type 1 than for type 2 sequences. However a prominent feature of either regression coefficient was a wide scattering in each cat (average variation coefficient 50.9 +/- 5.5%). The regression coefficient values were related to some extent to the PI but not to the SBP existing at the beginning of the sequence. Sinoaortic denervation dramatically reduced the number of sequences of either type. These data validate a method for collecting a large number of observations on the baroreceptor-heart rate reflex in physiological conditions. This method may improve understanding of baroreflex involvement in integrated cardiovascular regulation.
Distensibility of hepatic venous resistance sites and consequences on portal pressure
Authors: Greenway C. V. , Lautt W. W.
Published: December 2017

Hepatic venous resistance was measured in cats anesthetized with pentobarbital sodium during changes in hepatic blood flow and in inferior vena cava (IVC) pressure, in an attempt to explain the variable and partial transmission of pressure from IVC to portal vein. Problems with earlier explanations based on a "vascular waterfall" or a "Starling resistor" are discussed. Our data and previously published data can be explained by the hypothesis that hepatic venous resistance decreases as the resistance site is distended by the pressure within the resistance vessels. The product of resistance and distending pressure was a constant. This constant equals the resistance at unit-distending pressure, and it is an index of active contraction of the resistance sites in acute experiments. It is increased during infusions of norepinephrine, and it is higher in innervated than in denervated livers. A distensible hepatic venous resistance is a passive mechanism for partial autoregulation of portal pressure. It also serves as a mechanism for regulation of the splanchnic capacitance response to changes in IVC pressure.
Effects of dietary fish oil on cardiac responsiveness to adrenoceptor stimulation
Authors: Reibel D. K. , Holahan M. A. , Hock C. E.
Published: December 2017

The effect of dietary fish oil on cardiac function and responsiveness to alpha- and beta-adrenergic receptor agonists was examined in isolated perfused rat hearts. Rats were fed either a standard laboratory diet (SD) or diets containing 5% corn oil (CO) or 5% menhaden oil (MO) for 4 wk. When perfused as working preparations at varying preloads and afterloads, the peak aortic pressures, aortic outputs, and coronary flows were comparable in hearts of rats fed the three experimental diets. Inotropic responsiveness to phenylephrine was examined by infusing graded doses of the drug into the heart while monitoring changes in the rate of left ventricular pressure development (+dP/dt). Prior to phenylephrine administration +dP/dt was not different among the three groups of hearts. However, at each dose of phenylephrine employed, delta +dP/dt was approximately 50% less in hearts of rats fed MO when compared with either SD or CO. Thus cardiac inotropic responsiveness to this alpha-agonist was reduced by dietary fish oil. In contrast, cardiac inotropic responsiveness to isoproterenol was not altered with MO feeding. The data demonstrate that dietary fish oil results in alterations in alpha- but not beta-adrenoceptor mediated changes in cardiac inotropy.
Development of pulmonary vascular response to oxygen
Authors: Morin F. C. , Egan E. A. , Ferguson W. , Lundgren C. E.
Published: December 2017

The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs (132 to 146 days of gestation), fetal arterial oxygen tension (PaO2) increased from 25 +/- 1 to 55 +/- 6 Torr (mean +/- SE), which increased the proportion of right ventricular output distributed to the fetal lungs from 8 +/- 1 to 59 +/- 5%. In five very immature lambs (94 to 101 days of gestation), fetal PaO2 increased from 27 +/- 1 to 174 +/- 70 Torr, but the proportion of right ventricular output distributed to the lung did not change, 8 +/- 1 to 9 +/- 1%. In five of the near-term lambs, pulmonary blood flow was measured. It increased from 34 +/- 3 to 298 +/- 35 ml.kg fetal wt-1.min-1, an 8.8-fold increase. We conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth.
Response of hypertensive rats to acute and chronic conditions of static exercise
Authors: Tipton C. M. , McMahon S. , Youmans E. M. , Overton J. M. , Edwards J. G. , Pepin E. B. , Lauber C.
Published: December 2017

To determine whether chronic static exercise would alter resting caudal artery systolic blood pressure (RSBP) in stroke-prone hypertensive rats (SP-SHR), a 20- to 21-wk experimental study was initiated with 24 male and 16 female rats. In addition, eight rats were cannulated for heart rate and blood pressure measurements and implemented with Doppler flow probes (mesenteric and iliac arteries) for determination of the acute responses. The rats were trained to perform static exercise by forelimb hanging over an electrical grid (3-5 mA) activated with a high-frequency sound (2.5-10kHz) of 60 dB. Acute forelimb hanging by nontrained rats caused a 70-mmHg elevation in mean blood pressure, 115-beat/min increase in heart rate, and 71% decrease in mesenteric blood flow. The procedure for chronic forelimb hanging included increasing the number of sets per session from one to three, maintaining the number of repetitions between 6 and 10 and the hang time within 7-10 s/hang, while increasing the amount of weight supported per set from 0 to 12% of body weights for males and 30% for females. Two performance tests, one for endurance (no weights) and one for "strength" (weights), demonstrated that the hanging animals increased their endurance ability by 103% and their strength by 115%. RSBP was not significantly increased in either the male or female trained populations when evaluated by analysis of variance or trend-analysis procedures. Food and water consumption, sodium and potassium excretion, and blood volume measurements exhibited no group differences that had statistical significance. Five animals had evidence for previous strokes, with four being associated with the nonhanging animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Beta-adrenergic control of resistance in individual vessels in rabbit tenuissimus muscle
Authors: Borgstrom P. , Lindbom L. , Arfors K. E. , Intaglietta M.
Published: December 2017

The microvascular responses to topically applied isoproterenol and to epinephrine in the intact and beta-adrenoceptor-blocked microcirculation were studied in the rabbit tenuissimus muscle by direct intravital microscopy. The main feeding arterioles in this muscle supply two vascular areas, the muscle capillaries and the adjacent connective tissue. beta-Adrenergic stimulation with isoproterenol and epinephrine dilated the transverse arterioles that supply muscle and connective tissues, whereas their first-order side branches (terminal arterioles), which only supply the muscle capillaries, were little affected. Flow measurements were made at two different sites in the transverse arterioles to determine the relative changes in muscle capillary flow and connective tissue flow. These measurements showed that beta-adrenergic stimulation caused a fractional redistribution of microvascular blood flow from the muscle tissue proper to the adjacent connective tissue.
Adrenergic and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs
Authors: Armstead W. M. , Leffler C. W. , Busija D. W. , Beasley D. G. , Mirro R.
Published: December 2017

The interaction between adrenergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious, hypotensive newborn pig was investigated. Pretreatment with the selective alpha 1- and alpha 2-adrenoceptor antagonists prazosin and yohimbine, respectively, had no effect on cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or after hemorrhagic hypotension. Indomethacin treatment (5 mg/kg ia) of piglets following hemorrhage caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 54 and 177%, 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.42 +/- 0.28 to 1.45 +/- 0.28 ml.100 g-1.min-1 and to 1.0 +/- 0.28 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were the same as in animals pretreated with vehicle, prazosin, or yohimbine. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn, as reported previously. These data do not implicate removal of sympathetic modulation by prostanoids as a mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.
Vasoconstriction is amplified by autoregulation during vasoconstrictor-induced hypertension
Authors: Meininger G. A. , Trzeciakowski J. P.
Published: December 2017

This study investigated the degree to which autoregulation of blood flow interacts with vasoconstrictors to determine vascular resistance. Anesthetized rats were instrumented with a Doppler flow probe on the superior mesenteric artery (SMA) to measure blood flow and for calculation of vascular resistance. An adjustable occluder was placed on the SMA to set local perfusion pressure at values independent of mean arterial pressure (MAP) even when MAP was increased by the vasoconstrictors. Infusion of angiotensin II (ANG II, 50-1,247 ng.kg-1.min-1) produced a dose-dependent rightward shift in the intestinal pressure-flow relationship and elevated MAP from 85 to 127 mmHg. Low doses of phenylephrine (PE, 2.5-12.4 micrograms.kg-1.min-1) failed to shift the pressure-flow curve but did increase arterial pressure from 83 to 102 mmHg. At higher doses (25-62 micrograms.kg-1.min-1), PE also shifted the pressure-flow curve to the right. Maintaining local perfusion pressure at different values during the infusion of ANG II or PE produced a family of dose-response curves, with each exhibiting a different maximum change in resistance. When local pressure was permitted to increase with MAP, the composite dose-response curve for resistance that was obtained reflected the influence of the rise in local pressure (i.e., auto-regulation) and vasoconstrictor dose. At low doses of PE the increase in vascular resistance was attributable solely to an autoregulatory response related to the rise in MAP and not due to the constrictor effects of PE. Thus these data indicate that the rise in MAP accompanying systemic infusion of a vasoconstrictor stimulates autoregulation to amplify the local increase in vascular resistance.
Effect of nitroglycerin on myocardial collateral conductance in awake dogs
Authors: Brazzamano S. , Rembert J. C. , Greenfield J. C.
Published: December 2017

Conductance of the coronary collateral circulation during the course of two abrupt circumflex coronary occlusions (pre- and posttreatment with nitroglycerin) was measured in awake dogs approximately 2 wk after collateral vessels were stimulated to develop. The pressure gradient from the central aorta to the distal circumflex coronary artery was measured, and myocardial blood flow was determined by 9-microns radioactive microspheres at 30 s and 4 min after coronary occlusions. Collateral conductance was calculated as mean collateral blood flow divided by the mean aorta-coronary pressure gradient. Before nitroglycerin, collateral conductance increased in all eight dogs from 30 s to 4 min by a mean value of 0.006 +/- 0.003 ml.min-1.g-1.mmHg-1. After nitroglycerin administration, the conductance at 30 s increased from the prenitroglycerin control value of 0.009 +/- 0.008 to 0.014 +/- 0.012 ml.min-1.g-1.mmHg-1, P less than 0.03. The mean change in conductance from 30 s to 4 min postnitroglycerin 0.003 +/- 0.003 ml.min-1.g-1.mmHg-1 was significantly less than during prenitroglycerin (P = 0.01). These data indicate that an increase in conductance during coronary occlusion occurs even in the immature collateral circulation. This effect presumably takes place in the arterial smooth muscle at the origin of the collateral vasculature.
Intra- and extracellular markers in interstitial transudate of perfused rat hearts
Authors: Wienen W. , Kammermeier H.
Published: December 2017

The interstitial transudate was investigated in isolated perfused rat hearts. Capillary permeability and the kinetics of interstitial uptake and release were characterized using four different marker molecules (mol wt 522 to 2 X 10(6)). The half-time (t1/2) values (less than 30 to 170 s) and the interstitial concentration after 30 min (100-44% of arterial concentration) reflected the order and inverse order of their molecular weights, respectively. Creatine kinase (CK) and glutathione (GSH) were measured during control state, hypoxia, and anoxia, followed by reoxygenation. Interstitial concentrations of CK and GSH were higher by a factor of 100 and 8, respectively, compared with the venous effluent. During hypoxia (PO2 = 110 mmHg, i.e., O2 supply = 30% of demand) and reoxygenation there was a significant increase only in the interstitial (not venous) release of CK and GSH, which was further increased during anoxia. Ischemia (75 min) and reperfusion cause no interstitial release of lysosomal (acid phosphatase) and mitochondrial (glutamate dehydrogenase) enzymes despite a massive loss of cytosolic enzymes. Examination of the interstitial transudate allows characterization of capillary transfer and provides a very sensitive measure of sarcolemmal release phenomena.
Piezoelectric polymer curvature sensor for measurement of regional curvature radius of LV wall
Authors: Tsujioka K. , Ogasawara Y. , Mito K. , Hiramatsu O. , Wada Y. , Goto M. , Matsuoka S. , Kagiyama M. , Kajiya F.
Published: December 2017

To evaluate regional myocardial function, we developed a curvature sensor for direct and instantaneous measurement of the regional curvature radius of the LV wall. The sensor is a bimorph of two sheets of thin piezoelectric polymer film. The relation between output voltage of the sensor and the reciprocal of the known curvature radius has been shown to be linear. In anesthetized dogs, we inserted the curvature sensor into the subepimyocardium with a specially designed introducer. Special care was taken to insert it parallel to the epicardial surface. Circumferential regional curvature radius, which is defined as the reciprocal of regional curvature, showed the same phasic changes as the short-axis diameter under control conditions. Under regional ischemia caused by transient occlusion of the coronary artery, amplitude of the phasic change in regional curvature radius decreased, whereas that of the short-axis diameter did not change or slightly increased. Phasic changes in regional curvature radius cannot be estimated from short-axis diameter during regional ischemia. We calculated regional wall tension from the directly measured regional curvature radius and LV pressure and found that tension-length loop clearly differentiates between regional myocardial function under control and ischemic conditions. We have concluded that our newly developed curvature sensor is accurate, that its practical use is feasible, and that measurement of the regional curvature radius of the LV wall provides detailed and accurate information on regional shape and function of the left ventricle.
Integrated regional work equals total left ventricular work in regionally ischemic canine heart
Authors: Goto Y. , Igarashi Y. , Yasumura Y. , Nozawa T. , Futaki S. , Hiramori K. , Suga H.
Published: December 2017

To assess left ventricular (LV) regional work with physically correct dimensions, wall tension-regional area (T-A) loops were analyzed before and after coronary occlusion in the excised cross-circulated canine LV (n = 11) connected to a volume-servo pump. Wall tension was calculated with the force equilibrium equation for a sphere, and regional areas were determined from pairs of orthogonal sonomicrometers in ischemic and nonischemic regions. LV and regional stroke work were simultaneously assessed from the pressure-volume and T-A loops during one cardiac cycle at various end-diastolic and stroke volumes. After coronary occlusion, regional work of the ischemic region markedly decreased to near or even below zero. Although regional work of the nonischemic region moderately decreased at constant LV end-diastolic and stroke volumes, the contribution of the nonischemic region to LV stroke work increased. Globally integrated regional work calculated from regional work/unit area and estimates of the extent of ischemia closely agreed with measured LV stroke work either before (n = 119; r = 0.92) or after coronary occlusion (n = 141; r = 0.93) despite the marked changes in regional work in both regions. We conclude that the global integral of regional work equals the total LV work and that regional work of the LV can be reliably assessed from the T-A loop with the same dimensions as energy in both normal and regionally ischemic hearts.
Response of arteriolar network of skeletal muscle to sympathetic nerve stimulation
Authors: Boegehold M. A. , Johnson P. C.
Published: December 2017

The influence of vessel location on arteriolar responses to sympathetic nerve stimulation was systematically studied in a skeletal muscle arteriolar network under normal and altered tissue O2 levels. The exteriorized cat sartorius muscle was exposed to 0, 5, and 10% ambient O2 during sympathetic chain stimulation at 8 pulses/s. Under 0% O2, stimulation initially caused a 25-45% constriction that was faster and more pronounced in distal arterioles. Ninety-one percent of vessels showed a secondary dilation (sympathetic escape), which was largest in distal arterioles. Escape had little effect on calculated volume flow, which, after a large initial fall, showed a modest secondary increase. Under 5 and 10% O2, resting arteriolar diameter was reduced by 12 and 17%, respectively, and escape was reduced by 60 and 73%. Escape was not attenuated in proximal arterioles preconstricted with vasopressin, suggesting that O2 did not attenuate escape through increased vascular tone. Therefore, the arteriolar response to sympathetic stimulation depends largely on location within the network and is modulated to varying degrees by metabolic influences.
Release of norepinephrine from the paraventricular hypothalamic nucleus of hypertensive rats
Authors: Qualy J. M. , Westfall T. C.
Published: December 2017

The push-pull cannula was used to examine the release of endogenous norepinephrine (NE) from the paraventricular hypothalamic nucleus (PVH) of unanesthetized freely moving 7- to 10- and 12- to 14-wk-old Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rats. Basal NE release, K+ (56 mM) stimulation-induced NE release, and NE release in response to pressor/depressor drugs were examined in all three strains at both ages. Significant increases in basal and K+-stimulated release of endogenous NE from the PVH were observed in 7- to 10- and 12- to 14-wk-old SHR compared with the normotensive control rats suggesting that enhanced central noradrenergic nerve activity may be involved in the development and maintenance of hypertension in the SHR. In addition, a reciprocal relationship exists with respect to blood pressure and NE release from the PVH, i.e., decreases in blood pressure elicit increases in NE release, and increases in blood pressure elicit decreases in NE release in all three strains at both age groups, suggesting that the noradrenergic pathways of the PVH contribute to the maintenance of arterial blood pressure homeostasis.
Altered intracellular adrenoceptor distribution in myocardium of spontaneously hypertensive rats
Authors: Limas C. J. , Limas C.
Published: December 2017

Page H904: C. J. Limas and C. Limas. “Altered intracellular adrenoceptor distribution in myocardium of spontaneously hypertensive rats.” The introductory sentence should read: “There is considerable evidence that inotropic responsiveness to β-adrenergic agonists is decreased in the myocardium of spontaneously hypertensive rats (SHRs) (3, 21).
Optimal matching between canine left ventricle and afterload
Authors: Myhre E. S. , Johansen A. , Piene H.
Published: December 2017

A parabolic relationship exists between ventricular external work and arterial load at given preload and contractility. Previous data indicate that the working point falls close to the parabola optimum. By combining the left ventricular (LV) end-systolic pressure-volume relationship (ESPVR) and an equation describing external stroke work, optimum values of stroke volume (SV), the slope (Emax) of the ESPVR, and arterial resistance (Rp) corresponding with the optimum (i.e., mSV, mEmax, mRp) were obtained. Experiments in anesthetized dogs were performed to test whether mSV, mEmax, and mRp also correspond to observed SV, Emax, and Rp at three different levels of volume load (right atrial pressure, RAP) before and after acute depression of LV contractility. Comparisons of observed and optimal values of SV, Emax, and Rp were made before and after LV depression. Before embolization, the ratios were SV/mSV 1.10–1.20 (RAP 5–15 mmHg); Emax/mEmax 1.21–1.41; and Rp/mRp 0.84–0.69. After LV depression, SV/mSV was 0.80–0.83, Emax/mEmax was 0.78–0.71, and Rp/mRp was 1.56–1.46. The ratios were all significantly changed (P less than 0.01) by the induced LV depression. The present analysis may offer a new tool to detect nonoptimal relations between cardiac and arterial functions.
Different ATP-catabolism in reperfused adult and newborn rat hearts
Authors: Achterberg P. W. , Nieukoop A. S. , Schoutsen B. , de Jong J. W.
Published: December 2017

Age-dependent differences in the effects of ischemia and reperfusion on ATP breakdown were studied in perfused adult and newborn (10 days old) rat hearts. No-flow ischemia (15 min at 37, 30, or 23 degrees C) was applied and reperfusion (20 min at 37 degrees C) was studied after ischemia at 23 or 37 degrees C. Hypothermia during ischemia protected both age groups to a similar degree against ATP decline, which was linear with temperature. Reperfusion after normothermic ischemia resulted in higher ATP levels in newborn hearts with less release of ATP catabolites (purines). We found no age-related differences in lactate release but large differences in purine release. During normoxia, adult hearts released mainly urate (80% of total) and inosine (7%), but newborns released hypoxanthine (64%) and inosine (15%). Early during reperfusion adult hearts released inosine (58%) and adenosine (18%), but newborns released inosine (53%) and hypoxanthine (38%). These data suggested a lower activity of the potentially deleterious enzyme xanthine oxidoreductase in newborn hearts, which was confirmed by enzymatic assay. ATP-catabolite release during reperfusion was less in newborn than adult hearts, and this coincided with lower xanthine oxidase activity.
Mechanisms of reoxygenation-induced calcium overload in cultured chick embryo heart cells
Authors: Murphy J. G. , Smith T. W. , Marsh J. D.
Published: December 2017

We examined mechanisms by which Ca enters cultured myocardial cells during posthypoxic reoxygenation. Monolayer cultures of chick embryo ventricular cells were prepared from hearts 10 days in ovo. Cells were exposed to hypoxic conditions (PO2 less than 1.5 Torr), and 45Ca uptake during subsequent reoxygenation was then examined in the absence and presence of modulators of Ca channel-dependent Ca entry and Na-Ca exchange. Modulation of Ca entry by free radical-scavenging enzymes was also examined. Hypoxia for 120 min followed by reoxygenation increased Ca content from 1.9 to 6.1 nmol/mg protein (P less than 0.05) at 30 min. Verapamil (10(-5) M) added before reoxygenation reduced Ca overload to 3.1 +/- 0.2 nmol/mg protein (P less than 0.05), but both verapamil and BAY K 8644 were without effect on modulating Ca entry if added 30 min after reoxygenation. 24Na content of cells increased from 70 nmol/mg protein in control cells to 157 nmol/mg protein (P less than 0.05) after hypoxia and reoxygenation, favoring Ca entry via Na-Ca exchange. Dichlorobenzamil significantly ameliorated reoxygenation-induced Ca overload, as did catalase and superoxide dismutase. We conclude that reoxygenation-induced Ca overload is unlikely to occur via the Ca channel. It occurs in part via Na-Ca exchange and is substantially ameliorated by enzymatic O2 free radical scavengers.
Distribution of vascular resistance in terminal arteriolar networks of cat sartorius muscle
Authors: Popel A. S. , Liu A. , Dawant B. , Koller A. , Johnson P. C.
Published: December 2017

Morphometric information on the terminal arteriolar networks (n = 10) in cat sartorius muscle [Koller et al., Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H154-H164, 1987] is utilized in the calculations of distribution of vascular hindrance throughout the networks. These networks have tree-type geometry, i.e., they do not contain closed loops. The results are discussed in terms of simulated flow distribution. The flow calculations are based on the exact geometry of the arteriolar networks (the control and dilated diameter and the length of each vascular segment) and on assumed values of postarteriolar resistances. Three cases of postarteriolar resistances are considered: zero, constant, and randomly distributed. With zero postarteriolar resistances, the distribution of flow in the terminal arteriolar segments would be highly heterogenous. The simulated flow in each terminal segment is determined primarily by the number of bifurcations on the pathway leading to the terminal segment, with a slight compensation for the length of the pathways. The coefficient of variation of flow in the control state, CV(Qc), would be close to the value in the dilated state, CV(Qd). When each of the terminal segments is connected to a constant postarteriolar resistance, the CV's in both states decrease. The coefficient of variation in the dilated state becomes significantly smaller than in the control state. When postarteriolar resistances are randomly distributed, both CV's increase, and their values become closer to each other. These results suggest that postarteriolar resistances may play a very important role in distribution of flow in the microvascular network. This study formulates a framework for the quantification of the effect of arteriolar dilation on flow redistribution in the network.
Studies on sequestration of neuraminidase-treated red blood cells
Authors: Simchon S. , Jan K. M. , Chien S.
Published: December 2017

The effects of reduction in the surface charge of red blood cells (RBCs) on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were treated with neuraminidase to reduce their electrophoretic mobility by 56%. Normal and neuraminidase-treated RBCs labeled with 51Cr or 111In were injected into a femoral vein while an equal volume of blood was simultaneously withdrawn from a femoral artery. More than 70% of the neuraminidase-treated RBCs injected disappeared from the circulating blood in 30 min compared with less than 2% of normal RBCs. The relative distributions of neuraminidase-treated RBCs to normal RBCs, as determined from radioactivity counting, were significantly greater than 1 in the spleen (5.65 +/- 0.97, mean +/- SD), the liver (2.84 +/- 0.21), the lung (1.48 +/- 0.31), and the kidney (1.49 +/- 0.27), indicating a preferential trapping of neuraminidase-treated RBCs in these regions. This ratio was approximately 1 in all other organs. Regional blood flows in tissues were determined with 15-micron microspheres in the control period and after the infusion of neuraminidase-treated RBCs (experimental). Experimental-to-control blood flow ratios were 0.40 +/- 0.05 in the spleen, 0.66 +/- 0.06 in the liver, 0.78 +/- 0.03 in the lung, and 0.78 +/- 0.09 in the kidneys; this ratio was approximately 1 in all other organs. An experimental-to-control blood flow ratio less than 1 indicates a reduction in blood flow; this occurred in the same organs as those with trapping of neuraminidase-treated RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)