bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta-adrenergic receptors on canine coronary collateral vessels: characterization and function
Authors: Feldman R. D. , Christy J. P. , Paul S. T. , Harrison D. G.
Published: December 2017

The present studies were performed to examine the role of beta-adrenergic receptors in modulating smooth muscle tone in mature coronary collaterals. To examine the beta-adrenergic receptor population present, radioligand binding-cover slip autoradiographic studies were performed on sections of native canine coronary vessels and sections of coronary collaterals developed after placement of Ameroid constrictors. Specific binding of the nonselective beta-adrenergic antagonist [125I]iodopindolol to vascular smooth muscle in segments of both collaterals and native coronary arteries was saturable and stereospecific. Maximal binding and the potency of beta-adrenergic subtype-selective antagonists were similar in all segments. Beta-adrenergic relaxation of native coronary vessels and collateral vessels were studied in isolated organ chambers after preconstriction with prostaglandin F2 alpha. Both native coronary arteries and collateral segments demonstrated beta-adrenergic-mediated relaxation with affinities for both agonists and antagonists compatible with a mixed population of beta 1- and beta 2-adrenergic receptors. These studies indicate that during development, the new collateral vascular smooth muscle expresses a functional population of beta-adrenergic receptors, comparable to that in native vessels.
Control of hypertrophic versus hyperplastic growth of vascular smooth muscle cells
Authors: Owens G. K.
Published: December 2017

A long-term objective of my laboratory has been to understand the mechanisms that regulate both normal and developmental growth of vascular smooth muscle as well as the accelerated growth of smooth muscle that occurs in atherosclerotic lesions or arteries of hypertensive patients and animals. Previous studies in this and other laboratories have demonstrated that smooth muscle cells are capable of two distinct growth responses in vivo, depending on the nature of the growth stimulus. Smooth muscle cell growth in large vessels of chronically hypertensive animals appears to occur primarily by enlargement of preexisting cells (i.e., cellular hypertrophy) with little or no cell proliferation (hyperplasia) and is accompanied by development of polyploidy in a large fraction of the cells. In contrast, in experimental injury models of atherogenesis, or after induction of severe acute hypertension, aortic smooth muscle cells undergo a classic proliferative response. This lecture focuses on possible control mechanisms for hypertrophy of vascular smooth muscle, with particular emphasis on examination of the possible role of contractile agonists as hypertrophic agents, exploration of how this process differs from cellular hyperplasia, discussion of the possible mechanisms for formation of polyploid cells, and examination of the role of mechanical factors in growth regulation of vascular smooth muscle cells.
Long-term pressure-induced cardiac hypertrophy: capillary and mast cell proliferation
Authors: Olivetti G. , Lagrasta C. , Ricci R. , Sonnenblick E. H. , Capasso J. M. , Anversa P.
Published: December 2017

To determine whether a prolonged duration of mechanical load on the ventricular myocardium leads to capillary proliferation, constriction of the pulmonary artery was produced in rats at 3 mo of age, and the hearts were examined 200 days later. Functionally, elevations of right ventricular systolic pressure, from 30 +/- 12 to 67 +/- 11 mmHg, and right ventricular end-diastolic pressure, from 2.4 +/- 1.4 to 8.6 +/- 2.4 mmHg, were found. Anatomically, a 69% enlargement in right ventricular mass was observed, and this hypertrophic growth was characterized by a 78% thickening of the wall with no change in ventricular wall area, the latter calculated from the quotient of ventricular volume and wall thickness. Morphometric data showed a 44% increase in the capillary-to-myocyte ratio, a 66% augmentation of the total length of capillaries in the whole ventricle, and a 77% greater number of capillaries across the ventricular wall. Furthermore, these indexes of neogenesis of capillary units were associated with a more than three fold increase in the numerical density of mast cell profiles in the myocardium. In conclusion, capillary proliferation occurs in the adult rat heart, and this process appears to be coupled with mast cell hyperplasia.
Mechanical and electrical properties of cardiomyopathic hearts of Syrian hamsters
Authors: Capasso J. M. , Olivetti G. , Anversa P.
Published: December 2017

To determine whether the cardiomyopathy that develops in the Syrian hamster before the occurrence of congestive heart failure is associated with mechanical and electrical alterations consistent with myocardial dysfunction, left ventricular posterior papillary muscles of control and cardiomyopathic animals at 120 days of age were studied in vitro. Moreover, the electrocardiographic response to ouabain was investigated in vivo to analyze the arrhythmogenic potential of the cardiomyopathic heart to glycoside exposure. Results showed a decreased tension-generating ability of the myocardium in the diseased animals, which was accompanied by a prolongation of the timing parameters of contraction and an increase in the duration of the repolarization phase of the transmembrane action potential. Furthermore, the velocity of isotonic muscle shortening and relengthening was depressed at all physiological loads. Glycoside infusion elicited premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation in diseased hamsters much earlier in time than in healthy controls. The impairment in mechanical performance in association with the abnormality in membrane electrical activity may be responsible for the progression of the disease process and the occurrence of lethal arrhythmias in this animal model.
Nonuniformity and volume loading independently influence isovolumic relaxation rates
Authors: Gillebert T. C. , Lew W. Y.
Published: December 2017

We examined the influence of loading conditions and nonuniformity of left ventricular (LV) function on the rate of LV pressure fall in seven anesthetized dogs. Loading conditions were altered with vena cavae occlusions and/or intravenous infusions of dextran. Nonuniformity was produced by injecting 8-20 ng of isoproterenol into the mild left anterior descending coronary artery to produce an asynchronous and early onset of segment lengthening in the anterior wall. Temporal and regional nonuniformity were quantified with indexes derived by comparing segment lengths in the anterior and posterior walls, measured with midwall sonomicrometers. The rate of LV pressure fall was assessed with peak -dP/dt, the time constant, tau, and the duration of isovolumic relaxation. Volume loading decreased the rate of LV pressure fall without altering the nonuniformity indexes. Intracoronary isoproterenol produced nonuniformity and decreased the rate of LV pressure fall without altering global loading conditions. The effects of isoproterenol (in a constant dose) were similar irrespective of the LV volume. We conclude that in the intact, ejecting left ventricle, loading conditions and nonuniformity are important determinants of the rate of LV pressure fall, but these two factors exert their influence by mechanisms that are largely independent.
Reflex release of vasopressin and renin in hemorrhage is enhanced by autonomic blockade
Authors: Oliver J. R. , Korner P. I. , Woods R. L. , Zhu J. L.
Published: December 2017

We determined the relationships during hemorrhage between nominal blood volume (BV) and 1) plasma arginine vasopressin (AVP), 2) plasma renin activity (PRA), and 3) mean arterial pressure (MAP). Conscious rabbits were studied under normal conditions and during total autonomic blockade (TAB) at bleeding rates of 2 and 4 ml/min. Normally, MAP was well maintained until BV had been reduced to approximately 65% of control (termed 65% BV) after which it fell abruptly. The threshold for a rise in AVP was 80–75% BV, followed by exponential rises to levels of 14 and 24 times control at the slow and fast rate of bleeding. PRA rose earlier in hemorrhage, but this rise was more gradual, to values at 60% BV of 5.5 and 7 times control at the two rates of bleeding. During TAB, MAP fell rapidly and both BV concentration curves were shifted to the left with the rises in AVP and PRA/unit delta BV greater than normal; at 75% BV at each rate of hemorrhage, AVP and PRA had risen, respectively, to approximately 40 and 8 times control. Normally, the rises in the AVP and PRA (i.e., angiotensin II) concentrations were modest during the nonhypotensive phase, consistent with their minimal constrictor action observed in a parallel study. During the hypotensive phase, both reached high levels in the constrictor range. During TAB, high concentrations were reached with small BV loss, representing a model of near-maximum release of PRA and AVP.
Hepatic microvascular changes associated with development of liver fibrosis and cirrhosis
Authors: Sherman I. A. , Pappas S. C. , Fisher M. M.
Published: December 2017

Quantitative data defining basic microvascular parameters are needed for better understanding of the relationship between liver blood flow and function under normal and pathological conditions. The present study was undertaken to quantitate the following microvascular parameters: flow velocities in sinusoids and terminal hepatic venules; the range of sizes of terminal hepatic vessels; and acinar sizes in both normal rat livers and during the development of liver cirrhosis. Fibrosis and cirrhosis were induced by either weekly administration of carbon tetrachloride (CCl4) or by choline-deficient diet. Microcirculation was observed using intravital epifluorescent video microscopy and recorded on a videotape for subsequent analysis. It was found that even early stages of liver disease, when only mild hepatic fibrosis was present, are associated with profound changes in the hepatic microvasculature. These changes include the appearance of highly fluorescent cells in the liver parenchyma (mainly in the areas where collagen is being deposited), a marked dilatation of the terminal hepatic venules, an increase in hepatic venous outflow, and appearance of sinusoids with very high flow velocities. As fibrosis progresses to cirrhosis, the proportion of these “fast sinusoids” increases from 7% in fibrotic livers to 33% in cirrhotic livers. These results demonstrate the presence of functional intrahepatic shunts in cirrhotic livers and support the hypothesis that hyperdynamic splanchnic circulation may be an important factor in the etiology of portal hypertension in liver disease.
Interaction between left ventricular end-diastolic and end-systolic volumes in normal humans
Authors: Renlund D. G. , Gerstenblith G. , Fleg J. L. , Becker L. C. , Lakatta E. G.
Published: December 2017

The extent to which the end-systolic volume (ESV) “follows” the end-diastolic volume (EDV) when the latter changes in response to various perturbations is a major determinant of the cardiac ejection fraction (EF) and has not been studied in humans. We measured EDV, ESV, and EF, determined by gated blood pool scans, during a change in posture from the supine to the upright seated position and during graded upright bicycle exercise. The experimental group consisted of 119 healthy individuals (79 males and 40 females) ranging in age from 21 to 81 yr and in physical-conditioning status (75–225 W maximum work load); rigorous screening excluded cardiac disease. Multiple regression analysis showed that the change in ESV (delta ESV) during a postural shift or during graded exercise was highly statistically correlated with the change in EDV (delta EDV) that occurred (r2 ranged from 0.34 to 0.49, correlation is positive) regardless of age, sex, or exercise work load. The correlation of delta ESV with delta EDV observed in this large sample, heterogeneous with respect to age, sex, and physical fitness, was also present in additional 31 subjects who exercised during beta-adrenergic blockade (propranolol 0.15 mg/kg). The delta EF with posture change and exercise in all subjects under all conditions was highly and inversely correlated with the delta ESV (r2 ranged from 0.38 to 0.81). Thus the delta ESV during the circulatory adaptive response to orthostatic and exercise stresses in humans is related to the delta EDV, and this relationship modulates the delta EF in response to these stresses.
Ejection- and isovolumic contraction-phase wall thickening in nonischemic myocardium during coronary occlusion
Authors: Ning X. H. , Zweng T. N. , Gallagher K. P.
Published: December 2017

During acute regional ischemia in open-chest anesthetized dogs, contraction is augmented in nonischemic myocardium. The effectiveness of enhanced contraction, however, has been questioned based on recent studies (using midwall segment length measurements) that reported that most of the increase occurred only during the isovolumic contraction phase (ICP) and not the ejection phase (EP) of systole. We evaluated this issue retrospectively using a different means of measuring regional myocardial function, systolic wall thickening (measured with sonomicrometers). In open-chest anesthetized dogs we observed a significant increase in both ICP and EP wall thickening. With circumflex occlusion, ICP and EP thickening each contributed an average of 50% to the augmentation in total thickening. With left anterior descending occlusion, ICP thickening contributed a significantly greater proportion (71%) to the total increase, but the change in EP thickening was also significant (29%). Therefore, in open-chest dogs we observed evidence of intraventricular unloading (in that ICP thickening increased), but we also observed an increase in effective (EP) thickening. In a series of conscious dogs, however, we observed no significant change in total nonischemic thickening after circumflex coronary occlusion. There was a statistically significant increase in the ICP component acutely after coronary occlusion, but its contribution to total wall thickening was small. In a group of dogs studied at intervals for 2 wk after circumflex occlusion, there was no evidence of intraventricular unloading beyond 3-5 days postocclusion. Therefore, we conclude that significant intraventricular unloading is restricted to the acute phases of myocardial infarction, and we suggest that its functional importance is smaller in conscious closed-chest chest dogs than in open-chest dogs.
Graded modulation of frog microvessel permeability to albumin using ionophore A23187
Authors: Curry F. E. , Joyner W. L. , Rutledge J. C.
Published: December 2017

We investigated the exchange of water and macromolecules across venular microvessels after permeability was increased. Quantitative fluorescence microscopy was used to measure albumin permeability coefficients in individually perfused microvessels of decerebrate frogs. Control permeability coefficient was 2.3 +/- 0.25 X 10(-7) cm/s. Solvent drag increased the apparent solute permeability coefficient (Ps) by 0.57 +/- 0.05 X 10(-7) cm/s for each cmH2O increase in microvessel pressure. The divalent cation ionophore A23187 (0.1–5 microM) produced a transient increase in Ps to a peak value (within 1–3 min), followed (after 4–8 min) by a sustained increase in permeability (16–34% of peak values). Peak values of Ps were 13 and 80 times control for 0.1 and 5 microM A23187, respectively. Both diffusion and solvent drag contributed to the sustained increase in Ps. The equivalent pore radius of the structures determining diffusion and solvent drag was less than or equal to 25 nm during the sustained increase in permeability, smaller than observed gaps between adjacent endothelial cells. The basement membrane and a fibrous matrix secreted by endothelial cells into the gaps may offer resistance to exchange in the high permeability state.
Left ventricular function and beta-adrenoceptors in rabbit failing heart
Authors: Gilson N. , el Houda Bouanani N. , Corsin A. , Crozatier B.
Published: December 2017

Few models of heart failure (HF) are available for physiological and pharmacological studies. We report here a model of pressure plus volume overload induced in rabbits in which left ventricular (LV) function was studied in the conscious state after instrumentation of the animals with LV pressure catheter and ultrasonic crystals measuring LV diameter. Beta-Adrenoceptors were studied on crude membranes obtained from control (C) and HF rabbits using [3H]CGP 12177. LV weights and end-diastolic diameters were significantly increased in the HF group compared with the C group (by 79 and 38%, respectively). The percentage of diameter systolic shortening was decreased, in the control state, in rabbits with HF (15.3 +/- 1.6%) as compared with C rabbits (29.6 +/- 2.5%) and remained lower in the HF group when end-systolic pressures were matched. Chronotropic response to isoproterenol injection was significantly decreased in rabbits with HF compared with that of C rabbits. Beta-Adrenergic receptor density was decreased in rabbits with HF (39.3 +/- 3.7 fmol/mg) compared with C rabbits (56.7 +/- 4.2 fmol/mg) without affinity changes. This model of chronic HF thus produces a marked hypertrophy with ventricular dilatation and a depression of LV function within 2 mo, factors that are associated with a reduced cardiac responsiveness to catecholamines and a decreased ventricular beta-adrenergic receptor density.
Heparinase treatment suggests a role for the endothelial cell glycocalyx in regulation of capillary hematocrit
Authors: Desjardins C. , Duling B. R.
Published: December 2017

Physiological stimuli induce rapid and unexplained increases in the number of red blood cells within capillaries of skeletal muscle. We hypothesized that such alterations in intracapillary red cell numbers might be due to an undefined interaction between one or more components of blood and the luminal surface of the capillary. This proposition was tested by in situ microperfusion of capillaries with enzymes directed against macromolecules likely to be expressed on the surface of endothelial cells. The instantaneous fractional volume of red blood cells within a capillary (tube hematocrit) was used as an index of a capillary's response to enzyme microperfusion. Five to 8 min of perfusion with enzyme vehicle (0.25% albumin-Ringer solution) produced no significant alteration in capillary tube hematocrit. Perfusion with solutions containing heparinase raised the tube hematocrit at least twofold (P less than 0.05) without a significant change in red cell velocity. Heat-denatured heparinase and other enzymes such as neuraminidase, hyaluronidase, papain, pronase E, and clostripain had no detectable effect on the tube hematocrit (P greater than 0.05). After enzyme treatment, application of adenosine (10(-4) M) or oxygen caused brisk vasomotor responses in arterioles feeding perfused capillary units, but the usual changes in the tube hematocrit were not observed. Thus heparinase treatment results in a sustained elevation in the capillary tube hematocrit and a dissociation of the typical relationship between vasomotor changes and red cell distribution in capillaries. These findings suggest that physiological stimuli which alter the number of red blood cells within capillaries may operate by modifying interactions between plasma and one or more components on the luminal surface of capillaries.
Macromolecular transport in canine coronary microvasculature
Authors: Pilati C. F.
Published: December 2017

Coronary vascular osmotic reflection coefficients (sigma dS) for total protein, albumin (Alb), immunoglobulin (Ig)G, and IgM were determined in the anesthetized dog. Myocardial lymph was collected from the anterior interventricular lymphatic trunk, and the sigma dS estimated from filtration rate-independent lymph-to-plasma protein concentration ratios (CL/CPS). Lymph flows of at least 12 times base line were needed to produce filtration rate-independent CL/CPS, and these were achieved in 9 of 12 experiments. In these nine experiments, sigma dS for total protein, Alb, IgG, and IgM were, respectively, 0.67 +/- 0.02 (SE), 0.59 +/- 0.05, 0.70 +/- 0.03, and 0.87 +/- 0.01. The data were fitted to a model that showed that transvascular fluid and solute flux could be described by two populations of pores. A large pore system with an equivalent radius of 235 A was responsible for 39% of the transvascular volume flow. A small pore system less than 53 A accounted for the remaining flow. In a second group of experiments (n = 8), 60 min of ischemia decreased the sigma dS to 0.27 +/- 0.03, 0.07 +/- 0.05, 0.22 +/- 0.03, and 0.69 +/- 0.04 for total protein, Alb, IgG, and IgM, respectively. A single population of pores of 220 A could describe the entire transvascular volume flow. These results indicate that coronary vascular protein permeability is moderately high and can be increased significantly by ischemia.
[Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells
Authors: Aceto J. F. , Baker K. M.
Published: December 2017

Cardiac hypertrophy is a process that occurs in response to various mechanical or hormonal stimuli. Stimulation of the renin-angiotensin system is involved in the process of cardiac hypertrophy through mechanisms related to increased peripheral vascular resistance and increased cardiac afterload. In this study we determined whether [Sar1]angiotensin II (ANG II) directly stimulated protein synthesis and cell growth in embryonic chick myocytes in cell culture. Eighteen-day-old embryonic chick myocytes in subconfluent cell culture, incubated in a chemically defined serum-free media, showed a significant increase in total protein content, 18.5, 26.2, and 22.2%, respectively, when exposed to [Sar1]ANG II (1 microM/day) for 5, 7, and 9 days, respectively. The increase in total protein resulted in part from an increase in the fractional protein synthesis rate of 21.7, 16.5, and 14.9% at 5, 7, and 9 days, respectively. Total DNA and RNA levels did not change significantly following a 4-day exposure to [Sar1]ANG II in subconfluent culture. The relative rate of protein synthesis, determined by pulse labeling for 3 h with [3H]phenylalanine, showed increases of 23.4, 22.9, and 17.8% over control after 4, 5, and 6 days of exposure to [Sar1]ANG II. The incorporation of [3H]phenylalanine was blocked by the specific ANG II-receptor antagonist [Sar1,Ile8]ANG II. The data demonstrate a receptor-mediated increase in the rate of protein synthesis in cultured chick myocytes in response to [Sar1]ANG II, with a resultant increase in total cellular protein. This angiotensin peptide appears to directly stimulate protein synthesis in cultured embryonic chick myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Heat production in isolated heart myocytes: differences among species
Authors: Ponce-Hornos J. E. , Parker J. M. , Langer G. A.
Published: December 2017

A new calorimetry method has been developed to measure heat production from heart cell suspensions under continuous perfusion. The method is technically independent of the temperature at which the measurements are made, allows full control of the perfusion media, and is suitable for various biological preparations such as cells from diverse tissues, membrane vesicles, or skinned cells. The resting heat rate (Hr) measured at 18.5 degrees C in three different species (19.2 +/- 0.43, 12.8 +/- 0.56, and 9.4 +/- 0.52 mW/g dry wt for rat, guinea pig, and rabbit ventricular myocytes, respectively) agrees with that obtained with other methodologies such as oxygen consumption, thermopiles, and whole heart calorimetry. The Hr measurements showed an excellent correlation with the percentage of rod-shaped cells, indicating that rounded cells are metabolically inactive. Although the time course of the effect of increasing extracellular [K] was dependent on the species, the new steady level of Hr observed under higher extracellular [K] was significantly higher in all three species (+8.3 +/- 1.2, +9.5 +/- 4.0, and +9.3 +/- 2.7 mW/g dry wt for rat, guinea pig, and rabbit ventricular cells, respectively). This indicates that the commonly used "arrested-heart" preparation (with high extracellular [K]) for evaluation of basal metabolism most probably overestimates the real resting values. The present results also show that the wide range of resting metabolism reported in whole tissue is not due to cellular heterogeneity nor to myocyte interaction and supports the idea of an inverse relationship between resting metabolism and body weight or animal size across species.
External pressure of undisturbed left ventricle
Authors: Applegate R. J. , Santamore W. P. , Klopfenstein H. S. , Little W. C.
Published: December 2017

We evaluated the contribution of the thorax and the undisturbed pericardium to the external pressure of the euvolemic left ventricle in thirteen anesthetized dogs. Left ventricular (LV) end-diastolic pressure (EDP) in the euvolemic state was 7 +/- 2 mmHg initially and increased to 10 +/- 2 mmHg after the chest and pericardium were opened. LV end-diastolic volume (conductance catheter) was 43 +/- 20 ml initially and did not change after the chest or the pericardium was opened. Intrathoracic (PIT) and pericardial (PPER) pressures were calculated as the difference in LV chamber pressure before and after opening these spaces. Thus for the LV, PIT was -3 +/- 1 mmHg, and PPER was 0 +/- 2 mmHg. Isovolumic relaxation, early diastolic filling, and total diastolic filling were not significantly altered after the chest or pericardium was opened. Thus under euvolemic conditions in this model pericardial pressure is negligible, and the external pressure of the undisturbed left ventricle is negative and equal to intrathoracic pressure.
LV pressure-volume area and oxygen consumption: evaluation in intact dog by fast CT
Authors: Chung N. , Wu X. , Bailey K. R. , Ritman E. L.
Published: December 2017

The relationship between left ventricular (LV) myocardial oxygen consumption (MVO2) and LV systolic pressure-volume area (PVA) was investigated in anesthetized closed-chest dogs with intact reflexes and subsequently with beta-adrenergic blockade, with or without simultaneous muscarinic blockade. LV chamber volumes were measured using a fast computerized tomography (CT) scanner (dynamic spatial reconstructor, DSR) at 33-ms intervals. Myocardial blood flow was measured from the DSR scans of aortic root angiograms. With intact reflexes, LV MVO2 (Y) related to PVA (X) values as Y = (4.28 +/- 1.81)X + (1.94 +/- 6.0) (n = 24) (mJ.g-1.cycle-1). With beta-adrenergic blockade, LV MVO2 (Y) related to PVA (X) value as Y = (4.24 +/- 1.03)X - (6.43 +/- 6.5), (n = 9) (mJ.g-1.cycle-1). With beta-adrenergic and muscarinic blockade, LV MVO2 (Y) related to PVA (X) value as Y = (2.84 +/- 1.72)X + (3.51 +/- 5.15), (n = 13) (mJ.g-1.cycle-1). The slopes of these regressions are higher than the slopes demonstrated by others in isolated ventricles but very similar to those demonstrated in open-chest dogs.
Arterioles supply oxygen to capillaries by diffusion as well as by convection
Authors: Ellsworth M. L. , Pittman R. N.
Published: December 2017

In the early part of this century, August Krogh proposed a model of oxygen transport in capillaries that assumes that all oxygen is delivered to the capillaries by convection from small terminal arterioles and lost from these capillaries by diffusion. This model and its consequences have been used extensively to interpret whole organ oxygen transport data in terms of diffusion between capillaries and tissues and to relate changes in microvascular hemodynamics to alterations in oxygen transport. We evaluated the appropriateness of such extrapolation by measuring oxygen saturation at discrete locations along the lengths of individual capillaries in the hamster cheek pouch retractor muscle. Our results indicate that the amount of oxygen lost from individual capillaries can be markedly affected by the presence of larger microvessels that frequently cross the capillary path. These larger vessels act either as a diffusive supply of oxygen for the red blood cells within the capillary or as an additional sink for the oxygen depending on the direction of the oxygen tension gradient. This transfer of oxygen between larger microvessels and capillaries attenuates the importance of capillary hemodynamics in oxygen exchange. Therefore, conclusions about local oxygen exchange that utilize only hemodynamic data from whole organ or microvascular experiments and the Krogh model will generally be invalid and should be viewed with caution.
Cholinergic prejunctional inhibition of vasodilator nerve function in bovine basilar arteries
Authors: Toda N. , Ayajiki K.
Published: December 2017

Helical strips of bovine basilar arteries responded to transmural electrical stimulation with moderate relaxations that were abolished by treatment with tetrodotoxin and oxyhemoglobin and were significantly attenuated by quinidine, as were the relaxations previously seen in dog and monkey cerebral arteries. The relaxant response of the bovine arteries was attenuated by treatment with acetylcholine and physostigmine and was significantly potentiated by atropine. In contrast, relaxations of dog coronary arteries to transmural stimulation, mediated via beta-adrenoceptors, were not influenced by physostigmine and atropine but were attenuated by acetylcholine. Abundant fibers containing cholinesterase were histologically demonstrated in bovine basilar arteries, suggesting the presence of cholinergic innervation. Acetylcholine liberated from the cholinergic nerve appears to act on muscarinic receptors located in vasodilator nerve terminals in bovine cerebral arteries and to interfere with the release of vasodilator transmitters.
Endothelial and epithelial permeabilities to antipyrine in rat and dog lungs
Authors: Cua W. O. , Basset G. , Bouchonnet F. , Garrick R. A. , Saumon G. , Chinard F. P.
Published: December 2017

Temperature effects on the permeabilities of the structured endothelium and epithelium to antipyrine (AP) have been determined with the indicator dilution technique in isolated rat and dog lungs perfused between 38 and 8 degrees C. Permeability coefficients of the endothelium to AP [Pendo(AP)] from the Crone equation are smaller than values for isolated endothelial cells but close to the permeability coefficient of the interstitial epithelial plasmalemma [Pepi(AP)] obtained from physical and mathematical models. In these, tracer water is flow limited at the endothelium and the epithelium at all temperatures; AP is flow limited at the endothelium at T greater than 20 degrees C but barrier limited at the endothelium for T less than 20 degrees C and at the epithelium at all temperatures. At T less than 20 degrees C, log Pendo(AP) decreases regularly with 1/T, with a slope close to that found in cultured bovine pulmonary artery endothelial cells. At 15 degrees C, Pendo(AP) for the endothelial plasmalemma in situ is 30 X 10(-5) cm/s and is 56 X 10(-5) cm/s for the isolated cells in support of transcellular rather than paracellular passage. At T greater than 20 degrees C, log Pepi(AP) in situ decreases slightly with 1/T, with a discontinuity at T = 20 degrees C, and for T less than 20 degrees C, decreases with 1/T with a slope close to that of Pendo(AP). At 15 degrees C, Pepi(AP) is 2.8 X 10(-5) cm/s. The discontinuity may represent a change in the physical state of lipids in the interstitial plasmalemma of the epithelial cells.
Time dependence of regional systolic left ventricular relationships in intact hearts
Authors: Miller W. P. , Nellis S. H. , Liedtke A. J.
Published: December 2017

In intact hearts the beat-to-beat left ventricular systolic pressure-length relationship is not uniquely defined, but rather is history dependent and appears hysteretic. The purpose of these studies was to assess the time course of this phenomenon. In an open chest swine heart preparation, left ventricular pressure, regional lengths, and wall thickness were measured. Loading conditions were altered by the infusion of volume into the left ventricle to increase peak systolic pressure approximately 30 mmHg. The resultant interbeat systolic pressure-dimension relationships were hysteretic. The first part of the study (n = 13) was to test whether the myocardium exhibited a long-term memory of prior mechanical events. Measurements obtained 30 and 120 s after volume loading revealed no residual differences in pressure or dimension compared with preinjection values. Thus the phenomenon was transient and complete (reversible) by 30 s. To better characterize this event, the temporal effects of myocardial loading were studied (n = 8). A randomized comparison of two different rates of volume infusions (27 +/- 2 vs. 56 +/- 2 ml/s, P less than 0.001) was performed. Varying the volume loading resulted in similar increases in peak left ventricular pressure (35 +/- 3 vs. 31 +/- 3 mmHg) but at different increments of development, i.e., greater than 5-7 cardiac cycles at the slower rate of volume infusion vs. greater than 2-3 cardiac cycles (P less than 0.001) at the faster rate. The isochronal systolic pressure-dimension relationships were quantitated by measuring the area of the hysteretic relationship and its slope.(ABSTRACT TRUNCATED AT 250 WORDS)
Independent role of arterial O2 tension in local control of coronary blood flow
Authors: Baron J. F. , Vicaut E. , Hou X. , Duvelleroy M.
Published: December 2017

The aim of this study of a blood-perfused isolated rabbit heart preparation was to differentiate the effects on coronary resistance of large changes in arterial O2 tension (arterial PO2 = 45-400 Torr) from the effects of variations in arterial O2 content or myocardial O2 delivery. Standard stored human blood was resuspended in Krebs-Henseleit buffer and was oxygenated to obtain normal PO2, high PO2, and low PO2. Hemoglobin concentrations were adjusted to obtain the same arterial O2 content (CaO2) for the three PO2s. In a first set of experiments, in which coronary blood flow (CBF) was free and adapted to a constant perfusion pressure, switching from control [138 +/- 17 (SE) Torr] to high PO2 blood (380 +/- 27 Torr) induced a significant decrease in CBF and myocardial O2 consumption (MVO2). Switching from control (125 +/- 3 Torr) to low PO2 blood (49 +/- 5 Torr) induced a significant increase in CBF and MVO2. In a second set of experiments, the switch from control (159 +/- 5 Torr) to high PO2 (389 +/- 32 Torr) was performed in a preparation in which CBF and consequently O2 delivery were constant. Under these conditions, the increase in perfusion pressure demonstrated that PO2 affected coronary resistance, even though the O2 delivery was constant. No significant change in myocardial performance was observed in any of these experimental procedures. These results show that arterial PO2 may affect coronary blood flow regulation independently of any mediation by the autonomic nervous system and of any associated changes in O2 content or O2 delivery.
Prediction of coronary blood flow with a numerical model based on collapsible tube dynamics
Authors: Guiot C. , Pianta P. G. , Cancelli C. , Pedley T. J.
Published: December 2017

We present a theoretical, hydrodynamic model of the vascular system feeding the left ventricle from which the inflow and outflow waveforms can be predicted given the waveforms of aortic and left ventricular pressure. The main feature of the model is that the central portion of the tubes representing intramyocardial vessels is subjected to an external pressure equal to left ventricular pressure, and they therefore collapse (and empty) when that pressure exceeds the internal pressure. The model is a one-dimensional model, so that the propagation of the collapse waves into the vessels can be properly described; this process takes a finite time, and volume change is not in phase with transmural pressure change. Parameters of the model are assessed from independent physiological data. The predicted inflow waveform is compared with experimental data, and the model is shown to reproduce all the main features, in particular the second minimum of flow rate in late systole as well as the first minimum in early systole. The corresponding lumped-parameter model, which cannot take account of wave propagation, is shown not to agree with experiments and in particular to predict unphysiological spikes in the inflow waveform.
Role of platelet-activating factor and eicosanoids during endotoxin-induced lung injury in pigs
Authors: Olson N. C. , Joyce P. B. , Fleisher L. N.
Published: December 2017

We hypothesized that platelet-activating factor (PAF) and eicosanoids might be important mediators of endotoxin-induced respiratory failure in pigs. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3 h in the presence and absence of SRI 63-675, a specific PAF receptor antagonist. During phase I (i.e., 0-2 h), endotoxin caused pulmonary hypertension and hypoxemia, decreased cardiac index, increased pulmonary vascular resistance, and increased plasma concentrations of thromboxane B2 (TxB2), prostaglandin (PG)F2 alpha, and 6-keto-PGF1 alpha. These phase I effects were attenuated or blocked by SRI 63-675 (10 mg/kg before endotoxin + 3 mg.kg-1.h-1 during endotoxemia). During phase II endotoxemia (i.e., 2-4 h), the PAF receptor antagonist blocked endotoxin-induced pulmonary edema and hypoxemia and increased relative permeability index of the alveolar-capillary membrane. SRI 63-675 also blocked the endotoxin-induced increases in plasma and bronchoalveolar lavage fluid concentrations of leukotriene B4 (LTB4). Ex vivo stimulation of whole blood with calcium ionophore caused large increases in plasma concentrations of TxB2 and LTB4. These increases were not significantly modified in blood derived from pigs treated with SRI 63-675, indicating no inhibition of cyclooxygenase or 5-lipoxygenase and suggesting that the in vivo effects were PAF receptor mediated. We conclude that PAF plays an important role in the release of eicosanoids during endotoxemia and in mediating, either directly or indirectly, endotoxin-induced lung injury in anesthetized pigs.
Ischemia and reperfusion induced formation of eicosanoids in isolated rat hearts
Authors: Engels W. , Van Bilsen M. , De Groot M. J. , Lemmens P. J. , Willemsen P. H. , Reneman R. S. , Van der Vusse G. J.
Published: December 2017

Isolated, ejecting rat hearts, perfused with Krebs-Henseleit buffer, were exposed to various periods of global ischemia. Arachidonic acid (AA) accumulated significantly in the ischemic heart when the duration of ischemia exceeded 45 min. During 30 min of reperfusion, tissue levels of AA raised steadily to values of 10.5, 17.7, and 63.1 nmol/g, after 30, 45, and 60 min of ischemia, respectively. During reperfusion, significant amounts of AA metabolite prostacyclin (determined as stable metabolite 6-ketoprostaglandin F1 alpha, by radioimmunoassay and high-performance liquid chromatography) were released after 30, 45, and 60 min of ischemia. Beside prostacyclin, only small amounts of thromboxane B2 could be found during reperfusion. In contrast to increasing amounts of AA in reperfused tissue, prostacyclin release was maximal during the first 5 min of reperfusion and declined rapidly thereafter. Relatively small proportions of the accumulated AA are converted into prostacyclin, i.e., less than 1%. When hearts were treated with mepacrine, AA accumulation was almost completely abolished during 60 min of ischemia. The cumulative release of prostacyclin was found to be reduced to 134 pmol/g during 30 min of subsequent reperfusion. A close, rectilinear correlation could be established between AA accumulation and cumulative prostacyclin release during reperfusion. It is likely, however, that the site of bulk AA accumulation and that of conversion of AA into eicosanoids does not coincide in the ischemic and reperfused heart because of the low conversion rates of AA into prostacyclin and the different time courses of AA accumulation and prostacyclin production after reinstallation of flow.
Arterial pH modulation of regional cerebral blood flow during hyperammonemia in dogs
Authors: Weigle C. G. , Koehler R. C. , Brusilow S. W. , Traystman R. J.
Published: December 2017

Acute hyperammonemia at normal arterial pH causes selective increases in midbrain blood flow in dogs. Unexpectedly, further increases occur with hypocapnia. We investigated whether metabolic acidemia and alkalemia modulate the distribution of ammonium across the blood-brain barrier and if, in turn, midbrain blood flow is effectively modulated. In dogs anesthetized with pentobarbital sodium, hyperammonemia (approximately 940 microM) was produced by a 210-min infusion of ammonium acetate. Concurrent infusion of NaHCO3 increased arterial pH to 7.53 +/- 0.02 (SE), whereas HCl infusion decreased pH to 7.11 +/- 0.01. Normocapnia was maintained. Cerebrospinal fluid [HCO3-] increased 5 mM with alkalemia (one-half of the increase in blood) and was unchanged with acidemia. Thus cerebrospinal fluid [H+]/blood [H+] was greater with alkalemia than acidemia. The corresponding ratio for ammonium was likewise greater with alkalemia (0.70 +/- 0.06) than acidemia (0.44 +/- 0.08). Microsphere-determined blood flow to midbrain more than doubled in the alkalemic group but was unchanged in the acidemic group. No other region along the neuraxis or in cerebrum showed increased blood flow in either hyperammonemic group. Alkalemia without hyperammonemia did not increase midbrain blood flow. Thus metabolic acidemia-alkalemia significantly alters ammonium partitioning into cerebrospinal fluid, and this alteration is sufficiently great to exert a specific physiological effect manifested by changes in midbrain blood flow.
Effects of atrial natriuretic peptide on isolated bovine mesenteric lymph vessels
Authors: Ohhashi T. , Watanabe N. , Kawai Y.
Published: December 2017

The mode of action of atrial natriuretic peptide (ANP) on bovine mesenteric lymphatics was investigated by recording isometric tensions in isolated cylindrical segments. ANP in concentrations from 5 to 30 ng/ml caused dose-related decreases in the rhythm and amplitude of spontaneous contractions. No tachyphylaxis was observed in the ANP-induced responses in lymph vessels. Addition of ANP in a low concentration ranging from 3 to 100 ng/ml produced a dose-dependent relaxation in the lymphatic preparations precontracted by 10(-7) M bradykinin. The ANP-induced relaxation was not modified by pretreatment with 5 x 10(-7) M propranolol, 5 x 10(-7) M atropine, 10(-6) M cimetidine, 5 x 10(-5) M aspirin, or 10(-5) M ouabain. The mechanical rubbing of endothelial cells in the lymph vessels caused no significant effect on the ANP-induced relaxation. The relaxation, however, was significantly reduced by pretreatment with 10(-5) M methylene blue. These results suggest that ANP in a low concentration seems to inhibit lymph transport through a reduction of spontaneous contractions and a marked relaxation of lymphatic smooth muscles in bovine mesenteric lymphatics and that ANP may produce the relaxation through synthesis of guanosine 3',5' cyclic monophosphate, independent of the lymphatic endothelium.
Hypothermia increases calcium content of hypoxic myocytes
Authors: Navas J. P. , Anderson W. , Marsh J. D.
Published: December 2017

To test the hypothesis that hypothermia prevents myocardial Ca2+ loading during reoxygenation, we examined the effects of 2 h of hypoxia with and without hypothermia on the Ca2+ content of cultured chick embryo ventricular cells. When compared with hypoxic cells at 37 degrees C, hypoxia at 11 degrees C (hypothermia) augmented the 45Ca content of cardiocytes after 30 min of normothermic reoxygenation from 3.85 +/- 0.2 to 4.7 +/- 0.1 nmol/mg protein (P less than 0.001). The Na+ content of hypoxic myocytes was also increased at the end of 2 h of hypoxia from 648 +/- 59 to 1,026 +/- 68 nmol/mg protein in cells exposed to hypoxia at 11 degrees C (P less than 0.001). Hypothermia ameliorated hypoxia-induced depression of cellular ATP content and did not result in significant membrane injury as determined by lactate dehydrogenase release. These data indicate that hypothermia augments rather than decreases the Ca2+ content of hypoxic myocytes during reoxygenation after hypoxia. Ca2+ loading appears to be secondary to an increase in Na+ content, creating a favorable gradient for Ca2+ influx through Na(+)-Ca2+ exchange or an unfavorable gradient for Ca2+ extrusion.
Angiotensin II and alpha-agonist. II. Effects on ovine fetoplacental prostaglandins
Authors: Yoshimura T. , Magness R. R. , Rosenfeld C. R.
Published: December 2017

The fetoplacental vasculature is more sensitive to angiotensin II (ANG II) than to alpha-agonists, possibly reflecting their differing effects on vascular prostaglandin (PG) production. To examine this we studied in fetal sheep (123-138 days) the effects of ANG II (n = 7; 0.057, 1.15, and 5.73 micrograms/min) and phenylephrine (PHEN, n = 7; 0.306, 1.53, and 7.64 micrograms/min) on mean arterial pressure (MAP), heart rate (HR), and simultaneous measurements of umbilical arterial and venous PGE2, 6-keto-PGF1 alpha (PGI2) and thromboxane B2 (TxB2) concentrations. ANG II increased MAP and decreased HR dose dependently (P less than 0.05). Basal umbilical venous plasma PGE2 levels exceeded PGI2 (P less than 0.001) and increased during ANG II infusions from 502 +/- 63 to 516 +/- 113, 647 +/- 188, and 1,968 +/- 541 pg/ml (mean +/- SE, P less than 0.05), as did venous-arterial concentration differences (129 +/- 26 to 179 +/- 47, 244 +/- 58, and 1,287 +/- 507 pg/ml, respectively; P less than 0.05). ANG II also increased umbilical venous PGI2 levels from 110 +/- 13 to 116 +/- 24, 144 +/- 46, and 680 +/- 147 pg/ml (P less than 0.01) and the venous-arterial concentration difference from 3 +/- 6 to 20 +/- 16, 41 +/- 27, and 405 +/- 122 pg/ml (P less than 0.05), respectively. ANG II had no effect on plasma TxB2, and no umbilical venous-arterial concentration differences existed. Although PHEN increased MAP and decreased HR, plasma eicosanoid concentrations were unaltered. The fetus is more sensitive to ANG II than PHEN; however, only ANG II increased placental PGE2 and PGI2 production.(ABSTRACT TRUNCATED AT 250 WORDS)
Superoxide dismutase reduces permeability and edema induced by hypertension in rats
Authors: Zhang X. M. , Ellis E. F.
Published: December 2017

These studies determined whether superoxide dismutase (SOD), an oxygen free-radical scavenger, affects brain and lung vascular protein extravasation and water content after acute hypertension. Hypertensive vascular injury was induced in rats by bolus injection of norepinephrine. Vascular permeability was assessed with 125I-labeled serum albumin and water content determined by wet and dry weight measurement. Pretreatment with SOD prevented or reduced the increase in brain water content and brain and lung protein extravasation caused by hypertension, whereas inactivated SOD had no effect. SOD also reduced mortality caused by acute hypertension. Treatment 30 min after hypertension with SOD or polyethylene glycol-conjugated SOD reduced edema caused by hypertension. In some instances SOD reduced tissue water content and permeability to below normal control levels found in animals without hypertension. These studies show that oxygen radicals contribute to increases in permeability and water content after hypertensive injury and also suggest that oxygen radicals may contribute to regulation of vascular permeability and water content in normal animals.