bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of veins and cerebral venous pressure in disruption of the blood-brain barrier.
Authors: Mayhan W G , Heistad D D
Published: June 2012

The goal of this study was to determine whether increases in cerebral venous pressure contribute to, and may account for, disruption of the blood-brain barrier during acute hypertension and hyperosmolar stimuli. We studied the relation between pial venous pressure and disruption of the blood-brain barrier during acute arterial hypertension, superior venae cavae occlusion, and superfusion with hyperosmolar arabinose. Sprague-Dawley rats were studied using intravital fluorescent microscopy and fluorescein-labelled dextran (mol. wt. = 70,000). Disruption of the blood-brain barrier was characterized by the appearance of microvascular leaky sites and quantitated by the clearance of fluorescein dextran. We measured pressure (servo null) in pial arterioles and venules 40-60 micron in diameter. Acute hypertension, occlusion of the superior venae cavae, and hyperosmolar arabinose produced leaky sites primarily in venules. Acute hypertension increased arteriolar pressure and also venular pressure, from 7 +/- 1 (mean +/- SE) to 28 +/- 2 mm Hg. Clearance of fluorescein dextran increased from 0.03 +/- 0.01 to 2.90 +/- 0.40 ml/sec X 10(-6). Occlusion of the superior venae cavae increased pial venous pressure from 7 +/- 1 to 30 +/- 3 mm Hg, and clearance of fluorescein dextran, from 0.02 +/- 0.01 to 3.10 +/- 0.59 ml/sec X 10(-6). In contrast to acute hypertension, there was a decrease in arterial and pial arteriolar pressure during occlusion of the superior venae cavae. Thus, similar increases in venous pressure during acute hypertension and superior venae cavae occlusion, despite directionally opposite changes in arterial and arteriolar pressure, produced similar disruption of the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
Excitation-contraction coupling in myocardium of nonhibernating and hibernating chipmunks: effects of isoprenaline, a high calcium medium, and ryanodine.
Authors: Kondo N
Published: June 2012

The electromechanical responses to isoprenaline and a high calcium medium on cardiac muscles from nonhibernating and hibernating chipmunks were studied in the presence and the absence of ryanodine. In nonhibernating animal preparations, isoprenaline (5 X 10(-8) M) caused a marked positive inotropic effect with an increase in the amplitude of the action potential plateau and augmented the slow action potential in muscle depolarized with 26 mM K+. In hibernating animal preparations, isoprenaline failed to cause a positive inotropic effect in spite of an increase in the amplitude of action potential plateau and slow action potentials. Similar inotropic effects were caused in the two preparations when extracellular calcium was raised to 6 mM, but action potential plateau and slow action potentials of the two preparations were less affected by this procedure; only in nonhibernating animal preparations was the amplitude of the slow action potential slightly increased. Ryanodine (2 X 10(-6) M) partially inhibited the contraction but augmented the action potential plateau and slow action potentials in nonhibernating animal preparations, while in hibernating animal preparations, it eliminated the contraction and severely inhibited the action potential plateau and slow action potentials. The electrical effects of isoprenaline on the two preparations and of a high calcium medium on nonhibernating animal preparations were more pronounced in the presence of ryanodine than in the absence of it. However, the electrical activity on hibernating animal preparations was unaffected by a high calcium medium in either the presence or absence of ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
Communication between feed arteries and microvessels in hamster striated muscle: segmental vascular responses are functionally coordinated.
Authors: Segal S S , Duling B R
Published: June 2012

Pressures in the primary arterioles of the cremaster muscle are reported to be approximately 50% of systemic, indicating that arterial resistance proximal to microvessels is high and may limit maximal blood flow. With no change in arterial resistance, increases in perfusion normally associated with muscle work either could not occur or would require increments in systemic pressure far greater than those actually observed in vivo. Therefore, we hypothesized that the small arteries feeding the muscle may participate in the hyperemic response. To test this hypothesis, male golden hamsters (n = 31, 118 g) were anesthetized (pentobarbital, 70 mg/kg i.p.), and the right cremaster was opened to expose its feed arteries, which originated from the iliac artery. Preparations were superfused and maintained at 35 +/- 1 degree C. Feed arteries had substantial tone, as shown by the fact that topical acetylcholine, applied at supramaximal concentration, dilated these vessels from 115 +/- 8 microns at rest to 158 +/- 9 microns (mean +/- SE; n = 38 vessels; p less than 0.01), corresponding to an estimated 4.4-fold increase in conductance. Stimulation of the sectioned motor nerve (8 Hz, 30 seconds) induced striated muscle contraction and increased feed vessel diameter from 93 +/- 5 microns to 116 +/- 5 microns (n = 14; p less than 0.01), consistent with a 2.6-fold increase in conductance. A 5-minute occlusion of the iliac artery resulted in feed artery dilation of similar magnitude. Supramaximal doses of acetylcholine applied topically to the distal portions of the cremaster resulted in striated muscle contraction and a dilation that propagated upstream to increase feed artery diameter by 25%.(ABSTRACT TRUNCATED AT 250 WORDS)
Membrane electrical properties of vesicular Na-Ca exchange inhibitors in single atrial myocytes.
Authors: Bielefeld D R , Hadley R W , Vassilev P M , Hume J R
Published: June 2012

Na-loading single frog atrial cells produce changes in membrane currents that are similar to the creep currents originally observed in Na-loaded cardiac Purkinje fibers. Exposure to the Na ionophore, monensin, was used to induce creep currents in isolated atrial cells. The sensitivity of myocardial creep currents to three compounds that have been shown to be inhibitors of Na-Ca exchange flux activity in isolated sarcolemmal vesicles was assessed. Dodecylamine, quinacrine, and the amiloride analog, 3',4'-dichlorobenzamil block creep currents at concentrations well below those required to block Na-dependent Ca uptake in sarcolemmal vesicles. The estimated Ki's for inhibition of myocardial creep currents were 3 microM for dodecylamin, 10 micron for quinacrine, and 4 microM for 3',4'-dichlorobenzamil. The sensitivity of creep currents to these compounds is consistent with the hypothesis that creep currents may represent the electrogenic activity of a Na-Ca exchange carrier. In an additional series of experiments, the relative specificity of these compounds was tested by examining their effects on myocardial membrane channels. Both dodecylamine and 3',4'-dichlorobenzamil were found to inhibit myocardial Ca and K currents over the same range of concentrations in which block of exchange activity occurs. These results seriously question the use of these exchange carrier inhibitors as selective experimental probes for defining the role of Na-Ca exchange in various physiological processes.
Effect of adenosine on atrioventricular conduction. I: Site and characterization of adenosine action in the guinea pig atrioventricular node.
Authors: Clemo H F , Belardinelli L
Published: June 2012

Adenosine has a negative dromotropic effect and modulates hypoxia-induced atrioventricular (AV) conduction delay. To further characterize the negative dromotropic effect of adenosine in the guinea pig heart, we determined the site of adenosine-induced AV conduction block; the effect of uptake and deamination of adenosine on its concentration-negative dromotropic effect, and the adenosine receptor that mediates this action. In isolated AV node preparations (n = 16), adenosine in a dose-dependent manner decreased significantly the duration and amplitude of the action potential of atrionodal and nodal cells and, in addition, markedly depressed the maximum rate of rise of the action potential of nodal cells. At high concentrations (greater than 20 microM), adenosine rendered nodal cells inexcitable. In isolated perfused hearts (n = 7), adenosine (5.7 microM) prolonged total AV conduction time by 21 +/- 2 msec. Of this prolongation, 83% was due to an increase in the nodal-to-His-bundle interval and the remaining 17% to an increase in the atrionodal to nodal interval. Infusion of adenosine to cause a 50% increase (EC50) in atria-to-His bundle (AH) interval prolongation resulted in a perfusate (arterial) adenosine concentration of 5.0 +/- 0.6 microM and effluent (venous) adenosine concentrations of 2.8 +/- 0.4 microM, i.e., an arteriovenous difference of 44% (n = 4). When adenosine uptake and deamination were inhibited with dipyridamole (0.5 microM) plus erythro-9-(2-hydroxy-3-nonyl)adenine (5 microM), respectively, the EC50s were 0.28 +/- 0.02 (perfusate) and 0.32 +/- 0.03 microM (effluent). These data indicate that when nucleoside metabolism is inhibited, arterial and venous concentrations of adenosine reach equilibrium. In an additional 10 hearts, the following rank order of potency of adenosine agonists in causing AH interval prolongation was found: N6-cyclopentyladenosine greater than N6-(L-2-phenyl-isopropyl)adenosine greater than 5'-N-ethylcarboxyamidoadenosine greater than or equal to 2-chloroadenosine greater than adenosine, which is compatible with activation of an A1-type receptor. In summary: the site of adenosine-induced AV conduction block is the nodal zone of the AV node, when adenosine uptake and deamination are inhibited, adenosine in concentrations similar to that released by hypoxia causes significant AH interval prolongation, and the adenosine receptor mediating the negative dromotropic effect of adenosine is of the A1-type.
Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists.
Authors: Ashton J H , Schmitz J M , Campbell W B , Ogletree M L , Raheja S , Taylor A L , Fitzgerald C , Buja L M , Willerson J T
Published: June 2012

We tested the hypothesis that thromboxane A2 and thromboxane A2/PGH2 receptor occupation are important in mediating cyclical reductions in coronary blood flow (CFVs) in concentrically narrowed canine coronary arteries. Two potent and selective thromboxane A2/PGH2 receptor antagonists, SQ29,548 and SQ28,668 eliminated CFVs and restored a normal pattern of blood flow through the severely narrowed vessels in 77 and 75% of the dogs, respectively. CFVs were eliminated within several minutes of an intravenous bolus injection of SQ29,548 or SQ28,688. A continuous infusion of SQ29,548 (0.2 mg/kg X min) prevented the recurrence of CFVs throughout the duration of its infusion. Left atrial infusion of the thromboxane A2 mimetic, U46619, restored CFVs in 5 of 8 SQ29,548-treated and in 5 of 7 SQ28,668-treated dogs. Circulating concentrations of the stable metabolites of TxA2 and PGI2, TxB2 and 6-keto-PGF1 alpha, respectively, were unaffected by administration of SQ29,548. However, stenosed vascular segments of the left anterior descending coronary artery (LAD) of SQ29,548-treated dogs produced significantly less thromboxane A2 than comparable segments from untreated dogs. Morphologic studies showed that stenosed coronary arteries in which CFVs had been abolished by either SQ29,548 or SQ28,668 had relatively few adherent platelets, whereas comparable coronary segments removed from untreated animals had relatively large, platelet-rich mural thrombi. SQ29,548 did not alter the synthesis of TxB2 by platelets. 6-keto-PGF1 alpha concentrations in the stenosed LAD and nonstenosed circumflex coronary arteries were not altered by SQ29,548 administration. These data suggest that the thromboxane A2/PGH2 receptor antagonists, SQ29,548 and SQ28,688, inhibit cyclic reductions in coronary blood flow in this model by preventing the accumulation of platelets at the site of a critical coronary arterial stenosis. The data also suggest that TxA2 is important in mediating the interaction between platelets and the constricted coronary artery that is responsible for the development and maintenance of CFVs in this experimental model.
Evaluation of the hereditary Syrian hamster cardiomyopathy by 31P nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy.
Authors: Markiewicz W , Wu S S , Parmley W W , Higgins C B , Sievers R , James T L , Wikman-Coffelt J , Jasmin G
Published: June 2012

The relation between metabolic and functional derangement in various cardiomyopathies has not been well characterized. This information was specifically sought in a spontaneous cardiomyopathic model. Metabolic and hemodynamic parameters were obtained in glucose-perfused beating hearts of 180-200-day-old cardiomyopathic Syrian hamsters and age-matched healthy animals. This period in the cardiomyopathic hamster lifetime is intermediary between the necrotic phase and the appearance of heart failure. We used 31P nuclear magnetic resonance spectroscopy to analyze energy metabolites and intracellular pH. Cardiomyopathic hamsters had significantly higher mole fraction values for inorganic phosphate, lower phosphocreatine mole fraction as well as lower phosphocreatine/inorganic phosphate and adenosine triphosphate/inorganic phosphate ratios. Analysis of pH indicated the presence of regions of increased acidity within the heart of myopathic hamsters. Cardiomyopathic hamsters also had significantly lower left ventricular pressure, coronary flow, and myocardial oxygen consumption. Separate groups of normal and myopathic hamsters were given verapamil for 24 hours (one injection of 4 mg/kg s.c. followed by 1.2 g/l in drinking water). Verapamil-treated myopathic hamsters had evidence of markedly improved mitochondrial function when compared with untreated animals. Left ventricular pressure and coronary flow rose to normal levels. Replacing glucose by pyruvate in the perfusate of myopathic hamsters results in a marked increase in left ventricular pressure, coronary flow, and oxygen consumption with a moderate rise in phosphocreatine. Thus, 180-200-day-old cardiomyopathic hamster heart is characterized by evidence of decreased mitochondrial function, by areas of increased acidity within the heart, and by reduced left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered norepinephrine turnover and metabolism in diabetic cardiomyopathy.
Authors: Ganguly P K , Dhalla K S , Innes I R , Beamish R E , Dhalla N S
Published: June 2012

Cardiac norepinephrine turnover and metabolism were examined in rats 8 weeks after the induction of chronic diabetes by an intravenous injection of streptozotocin (65 mg/kg). Cardiac norepinephrine concentration, norepinephrine turnover, and norepinephrine uptake were markedly increased in chronic diabetes in comparison with control values; these changes were reversible by 28-day insulin therapy. When the animals were exposed to cold for 6 hours, norepinephrine turnover rate constant increased in control and decreased in diabetic animals; cold exposure also increased norepinephrine concentration in diabetic hearts. Both cardiac norepinephrine concentration and turnover rate in diabetic rats were restored toward control values by ganglionic blockade with pentolinium. The conversion of [3H]tyrosine to [3H]catecholamine was enhanced and tyrosine hydroxylase as well as dopa decarboxylase activities were increased in diabetic hearts. The higher concentrations of [3H]normetanephrine and deaminated catechols indicated a faster metabolic rate of norepinephrine metabolism in hearts from diabetic rats; both monoamine oxidase and catechol-O-methyltransferase activities were also increased. The increased activities of the enzymes for the synthesis and metabolism of norepinephrine were not evident on treating the diabetic animals with insulin. These data not only support the view that chronic diabetes in rats is associated with increased sympathetic activity but also indicate that the cardiac norepinephrine concentration in diabetic rats may be maintained at a higher than normal level by an increased synthesis and uptake of norepinephrine in the adrenergic nerve terminals.
Contractile Properties of Glycerol-Extracted Muscle Bundles from the Chronically Failing Canine Heart
Authors: BENSON ELLIS S. , HALLAWAY BEN E. , TURBAK CHARLES E.
Published: June 2012

Chronic congestive heart failure was induced in dogs by the surgical production of tricuspid insufficiency and pulmonary stenosis. Glycerol-extracted trabecular bundles from the right and left ventricles of these dogs developed significantly less tension than did similar preparations from the hearts of normal dogs. The maximum working capacity of the bundles from failing hearts was lower than that of bundles from normal hearts, hut the rate of hydrolysis of adenosinetriphosphate was the same as that of normal heart preparations. Since glycerol-extracted muscle bundles retain the basic contractile properties of fresh, surviving whole muscle but are free from membrane, neurohormonal, ionic and pH effects and are isolated from energy-supplying systems of muscle, defective contractility and decreased working capacity of muscle bundles from failing hearts may be appropriately ascribed to physiochemical changes in the contractile protein, actomyosin. Such alterations are undoubtedly of structural significance, and are related to the conformation changes in actomyosin which characterize the contractile cycle of muscle.
Diffuse Bilateral Pulmonary Edema Associated with Unilobar Miliary Pulmonary Embolization in the Dog
Authors: SINGER DONALD , HESSER CHARLES , PICK RUTH , KATZ LOUIS N.
Published: June 2012

Unilobar injection of starch solution produced pulmonary infarction at the site of injection and diffuse bilateral pulmonary edema. The predominantly or entirely unilobar distribution of the embolizing material was established by histologic methods and by a technic using whole lung lobe suspension stained with Lugol's solution. Evidence is presented suggesting that the pulmonary edema in the nonembolized lobes is attributable to neural or neurohumoral mechanisms.
Inhibition of Dietary Hypercholesteremia and Atherogenesis in the Chicken by a New Synthetic Compound
Authors: BLOHM THOMAS R. , LERNER LEONARD J. , KARIYA TAKASHI , WINJE MARIE E.
Published: June 2012

Addition of 0.1 per cent MER-13 to an atherogenic, high-cholesterol diet largely prevented the development of hypercholesteremia and aortic and coronary artery atheromatosis in cockerels. The hypocholesteremic effect was not obtained when MER-13 was administered following the removal of cholesterol from the diet. It is concluded that MER-13 inhibits absorption of cholesterol from the gastrointestinal tract.
Influence of Modified Corticosteroids on Antitryptic Activity of Rat Serum
Authors: BLATT WILLIAM F. , SCHAEFER EDWARD H. , ZYLBER JOHN , JENSEN H.
Published: June 2012

This report deals with the influence of cortisone, prednisolone, prednisone and 9 α-fluorocortisol acetate on the serum antitryptic activity of normal, splenectomized, adrenalectomized and adrenalectomized-splenectomized rats. Elevation of serum antitryptic activity was most consistent with 9α-fluorocortisol acetate administration. Prednisolone and prednisone proved less effective while cortisone-induced changes were of small magnitude.
Sodium Restriction and Reserpine Administration in Experimental Renal Hypertension
Authors: REDLEAF PAUL D. , TOBIAN LOUIS
Published: June 2012

An increase of intracellular potassium and sodium content in the wall of the aorta occurs in experimental renal hypertension. The elevated potassium tends to revert toward normal when blood pressure is again lowered with reserpine. The efficacy of rigid restriction of dietary sodium intake in decreasing blood pressure proved quite limited. The development of renal hypertension in the face of rigid sodium restriction further demonstrates that dietary sodium plays no more than an enhancing role in the pathogenesis of renal "isehemic" hypertension.
Use of Trypsin in the Treatment of Experimental Coronary Thrombosis
Authors: CONRAD CARL R. , GEIS ARTHUR F.
Published: June 2012

A method for the production of experimental coronary thrombosis in dogs by the injection of thrombin into the anterior descending branch of the left coronary artery is presented. The clot-dissolving properties of trypsin in the form of Tryptar and Enzar were evaluated. The effect of trypsin was also studied in relation to changes in the clotting mechanism of the blood for the purpose of determining tolerated doses. Regardless of amounts of enzyme or time of administration, there was no evidence to indicate prevention of myocardial infarction.
Effect of Sodium and Calcium on Vascular Reactivity
Authors: ZSOTÉR THOMAS , SZABO MICHAEL
Published: June 2012

A study was made in the rat of variations in sodium and calcium content of the diet as Possible factors influencing vascular reactivity. The latter was estimated by the sensitivity of the mesoappendix vessels to epinephrine.
Baroceptor and Chemoceptor Reflexes in Monkeys
Authors: HEYMANS C.
Published: June 2012

Experiments on monkeys show that their carotid sinus areas are provided with baroceptors and chemoceptors acting reflexively on circulation and respiration.
Pressure and Oxygen Content Measurements Distal to Temporary and Permanent Unilateral Occlusion of a Pulmonary Artery in Dogs
Authors: CEDKOWICH LEON
Published: June 2012

Both pressure and oxygen content of blood in the left pulmonary artery distal to an inflated balloon simulate that observed in the wedged cardiac catheter position. Clamping the ipsilateral pulmonary veins after inflation of the left pulmonary artery balloon, in this or in the reverse order, produces a rise in pressure distal to the balloon that exceeds the resting left pulmonary artery pressure. No corresponding increase in oxygen content of blood sampled distal to the inflated balloon, compared with that in the unoccluded pulmonary artery, could be demonstrated. This contrasts with the flow of arterialised blood that had been sampled after some months of permanent left pulmonary artery occlusion from the same position. The pressures both proximal and distal to the site of permanent occlusion are approximately the same.
A Serum Protein System Affecting Contractility of the Frog Heart Present in Increased Amounts in Patients with Essential Hypertension
Authors: HAJDU STEPHEN , LEONARD EDWARD
Published: June 2012

Plasma samples from a group of patients with severe essential hypertension were formerly shown to have a cardiotonic action on the isolated frog heart. This effect is significantly greater than that observed with plasma from normal persons or those with other diseases. The material in plasma responsible for this action is a system of 3 proteins. These proteins have been distinguished by fractionation with sodium sulfate, and are found among the serum globulins. The protein, the concentration of which determines the activity of the whole system, is called component L. When applied to the frog heart it becomes strongly bound. Two other proteins are needed, one precipitated between 0 and 17 per cent sodium sulfate, the other between 22 and 30 per cent sodium sulfate. The 0 to 17 fraction is thought to require calcium for its activity, which is bound to the protein. Calcium can be released by the addition of component L in a reaction which is dependent on temperature, reversal being possible in high calcium concentrations in the cold. The protein system described causes contracture of frog heart muscle in the absence of ionic calcium, in contrast to other well-known contracture-causing agents which require the presence of free calcium for activity.
Cardiac Hypertrophy in Rats with Phenylhydrazine Anemia
Authors: NORMAN TOM D. , MCBROOM ROBERT D.
Published: June 2012

The effect of phenylhydrazine-produced anemia upon the hearts of rats was studied with observations upon the accompanying hypertrophy. Results indicated that the mechanism of hypertrophy under these conditions may be one of myocardial injury rather than mechanical.
Effect of Biphenylylbutyric Acid on the Cholesterol and Phospholipid Metabolism in the Rat
Authors: RANNEY R. E. , WEISS SALLY B.
Published: June 2012

The effects of treatment of rats with biphenylylbutyric acid were assessed by measuring the amount of acetate-1-C
14
incorporated into the cholesterol and phospholipid of several tissues. The drug inhibited the inclusion of the label into the plasma and hepatic lipid fractions. The treatment had no significant effect upon the lipid metabolism of either the testis or the adrenal. In the aorta, although the incorporation of the labeled acetate into cholesterol was unchanged, the amount of label found in the phospholipids was strikingly enhanced by the treatment. The unique nature of aortic lipid metabolism as evidenced by this work and previous reports is discussed.
Relation between myocardial perfusion and left ventricular function following acute coronary occlusion: disproportionate effects of anterior vs. inferior ischemia.
Authors: Schneider R M , Morris K G , Chu A , Roberts K B , Coleman R E , Cobb F R
Published: June 2012

This study examined the relation between left ventricular (LV) function and the severity of acute myocardial ischemia in a conscious dog model. The LV ejection fraction (EF) was measured by multigated equilibrium radionuclide angiography, and regional myocardial blood flow was measured with radioactive microspheres before and 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD, 13 dogs) or left circumflex (LC, 13 dogs) coronary artery. Two methods were used to evaluate the extent of ischemia. The first method determined the mass of myocardium that was ischemic based on different degrees of reduced blood flow. The second method estimated the severity of ischemia expressed as blood flow deficit resulting from each coronary occlusion. Global LV function was very sensitive to ischemia, and the relation between change in function and the degree of ischemia were described best by linear functions. The best linear correlation between mass of ischemic myocardium and percent reduction in EF resulted from the ischemic region defined as all tissue with 25% or greater reduction in blood flow, r = 0.84 for LAD (Y = 0.96X + 1.8) and r = 0.75 for LC (Y = 0.53X + 2.0) occlusions. Defining ischemic mass by more severe reduction in blood flow resulted in exclusion of ischemic myocardium that affected function. The myocardial blood flow deficit also correlated linearly with percent reduction in EF, r = 0.89 for LAD (Y = 1.31X + 2.7) and r = 0.81 for LC (Y = 0.83X - 0.1) occlusions. The slope of the regression lines using both analyses of ischemia were significantly greater (p less than 0.01) for LAD than LC occlusions, indicating that for comparable degrees of ischemia LAD as compared to LC occlusion decreased EF to a greater extent. Calculation of EF from attenuated corrected volumes resulted in small changes in LAD, but not LC, EF and did not account for the disproportionate effects of LAD and LC ischemia. In a separate group of studies (n = 18) EF measured by radionuclide angiography after LAD or LC occlusions correlated well with biplane contrast angiography r = 0.93, SEE 5.1. These data suggest that disproportionately greater effects of LAD compared to LC ischemia on global EF in the dog are due primarily to different pathophysiologic responses to ischemia.
Measurement by fluorescence of interstitial adenosine levels in normoxic, hypoxic, and ischemic perfused rat hearts.
Authors: Fenton R A , Dobson J G
Published: June 2012

An improved assay was used to investigate the effects of hypoxia or ischemia on interstitial fluid and coronary venous effluent levels of adenosine in isolated perfused nonworking rat hearts. The adenosine in 5- to 10-microliter samples of left ventricular epicardial surface transudates and coronary effluents was reacted with chloroacetaldehyde, and the fluorescent derivative (1,N6-ethenoadenosine) was quantitated using high pressure liquid chromatography and fluorescence detection. Hearts responding to hypoxia could be separated into two groups. In one group of hearts, the control (normoxic) transudate and effluent adenosine concentrations were 94 +/- 24 and 41 +/- 6 pmol/ml, respectively. These values increased by 118 and 96%, respectively, with 5 minutes of hypoxia (30% O2), and returned to control levels 5 minutes after resumption of normoxia. In a second group of hearts, the normoxic control levels of adenosine in the transudates (42 +/- 7 pmol/ml) and coronary effluents (62 +/- 17 pmol/ml) were increased with hypoxia by 174 and 1,178%, respectively. However, the transudate levels continued to rise for 5 minutes after resumption of normoxic perfusion while effluent levels fell. In another series of hearts, global ischemia for 30 seconds elicited an elevation of transudate adenosine levels by 362 to 641% above control (58 +/- 15 pmol/ml) as determined 30 seconds after resumption of perfusion flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased intrinsic pumping of intestinal lymphatics following hemorrhage in anesthetized sheep.
Authors: Hayashi A , Johnston M G , Nelson W , Hamilton S , McHale N G
Published: June 2012

The return of fluid and protein to the bloodstream by the lymphatic circulation may play an important role in reconstituting intravascular volume following hemorrhage. In this study, we have defined the lymph-flow changes that occur in cannulated mesenteric lymphatics following a 25% blood loss in anesthetized sheep and investigated the effects of hemorrhage on the intrinsic contractile activity (lymph pumping) of these vessels in vivo using a new model system. The removal of 25% of the calculated blood volume resulted in increases in lymph flow over a 6-hour period, with peak changes to 3.5 times the prebleed levels. Systemic arterial pressures dropped to roughly 50% of control values immediately following the bleed and returned to control in 3 hours. To directly assess the effects of hemorrhage on lymphatic pumping, a segment of intestinal lymphatic was isolated from all lymph input and supplied with fluid from a reservoir. While there was no net pressure driving fluid through the duct, a transmural distending pressure was applied to the vessel, which stimulated resting lymphatic contractions and fluid pumping. A 25% blood loss resulted in increased activity of the lymph pump; up to 6 times more fluid was propelled through this "isolated" vessel in vivo than in similar preparations in sheep that were not bled (p less than 0.01). Measurements of fluid pulse pressures in this preparation indicated increased pumping frequency and/or force after hemorrhage compared with prebleed levels. We conclude that lymphatic contractile activity is stimulated after a blood loss independent of changes in lymph formation and speculate that this mechanism may play an important role in the reexpansion of the vascular space.
Mechanisms of vasoconstriction induced by 9,11-epithio-11,12-methano-thromboxane A2 in the rabbit coronary artery.
Authors: Kanmura Y , Itoh T , Kuriyama H
Published: June 2012

The vasoconstrictor effects of 9,11-epithio-11,12-methano-thromboxane A2 (STA2) on smooth muscle strips of the rabbit coronary artery have been investigated in vitro. Right coronary artery (RCA) was more responsive to STA2 than either the left anterior descending or the circumflex coronary artery. On endothelium-denuded RCA strips, the sensitivity and responsiveness to STA2 were greater than observed on intact muscle strips. A thromboxane(Tx)-antagonist, (9,11), (11,12)-dideoxa-9 alpha, 11 alpha-dimethylmethano-11,12-methano-13,14-dihydro-13-aza-14-oxo-15 - cyclopenthyl-16,17,18,19,20-pethanol-15-epi-TxA2 (ONO-3708), inhibited the STA2-induced contraction, whereas atropine or prazosin had no effect. Nifedipine partly inhibited the STA2-induced contraction, one half of which was still evoked in Ca2+-free solution. When acetylcholine was applied prior to the application of STA2 in Ca2+-free solution, the STA2-vasoconstriction disappeared. In saponin-treated chemically skinned muscle strips, STA2 itself had no effect on either the pCa-tension relation or on the release of Ca2+ from intracellular stores. However, inositol 1,4,5-trisphosphate released Ca2+ from such stores, and 12-o-tetradecanoyl phorbol-13-acetate (TPA) and 1,2-diolein, activators of protein kinase C, enhanced the contraction induced by 0.3 microM Ca2+. It is concluded that STA2 acts on the TxA2 receptor and produces contraction due to an increase in both voltage- and agonist(receptor)-dependent Ca2+ influx. STA2 also releases Ca2+ from ACh- and caffeine-sensitive storage sites.
Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of angiotensins.
Authors: Kifor I , Dzau V J
Published: June 2012

Cultured bovine aortic endothelial cells (BAEC) contain renin and angiotensinogen. To examine whether angiotensins are synthesized intracellularly and secreted by these cells, we assayed cell extracts as well as serum-free media of intact confluent BAEC. Angiotensins were identified by their retention time on reverse phase high performance liquid chromatography and direct radioimmunoassay. BAEC and their media contain angiotensin II and angiotensin III. The rate of angiotensin accumulation in the media was a nonlinear function of time; the highest rate occurred in the first 15 minutes. The amount of angiotensin II accumulated in 30 minutes exceeded 200% of the intracellular concentration and that of angiotensin III exceeded 500% of the initial intracellular content. Neither renin nor angiotensinogen could be detected in the media. The viability of these cells was supported by low lactic dehydrogenase activity in the media (less than 0.5% of cellular level). These data suggest that BAEC is capable of synthesizing and secreting angiotensins. We postulate that this endothelial-derived angiotensin system may play an important paracrine or autocrine role in influencing local vascular tone.
Quantitative autoradiographic delineation of the distribution of beta-adrenergic receptors in canine and feline left ventricular myocardium.
Authors: Murphree S S , Saffitz J E
Published: June 2012

The distribution of adrenergic receptors in specific components of the heart such as vessels and myocytes cannot be determined easily with assays of membranes prepared from homogenates of whole tissue. Accordingly, we characterized the binding of the potent nonsubtype selective antagonist [125iodo]cyanopindolol to beta-receptors in unfixed transmural slices of feline and canine left ventricle. Specific binding ratios greater than 90% were achieved at radioligand concentrations near Kd and greater than 80% at saturating ligand concentrations. Binding of radioligand to receptors in transmural slices was rapid, saturable, stereoselective, and displaceable by antagonists and agonists with the rank order of potency expected of beta-adrenergic receptors. Analysis of binding isotherms indicated maximum binding capacities of 27.8 +/- 6.6 and 40.6 +/- 5.1 fmol/mg tissue protein and dissociation constants of 10.1 +/- 1.8 and 21.3 +/- 1.6 pM in feline and canine ventricular slices, respectively. The distribution of beta-receptors in myocytes and selected vascular components of the heart was determined with quantitative film autoradiography and high resolution computer-based analysis and display of the density of binding sites, maximum binding capacity, and binding affinity measurements. The results of autoradiographic analysis revealed a uniform transmural distribution of receptors in regions composed primarily of ventricular myocytes but an inverse relation between the density of beta-receptors and the diameter of coronary vessels. Large epicardial conductance arteries had half the receptor density of subjacent myocytes; small mural arteries had approximately 60% of the beta-receptor density of nearby myocytes, and the coronary resistance arterioles had the highest receptor density of any vascular compartment, which was equivalent to that of myocytes. The methods developed should be of particular value in characterizing the distribution and function of receptor subtypes and mechanisms of regulation of adrenergic responsiveness in intact myocardium.
Antithrombogenic endothelial cell defense. Basal characteristics in cultured endothelial cells and modulation by short-term and long-term exposure to isosorbide nitrates.
Authors: Berenger F P , Cano J P , Rolland P H
Published: June 2012

The antithrombogenic endothelial cell defense (ATECD) describes the properties that enable the endothelium to prevent circulating blood platelets from adhering to, or aggregating on, the vascular wall. ATECD was investigated in an experimental model in which bovine passage 0 cultured endothelial cells (EC) were incubated with aggregating platelets and autologous plasma in a computer-operated aggregometer-like device. A maximal platelet aggregation required 150 X 10(-6) M adenosine diphosphate (ADP) to be present in ECs. A 5-minute coincubation for ECs and platelets was found to be adequate in evaluating the maximal ATECD value. By increasing the EC number in the aggregation suspension, platelet aggregation was progressively inhibited through a sigmoid curve (50% inhibition of aggregation required 2 X 10(4) EC). Pharmacologic modulations of ATECD by isosorbide dinitrate (ISDN) + 2-isosorbide mononitrate (2-ISMN) + 5-isosorbide mononitrate (5-ISMN) were investigated under experimental conditions reflecting either an acute nitrate effect (platelet + control ECs + drug + ADP) or a chronic effect (platelet + 5-day nitrate-treated ECs + ADP). Under acute circumstances, ISDN antiplatelet activities were profoundly magnified by ECs. Aggregation was fully arrested with 5 X 10(-5) M ISDN and an EC number of 2 X 10(4), whereas the same ISDN concentration alone induced 30% inhibition of control aggregation. In contrast, there were no significant changes in platelet aggregation whether incubation was done in the presence or absence of 2-ISMN or 5-ISMN, ISDN metabolites. Long-term exposure of ECs to isosorbide nitrates (ISN) resulted in increased acquired EC changes in ATECD. 5-ISMN was a poor antiplatelet agent but was capable of counteracting ISDN effects on ATECD.(ABSTRACT TRUNCATED AT 250 WORDS)
Venous and arterial endothelia: different dilator abilities in dog vessels.
Authors: Seidel C L , LaRochelle J
Published: June 2012

It has been demonstrated by other investigators that endothelium-dependent vasodilators are more effective on arterial tissue than on venous tissue. The purpose of this study was to determine if this was due to a difference in the sensitivity of arterial and venous smooth muscle to the endothelial dilator (EDRF) or to a difference in the ability of arterial and venous endothelia to release EDRF. To differentiate between these two possibilities, an in vitro "sandwich" preparation was used in which the mechanical response to endothelium-dependent dilators of a de-endothelialized vessel was determined when "sandwiched" with an endothelialized vessel. Using dog femoral artery and saphenous vein, it was determined that acetylcholine (ACh), the ionophore A23187, and thrombin were endothelium-dependent dilators of the femoral artery, but their dilatory ability was significantly less in the saphenous vein. However, if the de-endothelialized saphenous vein was "sandwiched" with an endothelialized femoral artery, both ACh and A23187 significantly relaxed the vein. No relaxation of the de-endothelialized femoral artery occurred when it was "sandwiched" with an intact saphenous vein. Sodium nitroprusside, thought to act by a mechanism similar to EDRF, relaxed equally the saphenous vein and femoral artery. These observations suggest that the difference in responsiveness between femoral arteries and saphenous veins to endothelium-dependent dilators is due more to differences in the ability of their endothelia to release EDRF than to an inability of their smooth muscle to respond to EDRF.
Evidence for distinct calcium channel agonist and antagonist binding sites in intact cultured embryonic chick ventricular cells.
Authors: Lee R T , Smith T W , Marsh J D
Published: June 2012

To determine whether calcium channel agonists and antagonists bind to distinct pharmacologically active sites, the binding of dihydropyridine calcium channel agonists and antagonists was related to calcium flux and contractile state in primary monolayer cultures of spontaneously contracting chick embryo ventricular cells. Equilibrium binding studies using the antagonist (+)-[3H]PN200-110 demonstrated equilibrium binding to intact, beating cells consistent with a single class of binding sites (KD, 1.1 nM; Bmax, 40 fmol/mg protein). Membrane depolarization of the intact cells by incubation in 30 mM potassium caused a 91% increase in the apparent number of (+)-PN200-110 binding sites (Bmax 76 fmol/mg protein), but no significant change in the KD (1.2 nM). The (+)-PN200-110 produced a concentration-dependent decrease in calcium uptake (IC50 2.2 nM) and contractile amplitude (IC50 5.6 nM). The calcium channel agonist, (+/-)-[3H]BAY k 8644, bound to two distinct binding sites with high affinity (KD 1.0 nM) and low affinity (KD 1.9 microM). The (+/-)-BAY k 8644 produced biphasic modulation of calcium flux and contractile state. At concentrations of 100 nM or less, (+/-)-BAY k 8644 increased calcium flux and contractile amplitude, consistent with drug interaction with the high affinity agonist site. However, at higher concentrations, the stimulatory effect of (+/-)-BAY k 8644 on calcium flux and contractile amplitude was abolished, a finding that is consistent with drug interaction with the low affinity antagonist site.(ABSTRACT TRUNCATED AT 250 WORDS)
Myosin isozyme synthesis and mRNA levels in pressure-overloaded rabbit hearts.
Authors: Nagai R , Pritzl N , Low R B , Stirewalt W S , Zak R , Alpert N R , Litten R Z
Published: June 2012

The in vivo synthesis rates of myosin isozyme heavy chains beta and alpha were measured in right ventricular (RV) muscle at 2 and 4 days following pulmonary artery constriction in rabbits, together with measurements of their relative mRNA levels. The synthesis rate of beta-myosin heavy chains was elevated in 2-day (0.27 +/- 0.06 day-1 or 2.5 +/- 0.7 mg/g RV/day, mean +/- SD) and in 4-day (0.25 +/- 0.08 day-1 or 2.8 +/- 1.0 mg/g RV/day) pressure overload, when compared to untreated rabbits (0.15 +/- 0.04 day-1 or 1.5 +/- 0.4 mg/g RV/day). However, the synthesis rates of alpha-myosin heavy chains in the same hearts were not altered significantly. There was a differential increase in the fractional synthesis rate of beta vs. alpha heavy chains in 2-day and 4-day pressure overload and in 2-day shams, suggesting switching toward beta heavy chain synthesis had occurred at these time points. beta heavy chain synthesis, as a proportion of total (alpha + beta) heavy chain synthesis, was significantly higher in 4-day pressure overload (78 +/- 9%) than in 4-day sham rabbits (63 +/- 6%). This increase in relative beta-synthesis was associated with a significant increase in the relative proportion of beta heavy chain mRNA level (76 +/- 13% vs. 56 +/- 7%). Furthermore, relative beta-synthesis and the beta-mRNA levels correlated linearly with each other in all experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Association of decreased myocardial beta-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise.
Authors: Hammond H K , White F C , Brunton L L , Longhurst J C
Published: June 2012

The effects of chronic dynamic exercise on myocardial beta-adrenergic and muscarinic cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan miniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10-19 weeks of treadmill running. Radioligand studies using 125I-iodocyanopindolol (ICYP) and 3H-quinuclidinyl benzilate (QNB) were used to determine the number of beta-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 +/- 5 to 65 +/- 7 ml/kg/min (mean +/- SD; p less than 0.02), maximal workload from 530 +/- 111 to 1,074 +/- 179 KPM/min (p less than 0.01), resting heart rate decreased from 91 +/- 13 to 62 +/- 4 beats/min (p less than 0.01), heart rate at 75% of pretraining maximal workload decreased from 253 +/- 15 to 196 +/- 12 beats/min (p less than 0.01), and maximal exercise heart rate decreased from 273 +/- 6 to 254 +/- 9 beats/min (p less than 0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 +/- 13 to 185 +/- 28 beats/min (p less than 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 +/- 16 to 40 +/- 16 (p less than 0.05). Radioligand studies revealed a decrease in beta-receptor number in the right atrium following chronic exercise (61 +/- 9 vs. 34 +/- 8 fmol/mg; p less than 0.02), but receptor number in membranes from the left ventricle did not change (60 +/- 9 vs. 62 +/- 4 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular internal resistance and unloaded ejection flow assessed from pressure-flow relations: a flow-clamp study on isolated rabbit hearts.
Authors: Vaartjes S R , Boom H B
Published: June 2012

Left ventricular pressure-flow relations were studied, using excised working rabbit hearts and imposing constant flow ejections (flow-clamps) to separate the effects of flow on pressure from those of time, flow duration, starting volume, ejected volume, and volume at specified time. Pressure-flow data at given volume and time were independent of flow duration, starting volume, and ejected volume for flow-clamp durations exceeding 30 msec. Flow history independent of pressure-flow relations was linear for flow values larger than +/- 5 ml/sec. The time-varying elastance model, E(t), of the ventricle was extended with a resistive component. Transient effects of flow can be explained by including a second elastance. The resulting verified 3-component model is consistent with recent reported experimental findings. The properties of internal resistance correspond to a constant unloaded ejection flow Qmax, which was tested by extrapolating the linear pressure-flow relations to zero pressure. Qmax reached a plateau value of approximately 25 ml/sec within 50 msec after the start of contraction. In relaxation, Qmax is only slightly smaller. Qmax did not depend on volume; therefore, the following equation was adequate for the relation between pressure, p(t); volume, V(t); and flow Q(t), during the flow-clamped ejections from 30 minutes after the start of the flow: (t) = E(t).(V(t)-Vd).(1-Q(t)/Qmax)