bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure.
Authors: Bristow M R , Ginsburg R , Umans V , Fowler M , Minobe W , Rasmussen R , Zera P , Menlove R , Shah P , Jamieson S
Published: June 2012

We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were beta 1 (77%) and beta 2 (23%), with no evidence of an "atypical" beta-adrenergic receptor. In failing left ventricle the beta 1:beta 2 ratio was markedly different, i.e., 60:38. This decrease in the beta 1 proportion and increase in the beta 2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the beta 1 subpopulation, with little or no change in beta 2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both beta 1- and beta 2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, beta 1 responses predominated, as the selective beta 1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the beta 1 component was markedly decreased, while the beta 2 component was not significantly diminished. Moreover, in heart failure the beta 2 component increased in prominence, as the contractile response to the selective beta 2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of beta 2 receptors, due to selective down-regulation of beta 1 receptors. As a result, in the failing human heart the beta 2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective beta-agonist stimulation and is available for inotropic stimulation by selective beta 2 agonists.
Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells.
Authors: Filip D A , Radu A , Simionescu M
Published: June 2012

Interstitial cells of heart atrioventricular and sigmoid valves were examined in several laboratory animals (rabbit, hamster, rat, and mouse) and in humans. These cells constitute a large fraction of the total cell population of the valve; in mouse atrioventricular valves, they amount to approximately 30% of the volumetric density. By their ultrastructural features and functional properties, valvular interstitial cells are intermediate between fibroblasts and vascular smooth muscle cells. Like fibroblasts, valvular interstitial cells lack a basal lamina establishing direct and extensive contacts with collagen fibers, elastin microfibrils, and proteoglycans of the matrix. The cells have numerous slender and long processes, connected to one another, forming a complex cellular framework spanning the entire valve. Similar to smooth muscle cells, valvular interstitial cells are extensively coupled by communicating junctions as shown by thin sections, freeze-fracture, lanthanum staining, and carboxyfluorescein microinjection. The cells contain numerous bundles of actin filaments, which are decorated by the S1 fragment of heavy meromyosin. Valvular interstitial cells also express cyclic guanosine-monophosphate-dependent protein kinase, as detected by immunofluorescence and immunoperoxidase histochemistry. Motor nerve endings are located closely apposed to valvular interstitial cells: structurally most of them appear to be of the adrenergic type. Valvular interstitial cells contract on epinephrine or angiotensin II stimulation as shown both in culture and in situ (valvular strips). Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole.
Superoxide dismutase prevents the thrombin-induced increase in lung vascular permeability: role of superoxide in mediating the alterations in lung fluid balance.
Authors: Johnson A , Perlman M B , Blumenstock F A , Malik A B
Published: June 2012

We investigated the effects of superoxide dismutase (SOD) and SOD linked to Ficoll (mol. wt = 400,000) on the changes in pulmonary transvascular fluid and protein exchange following pulmonary microembolism induced with alpha-thrombin. Studies were made in chronically prepared unanesthetized sheep with lung lymph fistulas. Control thrombin challenged sheep (n = 5) were compared to animals infused with SOD (the SOD-thrombin group, n = 5) or animals infused with SOD linked to high molecular weight Ficoll (the Ficoll-SOD-thrombin group, n = 6). The Ficoll-SOD-thrombin animals were also compared to animals infused with Ficoll alone (the Ficoll-thrombin group, n = 4). In the control-thrombin group, thrombin induced sustained increases in the pulmonary transvascular protein clearance (pulmonary lymph flow X lymph/plasma protein concentration ratio) and pulmonary vascular resistance (PVR). In the SOD-thrombin group, thrombin initially increased both pulmonary transvascular protein clearance and PVR; however, the later increases in protein clearance and PVR were blunted. The pulmonary reflection coefficients for total protein (sigma), a measure of vascular permeability to protein, decreased from a value of 0.70 +/- 0.03 in normal sheep to 0.60 +/- 0.01 following thrombin challenge (p less than 0.05) indicating an increase in lung vascular permeability. The sigma value in the SOD-treated animals was 0.70 +/- 0.02, indicating a protective effect of SOD. The infusion of the Ficoll-SOD complex also attenuated the increases in pulmonary transvascular protein clearance and PVR after thrombin. However, the infusion of Ficoll alone induced a similar protection. The lymph from the SOD-thrombin and Ficoll-SOD-thrombin groups prevented the reduction of ferricytochrome C by xanthine/xanthine oxidase, whereas, the lymph from the Ficoll-thrombin animals did not have this effect, indicating SOD activity was present in the animals receiving the enzyme but not in the group infused with Ficoll alone. Differences in the degree of intravascular coagulation could not explain the response to Ficoll since the decreases in fibrinogen concentration following the thrombin were similar in all the groups. Since Ficoll and related dextrans may modify neutrophil function, in particular neutrophil adherence to the endothelium, we examined the effects of Ficoll on neutrophil adherence. The results indicated that when Ficoll was added to the endothelial medium Ficoll reduced the increase adherence of neutrophils to the endothelial cell monolayer. Therefore, Ficoll as a carrier for SOD may provide a direct protection in models of lung vascular injury that are dependent on neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)
Subtypes of beta-adrenergic receptors in bovine coronary arteries.
Authors: Vatner D E , Knight D R , Homcy C J , Vatner S F , Young M A
Published: June 2012

Whether large coronary artery dilation induced by beta-adrenergic stimulation is mediated by beta 1- or beta 2-adrenergic receptors remains controversial. This problem is particularly difficult to address in vivo due to the concomitant increase in coronary blood flow with beta-adrenergic stimulation, which by itself can dilate large coronary arteries. To reconcile this problem, 5 calves were instrumented with intraaortic and intracoronary (i.c.) catheters, ultrasonic diameter transducers, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. Two to six weeks following surgery, beta-adrenergic agonists were administered i.c. to avoid complicating systemic effects. Isoproterenol (0.0025 micrograms/kg, a beta 1 + beta 2-adrenergic agonist) increased coronary diameter (7.1 +/- 0.8% from 5.80 +/- 0.58 mm) (p less than 0.01). Similar increases (p less than 0.01) in coronary diameter occurred with prenalterol (0.4 micrograms/kg, beta 1-adrenergic agonist) (9.5 +/- 1.4%) and pirbuterol (0.25 micrograms/kg, beta 2-adrenergic agonist) (8.1 +/- 1.2%). When coronary blood flow was prevented from rising with the hydraulic constrictor, increases in coronary diameter to all three beta-adrenergic agonists were not attenuated. Large coronary artery dilation with prenalterol and pirbuterol was abolished with beta 1- and beta 2-adrenergic receptor blockade, respectively, while neither beta 1- nor beta 2-adrenergic blockade alone abolished the large coronary artery dilation with isoproterenol. To identify the predominant subtype of beta-adrenergic receptor, competitive inhibition curves utilizing 125I-cyanopindolol (125I-CYP) as the radiolabel versus isoproterenol, epinephrine, and norepinephrine were generated in membrane preparations from calf heart (predominant beta 1), calf lung (predominant beta 2) and calf coronary artery. The coronary artery membrane preparations demonstrated an intermediate pattern. Competition curves with selective beta 1- and beta 2-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both beta-adrenergic receptor subtypes in large coronary arteries, with a ratio of beta 1: beta 2 of 1.5-2.0:1.0. Thus, large coronary arteries of the calf contain both beta 1- and beta 2-adrenergic receptors identified utilizing ligand binding techniques, and stimulation of both receptor subtypes in the intact conscious animal results in large coronary artery dilation, independent of blood-flow-mediated vasodilation.
Possible role for adenosine in local regulation of absorptive hyperemia in rat intestine.
Authors: Proctor K G
Published: June 2012

To test whether extracellular adenosine participates in the local regulation of intestinal blood flow during nutrient absorption, the serosa of the jejunum was continuously suffused with adenosine deaminase (7 micrograms protein/ml) or theophylline (10(-4) M) in Ringer's solution. Using video microscopy, blood flow was calculated in submucosal arterioles from diameter and red cell velocity measurements. After a steady-state baseline, oleic acid (20 mM) + glucose (56 mM) were added to a bile salt solution suffusing the mucosa. Baseline arteriolar diameters and blood flows were 52 +/- 2 micron and 20 +/- 2 nl/sec with the serosal suffusate containing Ringer's; these values were not significantly altered by theophylline or deaminase treatment. During suffusion of the mucosa with a nutrient solution, diameter and blood flow transiently increased and these responses were not altered by deaminase or theophylline. Thereafter, diameter and blood flow stabilized at lower values for the duration of absorption. Diameter and blood flow were increased to 111 +/- 1% and 134 +/- 5% of control during absorption with Ringer's; the corresponding values were significantly lower with deaminase or theophylline. After absorption, diameter and blood flow stabilized near baseline with Ringer's within 7-12 minutes; the corresponding values were significantly lower with deaminase or theophylline for at least 30 minutes. Since deaminase and theophylline produced similar effects on absorptive hyperemia, adenosine might participate with other factors in the local regulation of that response. Adenosine applied to the serosa caused dose-dependent increases in calculated blood flow with a threshold near 10(-5) M and a maximum near 10(-3) M. In contrast, even 10(-2) M adenosine in the mucosal suffusate did not increase blood flow above baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic changes in chick embryos precede heart defects after cardiac neural crest ablation.
Authors: Stewart D E , Kirby M L , Sulik K K
Published: June 2012

Neural crest cells are known to contribute to the normal architecture of the heart and aortic arch arteries. Ablation of neural crest cells over somites 1 to 3 in the chick embryo prevents conotruncal septation and results in persistent truncus arteriosus. To determine whether a deficiency of cardiac neural crest cells produces hemodynamic changes prior to the development of identifiable structural defects in the heart, we measured dorsal aortic blood velocity and vitelline artery blood pressure in lesioned and control embryos at a period of cardiac morphogenesis prior to septal formation. The internal diameter of the dorsal aorta at the level of the sinus venosus and the internal diameter of the aortic arch arteries at their midpoints were measured in embryos at Stage 18 of development using a filar micrometer eyepiece and a dissecting microscope. Embryos with neural crest lesions had significantly greater dorsal aortic blood flow velocity than control embryos. In addition, embryos lacking cardiac neural crest had significantly lower systolic and diastolic blood pressures than control embryos. There was no difference in heart rate, dorsal aortic diameter or internal diameter of the aortic arch arteries between lesioned and control embryos. Scanning electron micrographs revealed no gross morphological differences in cardiac looping or conotruncal wall development between lesioned and control embryos; however, embryos with cardiac neural crest ablations developed markedly hypoplastic 4th pharyngeal arches. This data suggests that hemodynamic changes precede the onset of structural heart defects in embryos with cardiac neural crest ablations.
Induction of polyploidy in cultures of neonatal rat aortic smooth muscle cells.
Authors: Gordon D , Mohai L G , Schwartz S M
Published: June 2012

Arterial smooth muscle cells become tetraploid with age and hypertension. To further study this phenomenon, neonatal rat aortic smooth muscle cells were placed in cell culture and studied over time. Numerous cells with tetraploid and even octaploid DNA content appeared beginning in primary cultures. These increases in DNA content per cell were determined by quantitative fluorescence microscopy and flow cytometry, and true polyploidy was confirmed by chromosome counts. In contrast, cells from adult rat aortas failed to produce significant polyploid cells over time in culture. In vitro culture of neonatal aortic cells may therefore be a model system for studying the initiation of polyploidy in arterial smooth muscle.
Action of Hypoxia on the Pulmonary Vasculature
Authors: RIVERA-ESTRADA CARMEN , SALTZMAN PAUL W. , SINGER DONALD , KATZ LOUIS N.
Published: June 2012

The hemodynamic effects of acute hypoxia upon the pulmonary circulation were studied in dogs. The most striking changes were observed on the venous side of the circuit, consisting of a rise in venous (and arterial wedge) pressure greater than that in the pulmonary artery and an increase in the pressure gradient between the venules and the left atrium. These alterations are discussed and interpreted in an attempt to further clarify the response of the pulmonary circulation to hypoxia. It is suggested that there is arteriolar dilatation associated with increased postcapillary vascular resistance.
Flow as a Function of Arterial Pressure in the Oil Perfused Kidney
Authors: WAUGH WILLIAM H.
Published: June 2012

Isolated canine kidneys were perfused with oil which did not accumulate extravascularly and which prevented renal vasomotor responses. The purely physical effects of changed arterial pressure on renal vascular flow and resistance were studied.
Ventricular Fibrillation Studied by the Microelectrode Method
Authors: SANO TOYOMI , TSUCHIHASHI HIROMICHI , SHIMAMOTO TAKIO
Published: June 2012

Capillary ultramicroelectrodes were inserted into ventricular muscle fibers of dogs in ventricular fibrillation and action potentials obtained were compared with deflections of unipolar direct lead, adjoining bipolar direct lead or other electrocardiograms taken simultaneously. In most stages of ventricular fibrillation neither synehronism nor any other regular time relationship could he found between them. Microelectrodes inserted at two points variously distant on various regions of the ventricular surface also failed to show any regular time relationship. Total incoordination of ventricular muscle fibers was thus supported.
A Saline Conductivity Method for Detection of Cardiac Shunts by Indicator-Dilution Technic
Authors: BOOTH RICHARD W. , RYAN JOSEPH M. , GOODWIN RICHARD S.
Published: June 2012

A new method for cardiovascular shunt detection is described using the indicator-dilution principle applied to blood conductivity changes produced by 5 per cent saline. It possesses these distinct advantages over the Evans blue technic: (1) an unlimited number of determinations can be made without an increasing blood dye background or bluish discoloration of the patient, (2) oximetric determination of blood oxygen saturation is not interferred with, and (3) a simple modification of the carrier amplifiers of commonly used recording systems supplies most of the necessary instrumentation.
Conditioning by Cortisol for the Production of Acute Massive Myocardial Necroses During Neuromuscular Exertion
Authors: SELYE HANS
Published: June 2012

Following pretreatment with cortisol and NaH
2
PO
4
, a brief period of neuromuscular stress regularly produces massive myocardial necroses in the rat. Pretreatment with desoxycorticosterone and the phosphate is less effective in this respect.
Circulation of Iodinated Albumin Through Aortic and Other Connective Tissues of the Rabbit
Authors: DUNCAN LEROY E. , CORNFIELD JEROME , BUCK KATHERIN
Published: June 2012

A method is presented for the determination of the rates of movement of macromolecules into and out of specific tissues by analysis of the serum and tissue concentrations of the intravenously injected labeled macromolecule. Transfer rates of albumin into and out of rabbit aorta, skin, tendon, sclera, and cornea are given. These rates, and the steady-state ratios of tissue albumin to serum albumin, are interpreted in terms of current theory regarding the diffusion and filtration of albumin at capillary and lymphatic exchange sites in the tissues. Transfer rates for average body tissue, obtained by analysis of the serum concentration of intravenously injected labeled albumin, are compared with the transfer rates for the specific tissues studied.
Influence of Gallogen and Diethanolamine Upon Induced Hypercholesterolemia in the Rat
Authors: DAYTON SEYMOUR
Published: June 2012

The diethanolamine salt of the mono (α,p-dimethylbenzyl) ester of d-camphoric acid (Gallogen) augmented diet-induced hypercholesterolemia and hyperlipemia in the rat, while depressing liver cholesterol and total lipid concentrations. Diethanolamine had virtually identical effects. Gallogen, given orally to rats with biliary fistulas had a slight hydrocholeretic effect, but did not influence biliary excretion of cholesterol, cholic acid, or chenodeoxycholic acid.
Pulmonary Vascular Responses to Serotonin and Effects of Certain Serotonin Antagonists
Authors: ROSE JOHN C. , TAZARO ERIC J.
Published: June 2012

Serotonin was the most potent pulmonary vasoconstrictor studied in an experimental preparation in which drugs injected into the pulmonary artery are temporarily excluded from the systemic circulation. Alterations in bronchomotor tone did not approach those produced by acetylcholine. Simultaneous systemic vascular or cardiac reflexes were not noted. Promethazine, LSD-25 and its 2-brom derivative were potent blockers of serotonin effects in the pulmonary circulation.
Acute Circulatory Collapse of the Adrenalectomized Dog Following Plasma Infusion
Authors: BAKER CARLETON H. , REMINGTON JOHN W.
Published: June 2012

Adrenalectomized dogs maintained on desoxyeorticosterone acetate developed a fatal circulatory collapse when given normal dog plasma. They showed general restlessness, a rapid fall in blood pressure and cardiac index, a decline in central venous pressure and general prostration. Most dogs developed a bloody diarrhea and a minority showed edematous swelling of the face with itching. Animals with intact spleens exhibited marked hemoconcentration, splenectomized animals did not. Blood and plasma specific gravity determinations offered no evidence for gross plasma loss. Diphenhydramine prevented the collapse.
Effect of Hypertonic Saline on the Pulmonary and Systemic Pressures
Authors: ELIAKIM M. , ROSENBERG S. Z. , BRAUN K.
Published: June 2012

The intravenous injection of 20 per cent saline in anesthetized closed chest dogs causes a rise in pulmonary venous, pulmonary arterial, right ventricular and peripheral venous pressures. Left atrial pressure does not change or falls, and systemic arterial pressure decreases very markedly. These changes are shown to result from spasm at the pulmonary vein--left atrial junction. Stimulation of chemoreceptors in this region is assumed to be the cause of the spasm.
Coronary Artery Catheterization in the Intact Dog
Authors: WEST JAMES W. , KOBAYASHI TACHIO , GUZMAN SANTIAGO V.
Published: June 2012

A technic is described for selective catheterization of individual coronary arterial branches in intact dogs by means of special catheters which permit intracoronary injections of pharmacologic agents or radio-opaque materials. All the main coronary arteries (right, left anterior descending, left circumflex) have been successfully catheterized and injected, both alone and in combination.
Effects of Dietary Proteins, Methionine and Vitamins on Plasma Lipids and Atherogenesis in Cholesterol-Fed Cockerels
Authors: STAMLER JEREMIAH , PICK RUTH , KATZ LOUIS N.
Published: June 2012

Methionine deficiency in the presence of a high-fat, high-cholesterol diet aggravates atherogenesis in the cockerel. High-protein, high-vitamin supplementation suppresses the atherogenic effect of a cholesterol-fat-containing diet. High-protein supplementation alone had a suppressive effect; high-vitamin supplementation had no effect. However, the combined protein and vitamin supplement was the most effective.
Observations on the Vasodilator Properties of Urine
Authors: SARNOFF S. J. , CASE R. B. , MACRUZ R. , SARNOFF L. C. , SUSSMAN K. E. , PIERCE J. V.
Published: June 2012

These experiments trace the recent interest in the vasodilator properties of urine. This interest was triggered by the incidental observation of a potent coronary dilator influence when urine was introduced into the reservoir of the isolated supported heart preparation. A comparison of human urine with nitroglycerin then revealed that 10 ml. of urine had 2 to 3 times the dilator potency of 0.6 mg. nitroglycerin. Neither agent altered myocardial oxygen consumption or efficiency at the peak of their effect.

The development of a simple, rapid and reproducible bioassay technic which would permit the comparative examination of numerous samples in the same preparation was a necessary precursor to realizing the broader objective of ascertaining whether the vasodilator substance in urine has physiologic significance for circulatory regulation. Accordingly, a re-examination was made of the limitations of the femoral arterial flow technic. The irregularity in the amplitude and contour of sequential responses to the same test substance in spite of an apparently steady hemodynamic state suggested the possibility of inadequate mixing after injections into the external circuit. Model studies with blue dye confirmed this impression and a magnetic mixer was therefore introduced into the external circuit in order to thoroughly mix the injected material. This resulted in substantially improved reproducibility and the obtaining of satisfactory dose-response curves.

This technic was then used to assay the 24 hour output of vasodilator activity in the urine of 5 hypotensive patients and 5 normal individuals. The hypotensive group exhibited something less than 15 per cent of that secreted by the control group. The substance under examination is non-dialyzable and, chemically, resembles callicrein. The urines from 9 mammalian species all exhibited high activity. These observations were construed as being compatible with the hypothesis that the vasodilator agent under examination is, in some way, associated with autonomic function and/or the regulation of arterial pressure. This view was supported by the observation of a diminished vasodilator output in the sheep while under the influence of ganglionic blockade with hexamethonium.
Critical Review of Recent Work on Ventricular Diastolic Suction
Authors: BRECHER GERHARD A.
Published: June 2012

Unequivocal evidence in favor of the concept that a ventricular diastolic
vis a fronte
contributes to ventricular filling has been established only in the following conditions: a. When the ventricle contains an abnormally small residual volume (rat, dog, turtle) b. When the ventricle contains a more nearly normal, residual volume due to ejection against the resistance of a fluid column (dog, turtle). The quantitative contribution of the ventricular
vis a fronte
to ventricular filling at various residual volumes and various levels of cardiac activity is still unknown. The physiological significance of diastolic suction for the return flow of blood can therefore not yet he evaluated.
The Response to Catechol Amine Infusion During Salicylate-Induced Hypermetabolism in Man
Authors: JOY ROBERT J. T. , AUSTEN FRANK K.
Published: June 2012

The increase in oxygen consumption produced in man by salieylate administration is not associated with a rise in pulse rate or an increase in responsiveness to infusions of epinephrine or norepinephrine. It is suggested that the effects of thyroid hormone on the cardiovascular system are more dependent on the concentration of circulating thyroid hormone per se than on the concomitant increase in tissue oxygen consumption.
Circulatory and Renal Adjustments to Acute Femoral Arteriovenous Fistulas
Authors: MURPHY Q. R. , GULLIXSON K. S. , KRATOCHVIL C. H. , SILVA J. SIMOES E.
Published: June 2012

This Paper is concerned with the pattern of cardiorespiratory and renal changes produced by opening a systemic arteriovenous fistula. Flow through bilateral femoral arteriovenous fistulas averaged approximately 53 per cent of the control cardiac output. The rise in cardiac output elicited by the shunt averaged 51 per cent of the shunt flow PAH clearances decreased 23 per cent in animals anesthetized with sodium pentobarbital, and 46 per cent in animals premedicated with morphine sulfate prior to administration of sodium pentobarbital. The per cent reduction in renal blood flow did not differ significantly from the per cent reduction in flow through the extrarenal systemic capillary beds.
Studies of the Rate of Transfer of Rb
86
, K
39
, Na
24
, Na
23
. Cl
36
, and Cl
35
Across the Pericardium of Dogs
Authors: BURCH G. E. , RAV C. T.
Published: June 2012

Studies of the simultaneous rates of transfer of various tracers and stable isotopes from the pericardium of normal dogs under pentobarbital anesthesia indicated that the rate of transfer of Rb
86
was greater than that of Na
24
and Cl
36
, which were approximately equal. These observations show the pericardium to be a very active serous membrane concerned with electrolyte transfer phenomena as well as an excellent experimental model for the study of the kinetics of exchange of electrolytes across a normal living membrane.
Propranolol treatment externalizes beta-adrenergic receptors in guinea pig myocardium and prevents further externalization by ischemia.
Authors: Maisel A S , Motulsky H J , Insel P A
Published: June 2012

Purified sarcolemmal and light vesicle (intracellular) fractions of beta-adrenergic receptors were used to examine the effects of propranolol on receptor translocation in guinea pig heart. Guinea pigs were given propranolol (0.15 mg/kg/hr) via minipumps for 7 days and either killed or made ischemic for 1 hour via a coronary ligature. Propranolol treatment led to an externalization of beta-receptors from light vesicle to sarcolemmal fractions. This externalization increased the number of surface beta-adrenergic receptors that were functional, as assessed by isoproterenol-stimulated adenylate cyclase activity. After chronic propranolol treatment, ischemia did not further alter receptor distribution. These results suggest that externalization of beta-adrenergic receptors from a light vesicle fraction to the sarcolemma contributes to up-regulation of beta-receptors that occur in response to both propranolol treatment and ischemia. Because propranolol-treated animals show blunting in externalization after myocardial ischemia, propranolol treatment and myocardial ischemia appear to access the same pool of intracellular beta-adrenergic receptors. Depletion of this pool of receptors along with receptor blockade may thus contribute to the mechanism by which the drug is efficacious in preventing some adverse effects of ischemia.
Intracellular K+ activity, intracellular Na+ activity and maximum diastolic potential of canine subendocardial Purkinje cells from one-day-old infarcts.
Authors: Dresdner K P , Kline R P , Wit A L
Published: June 2012

The basis for the reduced maximum diastolic potential of canine cardiac subendocardial Purkinje fibers surviving one day after extensive transmural infarction was investigated, using double-barrel potassium and sodium ion-sensitive microelectrodes. The maximum diastolic potential of Purkinje fibers in infarct preparations from the left ventricular apex measured during the first hour of superfusion in a tissue bath was -50.1 +/- 13.7 mV, a value markedly reduced from the value in control Purkinje fibers from noninfarcted preparations (-85.0 +/- 4.5 mV). The intracellular potassium ion activity was reduced by 50.4 mM during this time (intracellular potassium ion activity equals 61.6 +/- 16.1 mM, as compared to control intracellular potassium ion activity of 112 +/- 19.8 mM). The potassium equilibrium potential was reduced by 16.0 mV (from -97.2 +/- 4.7 mV in controls to -81.2 +/- 6.9 mV), thus accounting for about one half of the reduction in the maximum diastolic potential. After 6 hours of superfusion, the maximum diastolic potential increased to -78.9 +/- 8.7 mV (still significantly less than control). The potassium equilibrium potential had largely recovered (-93.8 +/- 5.9 mV). The intracellular sodium ion activity of Purkinje fibers in the infarcts (15.6 +/- 6.9 mM) was elevated during the first hour of superfusion by 6.2 mM compared to control (9.4 +/- 2.6 mM), and this was only 12% as much as the initial intracellular potassium ion activity decrease. Sodium ion activity after 3-6 hours of superfusion was not significantly different than normal (12.1 +/- 4.9 mM). In conclusion, only a portion of the maximum diastolic potential changes can be explained by a reduction of the potassium equilibrium potential. It is likely that change(s) in the cell membrane sodium-potassium pump's function and in the membrane conductance are also involved. Furthermore, the lack of a compensatory increase in intracellular sodium ion activity accompanying the large reduction of intracellular potassium ion activity may be a consequence of the cellular acidosis, which is known to occur during myocardial ischemia.
Simultaneous measurement of force and calcium uptake during acetylcholine-induced endothelium-dependent relaxation of rabbit thoracic aorta.
Authors: Ratz P H , Gleason M M , Flaim S F
Published: June 2012

This study was designed to determine whether the endothelium-derived relaxing factor induced by acetylcholine (1 microM) in rabbit thoracic aorta inhibits agonist-induced calcium mobilization, specifically calcium influx. Force generated in rings of rabbit thoracic aorta by norepinephrine (1 microM) was measured under isometric conditions. At the appropriate time during 1 microM acetylcholine-induced relaxation of 1 microM norepinephrine-contracted rabbit thoracic aorta, the rings were pulse-labelled with calcium-45 to measure calcium influx. When measured in this fashion, 1 microM acetylcholine decreased the 1 microM norepinephrine-induced increase in calcium influx. This effect was eliminated by removal of the endothelium and by atropine (1 microM), but not by indomethacin (14 microM). Acetylcholine (1 microM) also blocked the 60 mM potassium-chloride-induced increase in calcium influx without dramatically affecting force. The phasic contraction produced by norepinephrine (1 microM) with 2 mM lanthanum pretreatment, which is caused by release of intracellular calcium, was inhibited by acetylcholine (1 microM) in a fashion similar to 1 microM nitroglycerin. The tonic contraction produced by norepinephrine (1 microM) after depletion of the agonist-releasable pool of intracellular calcium, which is thought to be due to calcium influx, was depressed by acetylcholine (1 microM). These data suggest that endothelium-derived relaxing factor relaxes 1 microM norepinephrine-contracted rings of rabbit thoracic aorta by decreasing calcium entry and by producing an extracellular calcium-independent relaxant effect.
Nonexocytotic release of endogenous noradrenaline in the ischemic and anoxic rat heart: mechanism and metabolic requirements.
Authors: Schömig A , Fischer S , Kurz T , Richardt G , Schömig E
Published: June 2012

The release of endogenous noradrenaline and its deaminated metabolite dihydroxyphenylglycol in the myocardium have been studied in the isolated perfused heart of the rat subjected to three models of energy depletion: ischemia, anoxia, and cyanide intoxication. Anoxia and cyanide intoxication were combined with substrate deficiency at constant perfusion flow. All three energy-depleting procedures caused a similar overflow of noradrenaline which, following a constant delay of 10 minutes without increased release, amounted to more than 25% of total heart content within 40 minutes. This noradrenaline overflow was not diminished in the absence of extracellular calcium and was inhibited by the uptake1 blocker desipramine in all three experimental models, indicating a common and nonexocytotic release mechanism. In the presence of glucose, neither anoxia nor cyanide intoxication resulted in a measurable noradrenaline overflow. Conversely, blockade of glycolysis or glucose depletion prior to ischemia or cyanide poisoning accelerated the noradrenaline overflow, demonstrating a key role of the sympathetic nerve cells' energy status in causing nonexocytotic catecholamine release. Blockade of energy metabolism in the presence of oxygen (cyanide model) resulted in the overflow of high amounts of dihydroxyphenylglycol that was not inhibited by uptake1 blockade. The release of the lipophilic dihydroxyphenylglycol by diffusion reflects deamination of axoplasmic noradrenaline by monoamine oxidase. Since saturation of the enzyme could be excluded in this model dihydroxyphenylglycol release can be taken as a mirror of cytoplasmic noradrenaline concentration. The results obtained by these studies indicate that nonexocytotic catecholamine release is a two-step process induced by energy deficiency in the sympathetic varicosity. In a first step, noradrenaline is lost from storage vesicles, resulting in increasing axoplasmic concentrations. The second step is the rate-limiting transport of intracellular noradrenaline across the cell membrane by the uptake1 carrier that has reversed its normal net transport direction.
Propagating depolarization in anisotropic human and canine cardiac muscle: apparent directional differences in membrane capacitance. A simplified model for selective directional effects of modifying the sodium conductance on Vmax, tau foot, and the propagation safety factor.
Authors: Spach M S , Dolber P C , Heidlage J F , Kootsey J M , Johnson E A
Published: June 2012

As yet there is no model or simulation that accounts for the anisotropic difference in the shape of the upstroke and safety factor of propagating cardiac action potentials: fast upstrokes occur with slow transverse propagation and slow upstrokes occur with fast longitudinal propagation. The purpose of this paper is to demonstrate, however, that a simplified cable model based on directional differences in the effective membrane capacitance predicts in detail the experimentally measured directionally dependent behavior of the upstroke in response to modification of the sodium conductance. Quinidine and lidocaine produced greater relative decreases in Vmax and conduction velocity with longitudinal propagation than with transverse propagation, as predicted on the basis that the shape differences should produce an anisotropic distribution in the membrane uptake of sodium channel binding drugs. The simulation predictions of the effects of positive shifts of the take-off potential due to premature action potentials were also confirmed experimentally: there was a greater relative decrease in conduction velocity, Vmax, and Vamp with a greater increase in tau foot during longitudinal propagation than with transverse propagation. The major anisotropic differences in shape occurred when the take-off potential approached the least negative value that produced a propagated response. The extensive experimental verification of the results of a simplified model based on directional differences of effective membrane capacitance, combined with directional differences in effective axial resistivity, provides an initial quantitative basis for the anisotropic behavior of propagating depolarization in response to modification of the sodium conductance in cardiac muscle.
Gas chromatographic-light microscopic correlative analysis of excimer laser photoablation of cardiovascular tissues: evidence for a thermal mechanism.
Authors: Clarke R H , Isner J M , Donaldson R F , Jones G
Published: June 2012

The present series of experiments used gas chromatography to identify vapor-phase photoproducts liberated during excimer laser irradiation of cardiovascular tissues in air and blood. In air, laser beams produced from ArF (193 nm) and XeF (351 nm) excimer laser gas mixtures were delivered to samples of myocardium and atherosclerotic coronary arterial segments through the wall of a quartz cell, using 8-40 mJ/pulse. In blood, 351 nm were delivered via an optical fiber, using 14 mJ/pulse. When the experiments were performed using an air-tissue interface, the dominant photoproducts identified in order of elution from the gas chromatographic column were methane, acetylene, ethylene, ethane, propyne, allene, propylene, propane, and butene. When a fiberoptic was used to accomplish 351-nm excimer laser tissue ablation in a blood field, a similar gas chromatographic spectral distribution was observed. These vapor-phase photoproducts are indistinguishable from those observed following continuous wave laser irradiation or flame torching of cardiovascular tissues. Thus, despite the fact that excimer laser ablation of cardiovascular tissues is characterized by the absence of signs of thermal injury, the results of these experiments suggest that the predominant mechanism of excimer ablation is, like continuous-wave laser irradiation, a thermal process.
Parasympathetic effects on in vivo rat heart can be regulated through an alpha 1-adrenergic receptor.
Authors: McGrattan P A , Brown J H , Brown O M
Published: June 2012

A prejunctional mechanism involving an alpha 1-adrenergic receptor may exert control on the release of acetylcholine from parasympathetic nerve endings in the heart. To test this hypothesis in vivo, rats were prepared for electrical stimulation of the vagus nerves. Blood pressures and heart rates were monitored, and the animals were treated with alpha-agonists and alpha-antagonists. The alpha 1-selective agonist phenylephrine significantly attenuated vagally induced bradycardia in a dose-dependent fashion (ED50 = 19 micrograms/kg). This is consistent with the hypothesis that there is alpha-adrenergic inhibition of ACh release. In contrast, the alpha 2-selective agonist, BHT-920, caused no change in heart rate during vagal stimulation. The effects of phenylephrine to raise heart rate and blood pressure during vagal stimulation were blocked by the alpha 1-selective antagonist prazosin (ID50 approximately 1 microgram/kg) but not by the alpha 2-selective antagonists yohimbine and rauwolscine. This further supports an alpha 1 assignment to the prejunctional adrenergic receptor mechanism, which can regulate the release of acetylcholine from cardiac parasympathetic neurons.
Phenylphosphonate: a 31P-NMR indicator of extracellular pH and volume in the isolated perfused rabbit bladder.
Authors: Fisher M J , Dillon P F
Published: June 2012

31P-NMR has been used extensively to estimate intracellular pH. It also can be used to measure extracellular pH and volume when an NMR-detectable extracellular phosphorous probe is used. Phosphonic acids have been suggested as useful 31P-NMR extracellular markers. The present study was designed to assess the utility of phenylphosphonic acid (PPA) as a 31P-NMR extracellular marker in perfused smooth muscle. Rabbit bladder strips were exposed to PPA concentrations of 1-20 mM. Tension development in response to maximal carbachol challenges (10 microM) was independent of PPA concentration. Addition of PPA (6 mM) to the perfusate supplying the isolated resting rabbit bladder had no effect on 31P-NMR-detectable phosphatic compounds. PPA's resonance frequency was distinctly downfield from endogenous phosphates and demonstrated a pH-dependent chemical shift of +/- 1.12 ppm/pH unit over the range of 6.4 to 7.6 with a pK' of 7.09 at 23 degrees C. The time courses for washing PPA in and out of the resting bladder were best described by monotonic exponential growth (r = 0.972; n = 3) and decay (r = 0.972; n = 3) equations, respectively. Rate and time constants for PPA wash-in (0.039 +/- 0.004 min-1 and 25.7 +/- 2.3 minutes) and washout (0.038 +/- 0.000 min-1 and 26.3 +/- 0.0 minutes) were not significantly different. Using steady state PPA and ATP peak intensities and concentrations, an extracellular-to-intracellular ratio was calculated to be 0.31 +/- 0.03 (n = 3). These data indicate that PPA remains distributed exclusively in the extracellular spaces.(ABSTRACT TRUNCATED AT 250 WORDS)
L-platelet activating factor induces changes on renal vascular resistance, vascular reactivity, and renin release in the isolated perfused rat kidney.
Authors: Schwertschlag U , Scherf H , Gerber J G , Mathias M , Nies A S
Published: June 2012

Rat kidneys were isolated and perfused with a modified Krebs-Henseleit buffer containing 4% albumin. Perfusate recirculated except during L-platelet activating factor (L-PAF), angiotensin II (ang II), and norepinephrine (NE) infusions. L-PAF caused a dose-dependent decrease in renovascular resistance (RVR): -6 +/- 3% at 10(-9)M, -12 +/- 6% at 10(-8)M, -18 +/- 3% at 10(-7) and -20 +/- 7% at 10(-6)M. L-PAF increased immunoreactive PGE (iPGE) and thromboxane (iTXB) release into the venous effluent from 2.4 +/- 0.2 to 3.9 +/- 0.4 ng/min (p less than 0.05) and from 2.1 +/- 0.4 to 3.5 +/- 0.5 ng/min (p less than 0.05), respectively. Vasodilation by L-PAF (10(-7) M) in the presence of indomethacin (INDO) (5 microM) was enhanced compared to the non-INDO response (RVR change: L-PAF = -18 +/- 3% vs. L-PAF = -26 +/- 3%; p less than 0.05). As a control for specificity, the was infused at 10(-9) M, 10(-8) M, and 10(-7) M. None of these concentrations changed renal vascular resistance. To study the vascular receptor responsible for L-PAF-induced vasodilation, dose-response curves to NE and ang II were established with and without L-PAF (10(-7) M). The NE dose-response curve was unchanged by L-PAF, whereas the ang II dose-response curve was shifted to the right by one order of magnitude. In kidneys pretreated with INDO (5 microM), the L-PAF-induced shift of the ang II dose-response relation was increased to 2-3 orders of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)
Use-dependence of ryanodine effects on postrest contraction in ferret cardiac muscle.
Authors: Malecot C O , Katzung B G
Published: June 2012

During an investigation of the effect of ryanodine on contractions in cardiac muscle, it was found that long rest periods removed all or most of the drug's effect. Therefore, we studied the kinetics of block development and recovery from block produced by low concentrations of ryanodine (1-100 pM) on the postrest contractions of ferret papillary muscle. At 100 pM, ryanodine depressed steady-state contraction amplitude slightly (4.2 +/- 1.1% mean +/- SEM, n = 10) but strongly inhibited (40-80%) the first contraction (postrest contraction) elicited on restimulation of the preparation after rest periods of 1 second to 5 minutes. Under control conditions, the nearly maximal potentiation of the twitch occurring after a standard test rest period (30 seconds of rest) was not affected by a preceding conditioning rest of up to 20 minutes. In the presence of 100 pM ryanodine, a conditioning rest increased the amplitude of the twitch elicited after a test rest, and the test rest contraction recovered toward control (drug-free) amplitude monoexponentially (time constant, 582 +/- 105 seconds). Block of postrest contraction could be reinduced by stimulation and occurred faster when higher rates were used (time constants, 758 seconds at 1 Hz and 107 +/- 26 seconds at 3 Hz). Since rest potentiation of twitch tension is believed to be mostly dependent on extra calcium released from the sarcoplasmic reticulum, the results suggest that the ryanodine-induced blockade of calcium release from the sarcoplasmic reticulum is use-dependent and recovers during diastole.(ABSTRACT TRUNCATED AT 250 WORDS)
Fluid reabsorption and glucose consumption in edematous rat lungs.
Authors: Effros R M , Mason G R , Sietsema K , Silverman P , Hukkanen J
Published: June 2012

Solute and water uptake were studied in isolated perfused rat lungs with airspaces filled with the perfusion fluid. The albumin in this solution was labelled with Evans blue (T-1824), and uptake of fluid from the airspaces was documented by an increase in T-1824 concentration in airway fluid of 6.5 +/- 1.6% (n = 5, SEM) at 1 hour and 12.2 +/- 0.9% (n = 10) at 2 hours. The only detectable osmotic force that could have contributed to a loss of fluid from the alveolar fluid was a decrease in airspace glucose concentrations, which fell much more rapidly (from 150 mg/dl to 58.7 +/- 7.1 mg/dl, n = 10, after 2 hours) than plasma glucose (from 150 mg/dl to 128.9 +/- 3.7 mg/dl). Addition of 5 X 10(-5) M terbutaline to the perfusate and airspace solutions nearly doubled fluid reabsorption at 1 hour, an effect that was inhibited by propranolol and did not appear to be related to glucose consumption. Exposure to terbutaline for 2 hours increased epithelial permeability to 3H-mannitol and 22Na+. These observations suggest that active sodium transport and epithelial metabolism or transport of glucose in airway fluid may each play a role in the reabsorption of edema fluid.