bluuebunny/crossref_metadata_2025 huggingface dataset:
Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age.
Authors: Spach M S , Dolber P C
Published: June 2012

Elucidation of the mechanisms of cardiac conduction disturbances leading to reentry will require resolution of the details of multidimensional propagation at a microscopic size scale (less than 200 micron). In practice, this will necessitate the combined analysis of extracellular and transmembrane action potentials. The purpose of this paper is to demonstrate the relationships between the time derivatives of the extracellular waveforms and the underlying action potentials in the experimental analysis of anisotropic propagation at this small size scale, and apply these relationships to human atrial muscle at different ages. The extracellular waveforms and their derivatives changed from a smooth contour during transverse propagation in young preparations to complex polyphasic waveforms in the older preparations. The major problem was to estimate the size and location of small groups of fibers that generated the complex waveforms in the older preparations. We found dissimilarities in the derivatives that distinguished source (bundle) size from the distance of the source to the measurement site. The differences in the extracellular waveforms and their derivatives indicated that there was electrical uncoupling of the side-to-side connections between small groups of fibers with aging. These changes produced a prominent zigzag course of transverse propagation at a microscopic level which, in turn, accounted for the increased complexity of the waveforms. The waveform differences also correlated with the development of extensive collagenous septa that separated small groups of fibers. The electrophysiological consequence was an age-related decrease in the "effective" transverse conduction velocities to the range of the very slow conduction (less than 0.08 m/sec) which makes it possible for reentry to occur in small regions of cardiac muscle with normal cellular electrophysiological properties.
Effect of reduced oxygen availability upon myogenic depolarization and contraction of cat middle cerebral artery.
Authors: Lombard J H , Smeda J , Madden J A , Harder D R
Published: June 2012

The goal of this study was to determine whether electrophysiological mechanisms contribute to the relaxation of cat middle cerebral artery in response to decreased ambient Po2 and whether decreased Po2 alters the myogenic depolarization and contraction of this vessel in response to elevations in transmural pressure. In one series of experiments, arterial segments (200-500 micron outer diameter) were isolated and mounted in an in vitro tension transducer to allow continuous measurement of active tension as bath Po2 was reduced. In these experiments, vessel relaxation occurred primarily between 150 mm Hg Po2 and 40 mm Hg Po2, suggesting that cerebral arteries are sensitive to alterations of Po2 in the physiological range. Relaxation did not result from the activation of dilator nerves in the vessel wall, since it was unaffected by tetrodotoxin. Arterial segments were also cannulated with micropipettes and subjected to elevations in transmural pressure during 300 mm Hg Po2 and 50 mm Hg Po2 superfusion. During 300 mm Hg Po2 superfusion, cannulated vessels exhibited myogenic depolarization and maintained their diameter as transmural pressure was increased; 50 mm Hg Po2 superfusion inhibited spontaneous spike activity, decreased the slope of the myogenic depolarization, and partially inhibited vessel contraction in response to elevated transmural pressure. These effects are independent of the parenchymal cell environment and appear to be mediated, at least in part, by electrophysiological mechanisms.
Effect of calcium on the dissociation of the mature rat heart into individual and paired myocytes: electrical properties of cell pairs.
Authors: Wittenberg B A , White R L , Ginzberg R D , Spray D C
Published: June 2012

The dissociation of adult rat heart into individual, functionally intact, calcium-tolerant myocytes requires precise manipulation of extracellular calcium levels. Dissociation of intercellular connections is achieved by lowering extracellular calcium to micromolar levels for a short period. By imposing a very small increment in free calcium activity (from 14 to 17 microM) during this period, we achieve a significant yield of functionally intact pairs of myocytes still joined at the intercalated disc. We obtain fewer intact cells, but many of these are paired end to end. These findings permit us to describe some structural characteristics of intercellular connections between cardiac cells and to report unambiguous measurements of electrotonic coupling and dye transfer between rat cardiac cell pairs. We find that the strength of electrical coupling between cells isolated as pairs with intact junctional contacts is much greater than that measured between cell pairs that have formed new junctional contacts.
Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction.
Authors: Tsunoda K , Hodsman G P , Sumithran E , Johnston C I
Published: June 2012

To assess the relation between atrial natriuretic peptide and ventricular dysfunction, we simultaneously measured both atrial and plasma immunoreactive atrial natriuretic peptide concentrations in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. When compared to controls (n = 39), rats with infarction (n = 16) had markedly elevated plasma immunoreactive atrial natriuretic peptide concentrations (1205.8 +/- 180.9 vs. 126.7 +/- 8.9 pg/ml, p less than 0.001) and reduced immunoreactive atrial natriuretic peptide concentrations in right and left atria (31.4 +/- 4.6 vs. 61.2 +/- 3.2 ng/mg, p less than 0.001; 14.9 +/- 2.2 vs. 32.7 +/- 2.4 ng/mg, p less than 0.001, respectively). Right ventricular weight increased in proportion to infarct size, and both were correlated with plasma immunoreactive atrial natriuretic peptide levels (r = 0.825, p less than 0.001 and r = 0.816, p less than 0.001, respectively). Right atrial immunoreactive atrial natriuretic peptide content was significantly higher than left in both controls and rats with infarction. Both right and left atrial immunoreactive atrial natriuretic peptide concentrations were negatively correlated with both right ventricular weight as well as plasma immunoreactive atrial natriuretic peptide concentrations (right atrium: r = -0.816, p less than 0.001, r = -0.708, p less than 0.01; left atrium: r = -0.687, p less than 0.01, r = -0.644, p less than 0.01, respectively). These results suggest that chronic stimulation of atrial natriuretic peptide release from both atria is associated with increased turnover and depleted stores of atrial natriuretic peptide in atria in proportion to the severity of heart failure. It also suggests that plasma atrial natriuretic peptide levels may be used as a reliable index of cardiac decompensation in chronic heart failure.
PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH.
Authors: Kukreja R C , Kontos H A , Hess M L , Ellis E F
Published: June 2012

Purified PGH synthase when acting on arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate generated superoxide in burst-like fashion. In eight experiments using different batches of enzyme, the mean +/- SE rate of superoxide generation from 100 U of enzyme measured as the superoxide dismutase-inhibitable reduction of cytochrome c was 5.06 +/- 0.19 nmol/min in the first minute and 0.35 +/- 0.03 nmol/min subsequently. Optimum rates of superoxide were seen at concentrations of reduced nicotinamide-adenine dinucleotide in excess of 80 microM and reduced nicotinamide-adenine dinucleotide 3'-phosphate in excess of 100 microM. Using prostaglandin G2 or linoleic acid as substrate rather than arachidonate also resulted in superoxide generation. When prostaglandin H2 was used as substrate, no superoxide was generated. The rate of superoxide generation was markedly inhibited by cyclooxygenase inhibitors. Superoxide generation was also observed during the action of lipoxygenase on either linoleic or arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate but not in their absence. Indomethacin had no effect on superoxide generation from lipoxygenase. We conclude that PGH synthase and lipoxygenase produce superoxide via a side-chain reaction dependent on the presence of suitable reducing cosubstrate. This mechanism is analogous to that described for peroxidases in general.
Phasic blood flow velocity pattern in epimyocardial microvessels in the beating canine left ventricle.
Authors: Ashikawa K , Kanatsuka H , Suzuki T , Takishima T
Published: June 2012

We quantitated phasic epimyocardial microcirculatory coronary blood flow velocity patterns in the beating left ventricle. Using a newly developed floating objective and high-speed cinematography, red cell velocities in small arterioles, capillaries, and small venules and microvascular diameters in the superficial layer of the epimyocardium of beating left ventricle were determined throughout the entire cardiac cycle in open-chest anesthetized dogs. Heart rate was maintained at 140 beats/min by means of left atrial pacing. Peak red cell velocity was observed in midsystole in small arterioles and capillaries, and in late systole in small venules. Abrupt decline in red cell velocity and, in many cases, a momentary cessation or reverse of flow, was observed in these microvessels during the pre-ejection period. The internal diameter of small venule was increased in late systole, while that of small arteriole remained almost constant during the cardiac cycle. Furthermore, in these epimyocardial microvessels, a higher percentage of the total area under the velocity curve occurred during the ejection phase; 51% in small arterioles, 43% in capillaries, and 40% in small venules. These findings indicate that the phasic blood flow pattern is markedly different in the subepimyocardial microvessels from that in the large epicardial artery and the septal artery. During vasodilation following dilazep (50 micrograms/kg, i.v.), an adenosine potentiator, red cell velocity increased throughout the entire cardiac cycle in epimyocardial microvessels with significant increases in the total area under the velocity curves accompanied by significant dilation of the arterioles. The present data will provide information useful in predicting or simulating transmural differences in the phasic blood flow pattern.
Quantitation of Backflow in Patients with Aortic Insufficiency Using an Indicator Technic
Authors: WARNER HOMER R. , TORONTO ALAN F.
Published: June 2012

A method is reported which permits the estimation of the time-course of backflow velocity in the descending aorta of patients with insufficiency of the aortic valve. Instantaneous back-velocities in excess of 100 cm./sec. have been observed. Evidence suggesting the existence of an oscillation in aortic flow during diastole in some patients is presented. An index to the "volume of backflow per stroke" is described.
Effect of Hemorrhagic Shock on the Phagocytic Function of Kupffer Cells
Authors: ZWEIFACH BENJAMIN W. , BENACERRAF BARUJ
Published: June 2012

This report concerns the phagocytic behavior of the Kupffer cells in the rat during hemorrhagic studies by quantitative technics. The rate of clearance (measured by colloidal carbon) was suppressed by 50 per cent after 3 hours. Efficiency of clearance (measured by uptake of radioisotope labeled albumin and chromium phosphate) was likewise markedly below normal. This factor was not due to reduced blood flow through the liver, as evidenced by measurements made 1 hour after blood replacement. Histologic evidence suggests two possibilities: a localized impairment of Kupffer cell activity in the area about the central veins of the lobule, or an abnormal circulation through preferential pathways restricted to the periphery of the liver lobule.
The Question of Vascular Hyper-Responsiveness in Hypertension
Authors: REDLEAF PAUL D. , TOBIAN LOUIS
Published: June 2012

After inhibition of spontaneous tone, the contraction of spirally cut strips of aorta in response to norepinephrine was studied quantitatively in normotensive rats and in 4 different types of hypertensive rats. In no instance did the aortas of hypertensive rats show hyper-responsiveness to norepinephrine. The majority of responses were entirely normal; in a few instances there was decreased responsiveness. In vivo studies which fail to consider the critical effect of an altered "base-line" state in hypertension may demonstrate "hyper-responsiveness" which is more apparent than real.
Effect in Man of Large Doses of Pyridoxine on Serum Cholesterol
Authors: FAILEY ROBERT B.
Published: June 2012

Pyridoxine (400 mg./day) was given to 21 individuals for periods up to a maximum of 36 days. A slight but significant fall in serum cholesterol levels was observed, the effect being more marked in diabetic than in nondiabetic subjects.
The Blood Vascular Supply of the Dental Pulp with Emphasis on Capillary Circulation
Authors: PROVENZA D. VINCENT
Published: June 2012

Histologic study of the capillary bed contained within the pulps of human teeth shows components which differ as to the presence or absence of muscle in their walls. The vessels which supply the capillary network of the pulp are metarterioles and precapillaries with their sphincters. Arteriovenous anastomoses are also found in the pulp.
Reliability of the Determination of Cardiac Output in Man by Means of the Fick Principle
Authors: SELZER ARTHUR , SUDRANN ROBERT B.
Published: June 2012

Two determinations of cardiac output using the Fick principle were performed within a 15 min. time period in a series of 167 patients representing a wide spectrum of cardiac and pulmonary disorders. The reproducibility of the 2 readings was found to be satisfactory, attesting to the reliability of the practical application of the Fick principle as employed in clinical medicine.
Effect of Epinephrine and Norepinephrine on Coronary Circulation
Authors: BERNE ROBERT M.
Published: June 2012

Studies on the intracoronary administration of epinephrine and norepinephrine in the beating, fibrillating or potassium-arrested dog heart indicate that the primary action of these compounds on the coronary vessels is vasoconstriction. The vasodilation observed with epinephrine and norepinephrine is probably secondary to the increased rate of myocardial metabolism induced by these drugs.
The Relation of Cardiac Effort to Myocardial Oxygen Consumption and Coronary Flow
Authors: KATZ L. N. , FEINBERG H.
Published: June 2012

The current views of the authors regarding the relationship of the cardiac performance and its myocardial oxygen consumption and the relationship of the latter to coronary blood flow are presented. Recent attempts, including our own, to devise an index of total cardiac effort that will relate to the myocardial oxygen consumption are discussed. It is concluded that the cardiac performance requiring oxygen determines coronary flow while the arteriovenous oxygen difference across the bed remains constant. However, the level of the arteriovenous oxygen difference is altered by local conditions of oxygen and carbon dioxide concentrations, and the presence of catecholamines. Hence, the level of coronary flow for a given amount of cardiac oxygen consumption is altered by these circumstances.
An Electron Microscopic Study of Myocardial Ischemia in the Rat
Authors: BRYANT RICHARD E. , THOMAS WILBUR A. , O'NEAL ROBERT M.
Published: June 2012

Myocardial infarcts were produced in rats by ligating the anterior descending branch of the left coronary artery. After one hour, changes in the ultrastructure of myofibers in the infarcts were readily demonstrated by electron microscopy. These changes became progressively severe with time, and consisted primarily of swelling of mitochrondria and sarcoplasmic reticulum followed by increased lipid droplets and myolysis. Autolysis Atolysis of myocardium was also studied and the changes found to be similar to those of myocardial infarcts, but more uniform and slightly delayed in development. Perhaps the early ultrastructrural changes are related to hyperosmolarity of mitochondria and sarcoplasmic reticulum, especially after cell death. It is hoped that definition of ischemic ultrastructural change will be useful in defining electron microscopic lesions in other forms of myocardial damage.
Effect of Temperature on the Heart Rate, Electrocardiogram and Certain Myocardial Oxidations of the Rat
Authors: HANNON JOHN P.
Published: June 2012

Deep hypothermia in the rat was studied with respect to the sequential changes in body temperature, heart rate, and electrocardiogram. In vitro assays of myocardial metabolic activity were made at temperatures ranging from 5 to 35 C. These assays strongly suggested that the in vivo cardiac dysfunctions observed at low temperatures were attributable to shifts in temperature kinetics of enzyme systems at 20 to 21 C.
Pathogenesis of coronary artery spasm in miniature swine with regional intimal thickening after balloon denudation.
Authors: Yamamoto Y , Tomoike H , Egashira K , Kobayashi T , Kawasaki T , Nakamura M
Published: June 2012

Pathogenesis of coronary artery spasm induced by histamine in miniature pigs was studied angiographically in in vivo and in vitro conditions. Endothelial balloon denudation was performed and the animals were fed laboratory chow for 3 months, after which coronary artery spasm was repeatedly provoked by histamine given intracoronarily. Regional hypercontraction of the coronary artery was documented by selective coronary arteriography, and the resulting myocardial ischemia was confirmed by ECG-ST changes. To evaluate coronary artery spasm without the influence of blood constituents and neural control and to quantitate the pharmacophysiological characteristics of histamine-induced coronary constriction in the coronary spasm, the same heart was isolated and perfused with Krebs-Henseleit solution under a constant perfusion pressure of 90 mm Hg. Histamine (10(-5) M) reduced the diameter of the coronary artery of the isolated heart by 29 +/- 4 and 67 +/- 3% (p less than 0.001) in nondenuded and denuded areas, respectively. These figures were similar to data obtained angiographically in vivo after the administration of histamine 10 micrograms/kg. The constriction of the denuded areas in response to histamine was topologically the same in vivo and in vitro. The degree of focal constriction induced by histamine, defined as a percent of stenoses from the mean diameter of the areas of proximal and distal to the spastic site, was similar in in vivo (10 micrograms/kg i.c.) and in vitro (10(-5) M) conditions. KCl (40 mM) reduced both the denuded and nondenuded coronary artery diameter by 67 +/- 3% and 68 +/- 3% (NS), respectively. The dose-response relation of the coronary diameter to histamine was not influenced by pretreatment with the nerve transmitter blockers guanethidine (3 X 10(-6) M), atropine (10(-6) M), and tetrodotoxin (3 X 10(-7) M). Phenylephrine (10(-5) M) did not potentiate constriction of the denuded areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Abnormal calcium handling by platelets in thrombotic disorders.
Authors: Jy W , Ahn Y S , Shanbaky N , Fernandez L F , Harrington W J , Haynes D H
Published: June 2012

This study presents a quantitative comparison of the free cytoplasmic calcium concentration ([Ca2+]cyt) and the free concentration in the lumen of the dense tubules of the human platelet. The former was measured by the fluorescence of the high affinity indicator quin2 and latter by the fluorescence of chlorotetracycline (CTC). The CTC technique monitors calcium-CTC complex accumulation in the lumen of dense tubules and mitochondria when washed platelets were incubated in 2 mM Ca2+. Resting cytoplasmic and dense tubular Ca2+ concentrations were studied in platelets from patients suffering from venous and arterial thrombosis. Compared with normal controls (0.40 +/- 0.10, n = 54), the values of the calcium-CTC ratios were 0.68 +/- 0.19 (n = 16, p less than 0.005) in venous thrombosis; 0.75 +/- 0.18 (n = 14, p less than 0.005) in cardiovascular accident; 0.84 +/- 0.18 (n = 6, p less than 0.005) in occlusive peripheral vascular diseases; and 0.42 +/- 0.10 (n = 21, p greater than 0.1) in patient controls. The dense tubular Ca2+ levels for both patients and controls were perfectly correlated with the cytoplasmic levels using an equation that assumes that the dense tubular free calcium concentration ([Ca2+]dt) has a second power dependence on [Ca2+]cyt. The abnormal Ca2+ handling of platelets obtained from thrombotic patients could be completely reversed by preincubation with the calcium channel blocker verapamil. These observations suggest that the primary Ca2+ handling defect is the leakage through activated channels in the plasma membrane. The defect and the elevated resting [Ca2+]cyt and [Ca2+]dt are adequate to explain the observation of increased rates of collagen-activated aggregation in the above-mentioned group of patients. The results can be explained by platelets from thrombosis patients being exposed to activating factors in the circulation, resulting in Ca2+ channel activation. Channel activation persists through the process of platelet isolation and washing and is manifested in higher measured values of [Ca2+]cyt and [Ca2+]dt in the "resting state." This would bring the platelet closer to its aggregation when aggregation-inducing agents are added. The CTC test is shown to be a useful and convenient means of detecting this abnormality.
Cardiovascular effects of calcitonin gene-related peptides I and II in man.
Authors: Franco-Cereceda A , Gennari C , Nami R , Agnusdei D , Pernow J , Lundberg J M , Fischer J A
Published: June 2012

Calcitonin gene-related peptide (CGRP) is present in sensory nerve fibers in the heart and around peripheral arteries. On interaction with specific CGRP binding sites and activation of adenylate cyclase, CGRP causes vasodilation and has positive inotropic and chronotropic effects on the heart. In the present study, human CGRP I and II exerted positive inotropic effects on isolated human right auricles and relaxed small arteries from human skeletal muscle precontracted with norepinephrine (EC50 for CGRP I 0.59 nM and for CGRP II 0.37 nM). CGRP I and II (3.2 nmol) administered i.v. to 6 normal subjects exerted positive inotropic actions on the human heart concomitant with positive chronotropic effects, hypotension, and vasodilation. CGRP may, therefore, be of importance for cardiovascular control in man.
Morphometric analysis of cardiac hypertrophy during development, maturation, and senescence in spontaneously hypertensive rats.
Authors: Engelmann G L , Vitullo J C , Gerrity R G
Published: June 2012

Hypertrophy of the mammalian heart, regardless of the initiating event, results in architectural remodeling of ventricular components that maintain structural and functional characteristics of this organ. Ventricular components that vary their morphology and morphometry in a hypertrophic state are the muscle cells, connective tissue elements, vasculature, or a combination of some or all of the above. Morphologic quantification of the progressive tissue changes occurring throughout the natural life span of the spontaneously hypertensive and normotensive Wistar-Kyoto rats has not been thoroughly documented. Using perfused-fixed tissue from both strains at 1, 6, 12, 18, and 24 months of age, we have determined the morphometric changes that occurred in the subepicardial and midwall regions of the left ventricle. Myocyte cell size, wall thickness, and arterial blood pressure were elevated in 1-month-old spontaneously hypertensive rats, reached significance by 6 months, and remained significantly greater throughout the 24 months examined. Tissue morphometry demonstrated significant tissue component volumetric differences at 6 months in the spontaneously hypertensive rat. Age-related morphometric tissue changes occurred in both strains yet were exacerbated (percent volume of myocytes) or diminished (percent volume interstitial space) in the mature and aging spontaneously hypertensive rat. Capillary density of SHR left ventricle showed a drastic decline so that 6-month-old SHR had the same density as a senescent Wistar-Kyoto. Tissue morphometry and capillary density data strongly support the hypothesis that tissue oxygenation is diminished in the spontaneously hypertensive rat, and as a result, tissue necrosis and myocyte cell death occur.
Human neutrophils release serine proteases capable of activating prorenin.
Authors: Dzau V J , Gonzalez D , Kaempfer C , Dubin D , Wintroub B U
Published: June 2012

Proteases from human neutrophils can generate angiotensin II directly from angiotensin I or angiotensinogen. We examined whether neutrophil protease also influences angiotensin formation by activating human prorenin (also called inactive renin). When incubated with partially purified plasma and amniotic prorenin, sonicates from 10(6) neutrophils resulted in 120 +/- 30% and 1,240 +/- 290% increase in renin activity, respectively. The pH optimum of neutrophil prorenin-activating enzyme(s) is 6.5-7.0, and the activity of the enzyme(s) is inhibited by a mixture of serine protease inhibitors but not by inhibitors of other proteases, suggesting that prorenin-activating enzyme(s) is a neutral serine protease(s). Stimulation of neutrophils by f-met-leu-phe in the presence of cytochalasin B resulted in release of prorenin-activating enzyme(s) in a dose-dependent fashion. We attempted to isolate prorenin-activating enzyme(s) from neutrophil granules using aprotinin-affinity and carboxymethyl cellulose chromatographies. Prorenin-activating enzyme(s) coeluted with cathepsin G and elastase activities. Prorenin activation was greatly inhibited by anticathepsin G antiserum. Purified cathepsin G activated prorenin in a dose-dependent fashion. Elastase probably also contributes to prorenin activation since purified elastase also activated human prorenin. We speculate that this neutrophilic angiotensin-generating system may play a role in the local generation and concentration of angiotensins by influencing multiple steps of the renin-angiotensin system.
Alpha 1-adrenoceptor activity regulates release of adenosine from the ischemic myocardium in dogs.
Authors: Kitakaze M , Hori M , Tamai J , Iwakura K , Koretsune Y , Kagiya T , Iwai K , Kitabatake A , Inoue M , Kamada T
Published: June 2012

The goal of this study was to test the hypothesis that alpha 1-adrenoceptor activity plays a key role in the release of adenosine from the ischemic myocardium. In 51 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery, and adenosine release into the local coronary vein was measured by the radioimmunoassay technique following the reduction of perfusion pressure for 20 minutes under alpha 1-, alpha 2-, and beta-adrenoceptor attenuations. Adenosine and lactate concentrations in the coronary arterial and venous blood sampled from the perfused area were determined, as well as fractional shortening. In the untreated condition, adenosine release was significantly (p less than 0.01) increased from 1.7 +/- 0.8 (SEM) to 8.8 +/- 1.3 nmol/100 g/min, 20 minutes after the onset of hypoperfusion (coronary blood flow: 28 +/- 2 ml/100 g/min) following the initial overshoot release. Neither beta- nor alpha 2-adrenoceptor attenuation affected the increase in adenosine release during hypoperfusion except for the slight attenuation of the overshoot release by beta-attenuation. In contrast, intracoronary infusions of prazosin and phentolamine during coronary hypoperfusion markedly attenuated (p less than 0.01) release of adenosine (1.8 +/- 0.7 nmol/100 g/min at 20 minutes). The extents of decreases in fractional shortening and lactate production were comparable between the untreated and alpha 1-adrenoceptor attenuation.(ABSTRACT TRUNCATED AT 250 WORDS)
Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart.
Authors: Simpson P J , Mickelson J , Fantone J C , Gallagher K P , Lucchesi B R
Published: June 2012

The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Iloprost (0.1-100 microM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Iloprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5a in each of the groups was control 13.3 +/- 1.8 units/g tissue (n = 12) and iloprost 6.5 +/- 0.9 units/g (n = 12), p less than 0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 +/- 3.1% of the area at risk (n = 15) compared with 42.4 +/- 3.3% of control (n = 13), p less than 0.01. Iloprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the interface between infarcted and noninfarcted tissue: control (n = 9) 9.0 +/- 1.8 units/g tissue, iloprost (n = 6) 2.0 +/- 0.4 units/g, p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Vagal mediation of the effects of atrial natriuretic factor on blood pressure and arterial baroreflexes in the rabbit.
Authors: Volpe M , Cuocolo A , Vecchione F , Mele A F , Condorelli M , Trimarco B
Published: June 2012

We investigated the hemodynamic effect of synthetic atrial natriuretic factor Auriculin A (ANF) and its influence on arterial baroreflex control of heart rate, systemic blood pressure, and perfusion pressure in the hind limb (perfused at constant flow) in rabbits anesthetized with alpha-chloralose and urethane. The neural mechanisms underlying these effects were also studied. In the intact animal, a 45-minute constant infusion of ANF (2 micrograms/kg prime, 0.2 microgram/kg/min) significantly reduced mean blood pressure and increased mean perfusion pressure, while heart rate did not change. Comparable data were obtained with lower (0.5 microgram/kg + 0.05 microgram/kg/min; 1 microgram/kg + 0.1 microgram/kg/min) or higher (4 micrograms/kg + 0.4 microgram/kg/min; 8 micrograms/kg + 0.8 microgram/kg/min) doses of ANF. In addition, ANF enhanced bradycardic reflex responses to phenylephrine i.v. bolus administration, while it did not change baroreflex-mediated responses to nitroglycerin i.v. bolus administration and to 30-second bilateral carotid occlusion. The specificity of the influence of ANF on arterial baroreflex responses was confirmed by the observation that no significant change in reflex responses to phenylephrine or carotid occlusion was detectable during a comparable decrease in blood pressure induced by a constant infusion of nitroglycerin. Bilateral vagotomy prevented both the fall in blood pressure and the increase in perfusion pressure induced by ANF, while cholinergic blockade (atropine, 0.5 mg/kg i.v.) or adrenergic blockade (propranolol, 0.3 mg/kg i.v. + phentolamine, 0.3 mg/kg i.v.) did not modify the hemodynamic response to ANF observed in the intact animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle.
Authors: Delmar M , Michaels D C , Johnson T , Jalife J
Published: June 2012

Propagation in cardiac muscle is faster in the longitudinal than in the transverse axis of the cells. Yet, as a result of the larger upstroke velocity of action potentials propagating transversely, it has been suggested that longitudinal propagation is more vulnerable to block. To study the relation between conduction velocity and maximal upstroke velocity (Vmax), as well as the time course of conduction delay and block in the transverse vs. longitudinal direction, thin square pieces of sheep epicardial muscle were superfused with the cellular uncoupler heptanol (1.5 mM). Action potentials were recorded with microelectrodes at opposite corners of the preparation while stimulating alternately in the longitudinal or transverse direction with bipolar electrodes located at contralateral corners. In all cases, block occurred more promptly for transverse than for longitudinal propagation. The decrease in conduction velocity was greater than expected for Vmax decay and, in some cases, Vmax increased while conduction velocity decreased. In the presence of high grade conduction impairment, foot potentials appeared and the upstrokes became "notched." We conclude that when intercellular coupling is impaired, transverse propagation is more vulnerable to block, and need not be dependent on changes in Vmax.
Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family.
Authors: Mahdavi V , Izumo S , Nadal-Ginard B
Published: June 2012

Sarcomeric myosin heavy chain (MHC), the main component of the sarcomere, contains the ATPase activity that generates the contractile force of cardiac and skeletal muscles. The different MHC isoforms are encoded by a closely related multigene family. Most members (seven) of this gene family have been isolated and characterized in the rat, including the alpha- and beta-cardiac, skeletal embryonic, neonatal, fast IIA, fast IIB, and extraocular specific MHC. The slow type I skeletal MHC is encoded by the same gene that codes for the cardiac beta-MHC. Each MHC gene studied displays a pattern of expression that is tissue and developmental stage specific, both in cardiac and skeletal muscles. Furthermore, more than one MHC gene is expressed in each muscle while each gene is expressed in more than one tissue. The expression of each MHC gene in cardiac and skeletal muscles is modulated by thyroid hormone. Surprisingly, however, the same MHC gene can be regulated by the hormone in a significantly different manner, even in opposite directions, depending on the muscle in which it is expressed. Moreover, the skeletal embryonic and neonatal MHC genes, so far considered specific to these 2 developmental stages, are normally expressed in certain adult muscles and can be reinduced by hypothyroidism in specific muscles. This complex pattern of expression and regulation of the MHC gene family in cardiac and skeletal muscle sheds new light on the mechanisms involved in determining the biochemical basis of the contractile state. It also indicates that the cardiac contractile system needs to be examined in a broader context, including skeletal muscles, in order to understand fully its developmental and physiologic regulation.
Electrical stimulation of the endothelial surface of pressurized cat middle cerebral artery results in TTX-sensitive vasoconstriction.
Authors: Harder D R , Madden J A
Published: June 2012

The purpose of this study was to examine the electrical and mechanical responses of cat middle cerebral arteries to electrical stimulation of the adventitial vs. intimal surface of the vessels and to determine the responses as a function of transmural pressure. Middle cerebral arteries were cannulated at both ends. Within each cannula was a stimulating electrode. Electrical stimulation (0.5-msec square current pulses at 0.5 Hz yielding 160 microA of current between electrodes) resulted in significant reduction in diameter that was greater at both 40 and 80 mm Hg vs. 100 or 140 mm Hg. Conversely, adventitial stimulation of perivascular nerves with transmural platinum stimulating electrodes resulted in significant vasodilation. The constrictor response to intimal stimulation, as well as the dilatory response to adventitial stimulation, was blocked by tetrodotoxin. The constrictor response to luminal stimulation was enhanced by scorpion toxin demonstrating a functional role for tissues containing fast Na+ channels. Perfusion with collagenase to disrupt the endothelium also abolished the constrictor response to luminal stimulation. The divergence of responses between adventitial and luminal surface stimulation may suggest that different cell layers within a blood vessel serve different functions, one to increase resistance and another to decrease resistance. For example, in cat middle cerebral arteries, the adventitial nerves (i.e., via reflexes) may increase flow, while blood-borne substances may mediate release of agents that reduce flow.
Myogenic vasoregulation overrides local metabolic control in resting rat skeletal muscle.
Authors: Meininger G A , Mack C A , Fehr K L , Bohlen H G
Published: June 2012

Microvascular reactions to increases in intravascular pressure were studied in the cremaster muscle of the anesthetized rat by enclosing the animal in an airtight box with the muscle exteriorized for observation of the microcirculation. Since the cremaster was exposed to atmospheric pressure, increasing pressure within the box produced equal increases in arterial and venous pressures. Thus, intravascular pressure was altered without affecting the pressure gradient for blood flow. Raising box pressure had no effect on respiration or heart rate and did not change the systemic activity of the sympathetic system, angiotensin II, or vasopressin. Diameters and flows were measured for first (107 +/- 3 micron, mean +/- SEM), second (87 +/- 5), third (29 +/- 2), and fourth (15 +/- 2) order arterioles during increases in intravascular pressure of +10, +20, and +30 mm Hg. No significant changes in the diameters of first or second order arterioles were elicited when pressure was increased. However, when box pressure was increased to +10, +20, or +30 mm Hg, a sustained constriction occurred in third (29%, 45%, and 63%, respectively) and fourth (5%, 38%, and 57%, respectively) order arterioles. Blood flow was significantly reduced in all arterioles, and perivascular PO2 was decreased adjacent to third and fourth order arterioles. Furthermore, the third order arteriole constrictor response was not abolished by local alpha-receptor blockade (phentolamine), indicating that it was not mediated by a local sympathetic axon reflex. Collectively, these data indicate that a potent, non-neural, pressure-dependent mechanism for vasoregulation is present in small arterioles of the cremaster. The sustained constriction in the presence of reduced blood flow and reduced periarteriolar oxygen tension indicates that the vascular response is independent of and capable of overriding flow-dependent (i.e., metabolic) control in resting skeletal muscle. The observations are compatible with the operation of a powerful myogenic mechanism in small arterioles.
Endocardial, intramural, and epicardial activation patterns during sustained monomorphic ventricular tachycardia in late canine myocardial infarction.
Authors: Garan H , Fallon J T , Rosenthal S , Ruskin J N
Published: June 2012

Thirteen dogs in whom at least one morphologically distinct sustained ventricular tachycardia (VT) could be reproducibly initiated by programmed cardiac stimulation 18 +/- 3 days following experimental myocardial infarction were placed on total cardiopulmonary bypass for detailed study of the endocardial and epicardial activation during VT under hemodynamically stable conditions. Thirteen morphologically distinct monomorphic VTs were investigated by simultaneous epicardial, endocardial, and intramural bipolar recordings. Local electrograms were used to generate computer-assisted isochronous-activation sequence maps. A complete reentry circuit could be mapped on the epicardial surface in 4 animals and on the endocardial surface in one other animal. In the remaining 8 animals, there was a gap period lasting 43-62 msec in the cardiac cycle during which no endocardial or epicardial activity was observed. In 6 of the 8 animals, bipolar intramural recordings from sites closely associated with regions of endocardial and epicardial conduction block showed intramural activity progressing slowly during the gap period. In these 6 animals, a reentry circuit could be completed by incorporating the local electrograms recorded from the intramural sites. VT could be reproducibly terminated by selectively rendering only these intramural sites refractory by critically timed extrastimuli that failed to result in global ventricular capture. VT could be terminated by epicardial cooling in 2 of the 4 animals with epicardial reentry. By contrast, epicardial cryoablation did not effect intramural reentry and failed to interrupt VT. In this study, intramural pathways constituted an integral part of the reentry circuit in a large proportion of the VTs.
Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog.
Authors: Engler R , Covell J W
Published: June 2012

Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide-radical-induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15-minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (greater than 100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p less than 0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15-minute ischemia dog model. Other possible granulocyte-related mechanisms of reperfusion injury include capillary no-reflow, causing microvascular ischemia and degranulation leading to enzyme-induced damage.
Evidence for increased media thickness, increased neuronal amine uptake, and depressed excitation--contraction coupling in isolated resistance vessels from essential hypertensives.
Authors: Aalkjaer C , Heagerty A M , Petersen K K , Swales J D , Mulvany M J
Published: June 2012

The functional and morphologic characteristics of isolated subcutaneous resistance vessels (about 170 micron i.d.) from 15 untreated subjects with essential hypertension and 15 matched controls were examined. The vessels from the hypertensives had a 29% increase in the media-thickness-to-lumen-diameter ratio. The maximal force development to noradrenaline (NA) expressed as active pressure (an estimate of the pressure the vessels could have contracted against in vivo) was 30% higher in vessels from the hypertensives, while active media stress (force per square unit of smooth muscle) and sensitivity to NA was not significantly different. Increased active pressure, as well as unaltered active media stress and sensitivity, was seen for vasopressin, serotonin, angiotensin II, and K+. There was, however, an enhanced leftward shift of the NA sensitivity with cocaine (an inhibitor of the neuronal amine pump) in vessels from the hypertensives [pD2(+cocaine) and pD2(-cocaine) were 0.185 +/- 0.53) and 0.040 +/- 0.044, hypertensives and normotensives, respectively, p less than 0.05] suggesting an abnormality of presynaptic function in essential hypertension. Furthermore, the calcium sensitivity was depressed (pD2 was 4.197 +/- 0.050 and 4.381 +/- 0.068, hypertensives and normotensives, respectively, p less than 0.05), and the rate of relaxation was faster (p less than 0.05) in vessels from hypertensives, suggesting that excitation-contraction coupling might be depressed. The results suggest that the increased pressor response in essential hypertension can, to a large extent, be explained by altered vascular structure, while smooth muscle function is either unchanged or possibly depressed.
Protective effect of vagal stimulation on reperfusion arrhythmias in cats.
Authors: Zuanetti G , De Ferrari G M , Priori S G , Schwartz P J
Published: June 2012

The role of the autonomic nervous system in modulating reperfusion arrhythmias is still unclear. Experiments with sympathetic denervation or alpha- and beta-adrenergic blocking agents have provided mixed results, while the effect of parasympathetic activation has not been investigated extensively. The effect of bilateral vagotomy and of vagal stimulation was studied, with and without attendant bradycardia, on the incidence of reperfusion arrhythmias in alpha-chloralose anesthetized cats. The left anterior descending coronary artery was occluded for 20 minutes, followed by reperfusion in 105 animals. The incidence and severity of reperfusion arrhythmias was compared in 1) neurally intact animals (heart rate 208 +/- 24 beats/min), 2) animals with acute bilateral vagotomy (heart rate 233 +/- 25 beats/min), 3) animals with vagal stimulation adjusted to maintain heart rate at 90-100 beats/min, and 4) animals with vagal stimulation + ventricular pacing to maintain heart rate at prestimulation values. All the neurally intact and vagotomized animals developed complex reperfusion arrhythmias, but these arrhythmias occurred in only 60 and 72%, respectively, of the animals with vagal stimulation and vagal stimulation + pacing (p less than 0.005 vs. neurally intact and p less than 0.02 vs. vagotomy). The incidence of ventricular fibrillation was similar in neurally intact (62%) and vagotomized (58%) animals; it was strikingly lower (7%, p less than 0.01) in animals with vagal stimulation when heart rate was allowed to decrease, and it was 48% when heart rate was kept constant during vagal stimulation. A selective protection from sustained (greater than 30 seconds duration) ventricular tachycardia was observed in animals with vagal stimulation independent of heart rate changes.(ABSTRACT TRUNCATED AT 250 WORDS)