bluuebunny/crossref_metadata_2025 huggingface dataset:
Matching between ventricle and arterial load. An evolutionary process.
Authors: Elzinga G , Westerhof N
Published: June 2012

The hemodynamic properties of the ventricle are related to those of the arterial load. However, the precise nature of this relation is not known. At least three different matching criteria have been described in the literature: optimization of heart rate, of power output, and of external efficiency. Although these suggestions are based on experimental findings, there is little understanding of the underlying principles. We now suggest that the balance between the ventricle and its load is a result of the evolutionary process. To support our view, three simple assumptions are proposed regarding the evolutionary determinants underlying the relation between ventricle and arterial load: 1) Arterial pressure and flow to be generated by the ventricular pump under normal (control) conditions are set by the demands of the body. 2) Mechanical properties of contractile machinery and arterial wall material are given. 3) The heart and arterial system should have minimum size. On the basis thereof, we argue that heart rate is related to maintenance of diastolic pressure and show that the ventricle operates close to optimum power and efficiency to attain minimum size.
Angiotensin degradation products mediate endothelium-dependent dilation of rabbit brain arterioles.
Authors: Haberl R L , Decker P J , Einhäupl K M
Published: June 2012

This study demonstrates that the hexapeptide angiotensin II-(3-8) and L-arginine, generated through enzymatic degradation of angiotensin, mediate endothelium-dependent dilation in rabbit brain arterioles. Topical application of angiotensin II (10(-5) M) on the brain surface of anesthetized rabbits caused 21.6 +/- 4.5% (mean +/- SEM) cerebral arteriolar dilation. The cyclooxygenase inhibitor indomethacin did not change this dilation. The natural degradation product of angiotensin II in the brain, angiotensin III, also induced vasodilation at concentrations of 10(-7) to 10(-5) M. The dilation to angiotensin II and angiotensin III was eliminated in the presence of 10(-5) M methylene blue, a known inhibitor of endothelium-dependent vasodilation. Amastatin, an aminopeptidase inhibitor and blocker of enzymatic angiotensin degradation, also inhibited the response to angiotensin II and angiotensin III. The angiotensin fragment angiotensin II-(3-8), which lacks the amino-terminal L-arginine residue of angiotensin III, did not elicit an arteriolar response. When angiotensin II-(3-8) was topically applied subsequent to L-arginine, a 21.2 +/- 2.9% vasodilation was observed. L-Arginine itself induced only moderate vasodilation with a maximum of 4.0 +/- 0.9% at 10(-5) M L-arginine. The dilating response to angiotensin II-(3-8) after L-arginine was inhibited by methylene blue. It was not affected by amastatin. It is concluded that degradation products of angiotensin, rather than angiotensin II itself, induce endothelium-dependent dilation in rabbit brain arterioles without involvement of cyclooxygenase products.(ABSTRACT TRUNCATED AT 250 WORDS)
Spatial distribution of connexin43, the major cardiac gap junction protein, in the developing and adult rat heart.
Authors: van Kempen M J , Fromaget C , Gros D , Moorman A F , Lamers W H
Published: June 2012

The developmental appearance and spatial distribution pattern of gap junctions were studied in prenatal and adult rat hearts. Gap junctions were visualized immunohistochemically with an antibody raised against a unique cytoplasmic epitope of connexin43, and the spatial distribution pattern was determined by three-dimensional reconstruction. The results demonstrate that from embryonic day 13 onward, connexin43 becomes detectable immunohistochemically in the myocardium of atria and ventricles. No expression is initially detectable in the myocardium of the sinus venosus, the sinoatrial node, the posterior wall of the atrium and pulmonary veins, the interatrial septum, the atrioventricular canal, including atrioventricular node and bundle, the interventricular septum, and the outflow tract. The developmental increase in the density of gap junctions in atria and ventricles of prenatal hearts correlates well with the reported developmental increase in conduction velocity. Whereas connexin43 becomes expressed in the derivatives of the sinus venosus (except for the sinoatrial node) and in the subepicardial layer of the ventricular free wall shortly before birth, it remains undetectable in the atrioventricular node and bundle and the proximal part of the ventricular conduction tissue, even in the adult heart. The apparent absence of an abundant expression of connexin43 at a location with a supposedly high conduction velocity (i.e., the atrioventricular bundle and bundle branches) is unexpected. These observations were confirmed in studies of the adult mouse heart, which showed, in addition, that connexin32 is not expressed in any part of the heart.
Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis.
Authors: Kaiser L , Tithof P K , Lamb V L , Williams J F
Published: June 2012

A role for altered endothelial cell function is emerging in the pathogenesis of disease. We have previously demonstrated that Dirofilaria immitis, the canine heartworm, depresses endothelium-dependent responses and alters the mechanism of relaxation in the in vivo femoral artery of infected dogs. Exposure of rat aorta to the parasite or parasite-conditioned medium selectively depresses endothelium-dependent relaxation. D. immitis is closely related to the major human filarial pathogens. This study was designed to examine the effect of chronic infection with the filarial nematode Brugia pahangi on endothelium-mediated responses of the rat aorta in vitro. We tested the hypothesis that endothelium-dependent responses are depressed in the aorta from rats infected with B. pahangi. Rings of thoracic and abdominal aorta were suspended in muscle baths for measurement of isometric tension. Dose-response relations to norepinephrine, endothelium-dependent dilators (acetylcholine, histamine, and A23187), and nitroglycerin were done. In some experiments, inhibitors of cyclooxygenase (indomethacin and aspirin), guanylate cyclase (methylene blue), and nitric oxide formation (N-nitro-L-arginine methyl ester; L-NOARG) were used. No differences in vascular reactivity were detected in the thoracic aorta. In contrast, endothelium-dependent responses in abdominal aorta of Brugia-infected rats were significantly depressed when compared with control aorta from noninfected rats. Acetylcholine relaxation was further depressed by indomethacin and aspirin. After L-NOARG, acetylcholine relaxation in control abdominal aorta was completely abolished; however, in abdominal aorta of Brugia-infected rats, acetylcholine still caused relaxation. Methylene blue inhibited acetylcholine relaxation in both control and Brugia-infected abdominal aorta; however, relaxation in Brugia-infected aorta was significantly greater than control. This study demonstrates that endothelium-dependent relaxation can be altered by chronic experimental filarial infection in the absence of direct contact between the blood vessel and the parasite. The mechanism of relaxation in the Brugia-infected abdominal aorta appears to be altered when compared with control, suggesting that parasites are capable of modulating vascular reactivity by inducing changes in endothelial cell behavior. The mechanism may involve parasite-induced local inflammation or alterations in endothelial cell metabolism. Understanding how chronic experimental filarial infection alters vascular reactivity may enhance our understanding of the pathogenesis of human filariasis.
Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes.
Authors: Ito H , Hirata Y , Hiroe M , Tsujino M , Adachi S , Takamoto T , Nitta M , Taniguchi K , Marumo F
Published: June 2012

To determine whether endothelin-1 (ET-1) induces hypertrophy of cardiomyocytes, the effects of ET-1 on the expression of muscle-specific genes and a proto-oncogene, c-fos, in cultured neonatal rat cardiomyocytes were examined by Northern blot analysis. ET-1 (10(-7) M) induced about twofold to fourfold increases in the gene expression of myosin light chain 2, alpha-actin, and troponin I after 6 hours, which continued up to 24 hours. The ET-1-induced increases in mRNA levels for these muscle-specific genes were dose dependent (10(-9) to 10(-7) M). Run-on transcriptional assay showed that the changes in mRNA level for three muscle-specific genes were regulated, at least in part, at the transcriptional level. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a potent protein kinase C activator, and the Ca2+ ionophore ionomycin also increased mRNA levels of three muscle-specific genes. ET-1, TPA, and ionomycin similarly induced the expression of c-fos after 30 minutes, which returned to an undetectable level after 6 hours. ET-1 remarkably and dose-dependently stimulated accumulation of total inositol phosphates in cardiomyocytes. Morphometrical evaluation showed that ET-1 significantly increased surface area of cardiomyocytes without cell proliferation. ET-1 also dose-dependently stimulated the synthesis of protein and DNA, which was unaffected by the L-type calcium channel blocker nicardipine. These data suggest that ET-1 induces hypertrophy of cardiomyocytes associated with the induction of muscle-specific gene transcripts through the possible involvement of protein kinase C activation or intracellular Ca2+ mobilization.
Stimulation of skin sympathetic nerve discharge by central command. Differential control of sympathetic outflow to skin and skeletal muscle during static exercise.
Authors: Vissing S F , Scherrer U , Victor R G
Published: June 2012

Microneurographic measurements of muscle sympathetic nerve activity (SNA) have suggested that, during static exercise, central command is much less important than skeletal muscle afferents in causing sympathetic neural activation. The possibility remains, however, that the sympathetic discharge produced by central command is targeted mainly to tissues other than skeletal muscle. To examine this possibility, we recorded SNA with microelectrodes placed selectively in skin, as well as in muscle, nerve fascicles of the peroneal nerve during static handgrip maneuvers designed to separate the effects of central command from those of muscle afferents. To study the relative effects of cutaneous sympathetic activation on sudomotor versus vasomotor function, we simultaneously estimated changes in skin blood flow (laser Doppler velocimetry) and in sudomotor (electrodermal) activation in the region of skin innervated by the impaled nerve fascicle. Two minutes of static handgrip at 10%, 20%, and 30% of maximal voluntary contraction caused large and intensity-dependent increases in skin SNA. These increases in SNA immediately preceded the onset of muscle tension, accelerated progressively during sustained handgrip, and resolved promptly with the cessation of motor effort. The handgrip-induced increases in skin SNA were not maintained when handgrip was followed by arrest of the forearm circulation, a maneuver that maintains the stimulation of chemically sensitive muscle afferents while eliminating the influences of central command and mechanically sensitive muscle afferents. During normothermia, static handgrip at 30% maximal voluntary contraction caused sustained increases in skin SNA (+400 +/- 83%, mean +/- SEM, p less than 0.05) and in electrodermal activity (+276 +/- 56%, p less than 0.05) but only transient increases in estimated skin vascular resistance (+11 +/- 2%, p less than 0.05). When skin temperature was increased or decreased to a new stable baseline level, subsequent increases in skin SNA during handgrip were accompanied by sustained but directionally opposite changes in estimated skin vascular resistance, with exercise-induced vasodilation during hyperthermia but exercise-induced vasoconstriction during hypothermia. From these observations, we conclude the following: 1) static exercise markedly increases sympathetic outflow to skin as well as to skeletal muscle; 2) the increases in skin SNA, unlike muscle SNA, appear to be caused mainly by central command rather than by muscle afferent reflexes; and 3) this cutaneous sympathetic activation appears to be targeted both to sweat glands and to vascular smooth muscle, with the relative targeting being temperature dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
Effect of thyroid hormone on the expression of mRNA encoding sarcoplasmic reticulum proteins.
Authors: Arai M , Otsu K , MacLennan D H , Alpert N R , Periasamy M
Published: June 2012

The purpose of this study was to determine the expression of genes encoding various sarcoplasmic reticulum components that are functionally coupled with calcium release, uptake, and storage function during cardiac hypertrophy induced by thyroid hormone. Hyperthyroidism was induced in two groups of rabbits by the injection of 200 micrograms/kg L-thyroxine (T4) daily for 4 days (T4-4-day group) and 8 days (T4-8-day group). Hypothyroidism was induced in another group of rabbits by adding 0.8 mg/ml propylthiouracil to the drinking water for 4 weeks. The relative expression level of mRNA encoding different sarcoplasmic reticulum proteins was determined by RNA slot blot and Northern blot analysis. In hyperthyroid hearts, the steady-state level of cardiac ryanodine receptor mRNA and sarcoplasmic reticulum cardiac/slow-twitch Ca(2+)-ATPase mRNA were both increased to 147% (T4-4-day group) and 186% (T4-8-day group) of control, respectively, but decreased to 71% and 75%, respectively, in hypothyroid ventricles. The mRNA level for phospholamban was decreased in both hyperthyroidism (T4-8-day group, 72%) and hypothyroidism (77%) in these hearts. On the other hand, calsequestrin mRNA levels did not change in hyperthyroid and hypothyroid ventricles. In accord with the changes in Ca(2+)-ATPase mRNA levels, the Ca(2+)-ATPase protein was increased to 199% (T4-8-day group) in hyperthyroid ventricles and decreased to 86% of control in hypothyroid ventricles. The expression levels of ryanodine receptor, Ca(2+)-ATPase, phospholamban, and calsequestrin mRNAs were similarly altered in skeletal muscle tissues from hyperthyroid and hypothyroid rabbits. These results indicate that the mRNA levels of sarcoplasmic reticulum proteins responsible for calcium release and calcium uptake are coordinately regulated in response to changes in thyroid hormone level in both heart and skeletal muscle. These changes in mRNA level should lead to changes in protein levels and thus to altered calcium release and uptake in the chronic stages of hyperthyroidism and hypothyroidism.
Vascular response to basic fibroblast growth factor when infused onto the normal adventitia or into the injured media of the rat carotid artery.
Authors: Cuevas P , Gonzalez A M , Carceller F , Baird A
Published: June 2012

Immunohistochemical techniques localize basic fibroblast growth factor (FGF) in endothelial and smooth muscle cells of the common carotid artery. Thus, we studied the effect in rats of basic FGF infused for 14 days onto the adventitia or into the media in vivo. In untreated rats, the adventitial layer is uniform, and few vessels are observed in cross sections (mean +/- SEM is 0.351 +/- 0.16 capillaries/field at a magnification of x 480). Whereas saline infusion increases the mean number of vasa vasorum to 2.73 +/- 0.011 capillaries/field (p less than 0.01), basic FGF (1 ng/microliter/hr) increases the capillary number to 13.4 +/- 0.67 capillaries/field. The effects are local and restricted to the site of delivery; no cell proliferation is observed even 2 mm from the site of infusion. There is also no evidence of the infiltration of macrophages and monocytes. In an effort to determine the effect of basic FGF in the media, a small longitudinal (1-mm) incision was made in the adventitia, and saline or basic FGF (1 ng/microliter/hr) was infused for 14 days into the arterial wall. Under these conditions, basic FGF is a potent inducer of smooth muscle cell proliferation in the vascular wall as well as of new capillaries. In these instances, however, the capillaries formed are thick-walled. The results support the hypothesis that basic FGF may be contributing to the growth and maintenance of the vasa vasorum and of vascular smooth muscle cells.
Arterial wall and smooth muscle cell development in young Wistar rats and the effects of surgical denervation.
Authors: Todd M E , Gowen B
Published: June 2012

Development of the muscular saphenous artery and the effect of surgical denervation on normal development was investigated in young rats at 3 and 6 weeks of age. During this interval, the weight and blood pressures (systolic, diastolic, and mean) of the animals increased significantly. The tunica media of the artery and the lumen increased significantly with age, but the proportion of smooth muscle cell to paracellular matrix did not alter. Computer-assisted three-dimensional reconstructions were used to investigate the smooth muscle cells. They increased significantly in length, volume, and angle of orientation within the vessel wall with age but maintained an approximate surface area-to-volume ratio. The cells in any one vessel tended to be oriented in either a clockwise or counterclockwise direction. The size of the nucleus also increased significantly in length and volume with age, but an approximate surface area-to-volume ratio and a constant nucleocytoplasmic ratio were maintained. The nuclei tended to be eccentrically located, with less than half of all nuclei wholly within the middle third of the cell. Surgical denervation at 10 days of age resulted in abnormalities of growth in vessel dimensions, thinner tunica media at 3 weeks (denervated 11 days previously), and smaller lumen at 6 weeks (denervated 32 days previously). Elevated amounts of paracellular matrix occurred in both age groups, but denervation did not alter smooth muscle cell size. In the 3-week-old animals, denervation resulted in smooth muscle cells with hypertrophied nuclei. This may account for the increase in growth of the tunica media between 3 and 6 weeks of age in the denervated artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.
Authors: Venkatesh N , Lamp S T , Weiss J N
Published: June 2012

Sulfonylurea derivatives glibenclamide and tolbutamide are selective blockers of ATP-sensitive K+ (KATP) channels. However, their ability to prevent cellular K+ loss and shortening of action potential duration during ischemia or hypoxia in the intact heart is modest compared with their efficacy at blocking KATP channels in excised membrane patches. In the isolated arterially perfused rabbit interventricular septum, the increase in unidirectional K+ efflux and shortening of action potential duration during substrate-free hypoxia were effectively blocked by glibenclamide, but only by very high concentrations (100 microM); during hypoxia with glucose present, glibenclamide was only partially effective at reducing K+ loss. During total global ischemia (10 minutes), up to 100 microM glibenclamide or 1 mM tolbutamide attenuated shortening of action potential duration but only reduced [K+]0 accumulation by a maximum of 32 +/- 6%. In isolated patch-clamped guinea pig ventricular myocytes in which the whole-cell ATP-sensitive K+ current was activated by exposure to the metabolic inhibitors, glibenclamide (up to 100 microM) and tolbutamide (10 mM) were only partially effective at blocking the whole-cell ATP-sensitive K+ current (maximum block, 51 +/- 10% and 50 +/- 9%, respectively), especially when ADP was included in the patch electrode solution. In inside-out membrane patches excised from these myocytes, glibenclamide blocked unitary currents through KATP channels with a Kd of 0.5 microM and a Hill coefficient of 0.5 in the absence of ADP at the cytosolic membrane surface, but block was incomplete when 100 microM ADP (+2 mM free Mg2+) was present. ADP had a similar effect on block of KATP channels by tolbutamide. These findings suggest that free cytosolic [ADP], which rises rapidly to the 100 microM range during early myocardial ischemia and hypoxia, may account for the limited efficacy of sulfonylureas at blocking ischemic and hypoxic cellular K+ loss under these conditions.
Blockade of cardiac sodium channels by amitriptyline and diphenylhydantoin. Evidence for two use-dependent binding sites.
Authors: Barber M J , Starmer C F , Grant A O
Published: June 2012

Cardiac toxicity is a frequent manifestation in amitriptyline overdose and is felt to be due, in part, to sodium channel blockade by the drug. Another agent with sodium channel blocking properties, diphenylhydantoin, has been used clinically to reverse cardiac conduction abnormalities induced by amitriptyline. This reversal of toxicity is believed to occur secondary to competition for the sodium channel binding site. We evaluated individually and in combination the effects of amitriptyline (0.4 microM) and diphenylhydantoin (10-80 microM) on the sodium current in isolated rabbit atrial and ventricular myocytes at 17 degrees C. Using the whole-cell variant of the patch-clamp technique, we found that both amitriptyline and diphenylhydantoin reduced the sodium current in a use-dependent fashion. The time constant of recovery (tau r) from block by amitriptyline at -130 mV was very slow (13.6 +/- 3.2 seconds), whereas tau r during diphenylhydantoin exposure was fast (0.71 +/- 0.21 seconds, p less than 0.0001 compared with amitriptyline). During exposure of cells to a mixture of the two drugs, tau r was found to be 6.6 +/- 1.8 seconds, but no evidence of direct competition between amitriptyline and diphenylhydantoin was seen. Attempts to fit the recovery data of the mixture to two exponentials resulted in no significant improvement in the fit when compared with that using a single exponential. Use of the sodium channel blocking agent lidocaine (similar kinetics to diphenylhydantoin) in competition with amitriptyline resulted in findings consistent with direct competition of these two drugs for a single binding site. These observations prompted us to evaluate the possibility that diphenylhydantoin was not acting at (and therefore not competing for) the same channel binding site as amitriptyline. Experiments altering pHi and pHo revealed dramatic differences between amitriptyline and diphenylhydantoin. When pHo was increased from 7.4 to 8.0, tau r was reduced approximately threefold (from 13.6 +/- 3.2 to 4.2 +/- 0.1 seconds, p less than 0.0001) during exposure to amitriptyline, but no effect was seen on tau r after exposure to diphenylhydantoin. Conversely, when pHi was increased from 7.3 to 8.0, tau r after amitriptyline was unaffected, but tau r after diphenylhydantoin markedly increased (from 0.71 +/- 0.21 to 2.60 +/- 1.30 seconds, p less than 0.001). Additionally, diphenylhydantoin block demonstrated profound voltage dependence across the range of -130 to -90 mV, whereas amitriptyline block appeared less voltage sensitive. Single-channel studies using patch-clamp techniques in isolated ventricular myocytes supported these data.(ABSTRACT TRUNCATED AT 400 WORDS)
Flow-mediated dilatation of the basilar artery in vivo.
Authors: Fujii K , Heistad D D , Faraci F M
Published: June 2012

Flow-mediated dilatation has been described mainly in peripheral conduit arteries. The goal of this study was to examine mechanisms and functional implications of flow-mediated dilatation in large cerebral arteries in vivo. Vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in 45 anesthetized rats. Mean blood flow velocity through the basilar artery increased by 94 +/- 8% during unilateral common carotid artery occlusion and 203 +/- 13% during bilateral occlusion. Diameter of the basilar artery increased by 10 +/- 1% during unilateral common carotid artery occlusion and 29 +/- 2% during bilateral occlusion from control diameter of 275 +/- 8 microns. Vasodilatation appeared with a delay of 13 +/- 1 seconds after the onset of the increase in flow velocity. With systemic arterial pressure maintained at baseline levels, pressure in the basilar artery (servonull) decreased initially during carotid occlusion, and during dilatation of the basilar artery, pressure was restored partially toward normal. Indomethacin (10 mg/kg i.v.), topical application of tetrodotoxin (10(-6) M), NG-monomethyl L-arginine (5 x 10(-6) M), tetraethylammonium chloride (10(-2) M), glibenclamide (10(-5) M), SKF 525A (3 x 10(-5) M), and ouabain (10(-5) M) had no effect on flow-mediated dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
Copper loading of hearts increases postischemic reperfusion injury.
Authors: Powell S R , Hall D , Shih A
Published: June 2012

We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal.
Characteristics of giant cells and factors related to the formation of giant cells in myocarditis.
Authors: Kodama M , Matsumoto Y , Fujiwara M , Zhang S S , Hanawa H , Itoh E , Tsuda T , Izumi T , Shibata A
Published: June 2012

Giant cell myocarditis is a serious and frequently fatal inflammatory heart disease of which the etiology remains unknown. In the present study, we investigated the origin of multinucleated giant cells in myocarditis with the use of an experimental model. We also examined the factors relating to the formation of giant cells in myocarditis. Severe myocarditis characterized by the appearance of multinucleated giant cells was induced in Lewis rats by immunization with cardiac myosin in complete Freund's adjuvant. Two types of giant cells, foreign body giant cell-like and myocytelike, were observed in this myocarditis. Immunohistochemical studies revealed that both types of multinucleated giant cells were stained with OX42 and ED1 (macrophage markers) and were not stained with anti-desmin antibody and HHF35 (markers for muscle fibers). Therefore, it is likely that multinucleated giant cells in this myocarditis are derived from macrophages. During the course of the disease, the appearance of multinucleated giant cells was restricted to a period corresponding with the fulminant phase of inflammation. When the severity of the disease was modulated by immunization with various doses of the antigen, multinucleated giant cells appeared only in severe myocarditis after inoculation of a large dose of the antigen. Administration of immunoadjuvants also affected the formation of giant cells. Most of the rats injected with cardiac myosin in complete Freund's adjuvant developed giant cell myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cooperative effects due to calcium binding by troponin and their consequences for contraction and relaxation of cardiac muscle under various conditions of mechanical loading.
Authors: Izakov VYa  , Katsnelson L B , Blyakhman F A , Markhasin V S , Shklyar T F
Published: June 2012

A mathematical model for the regulation of mechanical activity in cardiac muscle has been developed based on a three-element rheological model of this muscle. The contractile element has been modeled taking into account the results of extensive mechanical tests that involved the recording of length-force and force-velocity relations and muscle responses to short-time deformations during various phases of the contraction-relaxation cycle. The best agreement between the experimental and the mathematical modeling results was obtained when a postulate stating two types of cooperativity to regulate the calcium binding by troponin was introduced into the model. Cooperativity of the first type is due to the dependence of the affinity of troponin C for Ca2+ on the concentration of myosin crossbridges in the vicinity of a given troponin C. Cooperativity of the second type assumes an increase in the affinity of a given troponin C for Ca2+ when the latter is bound by molecules neighboring troponin.
Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion.
Authors: Sheridan F M , Dauber I M , McMurtry I F , Lesnefsky E J , Horwitz L D
Published: June 2012

A possible cause of the coronary endothelial injury that occurs with ischemia and reperfusion is the local accumulation of leukocytes during these events. To investigate the role of leukocytes in coronary endothelial injury, we tested the effect of leukocyte removal by filtering on coronary endothelial function in a canine model of regional myocardial ischemia and reperfusion. Blood was supplied to the left anterior descending and circumflex arteries of anesthetized dogs via an extracorporeal circulation. A 60-minute left anterior descending occlusion was followed by 120 minutes of reperfusion either with (n = 6) or without (n = 6) leukocyte filters in the extracorporeal circuit. Regional myocardial blood flow was measured with radiolabeled microspheres. Radiolabeled autologous transferrin (113mIn) and erythrocytes (99mTc) were given intravenously during reperfusion for assessment of microvascular permeability. Left anterior descending and circumflex coronary artery rings were assessed in vitro for endothelium-dependent dilation to acetylcholine, ADP, and thrombin. In unfiltered dogs, ischemia and reperfusion increased the protein leak index of ischemic myocardium 2.3-fold compared with that of nonischemic myocardium (2.3 +/- 0.5 to 5.2 +/- 1.6, p less than 0.05). In filtered dogs, there was no difference in the protein leak index of nonischemic versus ischemic myocardium (1.5 +/- 0.4 versus 1.9 +/- 0.5, p = NS). There was impaired left anterior descending coronary artery relaxation (versus circumflex) in response to endothelium-dependent vasodilators in vitro. However, relaxation was not consistently improved by leukocyte filtering. We conclude that leukocytes are responsible for the endothelial injury secondary to ischemia and reperfusion in the coronary microvasculature but have little or no effect on the endothelial injury in epicardial coronary arteries.
The Influence of Tone upon Responses of Small and Large Vessels to Serotonin
Authors: HADDY F. J. , GORDON P. , EMANUEL D. A.
Published: June 2012

In the dog foreleg, serotonin antagonizes extremes of vascular tone induced by neurogenic means. It produces net dilatation when the bed is constricted and net constriction when the bed is dilated. This bidirectional response derives ultimately from the facts that changes in nervous activity change calibers of small vessels without greatly altering calibers of large vessels, and that serotonin produces small vessel dilatation at the same time that it constricts large vessels. When small vessels are already neurogenically dilated, serotonin cannot dilate them further, but continues to constrict large vessels. Thus, the net effect is constriction. When small vessels are highly constricted, serotonin dilates small vessels more than it constricts large vessels. The net effect is dilatation. The study also indicates why it is more difficult to demonstrate a similar antagonism when tone is varied by humoral means.
The Mechanism of Atrioventricular Conduction
Authors: SCHER A. M. , RODRIGUEZ MARIA I. , LIIKANE J. , YOUNG A. C.
Published: June 2012

Potentials recorded at various sites in the atrioventricular (A-V) conduction system indicate that conduction is continuously electrical in nature and involves no synapse-like (i.e., chemical) conduction. The region between atrium and atrioventricular node has the slowest conduction velocity (.05 M./sec.) and lowest safety factor. Conduction through the A-V node is at about .12 M./sec. Results demonstrate shapes of potentials recorded extracellularly at various sites within the A-V node, first degree and complete block during rapid atrial stimulation, and echo-like phenomena.
A Biochemical Study of Spontaneous Atherosclerosis in Pigeons
Authors: LOFLAND HUGH B. , CLARKSON THOMAS B.
Published: June 2012

Two breeds of pigeons (White Carneau and Silver King) have been found to have a high incidence of spontaneous atheromatous lesions in the aorta, while two breeds of homing pigeons (Racing Homers and Show Racers) seemed to be resistant to atherosclerosis. The weight of the aorta, and its cholesterol content, paralleled the severity of the disease. The levels of serum cholesterol and phospholipids, and the cholesterol: phospholipid ratio, however, appear to be unrelated to the incidence and severity of atherosclerosis in pigeons. The differences observed among the four breeds of birds showed little correlation with age, sex, diet, or physical activity.
Evidence for Reflex Control of Arterial Pressure from Abdominal Receptors with Special Reference to the Pancreas
Authors: SARNOFF STANLEY J. , YAMADA SAMUEL I.
Published: June 2012

Hypotension in cat abdominal viscera, especially the pancreas, produced substantial elevations of arterial pressure and heart rate even in the presence of intact sinoaortic receptors. Elevation of pressure in the distribution of the superior mesenteric artery had the reverse effect. When viewed in the light of the neurophysiologic data of Gammon and Bronk, it would appear that these sites make a significant contribution to cardiovascular regulation in that species, presumably as a result of impulses arising in abdominal pacinian corpuscles.
Alterations in Pulmonary and Peripheral Vascular Resistance in Immersion Hypothermia
Authors: KUHN LESLIE A. , TURNER JOHN K.
Published: June 2012

The effects of immersion hypothermia on the systemic and pulmonary circulations were investigated in anesthetized, closed-chest, untreated dogs, cold-adapted dogs and in dogs receiving sympathomimetic and sympatholytic agents. Evidence is presented that both pulmonary and systemic vascular resistances are increased progressively during hypothermia, the former to a greater extent than the latter. It is felt that the primary causes for the increase in vascular resistance are progressive diminution in the cardiac output and the local effect of low blood temperature on the vasculature.
Coronary Dilatation and Constriction Visualized by Selective Arteriography
Authors: WEST JAMES W. , GUZMAN SANTIAGO V.
Published: June 2012

Selective coronary angiograms were made in dogs with intact chests prior to and following various groups of drugs. They demonstrated visible constriction and dilatation of the coronary vessels and the appearance of previously invisible channels following coronary vasodilators and embolization with lycopodium spores.
Effect of Elevated Left Atrial Pressure and Decreased Plasma Protein Concentration on the Development of Pulmonary Edema
Authors: GUYTON ARTHUR C. , LINDSEY ARTHUR W. , JOHNNIE O. HOWELL, , JOHN W. WILLIAMS , MALCOLM A. FRANKLIN
Published: June 2012

In 97 dogs left atrial pressure was elevated to various levels up to 50 mm. Hg by partial constriction of the aorta. The effect of these pressures for from 30 min. to 3 hours on the accumulation of lung edema was then studied. Edema was estimated by determining the ratio of the weight of the wet lung to the weight of the same lung after drying. In animals with normal plasma protein concentrations fluid began to transude into the lungs when the left atrial pressure rose above an average of 24 mm. Hg. In another series of animals the plasma protein concentrations were reduced by plasmapheresis at the beginning of each experiment until the plasma protein concentration averaged 47 per cent of the control value. In these animals fluid began to transude into the lungs when the left atrial pressure rose above a critical value of 11 mm Hg. Furthermore, the rate at which fluid accumulated in the lungs, in all series of experiments, was directly proportional to the rise in left atrial pressure above the critical pressure at which fluid began to collect in the lungs.
Pressor Effect of Hypertonic Saline on Pulmonary Circulation
Authors: SEMLER HERBERT J. , SHEPHERD JOHN T. , SWAN H. J. C.
Published: June 2012

It has been suggested that the pressor effect of hypertonic solutions of sodium chloride on the Pulmonary circulation results from spasm of the pulmonary veins at their junction with the left atrium. These studies demonstrate that the increased resistance in the pulmonary vessels develops upstream to this site and that it may result primarily from mechanical blockage of vessels by clumped erythrocytes rather than from vasoconstriction.
Peripheral Venous Blood Concentrations of Epinephrine and Norepinephrine in Primary Raynaud's Disease
Authors: PEACOCK J. H.
Published: June 2012

Chromatographic separation and biologic assay of extracts from the peripheral venous blood of patients with primary Raynaud's disease have been performed. An increase in the venous concentration of epinephrine and norepinephrine was found, both under warm resting conditions and conditions of sympathetic stimulation by indirect cold, in patients with this disease.
Ultrastructure of the Dog Cardiac Muscle Cell
Authors: PRICE ZANE , EIDE BILLIE , PRINTZMETAL MYRON , CARPENTER CHARLES
Published: June 2012

Observations on the cellular structure of the dog heart as seen in the electron microscope are described. Electronmicrographs illustrate the ultrastructure of the dog myocardial cell, especially the relationships of the intercalated disc and the sarcolemma to form the cell boundaries and the relationships of the myofibrils and "Z" bands to the sarcolemma which result in an "accordion-like" appearance of the cell after contraction.
Fall in Pressure in Radial Artery during Reactive Hyperemia
Authors: WALLACE JOHN M. , STEAD EUGENE A.
Published: June 2012

Under conditions of rapid flow, the arterial bed between the aorta and radial artery offers an appreciable resistance to flow. During reactive hyperemia in normal subjects, approximately 30 per cent of the energy of pressure may be lost between the aorta and radial artery. Hypertension produced in normal subjects by infusion of levarterenol increases the gradient in pressure during reactive hyperemia between the aorta and radial artery. Hypertension in patients with hypertensive disease does not increase the gradient during reactive hyperemia beyond that which is produced in normal subjects.
Distribution of Acid Mucopolysaccharides in Inner and Outer Layers of Bovine Aorta
Authors: BERENSON GERALD S.
Published: June 2012

Bovine aortas were separated into 2 layers, an inner layer composed chiefly of intima and an outer layer composed of adventitia and most of the media. A greater concentration of acid mucopolysaccharides, especially of the chondroitin sulfuric acid group, was found in the inner layer of the aorta.
An Experimental Study on the Origin of T-Waves Based on Determinations of Effective Refractory Period from Epicardial and Endocardial Aspects of the Ventricle
Authors: REYNOLDS ERNEST W. , VANDER ARK CONDON R.
Published: June 2012

The effective refractory period was determined at the surface and in the deeper layers of the dog heart and was correlated with the surface T-waves. A small delay in recovery of cardiac excitability appeared at the surface when T-waves were negative and in the deeper layers when T-waves were positive. Acute injury produced by ligation of the coronary artery caused a marked acceleration of recovery in the deeper layers, sometimes extending to the surface.
Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.
Authors: Schobel H P , Oren R M , Mark A L , Ferguson D W
Published: June 2012

Naloxone, an opioid antagonist, augments baroreflex mechanisms in animals; this occurrence suggests that endogenous opioids blunt baroreflex responses. Limited human studies suggest an inhibitory action of endogenous opioids on baroreflex-mediated vagal responses during arterial baroreceptor deactivation. To evaluate the potential effect of endogenous opioids on cardiopulmonary baroreflex mechanisms in humans, we measured arterial and central venous pressures, heart rate, and efferent muscle sympathetic nerve activity (MSNA, by peroneal microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP, from 0 to -15 mm Hg) and during the cold pressor test in 21 normal subjects (aged 24 +/- 1 [mean +/- SEM] years). In 14 subjects, we performed LBNP before and after naloxone (0.15 mg/kg i.v.) and placebo (n = 11) on separate days. In six of these 14 subjects and an additional seven subjects (n = 13), studies were also performed before and after administration of a lower dose of naloxone (0.075 mg/kg i.v.) on separate days. Neither dose of naloxone significantly altered control arterial or central venous pressures or heart rate. Control MSNA was reduced after the higher but not after the lower dose of naloxone. Comparable reductions in central venous pressure were produced by LBNP in all groups before and after naloxone or placebo, whereas LBNP did not alter arterial pressure. Cardiopulmonary baroreflex sympathetic sensitivity, which was derived as the slope of the linear regression relation between percent change in total MSNA (units) per absolute change in central venous pressure (mm Hg) during incremental LBNP, was significantly augmented after both the high dose (from 18.6 +/- 4.7%/mm Hg to 39.3 +/- 8.1%/mm Hg, p = 0.001) and low dose of naloxone, whereas placebo had no effect. MSNA responses to the cold pressor test were not altered by either dose of naloxone. Thus, naloxone selectively potentiates cardiopulmonary baroreflex regulation of sympathetic neural activity in normal humans. These findings suggest that endogenous opioids exert a tonic inhibitory effect on sympathetic responses to orthostatic stress in normal humans.
Role of nitric oxide in reactive hyperemia of the guinea pig heart.
Authors: Kostic M M , Schrader J
Published: June 2012

To evaluate the role of nitric oxide (NO) in the flow response after brief coronary arterial occlusion, NO formation by the isolated guinea pig heart was assessed by a specific difference spectrophotometric assay. Release of NO under basal conditions was 121.8 +/- 10.5 pmol x min-1 and increased to 211.1 +/- 16.8 pmol x min-1 after 60 seconds of coronary occlusion. Simultaneously, release of cGMP and adenosine increased by 87% and 652%, respectively. The kinetics of NO release paralleled the reactive hyperemic flow response. Inhibition of NO synthesis with nitro-L-arginine methyl ester (L-NAME, 30 microM) significantly reduced basal flow and attenuated reactive hyperemia, flow repayment, and repayment ratio. L-NAME decreased release of cGMP but significantly increased adenosine release under basal conditions and during reactive hyperemia. Oxyhemoglobin (5 microM) potentiated the effects of L-NAME. The stereoisomer nitro-D-arginine methyl ester was ineffective. Our results suggest 1) NO is an important regulator of coronary flow during reactive hyperemia as well as under basal flow conditions and 2) the significance of the increased adenosine release when NO synthesis is inhibited remains to be determined.
Effects of adenine nucleotides on the proliferation of aortic endothelial cells.
Authors: Van Daele P , Van Coevorden A , Roger P P , Boeynaems J M
Published: June 2012

The effects of adenine nucleotides and adenosine on DNA synthesis and cell growth have been studied in bovine aortic endothelial cells (BAECs). ATP produced a small but significant (+44%) increase of the fraction of BAECs whose nuclei are labeled by [3H]thymidine. This mitogenic effect was mimicked by ADP, the phosphorothioate analogues ATP gamma S and ADP beta S, and the nonhydrolyzable analogue adenosine 5'-(beta, gamma-imido)triphosphate (APPNP), whereas adenosine 5'-(alpha, beta-methylene)triphosphate (APCPP), a selective agonist of P2x-purinoceptors, had no effect at 10 microM and a small one at 100 microM; this profile is consistent with the involvement of P2y-receptors. Adenosine induced a mitogenic response of a magnitude similar to that of ATP. This effect was not reproduced by R-phenylisopropyl adenosine, by 5'-N-ethylcarboxamide adenosine, or by 2',5'-dideoxyadenosine, selective ligands of the A1- and A2-receptors and the P site, respectively, nor was it inhibited by 8-phenyltheophylline, an antagonist of both A1- and A2-receptors. The mechanism of this adenosine action thus remains unclear. ATP and ATP gamma S did not enhance the proliferation of BAECs cultured in the presence of fetal calf serum concentrations ranging from 0.5% to 10%. They inhibited the growth-promoting effect of basic fibroblast growth factor; among the various nucleotides tested, APCPP was the least effective to reproduce the action of ATP, suggesting the possible involvement of P2y-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)