bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysfunction of the beta- and alpha-adrenergic systems in a model of congestive heart failure. The pacing-overdrive dog.
Authors: Calderone A , Bouvier M , Li K , Juneau C , de Champlain J , Rouleau J L
Published: June 2012

The functional integrity of the beta- and alpha-adrenergic stimulatory pathways in a rapid ventricular pacing model of congestive heart failure in dogs was investigated; normal dogs served as controls. Total beta-adrenergic receptor density was 35% lower (p less than 0.01) in the pacing-overdrive dogs, and the beta-adrenergic receptor-mediated stimulation of adenylate cyclase (Vmax) was found to be 68% and 72% lower (p less than 0.01) in the left and right ventricles of the paced dogs. In addition, the basal adenylate cyclase activity was found to be 56% and 68% lower (p less than 0.01) in the left and right ventricles of the failing heart. Similarly, the Vmax of 5'-guanylylimidodiphosphate (GppNHp) and forskolin stimulation of adenylate cyclase activity was significantly lower, 70% and 55%, respectively (p less than 0.01), in both ventricles of the paced dogs. However, although the concentration yielding half-maximal velocity for beta-agonist and GppNHp stimulation of adenylate cyclase was similar in both groups, that for forskolin stimulation of the enzyme was significantly increased (p less than 0.01). Pertussis toxin-mediated ADP-ribosylation of membranes from control and failing hearts revealed a significant decrease in the inhibitory guanine nucleotide binding protein content (48 +/- 9%, p less than 0.01) in the hearts of the paced dogs. Moreover, although the pertussis toxin treatment increased the basal and the forskolin-stimulated adenylate cyclase activity in both normal and failing heart membranes, the adenylate cyclase activity remained significantly depressed in the failing heart after pertussis toxin treatment (p less than 0.01). Consistent with the depressed adenylate cyclase activity, mechanical studies on isolated papillary muscles and trabeculae revealed a decrease in baseline total tension (from 7.0 +/- 0.7 to 3.8 +/- 0.4 g/mm2, p less than 0.01) and dT/dt (from 26 +/- 8 to 13 +/- 1 g/mm2/sec, p less than 0.01) in the pacing-overdrive model. Tension generation and dT/dt observed in the paced dogs in response to increasing concentrations of forskolin demonstrated a rightward shift in the dose-response curve and a decrease in maximal forskolin stimulation (p less than 0.01). Similarly, maximal tension and dT/dt in the presence of isoproterenol was significantly lower than in the normal dogs (p less than 0.01). The decrease in beta-adrenergic responsiveness was accompanied by a decrease and rightward shift in alpha 1-adrenergic responsiveness (increase in tension was 1.1 +/- 0.1 g/mm2 in paced dogs versus 2.1 +/- 0.1 g/mm2 in controls, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium.
Authors: Chilian W M
Published: June 2012

These experiments tested the hypothesis that differences in the distribution of subepicardial and subendocardial microvascular resistances may alter the transmural distributions of microvascular pressures. Isolated blood- and physiological saline-perfused porcine hearts were surgically incised to enable exposure of the subendocardial and subepicardial microcirculations. Microvascular pressures were measured during cardiac arrest and maximal vasodilation at various perfusion pressures to formulate relations between perfusion pressure and microvascular pressure in the different subendocardial (both free wall and papillary muscle) and subepicardial segments. Measurements of arteriolar and venular pressures in both myocardial regions were performed in comparably sized vessels (80-120 microns in diameter). At a coronary perfusion pressure of 100 mm Hg, subendocardial arteriolar and venular pressures were 60 +/- 4 and 33 +/- 3 mm Hg, respectively. In contrast, at the same coronary perfusion pressure, arteriolar and venular pressures in the subepicardial microcirculation averaged 80 +/- 6 and 22 +/- 3 mm Hg, respectively (p less than 0.05 versus subendocardium). At all levels of coronary perfusion pressure, arteriolar pressures were significantly lower in the subendocardium than in the subepicardium (p less than 0.05). Venular pressures were also higher in the subendocardial microcirculation than in the subepicardial microcirculation at all but the lowest perfusion pressure (p less than 0.05). The relative distribution of resistances in arteries, microvessels, and veins was also different between the subepicardium and subendocardium. Specifically, in the subendocardium, arterial and venous resistances were higher, percentage-wise, but microvascular resistance was proportionately lower than that in the subepicardium (p less than 0.05). From these data, it is concluded that the distribution of microvascular resistances and pressures is different during maximal vasodilation in the subepicardial and subendocardial microcirculations of the left ventricle. It is also speculated that differences in autoregulatory capacity and vulnerability to ischemia may be partially related to unequal distribution of microvascular resistances across the wall of the left ventricle.
Postischemic myocardial "stunning". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog.
Authors: Triana J F , Li X Y , Jamaluddin U , Thornby J I , Bolli R
Published: June 2012

Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial "stunning"). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically "protective" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS)
Platelets stimulate expression of endothelin mRNA and endothelin biosynthesis in cultured endothelial cells.
Authors: Ohlstein E H , Storer B L , Butcher J A , Debouck C , Feuerstein G
Published: June 2012

Modulation of the biosynthesis of the vasoconstrictor peptide endothelin was studied in cultured endothelial cells. Immunoreactive endothelin (irET) levels were significantly elevated in conditioned medium from bovine pulmonary artery endothelial (BPAE) or human umbilical vein endothelial cells when coincubated with washed human platelets. Platelets (approximately 200,000 cells/microliters) enhanced irET levels approximately 250% over basal levels. Stimulation of irET levels in BPAE cell-conditioned medium by platelets was time and platelet number dependent. Platelets, as well as thrombin and transforming growth factor-beta 1, stimulated the expression of preproendothelin-1 mRNA in a time-dependent manner. Coincubation of low doses of thrombin (0.1 unit/ml) and subthreshold concentrations of platelets with BPAE cells resulted in a further enhancement of irET levels in conditioned medium. Platelet-mediated stimulation of irET production was not significantly affected by indomethacin (1 microM) or the platelet-activating factor receptor antagonist WEB 2086 (1 microM); however, coincubation of endotoxin (100 ng/ml) with platelets and BPAE cells resulted in significantly higher levels of irET. Whether direct contact or adhesion between platelets and endothelial cells is necessary for stimulating irET release was studied by separating platelets from BPAE cells with a 0.4 microns permeable membrane. Under these conditions, platelets still produced significant elevations (approximately 190% over basal levels) in irET levels in BPAE cell-conditioned medium. In addition, platelet-free buffer from agonist-induced platelet aggregation also significantly enhanced irET production (200% over basal values). These data indicate that a platelet-derived regulatory factor can induce the biosynthesis of endothelin from cultured endothelial cells and also suggest that platelets might play a role in vasomotor regulation via a novel intercellular interaction with the endothelium.
Singlet oxygen interaction with Ca(2+)-ATPase of cardiac sarcoplasmic reticulum.
Authors: Kukreja R C , Kearns A A , Zweier J L , Kuppusamy P , Hess M L
Published: June 2012

We investigated the role of singlet oxygen (generated from photoactivation of rose bengal) on the calcium transport and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum (SR). Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at 560 nm resulted in significant inhibition of Ca2+ uptake (from 2.27 +/- 0.05 to 0.62 +/- 0.05 mumol Ca2+/mg.min [mean +/- SEM], p less than 0.01) and Ca(2+)-ATPase activity (from 2.08 +/- 0.05 to 0.28 +/- 0.04 mumol Pi/min.mg [mean +/- SEM], p less than 0.01). The inhibition of calcium uptake and Ca(2+)-ATPase activity by rose bengal-derived activated oxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. Singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca(2+)-ATPase against rose bengal-derived activated oxygen species, but superoxide dismutase and catalase did not attenuate the inhibition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal for up to 14 minutes demonstrated complete loss of the Ca(2+)-ATPase monomer band, which was significantly protected by histidine. The addition of dithiothreitol (5 mM) had a slight protective effect, showing that new disulfide bond formation was not a major cause of aggregation. The results were also confirmed by high-performance liquid chromatography of the SR exposed to irradiated rose bengal. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide radical (generated from xanthine oxidase action on xanthine) and hydroxyl radical (in the presence of Fe(3+)-EDTA or 0.5 mM H2O2 plus Fe(2+)-EDTA) as well as H2O2 (0.25-12 mM) were without any effect on the 97,000-d Ca(2+)-ATPase band of SR. Generation of radical species (superoxide and hydroxyl radical) from rose bengal was studied by electron paramagnetic resonance spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The results showed that irradiation of rose bengal formed a 1:2:2:1 quartet, characteristic of the DMPO-OH adduct, which was scavenged by ethanol but not by superoxide dismutase, catalase, or histidine. No radical species could be detected from irradiated rose bengal or irradiated DMPO under the assay conditions used. Peroxy adducts of DMPO might be produced but would be observed only at very low temperatures. Similarly, we could not detect any measurable.O2- anion from irradiation of rose bengal as indicated by either cytochrome c reduction at 550 nm or nitro blue tetrazolium reduction at 560 nm. These results show that SR is damaged most likely by singlet oxygen derived from rose bengal.(ABSTRACT TRUNCATED AT 400 WORDS)
Dihydropyridine receptors are primarily functional L-type calcium channels in rabbit ventricular myocytes.
Authors: Lew W Y , Hryshko L V , Bers D M
Published: June 2012

We measured [3H]PN200-110 binding and patch-clamp currents in rabbit ventricular myocytes to determine if there is a disparity between the density of dihydropyridine-specific receptors and functional L-type calcium channels, as has been reported for skeletal muscle. The dihydropyridine receptor density was 74.7 +/- 4.2 fmol/mg protein (mean +/- SEM, Kd = 1.73 +/- 0.29 nM, n = 6) in ventricular homogenates and 147 +/- 6 fmol/mg protein (Kd = 1.15 +/- 0.16 nM, n = 4) in myocytes. Ventricular homogenates contained 121 +/- 9 mg protein/g wet wt (n = 7). These values were used to calculate a dihydropyridine receptor density of 12.9 dihydropyridine sites/micron2 for ventricular homogenates and 14.8 dihydropyridine sites/micron2 for myocytes. The number of functional L-type calcium channels (N) was calculated from measurements of whole-cell current (I), single-channel current (i), and open probability (po), where N = I/(i x po). We measured sodium current through calcium channels (I(ns)) to avoid calcium-induced inactivation. Whole-cell (I(ns)) and single-channel (i(ns) and po) measurements were obtained under similar ionic conditions at a test potential of -20 mV. In six cells, the peak I(ns) was approximately 105 pA/pF. The single-channel conductance was 40.8 +/- 2.6 pS (n = 12), and i(ns) at -20 mV was 1.96 pA. The mean po at -20 mV was 0.030 +/- 0.002 in 16 patches in which only a single channel was evident. The calculated density of functional L-type calcium channels was approximately 18 channels/micron2.(ABSTRACT TRUNCATED AT 250 WORDS)
Rapid accumulation of elastin and collagen in the aortas of sheep in the immediate perinatal period.
Authors: Bendeck M P , Langille B L
Published: June 2012

While characterizing developmental changes in aortic wall composition in sheep, we observed very rapid accumulation of elastin and collagen in the immediate perinatal period. Thoracic aortic elastin content increased by 41%, and collagen content increased by 49% in approximately 1 week, between 140 days gestation and 3 days postpartum (term = 145 days). Even larger changes were observed in the abdominal aorta. Elastin content increased by 66%, and collagen increased by 57%. The pronounced increase in wall tissue accumulation near birth preceded a marked postnatal increase in arterial pressure. We propose that this elastin and collagen accumulation is a preadaptive response in preparation for the later increase in pressure. The prenatal and postnatal events that initiate this synthesis and accumulation are not known. We also found that, in the 3 weeks after this initial rapid increase, accumulation of elastin and collagen was markedly reduced in the abdominal, but not the thoracic, aorta. This latter finding may be linked to the dramatic decrease in flow through this vessel that results from the loss of the placental circulation. Finally, we observed that relatively high smooth muscle cell replication rates in the abdominal aorta postpartum resulted in no net DNA accumulation. This finding indicates that cell turnover plays an important role in postnatal arterial growth and development.
Preservation of endothelial cells in excised rat carotid arteries. Effects of transmural pressure and segment length.
Authors: Lewis D A , Loomis J L , Segal S S
Published: June 2012

When arteries are excised, they collapse and shorten spontaneously, which can result in damage to the endothelium. To determine if an intact endothelial cell layer could be preserved in excised vessels, we isolated and cannulated rat carotid artery segments (in situ length, Lis, 10-20 mm) at both ends while maintaining both transmural pressure (70 mm Hg) and Lis, while either transmural pressure or Lis, or after allowing vessel collapse and shortening (n = 4 vessels per treatment). After each treatment, vessel segments were perfused with fixative and stained with AgNO3 to visualize endothelial cells. The amount of endothelial cell loss was quantified using stereological analysis of video microscopic images of the luminal surface. Results demonstrated that maintenance of both Lis and transmural pressure minimized endothelial cell denudation (1.6 +/- 0.9%); permitting the vessel to collapse and shorten resulted in the greatest loss of endothelial cells (59.4 +/- 13.2%); and maintenance of either pressure or Lis resulted in intermediate endothelial cell loss (13-30%). We conclude that the spontaneous collapse and shortening that normally accompany the excision of arterial segments result in substantial endothelial cell loss, which can be virtually eliminated with the maintenance of transmural pressure and vessel segment length. These findings have implications for surgical and experimental procedures requiring intact endothelium.
Effects of endothelin-1 on endothelial cells in the porcine coronary artery.
Authors: Suzuki S , Kajikuri J , Suzuki A , Itoh T
Published: June 2012

The effects of endothelin-1 (ET-1) on endothelial cells from the porcine coronary artery were investigated using cascade bioassay and radioimmunoassay methods. For comparison, endothelial cells from the rabbit abdominal aorta were also used. Freshly isolated endothelial cells were perfused with Krebs' solution. Liberation of vasodilatory substances was detected under bioassay conditions by measuring the relaxing activity of the perfusate on endothelium-denuded strips of the porcine coronary artery contracted with ET-1. The perfusate in the absence of ET-1 slightly inhibited the contraction, suggesting that endothelial cells spontaneously release vasorelaxing substances. After application of ET-1, the perfusate-induced relaxation drastically increased. Oxyhemoglobin completely abolished the relaxation induced by perfusate from endothelial cells of the rabbit abdominal aorta but only marginally attenuated the relaxation induced by perfusate from endothelial cells of the porcine coronary artery. In contrast, indomethacin significantly attenuated the relaxation induced by perfusate from the endothelial cells of the porcine coronary artery. In endothelium-intact strips of the porcine coronary artery, ET-1 significantly increased the concentration of 6-ketoprostaglandin F1 alpha but did not modify the cellular concentration of either cAMP or cGMP. It is concluded that ET-1 augments the release of vasorelaxing factors from endothelial cells both in the porcine coronary artery and in the rabbit abdominal aorta and that the major vasorelaxing substance derived from endothelial cells may be different in these two blood vessels. Prostaglandin I2 in the former and nitric oxide in the latter are suggested as possible candidates. The vasorelaxation induced by prostaglandin I2 may not be mediated by cAMP-dependent mechanisms in the porcine coronary artery.
Expression of sarcoplasmic reticulum Ca(2+)-ATPase and calsequestrin genes in rat heart during ontogenic development and aging.
Authors: Lompré A M , Lambert F , Lakatta E G , Schwartz K
Published: June 2012

Little is known concerning the molecular mechanisms responsible for changes in sarcoplasmic reticulum (SR) function during ontogenic development and aging except that the amount of SR Ca(2+)-ATPase mRNA varies in these conditions. The aim of the present work was to determine whether SR maturation requires expression of specific isoforms and synchronous accumulation of mRNAs encoding proteins located in SR. Thus, we have studied expression of SR Ca(2+)-ATPase and calsequestrin genes in the rat at different developmental stages from 14 fetal days to 24 months of age. Analysis of alternative splicing of the major Ca(2+)-ATPase gene expressed in heart by nuclease S1 mapping led us to conclude that the Ca(2+)-ATPase gene expressed in heart was not differentially spliced during ontogenic development and senescence. A single calsequestrin mRNA isoform was also detected in rat heart whatever the developmental stage. The amount of specific mRNA was then measured by dot blot and normalized to 18S ribosomal RNA or to myosin heavy chain mRNA. The amount of Ca(2+)-ATPase mRNA relative to 18S RNA increases substantially at the end of fetal life and in the early postnatal period (9.5 +/- 0.5% in the 14-15 day fetus versus 99 +/- 7% in the 4-day-old rat). A stable high level is observed during adulthood. In aged rats (24 months), Ca(2+)-ATPase mRNA represents only 44.6% the amount observed in young adults (1-2 months).(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous adenosine inhibits platelet aggregation during myocardial ischemia in dogs.
Authors: Kitakaze M , Hori M , Sato H , Takashima S , Inoue M , Kitabatake A , Kamada T
Published: June 2012

The goal of this study was to clarify that blockade of adenosine receptors during myocardial ischemia causes further reductions in coronary blood flow due to platelet aggregation. Coronary perfusion pressure in 47 open-chest dogs was reduced such that coronary blood flow decreased to one fifth of the control value; thereafter, coronary perfusion pressure was maintained at the low levels. During hypoperfusion, coronary flow was kept low but constant with a massive release of adenosine. When 8-phenyltheophylline, an adenosine receptor antagonist, was infused during coronary hypoperfusion, coronary blood flow (18 +/- 2 ml/100 g/min) gradually decreased at 5-10 minutes of ischemia and reached almost zero at 20 minutes. Three minutes after the onset of ischemia, before further reduction of coronary flow, the microscopic examination revealed the existence of thromboembolization in the small coronary arteries, and the number of platelets in the regional coronary venous blood were significantly decreased, indicating that a further reduction of coronary flow due to treatment with 8-phenyltheophylline is attributed to thromboembolism caused by platelet aggregations. This reduction of coronary flow and formation of thromboembolism were inhibited by the treatments with dibutyryl cAMP, forskolin, and yohimbine, indicating that this thromboembolization during a lack of adenosine activity is due to platelet aggregation and that platelet aggregation caused by 8-phenyltheophylline is triggered by stimulation of alpha 2-adrenoceptors by released norepinephrine during ischemia. We demonstrate that adenosine, generated endogenously in response to ischemia, inhibits platelet aggregation. The finding that adenosine is not merely a vasodilator but that it also regulates thrombosis has major implications for designing new strategies of myocardial salvage.
Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine.
Authors: Arai A E , Pantely G A , Anselone C G , Bristow J , Bristow J D
Published: June 2012

We studied the effects of rapid atrial pacing during the final 10 minutes of a 70-minute, 31% reduction in coronary blood flow in anesthetized swine to understand the significance of apparent metabolic improvements during the initial 60 minutes of segmental ischemia. Within 5-10 minutes of ischemia, subendocardial phosphocreatine (PCr) and ATP were depleted to 47% and 63% of control, respectively; lactate accumulated within the subendocardium to 300% of control; and net arteriovenous lactate production occurred. Despite continued ischemia and no significant changes in the external determinants of myocardial oxygen consumption, by 60 minutes subendocardial PCr and lactate contents returned to near control levels and there was net arteriovenous lactate consumption. Ischemic left ventricular wall thickening and ATP levels remained depressed throughout the experiment. Atrial pacing during the final 10 minutes of ischemia again resulted in depletion of PCr and lactate production. Since the myocardium was capable of hydrolyzing PCr in response to atrial pacing at 60 minutes of ischemia, we conclude it was capable of hydrolyzing PCr during the period of constant ischemia when instead it was accumulating PCr. We propose the ischemic myocardium downregulates regional energy requirements below blood flow-limited rates of energy production during ischemia. This appears to be an active adaptation to ischemia and not a result of passive damage or cellular injury.
Morphological characterization of cardiomyocytes isolated from a transplantable cardiac tumor derived from transgenic mouse atria (AT-1 cells).
Authors: Delcarpio J B , Lanson N A , Field L J , Claycomb W C
Published: June 2012

We have developed a transplantable tumor lineage derived from transgenic mouse atrial cardiomyocytes that express the SV40 large T oncogene and have named these cardiomyocytes AT-1 cells. In this study, the transplantable tumors, freshly isolated tumor cardiomyocytes, and cultured tumor cardiomyocytes were examined using phase-contrast microscopy, autoradiography, and electron microscopy. The vast majority of the subcutaneous tumor cells, greater than 90% of the cellular mass of the tumor, exhibited sarcomeric banding. Ultrastructural characteristics typical of in vivo atrial cardiac muscle cells, including well-organized myofibrils, gap junctions, and atrial-specific cytoplasmic granules, were observed in in situ and in freshly isolated AT-1 cells. Those cells that did not contain some form of organized myofibrils were primarily vascular elements, such as endothelial cells. Labeling with [3H]thymidine indicated that greater than 90% of cultured AT-1 cells were synthesizing DNA; furthermore, many cells could be seen undergoing cell division. Electron microscopy revealed that the cultured AT-1 cardiomyocytes contained all of the above-described characteristics, including a well-developed transverse tubular system.
Effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium.
Authors: Walley K R , Ford L E , Wood L D
Published: June 2012

The separate effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium were compared in 10 papillary or trabecular muscles superfused using control (95% O2-5% CO2), hypoxic (18% O2), and hypercapnic (20% CO2) physiological salt solutions. This level of hypoxia did not irreversibly damage the muscles and reduced peak isometric force by 53 +/- 11%. The level of hypercapnia was chosen to match the force depression (50 +/- 12%) produced by hypoxia. Multiple force-velocity points were measured by applying critically damped isotonic force steps at 90% of the time to peak isometric force and at the time to 50% peak isometric force. These points defined the force-velocity relation and maximum velocity of shortening, the extrapolated isometric force, and the maximum power of nonpotentiated and postextrasytolic potentiated contractions. Hypoxia and hypercapnia reduced maximum force and maximum power nearly equally. Maximum velocity of shortening decreased more during hypoxia (21 +/- 12%) than during hypercapnia (12 +/- 9%) (p less than 0.01). Postextrasystolic potentiation completely reversed the reduction of maximum velocity of shortening during hypercapnia but not during hypoxia. A 6% internal load could account for the reduction in maximum velocity of shortening during hypercapnia and all but 9% of the reduction in maximum velocity of shortening during hypoxia. The relative time course of the force-velocity relation was not altered by either hypoxia or hypercapnia. We conclude that hypercapnia reduces the effect of activation because increased activation (by postextrasystolic potentiation) restored the force-velocity relation and maximum velocity of shortening to control values.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Acetylcholine on Single Fibers of the Atrioventricular Node
Authors: CRANEFIELD PAUL F. , HOFFMAN BRIAN F. , DE CARVALHO ANTONIO PAES
Published: June 2012

The action of acetylcholine on atrioventricular nodal fibers has been studied with the aid of intracellular microelectrodes. It has been found that during total atrioventricular dissociation no block of conduction occurs at the junction between the A-V node and the bundle of His or within fibers of the atrium. Failure of impulse transmission occurs in fibers in the atrial margin of the A-V node. The application of acetylcholine produces characteristic changes in the action potentials of fibers in the atrial margin of the A-V node: depolarization becomes slow, amplitude falls and notching and slurring appear in the upstrokes. These observations support the concept that transmission of excitation through the A-V node is decremental and that the excitatory process in nodal fibers consists of more than one excitatory event.
An Analysis of Coronary Flow and Related Factors Following Vagotomy, Atropine, and Sympathectomy
Authors: SCOTT J. C. , BALOURDAS T. A.
Published: June 2012

Coronary blood flow in the dog has been measured by the nitrous oxide desaturation method before and after acute bilateral cervical vagotomy, intravenous injection of atropine, and chronie sympathectomy. Vagotomy and atropine markedly increased coronary flow, myocardial oxygen consumption, and heart rate, but decreased left ventricular efficiency. Chronic sympathectomy resulted in the following smaller but statistically significant changes: a decrease in coronary flow, myocardial oxygen consumption, and heart rate, but an increase in left ventricular efficiency.

Increasing the oxygen content of the arterial blood decreased the coronary flow. A comparison of diallylbarbiturate acid and urethane with morphine and chloralose anesthesia gave similar flow values, but cardiac efficiency was increased in the latter case.

An analysis of the relationships between coronary flow, left ventricular oxygen consumption, and the arteriovenous oxygen difference is presented.
Effect of Chylomicrons on the Fibrinolytic Activity of Normal Human Plasma in Vitro
Authors: MERIGAN THOMAS C. , FARQUHAR JOHN W. , WILLIAMS JAMES H. , SOKOLOW MAURICE
Published: June 2012

The reported inhibition of fibrinolytic activity of blood plasma after ingestion of fat has been confirmed. It is shown that the chylomicrons present in such plasma are responsible for this phenomenon.
Properties of Hyperthyroid Rat Myocardium
Authors: WHITEHORN W. V. , ULLRICK W. C. , ANDERSEN B. R.
Published: June 2012

Electric and mechanical properties of right and left ventricular muscle of hyperthyroid rats have been studied in vitro. Excitability was not modified but refractory period was lengthened in left ventricular muscle. Developed tension was significantly reduced in both ventricles, the greater reduction being on the right. The results suggest direct and disproportionate effects of thyroid hormone on right and left ventricular myocardium.
Antilipemic Activity of an Extract of Hog Gastric Mucosa
Authors: CANTONE AURELIO , RULLI VINCENZO , ROSSI BALDO
Published: June 2012

In recent years numerous studies have been made on the clearing effect exerted by heparin on hyperlipemic plasma, specially in connection with the problem of atherogenesis. The present paper deals with investigations, carried out on both animals and men, concerning the hypocholesteremic, plasma-clearing, and lipotropic effects, as well as the inhibitory action on the electrocardiographic changes associated with alimentary hyperlipemia, exerted by orally active extracts of gastric juice and hog gastric mucosa.
Quantitative Comparison of Eight Vectorcardiographic Lead Systems
Authors: SIMONSON ERNST , SCHMITT OTTO H. , NAKAGAWA H.
Published: June 2012

The large number of different, but presumably equivalent, vectorcardiographic lead systems in current use makes it imperative that their degree of interchangeability be investigated, and that standardization on some compromise system be achieved if possible. The situation is reminiscent of the controversy over the CF, CL, CR, and V leads in the early 'forties. Large and erratic variations of spatial loop configuration, orientation, and magnitude among eight different, presumably orthogonal, vectorcardiographic lead systems were found, so that direct interchangeability is questionable. The discrepancies were far greater than those between the different types of chest leads. Standardization on a universally acceptable compromise vectorcardiographic lead system would be desirable, to avoid confusion in the rapidly accumulating body of vectorcardiographic material, even though the compromise falls short of a theoretic ideal.
Action of a Sympathomimetic Drug and of Theophylline Ethylene Diamine on the Pulmonary Circulation
Authors: BARER GWENDA R. , GUNNING A. J.
Published: June 2012

The action of two drugs, β-(2,5-diethoxyphenyl)-β-hydroxy-isopropylamine (BW 45/50) and theophylline ethylene diamine, on the pulmonary circulation of dogs and cats was tested. These experiments were made on intact animals, or animals with open chests, or on isolated perfused lungs. BW 45/50 reduced pulmonary arterial pressure in cats and dogs probably because of a fall in cardiac output; pulmonary vascular resistance was usually increased. Theophylline ethylene diamine caused a decrease in pulmonary vascular resistance; its value in pulmonary embolism is suggested.
Effect of Alterations in Systemic Pressure upon Oxygen Saturation in Patients with Congenital Heart Disease
Authors: LASSER RICHARD P. , GENKINS GABRIEL
Published: June 2012

The effect of alteration of systemic pressure upon peripheral arterial oxygen saturation was studied in patients with congenital heart disease. Vasodepression produced by amyl nitrite caused a fall in systemic oxygen saturation in five patients with tetralogy of Fallot, two with patent ductus arteriosus and severe pulmonary hypertension, and one with Eisenmenger's complex. These changes did not occur in normals or in those with isolated puhmonic stenosis, trilogy of Fallot, or uncomplicated interatrial septal defect or patent duetus. Levarterenol on the other hand produced a rise in systemic oxygen content in one patient with tetralogy of Fallot. The use of these technics is suggested as a diagnostic aid and for the study of venoarterial shunts.
Blood Flow in the Aortic Wall
Authors: SAPIRSTEIN LEO A. , MANDEL MORRIS J.
Published: June 2012

The indicator-fractionation technic for measurement of regional blood flow has been applied to the measurement of blood flow in the aortic wall, using Rb
86
. The aortic-indicator content declines slowly with time during the first minute, which shows that the aorta has a smaller extraction ratio for Rb
86
than the rest of the body. The application of the indicator-fractionation technic when organ content of indicator changes with time is discussed. It is shown that the perfusion rate of rat aorta is at least 1.70 ml./Gm./min. This value is much larger than would be expected from in vitro studies of aortic oxygen utilization.
Activation of the Ischemic Ventricle and Acute Peri-Infarction Block in Experimental Coronary Occlusion
Authors: CONRAD LOYAL L. , CUDDY T. EDWARD , BAYLEY ROBERT H.
Published: June 2012

Changes in left ventricular activation during the first 10 min. following occlusion of the anterior descending branch of the left coronary artery of dogs were studied by using multiple intramural electrodes. Intramural block and an increase in the amplitude of R were observed routinely in the outermost layers of muscle in the central zone of maximal ischemia as long as the occlusion was maintained. The changes were distinct from those produced by left bundle-branch block. Failure to propagate the accession process in normal fashion seems to be characteristic of ischemic heart muscle.
Radioautographic Study of Aortic Plaque Formation
Authors: FELS I. GORDON , THADDEUS KANABROCKI
Published: June 2012

Radioautographic evidence using Ca
45
Cl
2
is presented to demonstrate that the aorta has an inherent ability to bind calcium ion regardless of age, sex or species. The binding occurs primarily in the intima and is not homogeneously distributed. Experiments with boiled aorta suggest that the primary substance responsible is collagen. The binding of calcium by the aorta has a marked effect upon the stability of emulsions. A theory of arterial plaque formation is presented.
Histologic Examination of the Origin of the Action Potential Characteristically Obtained from the Region Bordering the Atrioventricular Node
Authors: SANO TOYOMI , TASAKI MINORU , SHIMAMOTO TAKIO
Published: June 2012

In the region of the atrioventricular node a characteristic cell potential was obtained by microelectrode recording in dogs. The resting and action potentials obtained here were small and the latter had a step-like potential before the steepest rise. The site of origin was examined histologically by a special staining technic and was found to be from a cell of the atrioventricular node or a part of the special junctional tissue adjacent to it.
Effects of Unilateral Nephrectomy and Mixed Infection on Blood Pressure of Rats with Experimental Chronic Pyelonephritis
Authors: SHAPIRO ALVIN P. , KOBERNICK JEAN L. , BLAIR CALVIN C.
Published: June 2012

Chronic pyelonephritis resulting from a mixed infection was produced in rats. They displayed marked hyposthenuria and azotemia and, on pathologic examination at the end of one year, revealed severe contraction and scarring of the kidneys. Hypertensive vascular disease did not develop even in rats with unilateral nephrectomy, although some animals succumbed to renal failure. The results indicate that parenchymal renal injury from chronic renal infection, even when it results from mixed infection and is associated with a decrease in renal mass, does not result in hypertensive disease. It is suggested that this is due to the absence of a vascular lesion producing renal ischemia.
Thromboplastic and Fibrinolytic Activity of the Human Aorta
Authors: ASTRUP TAGE , ALBRECHTSEN OLE K. , CLAASSEN MARYLIN , RASMUSSEN JORGEN
Published: June 2012

In the thrombogenic theory of the pathogenesis of arteriosclerotic lesions, parietal fibrin deposits in the arteries play a primary role. In an effort to elucidate the hemostatic system in the arterial wall, the thromboplastic activity and the fibrinolytic activity (estimated as plasminogen activator) in the layers of the human aorta have been estimated. The simultaneous presence of high thromboplastic activity and little or no fibrinolytic activity found in the intima and the media suggest that fibrin can easily he deposited after tissue injury and that its eventual removal depends upon the humoral fibrinolytic system in the circulating blood. The observations apparently support the thrombogenic theory.
Effects of Glucose Infusion on Dog Myocardial Metabolism
Authors: REBAR BLANCHE , OMACHI AKIRA , REBAR JOHN
Published: June 2012

Infusion of glucose to the whole animal results in increased myocardial content of phosphocreatine, glycogen and potassium. Metabolic alterations induced by coronary ligation were not modified by glucose infusion.
Behavior of genes directly injected into the rat heart in vivo.
Authors: Buttrick P M , Kass A , Kitsis R N , Kaplan M L , Leinwand L A
Published: June 2012

Gene transfer can be achieved in the adult rat heart in vivo by direct injection of plasmid DNA. In this report we define the spatial and temporal limits of reporter gene expression after a single intracardiac injection. pRSVCAT (100 micrograms), in which the Rous sarcoma virus long terminal repeat is fused to the chloramphenicol acetyltransferase reporter gene, and p alpha MHCluc (100 micrograms), in which the alpha-cardiac myosin heavy chain promoter is fused to the firefly luciferase gene, were injected into hearts, and reporter gene activities were assayed at various times. Both chloramphenicol acetyltransferase and luciferase were detectable in 100% of the rats from 1 to 7 days, in 60% of the rats from 17 to 23 days, and in 30% of the rats from 38 to 60 days after injection. Reporter gene activity was largely limited to a 1-2-mm region of the ventricle surrounding the injection site. Closed circular DNA was far more effective than linear DNA in transfecting cells in vivo. The relative strengths of three different promoters, Rous sarcoma virus long terminal repeat, alpha-myosin heavy chain, and alpha 1-antitrypsin, all fused to the luciferase reporter gene were determined. The constitutive viral promoter was approximately 20-fold more active than the cardiac-specific cellular promoter, and the liver-specific cellular promoter was not active at all in the cardiac environment. Thus, direct injection of genes into the heart offers a simple and powerful tool with which to assess the behavior of genes in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
An electron-microscopic study of smooth muscle cell dye coupling in the pig coronary arteries. Role of gap junctions.
Authors: Bény J L , Connat J L
Published: June 2012

Arterial smooth muscles behave like a syncytium, since they are electrically coupled. It is generally assumed that electrical coupling and dye coupling are mediated by gap junctions. No gap junctions could be detected by transmission electron microscopy in media of coronary arteries. We looked for the presence of gap junction protein in vascular smooth muscle by immunohistochemistry with light microscopy. Immunohistologically detectable connexin is expressed by smooth muscle cells of the media of pig coronary arteries, where staining occurs as a discrete punctation. We investigated the dye coupling in strips of pig coronary artery. The fluorescent dye lucifer yellow was microiontophoretically injected into a smooth muscle cell through an intracellular microelectrode. The dye was visualized on the entire strip, then on semithin sections with a fluorescence microscope, and at the ultrastructural level by using an anti-lucifer yellow antibody revealed by the protein A-gold technique. In all the tissues examined, the cells were dye-coupled. We conclude that in arterial media the smooth muscle cells are dye-coupled, despite the absence of detectable gap junctions by transmission electron microscopy, and suggest that dye coupling could occur via isolated gap junction channels.
Kappa and delta opioid receptor stimulation affects cardiac myocyte function and Ca2+ release from an intracellular pool in myocytes and neurons.
Authors: Ventura C , Spurgeon H , Lakatta E G , Guarnieri C , Capogrossi M C
Published: June 2012

We investigated the effects of mu, delta, and kappa opioid receptor stimulation on the contractile properties and cytosolic Ca2+ (Cai) of adult rat left ventricular myocytes. Cells were field-stimulated at 1 Hz in 1.5 mM bathing Ca2+ at 23 degrees C. The mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10(-5) M) had no effect on the twitch. The delta-agonists methionine enkephalin and leucine enkephalin (10(-10) to 10(-6) M) and the kappa-agonist (trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclo-hexyl]- benzeneacetamide)methanesulfonate hydrate (U-50,488H; 10(-7) to 2 x 10(-5) M) had a concentration-dependent negative inotropic action. The sustained decrease in twitch amplitude due to U-50,488H was preceded by a transient increase in contraction. The effects of delta- and kappa-receptor stimulation were antagonized by naloxone and (-)-N-(3-furyl-methyl)-alpha-normetazocine methanesulfonate, respectively. In myocytes loaded with the Ca2+ probe indo-1, the effects of leucine enkephalin (10(-8) M) and U-50,488H (10(-5) M) on the twitch were associated with similar directional changes in the Cai transient. Myofilament responsiveness to Ca2+ was assessed by the relation between twitch amplitude and systolic indo-1 transient. Leucine enkephalin (10(-8) M) had no effect, whereas U-50,488H (10(-5) M) increased myofilament responsiveness to Ca2+. We subsequently tested the hypothesis that delta and kappa opioid receptor stimulation may cause sarcoplasmic reticulum Ca2+ depletion. The sarcoplasmic reticulum Ca2+ content in myocytes and in a caffeine-sensitive intracellular Ca2+ store in neurons was probed in the absence of electrical stimulation via the rapid addition of a high concentration of caffeine from a patch pipette above the cell. U-50,488H and leucine enkephalin slowly increased Cai or caused Cai oscillations and eventually abolished the caffeine-triggered Cai transient. These effects occurred in both myocytes and neuroblastoma-2a cells. In cardiac myocyte suspensions U-50,488H and leucine enkephalin both caused a rapid and sustained increase in inositol 1,4,5-trisphosphate. Thus, delta and kappa but not mu opioids have a negative inotropic action due to a decreased Cai transient. The decreased twitch amplitude due to kappa-receptor stimulation is preceded by a transient increase in contractility, and it occurs despite an enhanced myofilament responsiveness to Ca2+. The effects of delta and kappa opioids appear coupled to phosphatidylinositol turnover and, at least in part, may be due to sarcoplasmic reticulum Ca2+ depletion.(ABSTRACT TRUNCATED AT 400 WORDS)
Identification and characterization of human myocardial phospholipase A2 from transplant recipients suffering from end-stage ischemic heart disease.
Authors: Hazen S L , Gross R W
Published: June 2012

Although numerous studies have implicated accelerated phospholipid catabolism during myocardial ischemia as an important contributor to ischemic membrane dysfunction, no information is currently available on the subcellular distribution, physical properties, or kinetic characteristics of human myocardial phospholipase A2. In this report, we demonstrate that the overwhelming majority (98%) of total phospholipase A2 activity in human myocardium (obtained from transplant recipients) is calcium independent, plasmalogen selective, and is distributed between the microsomal (60-70% of total activity) and cytosolic (30-40% of total activity) fractions. Both human myocardial microsomal and cytosolic phospholipase A2 enzymes 1) preferentially hydrolyze plasmalogen molecular species containing arachidonic acid at the sn-2 position, 2) are recalcitrant to chemical inactivation by the indole-reactive agent parabromophenacyl bromide, 3) are irreversibly inhibited by covalent modification of an essential thiol residue by 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB), and 4) are exquisitely sensitive to mechanism-based inhibition by (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (bromoenol lactone). In sharp contrast, human mitochondrial phospholipase A2 1) accounts for only a diminutive amount of total myocardial phospholipase A2 activity (1-2%), 2) is augmented by calcium ion, 3) exhibits a higher reaction velocity using phosphatidylcholine in comparison with plasmenylcholine substrate, and 4) is not substantially inhibited by either DTNB or bromoenol lactone. Collectively, these results demonstrate that the majority of phospholipase A2 activity in human myocardium is catalyzed by a novel class of calcium-independent plasmalogen-selective phospholipases A2 and underscore the potential importance of this class of enzymes in mediating membrane dysfunction during myocardial infarction in humans.