bluuebunny/crossref_metadata_2025 huggingface dataset:
Velocity profiles of blood platelets and red blood cells flowing in arterioles of the rabbit mesentery.
Authors: Tangelder G J , Slaaf D W , Muijtjens A M , Arts T , oude Egbrink M G , Reneman R S
Published: June 2012

Velocity profiles were determined in rabbit mesenteric arterioles (diameter 17-32 micron). A good spatial resolution was obtained by using the blood platelets as small and natural markers of flow, providing for the first time in vivo detailed, quantitative information about the shape of the velocity profiles in microvessels. In some experiments red blood cell velocity profiles were recorded as well. Easy detection of the cells of interest could be achieved by labelling them selectively with a fluorescent dye and visualizing them by intravital fluorescence video microscopy, using flashed illumination. Pairs of flashes were given with a short, preset time interval between both flashes, yielding in one TV picture two images of the same cell displaced over a certain distance for the given time interval. Velocity and mean radial position of cells, flowing within an optical section around the median plane of the vessel, were determined. The shape of the velocity profiles of platelets and red blood cells was similar. The profiles were flattened as compared to a parabola, both in systole and diastole. Vessel diameter did not change measurably during the cardiac cycle. As an index of the degree of blunting of the profiles, the ratio of the maximal and mean velocity of the profile was used, which is 2 for a parabola and 1 for complete plug flow. The index ranged from 1.39 to 1.54 (median 1.50), and increased with vessel diameter. Calculations showed that the blunting of the profiles cannot be explained by an influence of the finite depth of the optical section.
Alpha-skeletal muscle actin mRNA's accumulate in hypertrophied adult rat hearts.
Authors: Schwartz K , de la Bastie D , Bouveret P , Oliviéro P , Alonso S , Buckingham M
Published: June 2012

Cardiac hypertrophy due to a chronic hemodynamic overload is accompanied by isoformic changes of two proteins of the thick filament of the sarcomere, myosin, and creatine phosphokinase. We have looked for isoactin changes, using deoxyribonucleic acid probes complementary to alpha-skeletal and alpha-cardiac actin messenger ribonucleic acids. Three groups of rats were studied at various days after application of a pressure overload (2-4 days, n = 13, 8-15 days, n = 5, and 30-40 days, n = 7) and were compared to control animals (n = 11). Whereas alpha-skeletal actin messenger ribonucleic acids were hardly detectable in the normal hearts (0.6 +/- 0.16%), they accumulated significantly in the first 4 days after the aortic stenosis (4.6 +/- 3.1%, p less than 0.001 vs. controls) and then slowly declined (8-15 days, 3.2 +/- 1.7% and 30-40 days, 1.6 +/- 0.6%, p less than 0.05 and NS vs. controls). This figure is similar to that observed in 8-day-old rats (2.27 +/- 0.3%, p less than 0.01 vs. controls). We conclude that, in rat myocardium, the expression of messenger ribonucleic acids encoding the sarcomeric actins is altered at the onset of a pressure overload hypertrophy. Although the physiological significance of isoactin changes is unknown, our results show that the thin filament participates as well as the thick filament in the response of cardiac muscle to new functional requirements.
Faster time to peak tension and velocity of shortening in right versus left ventricular trabeculae and papillary muscles of dogs.
Authors: Rouleau J L , Paradis P , Shenasa H , Juneau C
Published: June 2012

Some of the mechanical characteristics of papillary muscles and trabeculae (n = 14) isolated from the free wall of the right ventricle of dogs were compared to those obtained from the free wall of the left ventricle (n = 14). Peak total tension (7.2 +/- 1.6 versus 7.9 +/- 1.7 g/mm2, p = NS) and peak velocity of tension development (31 +/- 8 vs. 28 +/- 4 g/mm2/sec, p = NS) were similar in both groups of muscles. However, right ventricular muscles shortened faster over nearly all loading conditions, and during isometric contraction, their time to attain peak total tension was shorter (336 +/- 26 vs. 401 +/- 42 msec, p less than 0.005) than that of left ventricular muscles. Varying stimulation rates (6, 12, 24, and 36 stimuli/min), increasing calcium concentration from 2.54 to 6.35 mM or adding norepinephrine 50 microM, did not significantly alter these differences. There were no differences in myosin isozymes (V1, V2, or V3) between ventricles to explain these differences. These results indicate that important mechanical differences exist between right and left ventricular myocardium and that these differences should be considered when extrapolations are made from myocardium of one area of the heart to another.
Evaluation of Mitral Insufficiency in Dogs by Electronic Analog Simulation of Radioisotope Dilution Data
Authors: HAYDEN DANIEL T. , GARRETT WAYNE , JORDAN P.
Published: June 2012

Left atrial and left ventricular volumes, regurgitant flows and systolic efficiencies have been calculated for dogs with and without mitral valve insufficiency, using a technic of electric analog simulation of radioisotope dilution data. Amounts of blood between the valve of the pulmonary artery and the left atrium were calculated by use of mean transit time and flow, and compared to those of the analog. It is concluded that the analog technic is practical and will be more useful when data is available on flow patterns in the pulmonary bed.
Circulatory Effects of Salicylates
Authors: WALTON R. P. , DARBY T. D.
Published: June 2012

Sodium salicylate consistently produces a prompt increase in heart contractile force when injected in anesthetized dogs in doses of 100 mg./Kg. intravenously. The increase in force is about 30 per cent and declines to control levels in 15 to 20 min. This effect is not considered of important therapeutic significance. Total doses of about 400 mg./Kg. consistently produce marked hyperpyrexia which closely resembles that of dinitrophenol and applied external heat in its circulatory characteristics; conspicuous features are extreme tachycardia, depressed S-T segment, moderate increase in heart force, and aortic pulse contours which indicate reduced stroke volume and vasodilation.
Determinants of Duration and Mean Rate of Ventricular Ejection
Authors: BRAUNWALD E. , SARNOFF S. J. , STAINSBY W. N.
Published: June 2012

The independent influences of stroke volume, heart rate, aortic pressure, hypothermia, sympathomimetic amines, metered mitral and aortic valvular regurgitation, and alterations in myocardial contractility on the duration and mean rate of ventricular ejection and filling were studied. These observations were made in a metabolically supported, isolated heart preparation with performance characteristics comparable to the non-isolated heart.
A Secondary Response to Pressor Stimuli Caused by Sensitization to an Endogenous Pituitary Hormone
Authors: CHENOWETH MAYNARD B. , ELLMAN GEORGE L. , REYNOLDS ROBERT C. , SHEA PHILIP J.
Published: June 2012

A prolonged and frequently extreme pressor response subsequent to the usual pressor response to asphyxia, nicotine injection or carotid occlusion has been observed in dogs, cats and monkeys treated with certain pressor aminies. Analysis of this phenomenon indicates that it is due to sensitization of the vascular bed, largely that of the intestine, by the amines to a pituitary hormone released by the various stimuli used. This hormone is probably equivalent to vasopressin.
Cardiac Effects of Intracoronary Arterial Injections of Nicotine
Authors: WEST JAMES W. , GUZMAN SANTIAGO V. , BELLET SAMUEL
Published: June 2012

The effects of intracoronary arterial injections of nicotine on coronary blood flow, myocardial contractility, cardiac rhythm and the QRS-T complex of the electrocardiogram were studied in intact dogs. The results indicate that nicotine stimulates intrinsic cardiac structures producing parasympathomimetic, sympathomimetic and Bezold-Jarisch reflex responses. The role of these intracardiac receptors is discussed in relation to the circulatory effects resulting from the ingestion of nicotine.
Control of Complete Heart Block by Use of an Artificial Pacemaker and a Myocardial Electrode
Authors: WEIRICH WILLIAM L. , PANETH MATTHIAS , GOTT VINCENT L. , LILLEHEI C. WALTON
Published: June 2012

The combined use of an artificial pacemaker and the insertion of a myocardial electrode has been described and demonstrated to be an effective method of controlling the heart rate at low voltages and low current amplitudes when complete heart block is present. The cardiac output and mean aortic pressures of dogs have been restored to preblock levels throngh the application of electric stimuli applied directly to the myocardium. No complications from insertion of removal of the wire in the heart wall were observed. The heart rates of 18 patients with surgically induced complete atrioventricular dissociation have been successfully managed by the method described with an important reduction in the mortality associated with this complication of open heart surgery.
Chemical Agents Capable of Affecting Lipid Metabolism in the Aorta
Authors: WERTHESSEN NICHOLAS T.
Published: June 2012

Control of lipid metabolism in the surviving bovine aorta by chemical agents has been demonstrated. For this demonstration an internally controlled technic was developed. This teehnic is briefly described as well as the results assaying several hormones and 2 vitamins.
Polarographic Oxygen, the Epicardial Electrocardiogram and Muscle Contraction in Experimental Acute Regional Ischemia of the Left Ventricle
Authors: SAYEN JOHN J. , SHELDON WARNER F. , PEIRCE GEORGE , KUO PETER T.
Published: June 2012

This study is the first attempt to correlate myocardial oxygen availability by the polaro-graphic method with direct electrocardiographic leads and cinematographic records of muscle contraction during experimental acute coronary branch occlusion and narrowing. The comparative insensitivity and slowness of the epicardial electrocardiogram as an index of acute regional ischemia is demonstrated. Special attention is given to the rates of myocardial oxygen change immediately following attainment of a significant degree of coronary obstruction, the effects of pure oxygen inhalation on the experimental situations, and alterations in coronary vein color following release of arterial occlusion.
Mechanism of attenuated pressure-flow autoregulation in right coronary circulation of dogs.
Authors: Yonekura S , Watanabe N , Caffrey J L , Gaugl J F , Downey H F
Published: June 2012

Right coronary autoregulation was assessed in 14 open-chest, anesthetized dogs. In Group 1 (n = 5), the left common and right coronary arteries were cannulated and perfused independently. As coronary perfusion pressures varied simultaneously between 70 and 120 mm Hg, right coronary blood flow changed by 48%, whereas left coronary flow changed by 13%. In this pressure range, the autoregulatory closed-loop gain of the right coronary circulation averaged 0.37 +/- 0.01, reflecting a modest autoregulatory capability but significantly less than that of the left coronary circulation, 0.78 +/- 0.08. In Group 2 (n = 9), only the right coronary artery was perfused, and right coronary venous blood was collected for determining arteriovenous oxygen extraction. Autoregulatory gain was similar to that of Group 1, indicating that collateral flow associated with intercoronary pressure gradients does not mask right coronary autoregulation. Right ventricular myocardial oxygen consumption varied directly with perfusion pressure, ranging from 7.1 +/- 1.0 to 2.9 +/- 0.8 ml O2/min/100 g as pressure was reduced from 160 to 40 mm Hg. Thus, right coronary autoregulation is masked by an opposing change in oxygen demand. When right ventricular oxygen consumption was altered by pacing, a linear flow-oxygen consumption relationship was observed (8.2 +/- 0.4 ml/min/100 g per ml O2/min/100 g). Subtraction of flows associated with pressure-induced changes in metabolism revealed a potential autoregulatory capability of the right coronary circulation similar to that manifested by the left coronary circulation.
Relations among sodium pump inhibition, Na-Ca and Na-H exchange activities, and Ca-H interaction in cultured chick heart cells.
Authors: Kim D , Cragoe E J , Smith T W
Published: June 2012

Sodium pump inhibition in cardiac muscle cells is associated with changes in intracellular sodium, calcium, and hydrogen concentrations as well as in membrane ion transport activity. We examined further the functional relations among these entities using cultured chick ventricular cells. [Ca]i and pHi were determined from fluorescence signals obtained from cells loaded with fura-2 or BCECF, respectively. Ouabain (100 microM) elevated [Ca]i eightfold and decreased pHi by 0.11 unit (a 30% increase in [H+]). In the presence of 10 microM ethylisopropylamiloride, a potent inhibitor of Na-H exchange, ouabain elevated [Ca]i 3.5-fold and reduced pHi by 0.16 unit (a 48% increase in [H+]). Exposure to sodium-free (sodium replaced with potassium) medium produced a twelvefold increase in [Ca]i and a 0.12 pH unit decrease in pHi. In cells treated with 100 microM ouabain, exposure to sodium-free (lithium) medium resulted in a 22-fold sustained increase in [Ca]i and a rapid intracellular acidification (pH 7.15 to 6.60). The effect of ouabain or sodium-free medium on pHi was abolished in calcium-free medium; addition of 1 mM Ca rapidly increased [Ca]i and decreased pHi. In cells treated with subtoxic (3 microM) or toxic (100 microM) concentrations of ouabain, initial 24Na uptake rates were significantly greater than in control cells and were significantly reduced in the presence of 10 microM ethylisopropylamiloride. We conclude that ouabain (100 microM) produces intracellular acidification as a result of sodium pump inhibition; calcium accumulation via Na-Ca exchange, and subsequent Ca-H interaction within the cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit.
Authors: Jayakody L , Senaratne M , Thomson A , Kappagoda T
Published: June 2012

The effect of feeding a diet supplemented with lipids and containing 2% cholesterol on the endothelium-dependent relaxation of rabbit aorta to acetylcholine was assessed. The effect of feeding a standard rabbit diet after an initial period of 2% cholesterol feeding was assessed also. Age-matched male, New Zealand white rabbits were fed either a 2% cholesterol diet or a standard rabbit diet. The animals were anesthetized with pentobarbitone sodium (25 mg/kg) and killed either at the beginning of the study (0 weeks) or at 4, 8, or 10 weeks. The animals in the reversal study were fed the 2% cholesterol diet for 6 weeks and killed after an additional 14 and 32 weeks on standard diet. The extent of atherosclerosis in the aorta was assessed by Sudan Red staining, estimation of tissue cholesterol, and light and electron microscopy. The relaxation response to acetylcholine was measured in rings of the thoracic aorta following precontraction with norepinephrine (-6.0 log mol/l). The relaxation was significantly impaired in aortas from rabbits fed the 2% cholesterol diet compared to aortas from animals fed the standard diet. The impairment of relaxation was apparent as early as 4 weeks after the start of the 2% cholesterol diet and remained impaired over the next 6 weeks. No improvement in endothelium-dependent relaxation was seen in rabbits on the reversal diet for 14 and 32 weeks. Thus, endothelium-dependent relaxation is attenuated in animals fed a 2% cholesterol diet, and the loss of relaxation persists for at least 32 weeks after the animals are returned to a standard diet.
Characterization of capacitance-free pressure-flow relations during single diastoles in dogs using an RC model with pressure-dependent parameters.
Authors: Canty J M , Klocke F J , Mates R E
Published: June 2012

Although previous studies have proposed a variety of models to characterize diastolic pressure-flow relations, the models' ability to predict capacitance-free pressure-flow relations from dynamic information in individual studies has not been determined. This study tested the ability of a lumped RC model with pressure-dependent parameters to predict diastolic capacitance-free flow during maximum vasodilation in anesthetized dogs. Model parameters were characterized by perturbing the circumflex coronary artery with a ramp pressure waveform that caused coronary artery pressure to decline at rates varying from 30-150 mm Hg/sec. Capacitance-free relations constructed from declining and rising ramp pressure-flow data corresponded with capacitance-free pressure-flow points constructed during constant-pressure coronary artery perfusion (which are model-independent). The model parameters derived from analysis of the ramp data indicate that conductance of the coronary bed varies directly with coronary pressure and is independent of the rate of coronary pressure decay. Values of coronary capacitance vary inversely with coronary artery pressure and with the magnitude of dPLC/dt. Thus, a simple, lumped diastolic model with pressure-dependent parameters can predict capacitance-free pressure-flow behavior from dynamic pressure-flow data and characterize model parameters over a wide range of coronary pressure.
Hypoxic vasoconstriction increases with postnatal age in lungs from newborn rabbits.
Authors: Fike C D , Hansen T N
Published: June 2012

Previous studies on the pressor response of the newborn pulmonary circulation to hypoxia have used intact animals and have reported conflicting results. Some have found an increase in responsiveness with increasing age; others have found a decrease. To circumvent many problems inherent in studies of pulmonary vascular reactivity in intact animals, we have developed methods for studying isolated, blood-perfused lungs from newborn rabbits. These methods have been used to study the influence of postnatal age on hypoxic pulmonary vasoconstriction. Two sets of experiments were performed. In the first, a stimulus response curve for hypoxic pulmonary vasoconstriction was constructed, using lungs from 19 rabbit pups that were 3-8 days old. At a constant blood flow, pulmonary artery pressure increased progressively as alveolar oxygen tension decreased so that the maximum increase from baseline (29.4 +/- 4.7%) occurred at PIO2 = 0. The pressor response to hypoxia was highly reproducible, and the entire system remained stable for over 2-3 hours. In the second set of experiments, we compared the pulmonary vascular response to hypoxia obtained using lungs from an additional 21 pups that were 3-8 days old with that obtained using lungs from 23 pups that were 10-14 days old. In response to the same hypoxic stimulus, pulmonary artery pressure increased more in lungs from older rabbit pups (56 +/- 4%) than in lungs from younger rabbit pups (34 +/- 7%) (p less than 0.001). We conclude that isolated perfused lungs from newborn rabbits exhibit a reproducible pressor response to alveolar hypoxia and that this response increases as a function of postnatal age.
Carotid sinus baroreceptors modulate tracheal smooth muscle tension in dogs.
Authors: Schultz H D , Pisarri T E , Coleridge H M , Coleridge J C
Published: June 2012

Arterial baroreceptors are known to influence airway smooth muscle tone. Thus, increasing carotid sinus pressure from 20 to 200 mm Hg causes reflex tracheal dilation. However, the effects of changing sinus pressure around a normal arterial pressure set-point of 100 mm Hg have not been examined. In anesthetized, artificially ventilated dogs, we distended the vascularly isolated carotid sinuses with a pulsatile pressure and recorded isometric tension in an upper tracheal segment. The aortic nerves were cut. Increasing mean carotid sinus pressure in steps between 100 and 200 mm Hg decreased tracheal tension, heart rate, and arterial blood pressure; decreasing sinus pressure between 100 and 25 mm Hg had the opposite effect. Changing carotid sinus pressure still evoked tracheal responses when systemic arterial pressure was held constant. Increasing and decreasing carotid sinus pulse pressure around a constant mean pressure evoked similar changes in tracheal tension. All reflex effects were abolished by cutting or cooling (0 degree C) the carotid sinus nerves; tracheal responses were abolished by the carotid baroreflex were of comparable magnitude to those triggered by stimulating pulmonary stretch receptors, laryngeal receptors, and pulmonary C-fibers. Our results indicate that carotid sinus baroreceptors exert a tonic influence on the upper airways by a vagal cholinergic pathway, increasing and decreasing tracheal smooth muscle tension as blood pressure varies around the normal set-point.
Free radicals and reperfusion-induced arrhythmias: protection by spin trap agent PBN in the rat heart.
Authors: Hearse D J , Tosaki A
Published: June 2012

Using the isolated perfused rat heart with transient (10-minute) regional ischemia induced by coronary artery ligation, we have shown that PBN (N-tert-butyl-alpha-phenylnitrone), an organic spin trap agent designed specifically to form "stable" adducts with free radicals in electron spin resonance studies, can dramatically reduce the vulnerability of the myocardium to reperfusion-induced ventricular fibrillation. Studied in the concentration range of 5-1,000 microM/L, PBN added to the perfusate 5 minutes prior to ischemia exerted a dose-dependent protective effect. At the optimum concentration of 30 microM/L PBN reduced the incidence of ventricular fibrillation to 50% (6 of 12) from its control value of 100% (12 of 12). The antiarrhythmic effect was achieved without any substantial effect on coronary flow or heart rate. Investigating whether this was a direct antiarrhythmic effect, operating during reperfusion, or an indirect effect arising from the action of PBN on the heart during ischemia, PBN (30 microM/L) was added to the perfusion fluid 2 minutes before reperfusion. In the control group, 100% of the hearts fibrillated whereas only 50% fibrillated in the PBN group. Additional studies were designed to ascertain whether the drug caused an absolute reduction in vulnerability to reperfusion-induced arrhythmias (irrespective of the duration of ischemia) or whether it only shifted the ischemic time-reperfusion vulnerability curve to the right (i.e., delayed the onset of vulnerability). Thus, studies were undertaken to define the relation between the duration of ischemia and the incidence of reperfusion-induced arrhythmias in control hearts and hearts treated with PBN.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative ultrasonic characterization of the nature of atherosclerotic plaques in human aorta.
Authors: Barzilai B , Saffitz J E , Miller J G , Sobel B E
Published: June 2012

To determine the feasibility of quantitative ultrasonic techniques to define the composition of atherosclerotic plaques, samples of freshly excised human aortas were sewn to a sample holder and immersed in a saline bath for ultrasonic interrogation. Integrated backscatter of a 2-microsecond portion of the backscattered radiofrequency signal was measured with a 10 MHz focused transducer. Integrated backscatter was calculated by normalizing the root-mean-square voltage of the gated signal to the root-mean-square voltage obtained by replacing the tissue sample with a nearly perfect reflector. Microscopic examination of the 124 interrogated sites allowed differentiation of normal, fibrous, fibrofatty, and calcified regions. A site was considered calcified if it contained any histochemically detectable calcium. Values of integrated backscatter were markedly elevated from calcified regions (-30.0 +/- 6.4 dB, n = 25; mean +/- SD; p less than 0.001) compared to normal (-43.2 +/- 2.4 dB, n = 20) and fibrofatty (-43.9 +/- 3.4 dB, n = 43) sites. Values from fibrous regions (-40.7 +/- 3.8 dB, n = 36) were also significantly different compared with the calcified and fibrofatty regions (p less than 0.001). Thus, we have demonstrated that quantitative ultrasonic backscatter identifies and differentiates calcification and fibrosis in atherosclerotic sites offering promise for the noninvasive assessment of the pathologic status of the arterial wall.
Glycolytic activity and enhancement of serotonin uptake by endothelial cells exposed to hypoxia/anoxia.
Authors: Lee S L , Fanburg B L
Published: June 2012

Serotonin (5-HT) uptake by bovine pulmonary artery endothelial cells in culture was stimulated several fold by exposure of cells for 24 hours to 0-3% O2. The cells appeared normal morphologically, excluded trypan blue dye, showed normal levels of release of lactate dehydrogenase, and contained normal amounts of adenosine triphosphate (ATP). Incubation of cells with iodoacetate (3-5 microM), an inhibitor of glycolytic metabolism, prevented the stimulation of 5-HT uptake but did not impair cellular proliferation. A similar, but less pronounced, effect was produced by 1 mM deoxyglucose. On the other hand, the mitochondrial inhibitors antimycin A, sodium azide, potassium cyanide, and 2,4-dinitrophenol inhibited cellular replication similar to the effect of anoxia but did not alter the stimulation of 5-HT uptake. 5-HT uptake correlated strongly with lactate production by the cells exposed to anoxia (r = 0.98). We conclude that stimulation of 5-HT uptake by prolonged exposure of the endothelial cell to hypoxia/anoxia causes alteration of a membrane function (serotonin transport) of the endothelial cell. This alteration is associated with enhanced glycolytic activity of the cell during exposure to hypoxia. The mechanism for translation of enhanced glycolysis to later stimulation of 5-HT uptake remains to be determined. Endothelial cellular replication is dependent on aerobic metabolism.
Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs.
Authors: Guth B D , Heusch G , Seitelberger R , Ross J
Published: June 2012

We examined the importance of decreased heart rate in the beneficial effect of beta-adrenergic blockade on exercise-induced regional myocardial ischemia and contractile dysfunction in conscious dogs with single vessel coronary stenosis (ameroid constrictor). Studies were performed during control treadmill exercise, which produced regional myocardial ischemia (blood flow measured with microspheres) and wall dysfunction (measured using sonomicrometers). A second run was performed after the administration of atenolol (0.3-1.0 mg/kg i.v.), and the reduced heart rate caused by atenolol during early steady-state running was then prevented by atrial pacing during the latter portion of the run. Atenolol reduced the exercise heart rate from 217 +/- 25 beats per minute (SD, n = 9) to 166 +/- 15, and ischemic zone wall thickening during systole improved from 27 +/- 22% of the resting value in the control run to 50 +/- 25% of the resting value in the atenolol run (p less than 0.01). Atrial pacing then increased heart rate to 217 +/- 23 beats per minute, and regional wall thickening deteriorated to 15 +/- 25% of the resting value. Regional subendocardial blood flow in the ischemic zone during atrial pacing with atenolol was slightly less than that observed in the control run, in both ischemic and control zones, indicating no remaining beneficial effect of atenolol when heart rate reduction was eliminated. We conclude that the only significant mechanism for the improvement in exercise-induced ischemia and wall motion produced by atenolol is a reduction in the exercise heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamic stiffness of barium-contractured cardiac muscles with different speeds of contraction.
Authors: Shibata T , Hunter W C , Sagawa K
Published: June 2012

The dynamic stiffness of excised cardiac muscles that would be likely to have different intrinsic speeds of contraction, as judged by previous biochemical reports of their myosin ATPase rates, was compared. This study included muscles from thyrotoxic rabbits and newborn rabbits, rabbit atria, and normal papillary muscles at different temperatures. The usual excitation-contraction coupling process was bypassed by replacing bathing Ca2+ with Ba2+. The ensuring actively maintained contracture allowed us to focus more specifically on the contractile properties of the myofilaments. Dynamic stiffness was determined by sinusoidally oscillating muscle length at many different frequencies over the range 0.05-50 Hz while holding average muscle length at 95% of the systolic length, thus giving maximal developed force. The form of the stiffness modulus spectrum was similar for all muscles studied: stiffness was fairly constant at low frequencies, decreased to a minimum at an intermediate frequency, and then increased steeply, followed by a milder rate of increase over high frequencies. Differences in contraction speed were evident by shifts in the frequencies at which corresponding portions of the stiffness spectrum appeared. The clearest landmark was the frequency where stiffness became minimum (fmin). This varied strongly with temperature (Q10 = 2.9). Compared to normal adult papillary muscles (fmin = 1.2 Hz), fmin was 2.2 times faster in thyrotoxic myocardium, 1.9 times faster in 1-week-old rabbits, and 3.7 times faster in atrial trabeculae. These ratios of functional speed are similar to the corresponding ratios of myosin Ca2+-ATPase activities reported in the literature.
Depolarization-stimulated 42K+ efflux in rat aorta is calcium- and cellular volume-dependent.
Authors: Magliola L , Jones A W
Published: June 2012

The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase 42K+ efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium-stimulated 36Cl- efflux. The addition of 25-150 mM KCl to normal physiologic solution stimulated 42K+ efflux in a concentration-dependent manner. Diltiazem suppressed potassium-stimulated 42K+ efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit 42K+ efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium-stimulated 42K+ efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the 42K+ efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization-mediated 42K+ efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists.
Adenosine inhibits exocytotic release of endogenous noradrenaline in rat heart: a protective mechanism in early myocardial ischemia.
Authors: Richardt G , Waas W , Kranzhöfer R , Mayer E , Schömig A
Published: June 2012

The effects of exogenous and endogenous adenosine on exocytotic noradrenaline release were studied in rat hearts perfused in situ. Exocytotic release of endogenous noradrenaline (determined by high pressure liquid chromatography) was induced by electrical stimulation of the left cervicothoracic ganglion. Exogenous adenosine significantly reduced noradrenaline overflow from the heart. This suppression of noradrenaline overflow was not influenced by desipramine, indicating a mechanism independent from noradrenaline reuptake. The A1 subtype specific agonists cyclohexyladenosine and R-phenylisopropyladenosine had inhibitory effects at lower concentrations than adenosine and S-phenylisopropyladenosine, suggesting the relevance of presynaptic inhibitory adenosine receptors of the A1 subtype. Short ischemic periods of 3 minutes resulted in a marked coronary venous overflow of adenosine during reperfusion. This was accompanied by an inhibition of noradrenaline release evoked by nerve stimulation during ischemia. The adenosine antagonists theophylline and 8-phenyltheophylline prevented this suppression of noradrenaline release. Blockade of oxidative phosphorylation by cyanide in combination with glucose-free perfusion induced an increased formation of endogenous adenosine and suppression of stimulation-evoked noradrenaline overflow. Again, in the presence of the adenosine antagonists theophylline or 8-phenyltheophylline, this suppression was abolished. These results indicate that adenosine is a potent inhibitor of exocytotic noradrenaline release in the heart with relevance during conditions of increased endogenous adenosine formation such as myocardial ischemia.
Effects of gonadectomy and hormonal replacement on rat hearts.
Authors: Scheuer J , Malhotra A , Schaible T F , Capasso J
Published: June 2012

To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham-operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one-half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of components of ischemia and metabolic inhibition on delayed afterdepolarizations in guinea pig papillary muscle.
Authors: Coetzee W A , Opie L H
Published: June 2012

Delayed afterdepolarizations (DADs) may develop into triggered automaticity and ventricular arrhythmias. However, the potential role of DADs in the genesis of ischemic arrhythmias is not clear. We studied the effects of different components of severe ischemia (acidosis, hypoxia, lactate, increased potassium, and the absence of glucose) on DADs. DADs were evoked using trains of 30-60 externally applied pulses at a rate of 4-5 Hz in the presence of isoproterenol (10(-7) M) or dibutyryl cyclic 3', 5' adenosine monophosphate (dB-cAMP, 10(-3) M). Acidosis, caused by the addition of protons (pH = 6.8), increased the amplitude of DADs from 3.2 +/- 0.4 to 5.9 +/- 0.5 mV (n = 8, p less than 0.001). DADs were abolished by hypoxia (pO2 less than 35 mm Hg, n = 7, p less than 0.001) from control values of 3.4 +/- 0.3 mV. DADs were also abolished by neutral lactate (20 mM, n = 7, p less than 0.001) in the absence of glucose. Acidotic lactate (20 mM, pH0 = 6.8), however, was unable to abolish DADs. Increasing the extracellular potassium concentration to 16.2 mM decreased DAD amplitude from 3.6 +/- 0.27 mV to 1.3 +/- 0.1 mV (n = 5, p less than 0.002) with an associated reduction of membrane potential from -86.2 +/- 0.9 to -58.6 +/- 0.9 mV. The overall effect of simulated ischemia (all components tested together) was to abolish DADs (n = 8, p less than 0.001), with hypoxia as the most important factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal vascular adjustments to partial renal venous obstruction in dog kidney.
Authors: Abildgaard U , Amtorp O , Agerskov K , Sjøntoft E , Christensen N J , Henriksen O
Published: June 2012

Blood flow studies were conducted in neurolept anesthetized dogs to characterize the involvement of renal nerves in ipsilateral renal vasoconstriction seen during acute elevation of renal venous pressure above 30 mm Hg. Renal blood flow was measured electromagnetically. The vasoconstrictor response was almost abolished by acute surgical denervation of the kidney, since renal vascular conductance remained unchanged during renal venous pressure elevation from 30-60 mm Hg. However, following additional alpha-adrenoceptor blockade or chronic renal denervation, renal vascular conductance increased progressively during renal venous pressure elevation to 60 mm Hg. The effect of acute decapsulation of kidney was studied in another group of dogs. Decapsulation induced a vasoconstriction. The decrease in renal vascular conductance observed during renal venous pressure elevation was unaffected by acute surgical denervation of decapsulated kidney, but was almost abolished following additional alpha-adrenoceptor blockade or chronic denervation. In decapsulated chronically denervated kidney, the increase in renal vascular conductance during renal venous pressure elevation to 60 mm Hg was still present but considerably attenuated as compared with the chronically denervated kidney with intact capsule. The renin-angiotensin system did not participate in acute vascular adjustments to renal venous stasis in intact kidney or in decapsulated acutely surgically denervated kidney. The data favor the view that neurogenic and myogenic mechanisms significantly influence the vasoconstrictor response to renal venous pressure elevation in dog kidney. The neurogenic contribution to the vasoconstrictor response comprises intrarenal and extrarenal vasoconstrictor mechanisms evoked reflexively by renal venous pressure elevation, and the myogenic contribution to the vasoconstrictor response comprises opposing vasodilator mechanisms due to increase in renal interstitial tissue pressure during renal venous pressure elevation.
Heparin regulates smooth muscle S phase entry in the injured rat carotid artery.
Authors: Majesky M W , Schwartz S M , Clowes M M , Clowes A W
Published: June 2012

Smooth muscle cell (SMC) proliferation in injured arteries is inhibited by heparin, but the mechanism of inhibition is unknown. In particular, it is not clear whether heparin prevents exit of quiescent SMC from the resting state, inhibits progression through the prereplicative (G1) sequence, or acts during DNA synthesis itself. In this study, induction of ornithine decarboxylase (ODC) activity was used as a marker of SMC entry into the cell cycle in an attempt to localize the site of heparin action during the initial hours after rat carotid injury. Rapid and transient induction of ODC activity was observed that reached a maximum (twenty-three-fold) 6 hours after wounding. Heparin failed to prevent ODC induction but greatly reduced frequencies of [3H]thymidine-labelled SMC nuclei 33 hours after injury. Moreover, heparin infusion could be delayed for up to 18 hours after the injury event with no significant loss of antiproliferative effect. Further delays resulted in marked loss of growth inhibition. The results of these studies show that SMC rapidly and synchronously leave the resting state after injury and suggest that heparin acts late in the prereplicative (G1) sequence or early in S phase to inhibit SMC proliferation in damaged arteries.
Correlation of force-length area with oxygen consumption in ferret papillary muscle.
Authors: Hisano R , Cooper G
Published: June 2012

The ventricular systolic pressure-volume area correlates well with myocardial oxygen consumption. However, in isolated muscle preparations, there are experimental data based on both mechanical and energetic measurements that suggest that the pressure-volume area concept may not obtain. In the present study, force-length area, the analog of pressure-volume area for a linear muscle, was examined in the ferret papillary muscle preparation under a wide range of loading conditions. There were two major findings: first, force-length area is closely correlated with oxygen consumption (r = 0.94-0.98); this correlation is better than those for such other indexes as peak force and force-time integral. Furthermore, this relation of oxygen consumption with force-length area is independent of the mode of contraction (isometric or shortening), while the relations with the other indexes are not. Second, quick release imposed after end-systole during isometric contraction was found to curtail oxygen consumption. The first finding, the optimal correlation of force-length area with oxygen consumption, suggests both that the correlation of pressure-volume area with oxygen consumption on the ventricular level arises from a basic property of cardiac muscle and that force-length area may be the best mechanical index to use in calculating regional oxygen consumption for a ventricular segment. The second finding, however, suggests that the time-varying elastance model, on which the concepts of pressure-volume area and force-length area are based, may not provide a complete description of the mechanical basis of cardiac muscle energetics, especially during the isometric contraction.
Developmental changes in the ultrastructure and sarcomere shortening of the isolated rabbit ventricular myocyte.
Authors: Nassar R , Reedy M C , Anderson P A
Published: June 2012

Sarcomere shortening and ultrastructure of intact isolated myocytes from ventricles of three-week-old and adult rabbits were examined. Cells were fixed and embedded, and after measuring their sarcomere shortening in response to electrical stimulation, they were examined in serial thin sections by electron microscopy. This structure-function analysis showed that adult cells were significantly larger, had longer rest sarcomere lengths, greater amount and velocity of sarcomere shortening, greater velocity of reextension, and shorter contraction duration than immature cells. In immature myocytes, a thin outer shell of myofibrils enveloped a central mass of mitochondria and nuclei, but in adult cells, the cytoskeleton divided the cell into compartments with the mitochondria arranged around and interspersed among the myofibrils. The different arrangement of the organelles and the cytoskeleton at the two ages may account for the shorter rest sarcomere length in the young myocytes and may confer differing internal loads that contribute to their smaller amount and velocity of sarcomere shortening. The corbular and longitudinal sarcoplasmic reticulum were less demarcated in immature than in adult cells. Myocytes from both ages showed postextrasystolic potentiation, suggesting that the sarcoplasmic reticulum modulates calcium at both ages. Restitution of contractility between contractions, obtained by measuring sarcomere shortening of interpolated extrasystoles, was faster in immature than in adult cells and may reflect the structural differences in the sarcoplasmic reticulum. The developmental differentiation in the sarcoplasmic reticulum suggests that changes in compartmentalization of calcium and in the distribution of putative calcium-release sites contribute to the increased contractility of adult myocytes.
Synchronous occurrence of spontaneous localized calcium release from the sarcoplasmic reticulum generates action potentials in rat cardiac ventricular myocytes at normal resting membrane potential.
Authors: Capogrossi M C , Houser S R , Bahinski A , Lakatta E G
Published: June 2012

Under certain conditions, spontaneous release of Ca2+ from the sarcoplasmic reticulum occurs in resting mammalian myocardium. In single rat ventricular myocytes, such spontaneous Ca2+ release appears localized rather than homogeneous. When the increase in cytosolic Ca2+ is present in a single locus within a cell, it causes a small depolarization, which, at the normal resting potential, is subthreshold for generating an action potential. However, when spontaneous Ca2+ release occurs simultaneously at more than a single discrete locus, the resultant sarcolemmal depolarization is augmented to levels that can induce an action potential, even when this depolarization begins at the normal resting membrane potential. Thus, the synchronous occurrence of multifocal localized increases in cytosolic Ca2+ due to spontaneous Ca2+ release from the sarcoplasmic reticulum within ventricular myocytes is a mechanism for "abnormal automaticity."
Subclasses of cyclic AMP-specific phosphodiesterase in left ventricular muscle and their involvement in regulating myocardial contractility.
Authors: Weishaar R E , Kobylarz-Singer D C , Steffen R P , Kaplan H R
Published: June 2012

Ventricular muscle contains a low Km, cyclic AMP-specific form of phosphodiesterase (PDE III), which is believed to represent the site of action for several of new cardiotonic agents including imazodan (CI-914), amrinone, cilostamide, and enoximone. However, species differences in the inotropic response to these agents have raised questions about the relationship between PDE III inhibition and cardiotonic activity. The present study demonstrates that these differences can be accounted for by the presence of two subclasses of PDE III in ventricular muscle and variations in the intracellular localization of these two enzymes. For these experiments, PDE III was initially isolated from canine, guinea pig, and rat left ventricular muscle. The results demonstrate that canine left ventricular muscle contains two functional subclasses of PDE III: an imazodan-sensitive form, which is membrane bound, and an imazodan-insensitive form, which is soluble. Although only weakly inhibited by imazodan, this latter enzyme is potently inhibited by the selective PDE III inhibitors, Ro 20-1724 and rolipram. Guinea pig ventricular muscle also contains the imazodan-sensitive subclass of PDE III. Unlike canine left ventricle, however, thi enzyme is soluble in the guinea pig. No membrane-bound subclass of PDE III was observed in the guinea pig. Rat left ventricle possesses only the soluble form of PDE III, which apparently represents a mixture of the imazodan-sensitive and imazodan-insensitive subclasses of PDE III. Measurement of in vivo contractility in these three species showed that imazodan exerts a potent positive inotropic effect only in the dog, in which the imazodan-sensitive subclass of PDE III is membrane bound.(ABSTRACT TRUNCATED AT 250 WORDS)