bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of instantaneous viscoelastic properties by impedance-frequency curve of the ventricle
Authors: Koiwa Y. , Hashiguchi R. , Ohyama T. , Isoyama S. , Satoh S. , Suzuki H. , Takishima T.
Published: December 2017

We developed a method for estimating the instantaneous viscoelastic properties of the left ventricle (LV). This impedance-curve method is based on the instantaneous impedance-frequency curve of the left ventricle generated by a rapidly oscillating mechanical impulse applied to the epicardial surface of the heart. The theoretical basis of the method and experimentally obtained instantaneous impedance-frequency curves were examined to evaluate the validity of our basic assumptions. Using these impedance-curve data, we calculated the instantaneous viscoelastic properties of the LV during the cardiac cycle. The impedance curve shows a configuration that is almost the same as the theoretical curve based on the assumption that an RCL (R, resistor; C, capacitor; L, inductor) parallel circuit is the electrical analog for the LV. The impedance curve varied moment by moment during the development of instantaneous LV pressure. The elastic and viscous coefficients, calculated from the impedance curve, increased with increase of LV pressure. We concluded that the impedance-curve method can delineate the instantaneous viscoelastic properties of the ventricle (especially of the ventricular myocardium).
Two calcium currents in a smooth muscle cell line
Authors: Friedman M. E. , Suarez-Kurtz G. , Kaczorowski G. J. , Katz G. M. , Reuben J. P.
Published: December 2017

Membrane currents in small cells of a smooth muscle cell line (A10) derived from embryonic rat thoracic aorta were monitored by the patch electrode whole-cell voltage clamp technique. Three currents, two divalent cation currents, and a Ca2+-activated K+ current have been observed. The latter is readily abolished pharmacologically, allowing the characterization of the divalent cation currents. With a holding potential of -50 mV, a single divalent current, which inactivates slowly, is elicited on depolarization of the membrane potential to values positive to ca. -10 mV. The second divalent cation current is only observed when the holding potential is negative to -55 mV and the membrane is pulsed to values positive to ca. -35 mV. This current is rapidly inactivating, peaking in approximately 5 ms and decaying with a t1/2 of ca. 15 ms at 0 mV when conveyed by Ba2+. The rapidly inactivating divalent cation current is depressed by substitution of Ba2+ for Ca2+ in the bathing solution and is highly insensitive to organic Ca2+ channel blockers. The slowly inactivating channel has more typical characteristics of Ca2+ channels; it is more permeable to Ba2+ than to Ca2+ and is sensitive to modulation by dihydropyridines. These data demonstrate the presence of two distinctly different Ca2+ channels in A10 cells.
Alpha-adrenoceptor subtypes and diltiazem actions in isolated human coronary arteries
Authors: Toda N.
Published: December 2017

Isolated human, monkey, and dog coronary arteries treated with propranolol responded to norepinephrine with concentration-related contractions; the magnitude was in the order of human greater than monkey greater than dog arteries. Phenylephrine also contracted these arteries, whereas clonidine produced contractions only in the primate arteries. Contractile responses of human coronary arteries to norepinephrine were not influenced by removal of endothelium. Norepinephrine-induced contractions of human and monkey coronary arteries were attenuated by prazosin and yohimbine in a dose-dependent manner; however, the amine-induced contractions of dog coronary arteries were attenuated only by prazosin. Diltiazem, a Ca2+ antagonist, relaxed human and dog coronary arteries contracted with norepinephrine to a similar extent, but produced a greater relaxation in the human arteries when partially contracted with prostaglandin F2 alpha. These findings suggest that alpha 1- and alpha 2-adrenoceptors are involved in the amine-induced contraction in human and monkey coronary arteries, whereas only alpha 1-receptors are involved in dog artery contraction. Human coronary artery contractions induced by norepinephrine do not appear to be more susceptible to Ca2+ antagonists than the dog artery contractions, which does not provide evidence supporting the hypothesis that Ca2+ antagonists interfere with contractions mediated by alpha 2-receptors to a greater extent than those mediated by alpha 1-receptors in large human coronary arteries.
Naloxone enhances myocardial responses to isoproterenol in dog isolated heart-lung
Authors: Caffrey J. L. , Wooldridge C. B. , Gaugl J. F.
Published: December 2017

Intracoronary injection of naloxone produces rapid local increases in myocardial performance. The role of beta-adrenergic activation in this response was investigated. Naloxone was injected into the left anterior descending artery (LAD) of anesthetized dogs with the adjacent circumflex territory serving as control. Naloxone increased the contractile state locally in the LAD region. Pretreatment with propranolol eliminated the regional inotropic response. An isolated heart-lung model was set up, and isoproterenol dose responses were determined. When repeated after naloxone, contractile (dP/dt) responses to isoproterenol were both augmented and prolonged. In a third study imipramine was used to determine whether naloxone might act by reducing neuronal uptake of the isoproterenol. Imipramine extended the effect of isoproterenol temporally but did not alter the peak response. Adding naloxone increased the peak response to isoproterenol and maintained it above the extended imipramine response. The data support the concept that the blockade of opiate receptors facilitates adrenergic activity mediated by myocardial beta 1-receptors 1) directly through postsynaptic mechanisms, 2) indirectly through beta 2-mediated release of norepinephrine, or 3) via interference with nonneuronal disposal mechanisms.
Analysis of phases of contraction during graded acute myocardial ischemia
Authors: Akaishi M. , Schneider R. M. , Mercier R. J. , Agarwal J. B. , Helfant R. H. , Weintraub W. S.
Published: December 2017

The quantitative effects of graded ischemia on the phases of contraction in ischemic and nonischemic myocardium were studied in 10 open-chest dogs. During progressive coronary stenosis, an index of the overall severity of ischemia, total myocardial blood flow deficit (TMFD), was measured using microspheres. Segment shortening (% delta L) during the isovolumic and ejection phases of systole in the ischemic and nonischemic zones was obtained with ultrasonic crystals. In the ischemic zone, total systolic and ejection phase % delta L decreased progressively as stenosis increased; isovolumic phase % delta L showed segment elongation (bulging) during mild ischemia, which was unchanged as ischemia became severe. Total % delta L in the nonischemic zone increased progressively with increasing stenosis, reaching 132 +/- 20% of the control value when TMFD was 24.8 +/- 6.5% of total expected left ventricular (LV) myocardial blood flow. The increase in total % delta L was entirely attributable to increased ejection % delta L and correlated with indices of preload (multivariate r = 0.65) and afterload (multivariate r = 0.62). Multiple linear regression analysis revealed that augmented contraction in the nonischemic zone was best described (multivariate r = 0.94) by a combination of four hemodynamic variables estimating LV preload and afterload, which correlated in turn with the overall severity of ischemia. Thus systolic bulging in the ischemic zone is primarily an isovolumic phase phenomenon that develops initially with mild ischemia. Little additional change occurs in the isovolumic phase as ischemic severity increases, although further reductions in shortening occur in the ejection phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Anticoagulantly active heparin-like molecules from mast cell-deficient mice
Authors: Marcum J. A. , McKenney J. B. , Galli S. J. , Jackman R. W. , Rosenberg R. D.
Published: December 2017

To assess the contribution of mast cells to the maintenance of blood fluidity, the hindlimb vasculature of mast cell-deficient mice (W/Wv) and littermates containing normal levels of mast cells (+/+), were perfused with purified human thrombin and antithrombin. Enzyme-inhibitor complex generation within the vasculature was enhanced to a comparable extent for W/Wv and +/+ mice over the uncatalyzed rate, that level of complex produced within a similar time interval in the absence of heparin. Perfusion of purified Flavobacterium heparinase prior to infusion of the hemostatic components, or perfusion of antithrombin modified at the heparin-binding domain, reduced W/Wv and +/+ hindlimb thrombin-antithrombin complex formation to the uncatalyzed rate. To further define the cellular source of the vascular-associated heparin-like molecules, endothelial cells isolated from epididymal fat pads of W/Wv and +/+ mice were grown in vitro. The acceleration of thrombin-antithrombin interactions in the presence of endothelial cell-derived glycosaminoglycans was similar for W/Wv and +/+ mice, was abolished with purified bacterial heparinase, and was expressed to only a minor extent when utilizing modified antithrombin. The biologically active mucopolysaccharides appear to be present on the cell surface.
Relationship between inotropy and relaxation in rat myocardium
Authors: Chemla D. , Lecarpentier Y. , Martin J. L. , Clergue M. , Antonetti A. , Hatt P. Y.
Published: December 2017

Myocardial mechanics of 56 rat papillary muscles were investigated in various inotropic states, i.e., early postpartum (1st day, 1st mo) and, in adult, by altering external calcium concentration, [Ca2+]0, stimulation frequency (F), and initial muscle length (L). In all these protocols, the decrease of the inotropic level paralleled a progressive diminution in load sensitivity of relaxation. In such protocols modifying cardiac contractility, peak shortening velocity of the twitch with preload only at Lmax (Vcmax) was always less depressed than peak lengthening velocity (Vrmax), and the ratio R1 = Vcmax/Vrmax always increased. This increase of R1 was linearly related with the decrease of the maximum unloaded shortening velocity (Vmax). The ratio R2 (positive over negative peak force derivatives of the isometric twich at Lmax) was significantly lowered in newborn and was lowered in adult for [Ca2+]0 less than or equal to 1 mM and L less than or equal to 94% Lmax. For a given change in Vmax, each of the experimental protocols gave rise to specific changes in contraction-relaxation coupling tested at low load (R1) and at heavy load (R2).
Endothelial extraction of tracer water is independent of temperature in dog lungs
Authors: Chinard F. P. , Cua W. O.
Published: December 2017

Diffusion and viscosity-dependent flow rates generally decrease with decrease of temperature in biological systems. We have examined the extraction (Ec) of tracer water in isolated dog lungs perfused near 37 degrees C and near 15 degrees C with multiple-indicator dilution experiments. If Ec were barrier limited, Ec should be less at lower temperatures. Two runs at 37 degrees C were followed by two runs at 15 degrees C. Evans blue (T-1824) was used as vascular reference, and tritium oxide (THO) was used as water tracer. Values of Ec were based on the ratio of the areas under the two indicator curves from appearance time to time of peak of T-1824. Values for permeability-surface area (PS) products were calculated from the classical Crone relationship in 14 experiments with a total of 56 runs. Neither Ec nor PS decreased with temperature. Instead, modest but statistically significant increases were found. We conclude that the extraction of tracer water in these preparations is not barrier limited.
Influence of training following bilateral stenosis of the femoral artery in rats
Authors: Mathien G. M. , Terjung R. L.
Published: December 2017

The influence of training on muscle performance in situ, exercise tolerance in vivo, and muscle blood flow, was assessed in rats in which femoral arteries were previously surgically constricted to severely limit active hyperemia but not to restrict normal resting blood flow (BF). Muscle BF to the different fiber type sections of the gastrocnemius plantaris soleus muscle group was determined during in situ stimulation (15 and 30 tetani/min) using 15-microns microspheres after 0, 1, 2, 3, and 5 wk (n = 5-6/wk) of daily treadmill training. Surgical stenosis was performed 48 h prior to the initiation of training. The ability of the hindlimb muscle of sedentary stenosed animals to maintain tension in situ improved from an extensive deficit to normal at 3 wk during relatively mild contractions (15 tetani/min) but not at 5 wk during 30 tetani/min. Although BF improved to normal at 15 tetani/min, a large BF deficit remained at 30 tetani/min. Exercise tolerance during running increased approximately twofold in duration. In contrast, trained stenosed animals demonstrated normal muscle tension in situ by 2 wk during 15 tetani/min and at 5 wk during 30 tetani/min. Exercise tolerance during running increased in duration (approximately fivefold) and intensity (approximately twofold). Although BF to the entire contracting muscle mass was not different between trained and sedentary stenosed animals, its distribution within the gastrocnemius was more homogenous (P less than 0.001). This was probably due to adaptations within the fast-twitch white muscle section and could have contributed to the dramatic improvement in muscle function and exercise tolerance exhibited by the trained stenosed animals.
Thyrotropin releasing hormone in hypovolemia: a hemodynamic evaluation in the rat
Authors: Siren A. L. , Powell E. , Feuerstein G.
Published: December 2017

In the present study the effects of thyrotropin releasing hormone (TRH) and its stable analogue, CG3703, on cardiac output (thermodilution, Cardiomax) and regional blood flow (BF; directional pulsed Doppler technique) were investigated in hypovolemic hypotension in the rat. In urethan-anesthetized rats TRH (0.5 or 2 mg/kg ia) or CG3703 (0.05 or 0.5 mg/kg ia) reversed the bleeding (27% of the blood volume)-induced decreases in mean arterial pressure (MAP) and cardiac index (CI) and increased the heart rate (HR) and total peripheral resistance index (TPRI) in a dose-related manner. In the conscious rat exposed to a 45% hemorrhage, CG3703 (0.5 mg/kg ia) significantly raised MAP, HR, and TPRI with maximum changes of +67 +/- 6 (SE) mmHg, +123 +/- 30 beats/min, and +101 +/- 2%, respectively, CG3703 (0.5 mg/kg ia) also further enhanced the hemorrhage-induced reduction of hindquarter, mesenteric, and renal BF. The changes in BF in saline-treated vs. CG3703-treated rats 2 h after the bleeding were -32 +/- 6 vs. -55 +/- 6% (P less than 0.001) in hindquarter, -9 +/- 8 vs. -61 +/- 11% (P less than 0.001) in mesenteric, and -2 +/- 9 vs. -33 +/- 9% (P less than 0.01) in the renal artery; the changes in vascular resistance +30 +/- 7 vs. +309 +/- 167% (P less than 0.001) in hindquarter, -4 +/- 8 vs. +349 +/- 244% in the mesenteric, and -10 +/- 9 vs. +80 +/- 10% (P less than 0.01) in the renal artery. The survival rate after the 45% hemorrhage was significantly reduced by both TRH and CG3703.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhancement of alpha- and beta-adrenoceptor responses by elevations in vascular tone in pulmonary circulation
Authors: Hyman A. L. , Kadowitz P. J.
Published: December 2017

The influence of increases in vascular tone on responses to selective alpha 1- and alpha 2-adrenoceptor agonists, norepinephrine, epinephrine, and isoproterenol was investigated in the feline pulmonary vascular bed. Under resting tone conditions with constant pulmonary blood flow and left atrial pressure, intralobar injections of the alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, and the alpha 2-adrenoceptor agonists, UK 14304 and B-HT 933, increased lobar arterial pressure. When pulmonary vascular resistance was raised to a high steady level, vasoconstrictor responses to the alpha 2-adrenoceptor agonists were markedly increased, responses to methoxamine were increased to a lesser extent, and pressor responses to phenylephrine and epinephrine were reversed. These vasodilator responses to phenylephrine and epinephrine at elevated vascular tone were blocked by propranolol. Moreover, after beta-adrenoceptor blockade, vasoconstrictor responses to phenylephrine, epinephrine, and norepinephrine were also greater at elevated tone than at resting tone. Vasodilator responses to the beta-adrenoceptor stimulant, isoproterenol, were enhanced at higher levels of vasoconstrictor tone and were blocked by propranolol and by albuterol, a selective beta 2-adrenoceptor antagonist. The enhanced vasoconstrictor responses to the alpha 2-adrenoceptor agonists were selectively blocked by yohimbine, whereas the enhanced responses to the alpha 1-adrenoceptor agonists and, for the most part, the vasoconstrictor responses to norepinephrine and epinephrine, were blocked by prazosin. The present data support the hypothesis that postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction and beta 2-adrenoceptors mediating vasodilation are present in the feline pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Microvascular hemodynamics during systemic hemodilution and hemoconcentration
Authors: Lipowsky H. H. , Firrell J. C.
Published: December 2017

Measurements of intravascular pressure, red blood cell (RBC) velocity, and microvessel hematocrit (Hctmicro) were made in arterioles and venules of the cat mesenteric microvasculature during systemic hemodilution (cell-free plasma) and hemoconcentration (packed cells). For a range of systemic hematocrits (Hctsys) from 5 to 67%, changes in volumetric flux of red cells (QRBC) were derived from the product of microvessel bulk flow and Hctmicro. During hemodilution, a heterogeneous response of changes in QRBC was found with larger distributing arterioles (43-54 microns) exhibiting a monotonic fall, whereas increases in QRBC above control were found in smaller arterioles that were indicative of a potential enhancement of oxygen delivery. Although the dilution response of all arterioles and venules averaged for all calibers of vessels demonstrated a decline in QRBC, alterations of Hctmicro suggested a lessening of the disparity between Hctsys and Hctmicro, which was indicative of a more efficient utilization of the remaining circulating RBC volume. In response to hemoconcentration, a decrease in QRBC also occurred, which, in concert with the dilution data, suggested that QRBC was maximized for a range of 28 less than Hctsys less than 46%. From measurements of the arteriovenous pressure drop across mesenteric modules, regional resistance was found to exhibit a relative plateau as Hctsys was increased above its control value. This behavior was attributed to a decrease in vascular hindrance of the principal resistance vessels and an invariance of blood viscosity at the capillary level due to RBC redistribution and the attendant viscous behavior of blood.
Adrenal medullary and cortical blood flow during hemorrhage
Authors: Breslow M. J. , Mennen A. , Koehler R. C. , Traystman R. J.
Published: December 2017

We used a radiolabeled microsphere technique to measure adrenal medullary and cortical blood flow during hemorrhagic hypotension. Twenty pentobarbital-anesthetized, ventilated, adult mongrel dogs were bled into a pressurized bottle system to reduce and maintain mean arterial blood pressure at 100, 80, 60, or 40 mmHg (n = 5/group). Blood flow was measured prior to and 2, 5, 10, 15, and 25 min posthemorrhage. Adrenal medullary blood flow increased markedly (100-400%) at all levels of hemorrhage. In contrast, decreases in cortical blood flow were observed (approximately 50%) with hemorrhage to 80, 60, and 40 mmHg. Cortical blood flow returned to control levels at 25 min, except in the 40-mmHg group. Whole adrenal gland blood flow showed early, transient decreases, consistent with the fact that the adrenal cortex comprises the bulk of the gland, but it did not precisely reflect either cortical or medullary blood flow changes. Since this method for measuring adrenal medullary and cortical blood flow was developed for the current experiment, extensive evaluation of the technique was performed (n = 31 animals). These studies included demonstration that injection of 4 X 10(6) microspheres results in sufficient numbers of microspheres in the adrenal medulla and cortex to permit estimation of blood flow (greater than or equal to 400 spheres/sample), that 15-micron spheres are almost completely entrapped in the adrenal gland (greater than 98%), that multiple injections of microspheres (n = 5) do not alter blood flow, and that streaming of microspheres does not appear to occur to any significant extent in this vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of heart rate on extracellular [K+] accumulation during myocardial ischemia
Authors: Weiss J. , Shine K. I.
Published: December 2017

The effect of heart rate on extracellular [K+] ([K+]o) accumulation during total global ischemia was investigated in the isolated arterially perfused (37 degrees C) rabbit interventricular septum using intramyocardial K+-sensitive electrodes (tip diameter, 0.3 mm) and intracellular microelectrodes. The heart rates tested were 0, 25, 75, 125, and 150 beats/min in aqueous-perfused septa and 25, 75, and 125 beats/min in blood-perfused septa. In the lower range of heart rates (0-75 beats/min) the rate and magnitude of [K+]o accumulation during 10 min of ischemia were markedly rate dependent, but in the higher range of rates (75-150 beats/min) the rate dependence was markedly attenuated in both aqueous and blood-perfused preparations. The latter finding could be largely attributed to the more rapid shortening of the action potential duration during ischemia at the higher rates and demonstrates that the amount of time the myocardium spends in the depolarized state is an important determinant of the rate of cellular K+ loss during ischemia. Progressive shortening of the action potential duration during ischemia is also a major factor determining the onset of the plateau phase of [K+]o accumulation. The findings help to resolve previous conflicting reports on the effects of heart rate on [K+]o accumulation during ischemia.
Effects of circulating catecholamines on hepatic blood volume in anesthetized cats
Authors: Greenway C. V. , Dettman R. , Burczynski F. , Sitar D. S.
Published: December 2017

Arterial and portal norepinephrine and epinephrine levels, and hepatic blood volumes were measured in cats anesthetized with pentobarbital sodium to determine the basal levels after surgery and adrenalectomy in comparison with levels during intravenous infusions of norepinephrine and epinephrine that produced hepatic venoconstriction. In addition, the hypothesis that norepinephrine released into portal blood during mesenteric nerve stimulation might produce hepatic venous responses was tested. No epinephrine was detected in any plasma samples except during intravenous epinephrine infusions. Surgery did not increase, and adrenalectomy did not decrease, the basal norepinephrine levels measured after anesthesia (0.8 +/- 0.1 ng/ml). These basal levels were below the minimal levels required to produce hepatic venous responses. Equal plasma levels of norepinephrine and epinephrine produced similar hepatic venous responses and maximal responses required increases in plasma levels of 100 times the basal levels. Stimulation of mesenteric nerves at 2 Hz produced no change in portal norepinephrine levels, whereas at 8 Hz it produced a doubling of these levels. No significant changes in hepatic volume occurred. It is concluded that although basal levels of circulating catecholamines may reflect overall sympathetic nervous activity, they are not high enough to produce hepatic venous responses. Sympathetic control of the hepatic venous bed is mediated through the hepatic innervation, and circulating catecholamines play at most a minor role.
Vascular hyperresponsiveness in perfused lungs from monocrotaline-treated rats
Authors: Gillespie M. N. , Olson J. W. , Reinsel C. N. , O'Connor W. N. , Altiere R. J.
Published: December 2017

Studies were conducted in isolated, buffer-perfused lungs to determine whether altered pulmonary vascular responsiveness could contribute to the evolution of monocrotaline (MCT)-induced pulmonary hypertension. Adult male rats were given a single subcutaneous injection of either 105 mg/kg MCT or its vehicle and vascular responsiveness to angiotensin II, ventilatory hypoxia (3% O2), and KCl was assessed in isolated, buffer-perfused lungs at 4, 7, and 14 days post-treatment. Relative to preparations derived from control animals, vasopressor responses induced by 0.1 microgram, but not 0.05 microgram angiotensin, were augmented at 4 and 7 days but not at 14 days post MCT. Pulmonary vasoconstriction evoked by hypoxic ventilation was enhanced at 4 days but not at 7 or 14 days posttreatment. Pressor responses induced by 30 and 45 mg KCl were not different in treated animals relative to controls at any time post-MCT administration. MCT provoked perivascular edema, but this factor did not seem to contribute to vascular hyperresponsiveness, since the time course of edema did not parallel the time course of augmented responsiveness. Results of the present study indicate that MCT, by an unknown mechanism, causes an early and transient increase in pulmonary vascular responsiveness to some but not all vasoconstrictors. Because the enhanced responsiveness occurred prior to development of pulmonary hypertension, it is unlikely that this alteration contributes to the sustained elevation in pulmonary arterial pressure.
Gated in vivo examination of cardiac metabolites with 31P nuclear magnetic resonance
Authors: Kantor H. L. , Briggs R. W. , Metz K. R. , Balaban R. S.
Published: December 2017

Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy was used to study the temporal aspects of metabolism of canine heart in vivo. An NMR catheter coil was passed through the jugular vein of a dog into the apex of the right ventricle, and spectra were recorded at four points in the cardiac cycle by triggering from the blood pressure trace of the animal. The 31P spin-lattice relaxation times of phosphocreatine (PC) and the gamma-, alpha-, and beta-phosphates of ATP at 1.89 Tesla are 4.4, 1.8, 1.7, and 1.6 s, respectively. The ratio of PC to ATP is 2.0. No changes in PC/ATP were noted in any of the four portions of the cardiac cycle examined, and difference spectra exhibited no observable signals, in contrast to previously reported results for glucose-perfused rat hearts. On the assumption that intracellular pH and the total creatine pool were constant, the equilibrium expression for the creatine kinase reaction was used to deduce that free ADP concentrations were invariant throughout the cardiac cycle. This is in apparent disagreement with the proposed regulatory role for ADP in heart oxidative phosphorylation.
Cold-induced vasodilatation in isolated, perfused rat tail artery
Authors: Gardner C. A. , Webb R. C.
Published: December 2017

This study characterizes an in vitro model of the "hunting response" (cold-induced vasoconstriction and vasodilatation). Two-centimeter segments of rat tail arteries (n = 15) were placed in a muscle bath (37 degrees C) and perfused (37 degrees C) at constant pressure (50 mmHg; flow = 14.5 +/- 0.8 ml/min) with physiological salt solution. Arteries constricted (23.7 +/- 2.8% decrease in flow) in response to activation of adrenergic nerves by electrical stimulation (9 V, 0.1-1.0 Hz, 0.1-4 ms). Cooling the bath to 4-12 degrees C (perfusate = 37 degrees C) caused further flow reduction (0-0.5 ml/min) in 14 arteries. After 20-40 min, 12 arteries dilated (7.4 +/- 1.2 ml/min) followed by constriction in 5-10 min. Typically, flow oscillated between periods of prolonged low flow and brief periods of high flow. Phentolamine (10(-6) M in bath) and acute adrenergic denervation blocked flow changes caused by decreased bath temperature. In unstimulated arteries, exogenous norepinephrine (6 X 10(-8) M in bath) decreased flow by 20%. On cooling (7-10 degrees C) flow decreased to zero, but did not oscillate. These results are consistent with the hypothesis that cold-induced vasoconstriction is caused by augmented smooth muscle responsiveness to norepinephrine, whereas cold-induced vasodilatation is caused by a cessation of transmitter release from adrenergic nerve endings.
A nimodipine-resistant Ca2+ pathway is involved in myogenic tone in a resistance artery
Authors: Hwa J. J. , Bevan J. A.
Published: December 2017

After stretch, tone develops in ring segments of rabbit ear resistance arteries (75-150 micron unstretched lumen diam). This is myogenic tone, since it is not dependent on the presence of sympathetic nerves, endothelial cells, or the local release of any known vasoactive autacoids. It is sensitive to the extracellular Ca2+ concentration, and disappears in a low Ca2+ (25 microM) environment. Tone is restored immediately on the reintroduction of Ca2+ (0.1-1.6 mM). High K+-induced tone in these resistance arteries is also extracellular Ca2+-dependent. The Ca2+ ED50 of this tone is 2.45 X 10(-4) M, which is significantly lower than that for myogenic tone (Ca2+ ED50; 8.31 X 10(-4) M). Both tone moieties are influenced by inorganic Ca2+ antagonists (Mn2+ and Mg2+) and some organic Ca2+ antagonists (verapamil and diltiazem). Among all the Ca2+ antagonists studied, only Mn2+ completely inhibits myogenic tone. In contrast, myogenic tone is resistant to nimodipine (up to 10(-6) M), the most potent Ca2+ antagonist of K+-induced contraction (ID50; 1.0 X 10(-9) M). Other 1,4-dihydropyridine Ca2+ antagonists such as nifedipine and (-)-PN 200-110 selectively antagonize K+-induced contractions, whereas they do not affect the development and the maintenance of myogenic tone. The fact that the (+)-enantiomer of PN 200-110 does not have an inhibitory effect proves that the 1,4-DHP site is stereospecific. These results indicate that extracellular Ca2+ is essential for both stretch-dependent (myogenic) and K+-induced tone, and the Ca2+ entry pathways for the two tone moieties are differently influenced by dihydropyridines.
Changes in K+ currents induced by Ba2+ in guinea pig ventricular muscles
Authors: Hirano Y. , Hiraoka M.
Published: December 2017

Effects of Ba2+ on the K+ currents of guinea pig ventricular muscle were studied using the single sucrose-gap voltage-clamp technique. Ba2+ decreased the late (1- or 2-s) current at any potential level, with stronger suppression in the slope conductance at resting potential level than at depolarized voltages above 0 mV. During depolarizing pulses beyond -40 mV, Ba2+ reduced both the time-dependent and time-independent current components, indicating suppression of both outward and background K+ currents (IK and IK1, respectively), whereas tail currents after repolarization to -40 mV increased, with their time courses having double exponentials. These apparent conflicting results between IK and the tail current could not be explained by extracellular K+ fluctuation, because 20 mM Cs+ alone depressed both factors, but an additional application of Ba2+ caused an increase in both components compared with those in the former condition. On hyperpolarization below -60 mV, a time-dependent decrease in the inward current was observed after Ba2+ application without an activation of If. The decrease was stronger and faster at negative potential levels. These results are compatible with a time- and voltage-dependent blocking action of Ba2+ on the inward rectifier K+ current reported in other cardiac and noncardiac tissues. In two components of the tail currents after repolarization from depolarizing voltage steps during Ba2+ application, the faster one can probably be attributed to this blocking action of IK1, whereas the slower one can be attributed to the deactivation of IK. This time-dependent component of IK1 may contribute to the generation of Ba2+-induced automaticity at the depolarized state.
Ventricular suction under zero source pressure for filling
Authors: Suga H. , Goto Y. , Igarashi Y. , Yamada O. , Nozawa T. , Yasumura Y.
Published: December 2017

We quantified ventricular suction flow, volume, and pressure under hydrostatically zero source pressure for filling. A large-bore electromagnetic flow probe was placed in the valve-free mitral annulus of the dog heart that had been excised and was cross circulated with the left atrium widely opened. With the heart immersed in a blood pool, ventricular suction flow and transmural pressure were measured. After a rapid ejection flow [peak: 110 +/- 47 (SD) ml . s-1 . 100 g left ventricle-1] during systole, a slow suction flow (peak: 26 +/- 20 ml . s-1 . 100 g-1) occurred during diastole despite the zero source pressure for filling. Peak transmural pressure during ejection was 6 +/- 3 mmHg, and peak negative transmural pressure during suction was 2 +/- 1 mmHg. Suction volume, which was equal to ejection volume in steady state, was 8 +/- 3 ml/100 g left ventricle. Increases in paced heart rate markedly decreased suction volume by curtailing diastolic filling time. Epinephrine, propranolol, calcium, and verapamil variably changed suction volume, and these effects were primarily accounted for by the accompanied heart rate changes.
Significance of production of peptide leukotrienes in murine traumatic shock
Authors: Craft D. V. , Lefer D. J. , Hock C. E. , Lefer A. M.
Published: December 2017

We studied the formation of a leukotriene metabolite in plasma and bile during traumatic shock. Anesthetized rats subjected to Noble-Collip drum trauma developed a lethal shock state characterized by a survival time of 1.9 +/- 0.3 h, a 4.5-fold increase in plasma cathepsin D activity, and a reduction in mean arterial blood pressure to 45 +/- 2 mmHg compared with 108 +/- 5 mmHg in sham-shock controls. Plasma and bile samples were analyzed by reverse-phase high-pressure liquid chromatography (HPLC) for peptide leukotrienes (e.g., LTC4, LTD4, and LTE4), and their retention times were confirmed by co-elution with radioactive standards, radioimmunoassay (RIA), and UV spectrophotometry. No leukotrienes or metabolites were found in plasma. The major peptide leukotriene from bile was eluted between LTC4 and LTD4 and corresponds to a metabolite of LTE4, N-acetyl-LTE4, which is also produced during endotoxin shock. The metabolite increased nearly sevenfold in traumatic shock compared with sham trauma. The identity of the metabolite was confirmed by UV scan, which revealed a spectrum consistent with a peptide leukotriene and similar to that of previously reported spectra for N-acetyl-LTE4. In conclusion, peptide leukotrienes are rapidly cleared from the blood and appear in the bile as N-acetyl-LTE4, a metabolite of the peptide leukotrienes. These findings support a role of the peptide leukotrienes in the pathogenesis of traumatic shock.
Accumulation of polymorphonuclear leukocytes during 3-h experimental myocardial ischemia
Authors: Engler R. L. , Dahlgren M. D. , Peterson M. A. , Dobbs A. , Schmid-Schonbein G. W.
Published: December 2017

Recent evidence indicates that mechanical obstruction of capillaries by leukocytes plays an important role in the "no-reflow" phenomenon in the heart. This entrapment of leukocytes in the microcirculation precedes their recognized role in an inflammatory reaction following ischemia. It is a fundamental rheological mechanism that may be associated with ischemic injury and reflow injury and it has not been elucidated. To explore the accumulation of granulocytes during myocardial ischemia we studied the accumulation of 111Inlabeled autologous granulocytes in acutely ischemic myocardium during 3 h of flow reduction with and without a subsequent period of reflow in open-chest dogs. Granulocytes accumulated in the ischemic endocardium of all animals and, for the majority of dogs, also in the epicardium. Accumulation in the endocardium was enhanced by reperfusion. The entrapped leukocytes may have an influence on the increase in resistance, since regional accumulation of leukocytes in the endocardium inversely correlated with ischemic blood flow during 3 h of ischemia. The tissue water content measured from the wet and dry weights of biopsies showed a significant positive correlation with the number of entrapped granulocytes. These results suggest that collateral flow is an important mechanism of leukocyte arrival early in ischemic myocardium and that reperfusion enhances granulocyte accumulation.
Validation of optional elastance-resistance left ventricle pump models
Authors: Campbell K. B. , Ringo J. A. , Knowlen G. G. , Kirkpatrick R. D. , Schmidt S. L.
Published: December 2017

Left ventricular pressure, P(t), and outflow Q(t), data were collected in anesthetized, open-chest rats and dogs. The data were used in a three-tiered validation procedure to evaluate 14 competing forms of elastance [E(t)]-resistance (R) left ventricle (LV) pump models. Competing models arose from considering two forms of parameterization of E(t), time variation versus no time variation in LV unstretched volume (Vd) and dependence versus no dependence of R on P(t) and isovolumic P(t). A descriptive test based on the normalized root-mean-square errors in the fit to P and, separately, in the fit to Q was used to distinguish between models. The best of the competing models was the one that treated Vd as a function of time and R as a constant. Models of this form fitted the data very well and were said to be descriptively valid. The best of the competing models were then asked to predict the observed responses to changes in afterload, preload, and prior-beat history. The models did not predict these conditions well and failed to pass the test for predictive validity. Additionally, the model parameters were judged not to represent their supposed physical homologs and, thus, failed the test for explanative validity. One cause for E(t)-R model failure was an inadequate representation of events at end systole. This deficiency was apparently due to not accounting for deactivation in the model. Other features may also be needed before a comprehensive LV model can be formulated. Identical conclusions were made from data from the rat and the dog.
Cardiac function and chronotropic sensitivity to beta-adrenergic stimulation in sepsis
Authors: Smith L. W. , Winbery S. L. , Barker L. A. , McDonough K. H.
Published: December 2017

An organism's cardiovascular response to sepsis is at least partly dependent on hormonal and neural modulation of myocardial function. We have investigated both intrinsic myocardial performance and one aspect of myocardial sensitivity to beta-adrenergic stimulation in a model of sepsis in which animals, at the time studied, exhibited bacteremia, normal arterial blood pressure and cardiac output, elevated heart rate, and elevated plasma catecholamines. Intrinsic myocardial contractile function, studied with the isolated, perfused working heart preparation, was depressed over a range of preloads in septic animals, whereas heart rate was elevated. To determine whether hearts from septic animals could respond normally to beta-adrenergic stimulation, we studied chronotropic responses to isoproterenol in both Langendorff perfused hearts and in isolated right atria. In langendorff perfused hearts from septic animals, basal rates were significantly increased and lower concentrations of isoproterenol elicited greater increases in heart rate. In isolated right atria from septic animals, basal rates were also elevated and the EC50 for the chronotropic response to isoproterenol was significantly less than in atria from control animals. The maximal heart rate response to isoproterenol was not significantly different from control. These results indicate that in sepsis, despite apparently adequate in vivo cardiac performance, intrinsic myocardial function is depressed, but chronotropic sensitivity to beta-adrenergic stimulation is increased.
Naloxone fails to reverse hemorrhagic hypotension
Authors: Brown D. F. , Burr R. E.
Published: December 2017

The effect of opiate antagonist therapy with naloxone on hemorrhagic shock was examined. An equivalent intravenous bolus of naloxone or normal saline had the same pressor effect in conscious, unrestrained, hypovolemic hypotensive rats. The proposal that opiate antagonists are of therapeutic value in the treatment of hemorrhage is questioned.
Modulation of synchrony of left ventricular contraction by regional adrenergic stimulation in conscious dogs
Authors: Gwirtz P. A. , Franklin D. , Mass H. J.
Published: December 2017

The sympathetic innervation of the left ventricle provides a potential mechanism for modulation of synchrony of myocardial contraction. Dogs were instrumented to measure left ventricular pressure and segment length in the posterior region of the left ventricle perfused by the circumflex artery (PSL) and in an anterior region perfused by the anterior descending artery (ASL). Norepinephrine (NE) was injected into the circumflex artery using an indwelling catheter in bolus doses sufficient to produce no direct systemic effects. Intracoronary injection of NE resulted in significant increases in percent segment shortening and mean shortening velocity in the PSL. Duration of shortening in the PSL was significantly reduced. Percent shortening, velocity of shortening, and shortening duration in the ASL were unchanged. While there was no change in left ventricular systolic pressure, +dP/dtmax and -dP/dt min increased with intracoronary NE. These results demonstrate alterations in the synchrony of myocardial contraction following regional myocardial stimulation with intracoronary injections of NE at doses within the expected physiological range and suggest that activation of localized sympathetic neural pathways may result in problems involving mechanical performance of the heart.
Platelets reduce coronary microvascular permeability to macromolecules
Authors: McDonagh P. F.
Published: December 2017

Several studies in organs other than the heart suggest that platelets play a role in maintenance of microvascular integrity. In an earlier study, we reported that coronary microvascular permeability to macromolecules was reduced when blood cells were added to a Krebs-albumin perfusate. At that time, we could not differentiate the contributions made by red cells and platelets. To examine the specific role of platelets in the cell effect, isolated rat hearts were perfused with a mixture of Krebs, albumin [2 g/100 ml bovine serum albumin (BSA)], and rat plasma that was either rich in platelets (PRP) or poor in platelets (PPP). For the nine PRP hearts studied, the perfusate contained an average of 10(4) platelets/microliter. For the nine PPP hearts, the perfusate contained 5 X 10(1) platelets/microliter. The left ventricular epicardial microcirculation was observed directly using intravital fluorescence microscopy, and coronary microvascular permeability to macromolecules was assessed by monitoring the transcoronary extravasation of fluorescent albumin (FITC-BSA). We found that the measure of transcoronary FITC-BSA extravasation, the (O/I) ratio, was 0.57 +/- 0.02 (n = 70 fields) for the PPP perfused hearts and 0.47 +/- 0.02 (n = 70) for the PRP hearts (P less than 0.05). The value for the PRP group was similar to that observed earlier with the red cell perfusate (0.45 +/- 0.02). These findings support the concept that platelets help maintain the normal semipermeable membrane characteristics of the coronary exchange vessels.
Vagally induced hyperpolarization in atrioventricular node
Authors: Mazgalev T. , Dreifus L. S. , Michelson E. L. , Pelleg A.
Published: December 2017

The effects of postganglionic vagal stimulation on atrioventricular nodal conduction were studied in 12 rabbit atrial-atrioventricular nodal preparations. Vagal stimulation was introduced in the sinus and atrioventricular nodes, separately or in combination, using single bursts of subthreshold stimuli. The sinus cycle length was scanned to identify the phasic effect of vagal stimulation. Action potentials from cells in the AN, N, and NH regions of the atrioventricular node were recorded by microelectrode techniques. Vagally induced hyperpolarization of cells in the atrioventricular node resulted in a phase-dependent prolongation of conduction time and reflected the level of residual hyperpolarization at the moment of arrival of the next atrial beat at the atrioventricular nodal input region. Vagally induced hyperpolarization was membrane potential dependent, although its overall time course was similar at different phases. Increased diastolic depolarization followed the maximal hyperpolarization. This "rebound" observed at certain phases was responsible for paradoxical shortening of the conduction time after vagal stimulation. The predominant effects of local vagal stimulation in the atrioventricular node were observed in cells in or near the N region. Slower rate of rise, shorter amplitude and duration, as well as step formations were among the changes in action potentials recorded from these cells. The effects of vagal stimulation were inhomogeneous between different regions of the atrioventricular node as well as within the N region, producing alternative pathways of conduction and the potential for reentry. The concomitant changes in sinus cycle length resulting from vagal stimulation in the sinus node region altered the phasic effects of vagal stimulation introduced in the atrioventricular node. This was related to a direct influence of the prolonged sinus cycle length on atrioventricular nodal refractoriness as well as an indirect effect on the degree of residual vagally induced hyperpolarization at the moment of arrival of the delayed atrial beat. These findings provide mechanistic explanations for the complex effects of vagal stimulation on atrioventricular nodal conduction.
Acetylcholine activation of K+ channels in cell-free membrane of atrial cells
Authors: Kurachi Y. , Nakajima T. , Sugimoto T.
Published: December 2017

The activation mechanisms of K+ channels by muscarinic acetylcholine (m-ACh) receptors were examined in isolated atrial cells by use of patch-recording technique. In "cell-attached" patch recordings, ACh, present in the pipette, activated an inwardly rectifying K+ channel. In "inside-out" patches, activation of the K+ channel by ACh diminished with time following excision of the patch, but it resumed when GTP was present in the solution bathing the intracellular side of the membrane. The A protomer of pertussis toxin, together with NAD, inhibited the channel activation in the presence of GTP. Since pertussis toxin specifically ADP-ribosylates GTP-binding proteins Ni and No, which can interact with m-ACh receptors, and inhibits their functions, it was concluded that m-ACh receptors communicate with the K+ channel via GTP-binding proteins, probably Ni and/or No, in atrial cell membrane.