bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial exclusion of albumin in rat dermis and subcutis in over- and dehydration
Authors: Reed R. K. , Lepsoe S. , Wiig H.
Published: December 2017

We have estimated exclusion of albumin from the interstitial matrix in rats based on measurement of albumin concentration in interstitial fluid, interstitial fluid volume (IFV), and interstitial albumin mass. Measurements were performed separately in dermis and subcutis during control, overhydration (saline infusion corresponding to 10% of body weight), and dehydration. Exclusion during control was 1.03 (SD = 0.47; n = 7 rats) and 0.85 (SD = 0.21; n = 7 rats) ml/g fat-free dry wt in subcutis and dermis, respectively. This corresponded to 44.1 and 57.8% of IFV, respectively. Collagen and hyaluronan were responsible for two-thirds and one-third of the exclusion, respectively. During overhydration the increase in albumin available volume was 70% of the increase in IFV. Both the collagen and the hyaluronan excluded compartment of the excluded volume changed when altering IFV. These data suggest that the colloid osmotic pressure in the albumin available compartment can change the volume of both the collagen and hyaluronan compartments of the excluded volume. The following changes in composition of the interstitial matrix were observed: albumin mass in subcutis decreased by 20% during dehydration and increased by 30% during overhydration, and overhydration reduced hyaluronan content by 20% in subcutis.
Cyclooxygenase inhibition potentiates myogenic activity in skeletal muscle arterioles
Authors: Hill M. A. , Davis M. J. , Meininger G. A.
Published: December 2017

The proposition that arteriolar constriction to increased intravascular pressure is mediated through either the increased local production of an eicosanoid constrictor factor or decreased production of a dilating factor was examined. The myogenic response of arterioles was studied by enclosing anesthetized rats in an airtight Plexiglas box with the cremaster muscle exteriorized into a tissue bath containing Krebs solution. Microvascular responses were observed by video microscopy. The arteriolar response to a 20-mmHg increase in intravascular pressure was examined in the absence or presence of cyclooxygenase inhibition. In the absence of cyclooxygenase inhibition, second-order arterioles (2As) responded passively to increased pressure by distending to 107 +/- 1% of control diameter. In the presence of the indomethacin, 2As constricted to 79 +/- 5% of control. Third-order arterioles (3As) constricted to 47 +/- 8% of control without indomethacin and similarly to 33 +/- 4% with indomethacin. To test whether inhibitors of endothelium-derived relaxation factor would potentiate the myogenic response of 3As, methylene blue or gossypol was topically applied to the cremaster muscle. Neither inhibitor was found to augment the myogenic vasoconstriction; however, these inhibitors were observed to significantly reduce basal vascular tone. In comparison, the tonic local production of dilating prostaglandins appears to attenuate myogenic activity as demonstrated by the appearance of myogenic activity in the normally passive 2As when exposed to cyclooxygenase inhibitors.
Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction
Authors: Litwin S. E. , Raya T. E. , Gay R. G. , Bedotto J. B. , Bahl J. J. , Anderson P. G. , Goldman S. , Bressler R.
Published: December 2017

This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mg.kg-1.day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increased, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.
Baroreflex attenuates pressor response to graded muscle ischemia in exercising dogs
Authors: Sheriff D. D. , O'Leary D. S. , Scher A. M. , Rowell L. B.
Published: December 2017

Graded reductions in hindlimb perfusion in dogs exercising at 2 miles/h (0% grade) elicited reflex pressor responses by what is referred to as the “muscle chemoreflex.” To determine the extent to which arterial baroreceptor reflexes oppose the muscle chemoreflex, we elicited pressor responses to muscle ischemia before and after chronic surgical denervation of the arterial baroreceptors. The muscle chemoreflex showed a threshold beyond which systemic pressure rose approximately 3 mmHg for each 1-mmHg decrease in hindlimb perfusion pressure when the arterial baroreceptors were intact. Arterial baroreceptor denervation approximately doubled the pressor responses, i.e., systemic pressure rose by approximately 6 mmHg for each 1-mmHg fall in hindlimb perfusion pressure, without alteration in threshold. We conclude that during mild dynamic exercise, the arterial baroreflexes oppose the pressor response to graded reductions in hindlimb perfusion, reducing it by approximately 50%. When unopposed by the arterial baroreflexes the muscle chemoreflex exhibits a gain (ratio of change in systemic pressure to change in hindlimb perfusion pressure) of approximately -6; thus this reflex can correct by 85% the decrease in muscle perfusion pressure caused by partial vascular occlusion.
Force measurements from voltage-clamped guinea pig ventricular myocytes
Authors: Shepherd N. , Vornanen M. , Isenberg G.
Published: December 2017

We describe the first observations of isolated mammalian guinea pig ventricular myocytes that combine measurements of contractile force with the voltage-clamp method. The myocytes were attached by poly-L-lysine to the beveled ends of a pair of thin glass rods having a compliance of 0.76 m/N. The contractile force of a cell caused a 1- to 3-microm displacement of the rods; the motion of which was converted to an output voltage by phototransistors. By the use of the whole cell patch-clamp technique, the cells were depolarized at 1 Hz with 200-ms-long clamp pulses from -45 to +5 mV (35 degrees C, 3.6 mM CaCl2). Isometric force began after a latency of 7 +/- 2 ms, peaked at 93 +/- 21 ms, and relaxed (90%) at 235 +/- 63 ms. The time course of force was always faster than that of isotonic shortening (time to peak 154 +/- 18 ms). With 400-ms-long depolarizations, a tonic component was recorded as either sustained force or sustained shortening that decayed on repolarization. Substitution of Ca by Sr in the bath increased the inward current through Ca channels but slowed down the time course of force development. The results are consistent with the hypothesis that activator calcium derives mainly from internal stores and that Ca release needs Ca entry through channels.
Calcium release from cardiac sarcoplasmic reticulum induced by photorelease of calcium or Ins(1,4,5)P3
Authors: Kentish J. C. , Barsotti R. J. , Lea T. J. , Mulligan I. P. , Patel J. R. , Ferenczi M. A.
Published: December 2017

The ability of Ca2+ or inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to release Ca2+ from cardiac sarcoplasmic reticulum (SR) was investigated using saponin-skinned ventricular trabeculae from rats. To overcome diffusion delays, rapid increases in the concentrations of Ca2+ and Ins(1,4,5)P3 were produced by laser photolysis of “caged Ca2+” (Nitr-5) and “caged Ins(1,4,5)P3”. Photolysis of Nitr-5 to produce a small jump in [Ca2+] from pCa 6.8 to 6.4 induced a large and rapid force response (t1/2 = 0.89 s at 12 degrees C); the source of the Ca2+ that activated the myofibrils was judged to be the SR, since it was blocked by 0.1 mM ryanodine or 5 mM caffeine. A smaller, slower, and less consistent release of SR Ca2+ was produced by photorelease of Ins(1,4,5)P3. The results demonstrate that these caged compounds can be used to study excitation-contraction coupling in skinned multicellular preparations of cardiac muscle. The data are consistent with a major role for Ca2(+)-induced Ca2+ release in cardiac activation, whereas the role for Ins(1,4,5)P3 may be to modulate, rather than directly stimulate, SR Ca2+ release.
Electrogenic Na(+)-K+ pump in Purkinje myocytes isolated from control noninfarcted and infarcted hearts
Authors: Boyden P. A. , Dresdner K. P.
Published: December 2017

We combined a method of Na+ loading (zero K+ exposure) with voltage-clamp techniques to determine whether malfunctioning of the Na(+)-K+ pump underlies the abnormalities in the resting potential and the repolarization process observed in subendocardial Purkinje cells dispersed from the canine infarcted ventricle (IZPCs) 24 h after coronary artery occlusion. Stimulation of the transient outward current (ipump) was produced by a 3-min exposure to zero K+ and then reexposure to 4 mM K+ Tyrode solution. We compared the properties of ipump in IZPCs to ipump in Purkinje cells dispersed from fiber strands (SPCs) or from the subendocardium of the normal hearts (NZPCs). For the holding potentials (mean values: SPC, -33 +/- 7; NZPC, -33 +/- 5; and IZPC, -35 +/- 4 mV), the time constant (tau) of ipump in IZPCs (55 +/- 18 s) was not significantly different (P greater than 0.05) from tau in SPCs (55 +/- 10 s) or NZPCs (57 +/- 11 s). Peak ipump (Imax) and total charge transfer (Q) in IZPCs were not different from control. In SPCs and NZPCs, there was an increase in Imax and Q when zero K+ exposure was prolonged to 6-8 min, whereas in some IZPCs, the increase in Imax or Q was smaller. We conclude that the Na(+)-K+ pump current kinetics are not altered in IZPCs compared with control. Thus the persistent electrophysiological abnormalities in IZPCs that can still be observed after single cell isolation (Boyden, P. A., A. Albala, and K. Dresdner. Circ. Res. 65: 955-970, 1989) are not explained by an alteration in the function of the Na(+)-K+ pump.
Systemic hemodynamic effects of endothelin in rats
Authors: King A. J. , Pfeffer J. M. , Pfeffer M. A. , Brenner B. M.
Published: December 2017

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.
Ischemia and reperfusion increase 125I-labeled endothelin-1 binding in rat cardiac membranes
Authors: Liu J. , Chen R. , Casley D. J. , Nayler W. G.
Published: December 2017

The effect of aerobic perfusion, of up to 90 min global ischemia, and of reperfusion on 125I-labeled porcine endothelin (125I-ET-1) binding site density (Bmax), affinity (KD), and selectivity was investigated using cardiac membranes harvested from adult Sprague-Dawley rats. Membranes from nonperfused hearts bound 125I-ET-1 with a Bmax of 117.0 +/- 8.8 fmol/mg protein, a KD of 0.076 +/- 0.005 nM, and a Hill coefficient approaching unity. Neither aerobic perfusion nor 10 min of normothermic ischemia and subsequent reperfusion altered these binding parameters. The extension of the ischemic episode increased Bmax (23, 32, 62, and 60% increase after 20, 30, 60, and 90 min ischemia, respectively). Reperfusion further increased Bmax (P less than 0.01 at 15 min reperfusion after 20 and 30 min ischemia, and after 30 min reperfusion following 60 min ischemia) without changing selectivity. Affinity was reduced after 60 (P less than 0.05) and 90 (P less than 0.01) min ischemia. Ischemia at 22 degrees C had no effect on the density or affinity of these binding sites.
Endothelium regulates skeletal muscle microcirculation by a blood flow velocity-sensing mechanism
Authors: Koller A. , Kaley G.
Published: December 2017

In rat cremaster muscle, utilizing parallel arteriolar occlusion, we found that an increase in red blood cell (RBC) velocity (3.5-26.5 mm/s) per se induced an increase in diameter (1.5-9.4 microns) of arterioles (mean control diam 21.5 +/- 0.6 microns; n = 25). The dilation of arterioles appeared only when RBC velocity increased and started always with a delay (mean 8.4 +/- 0.5 s) after the increase in flow velocity. A positive linear correlation was found between peak changes in RBC velocity and diameter (r = 0.87, P less than 0.05). The velocity sensor as well as the mechanism(s) that mediates this response is likely to be located in endothelial cells, because the dilation to increased RBC velocity was completely eliminated after impairment of arteriolar endothelium with light-dye (L-D) treatment. The in vivo demonstration of this phenomenon in arterioles suggests the existence of a new endothelium-dependent, flow velocity-sensitive mechanism for the regulation of blood flow in the microcirculation.
Cardiac electrical responses to vagal stimulation of fibers to discrete cardiac regions
Authors: Furukawa Y. , Wallick D. W. , Carlson M. D. , Martin P. J.
Published: December 2017

We stimulated regional intracardiac parasympathetic nerve fibers to the atrioventricular (AV) nodal area (AVP stimuli) or to the sinoatrial (SA) nodal area (SAP stimuli) in autonomically decentralized, anesthetized dogs. AVP stimuli increased the AV interval (AV conduction time); the magnitude of the response depended directly on the stimulation frequency. AVP stimuli did not alter the atrial interval (heart period) in spontaneously beating hearts. The magnitude of the negative dromotropic response increased when the atrial interval was shortened. SAP stimuli increased the atrial interval, and the magnitude of the response depended directly on the stimulation frequency. SAP stimuli evoked little or no change in the AV interval in the unpaced heart. When the atrium was paced, SAP stimuli did not change the AV interval in about half of the preparations, and there was a small but significant change in the remaining preparations. The negative dromotropic or chronotropic response to AVP or SAP stimuli was potentiated by physostigmine and blocked by atropine. These results suggest that 1) AVP stimuli induce a selective negative dromotropic response, and 2) this negative dromotropic effect is secondarily affected by heart period, by the pacemaking site, and by atrial activation patterns, but it does not affect the sinus cycle length in the dog heart.
Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity
Authors: Griffith T. M. , Edwards D. H.
Published: December 2017

The influence of basal endothelium-derived relaxing factor (EDRF) activity on autoregulation was studied under conditions of controlled-flow and controlled-pressure perfusion in the isolated rabbit ear, a weakly autoregulating vascular bed. Hemoglobin and NG-monomethyl-L-arginine were used to inhibit EDRF activity, and in some experiments resting tone was increased by serotonin. The diameters of five generations of resistance arteries (ranging from 70 to 1,000 microns in size) were measured at different flow rates by X-ray microangiography. Diameter-flow (D-Q) relationships were correlated with pressure-flow (P-Q) and conductance-flow (G-Q) relationships. In the presence of EDRF activity no autoregulation was observed, P-Q relationships being linear and G-Q and D-Q relationships common both to controlled-flow and to controlled-pressure modes of perfusion. After inhibition of EDRF activity in constricted preparations, P-Q relationships became sigmoidal in shape in controlled-pressure perfusion mode, reflecting a range of perfusion pressures/flow rates over which they were able to "autoregulate" flow. Over this autoregulatory range the corresponding G-Q and D-Q relationships exhibited regions of negative slope. Autoregulation was not observed in controlled-flow perfusion mode even in the absence of EDRF activity. The findings imply that flow- or pressure-dependent constriction can mediate autoregulation in controlled-pressure mode when not overridden by basal EDRF activity, as normally appears to be the case in these preparations. Differences in autoregulation in different organs may be inversely related to EDRF activity, which is known to differ between vascular beds.
A new method of sampling blood for measurement of plasma adenosine
Authors: Shryock J. C. , Boykin M. T. , Hill J. A. , Belardinelli L.
Published: December 2017

The half-life of adenosine in human blood is 1-2 s at 37 degrees C. To measure plasma adenosine concentration accurately, it is necessary to inhibit adenosine metabolism during transit of blood through the sampling catheter. We have tested a double-lumen catheter and a solution of compounds that inhibit adenosine metabolism (stop solution) for this purpose. Stop solution and radiolabeled adenosine were delivered via an inner lumen, mixed with blood at the catheter tip, and withdrawn to a collection syringe in an outer lumen. Extracellular recovery of label was 89 +/- 5% and proportional to the quantity of label added to blood. In contrast, when blood and radiolabel were mixed with stop solution in the collecting syringe only after passage through the catheter, recovery of radiolabel was 7 +/- 3%. The importance of inhibiting pathways of adenosine formation and degradation or uptake during transit of blood through the catheter was demonstrated. The results suggest that a double-lumen catheter and stop solution are both necessary and suitable for collection of human blood to determine the concentration of plasma adenosine.
Cocaine inhibits baroreflex control of blood pressure by actions at arterial baroreceptors
Authors: Andresen M. C. , Yang M. , Nelson S. H. , Steinsland O. S.
Published: December 2017

Blood pressure and heart rate often increase during cocaine intoxication, but the mechanisms of these cardiovascular responses are poorly understood. The most often suggested theories are central nervous system mechanisms involving the blockade of neuronal transmitter uptake. Cocaine also has potent local anesthetic properties, and in this study we tested the possible role of peripheral actions of cocaine at baroreceptor afferents. Single fiber baroreceptors were recorded using an in vitro preparation of the rat aortic arch. Diameter, pressure, and baroreceptor discharge were recorded. Cocaine perfused through the lumen of the aortic arch at a suprathreshold pressure reduced baroreceptor discharge within 90 s of entering the lumen of the aorta. Slow ramps of pressure elicited complete pressure- and diameter-discharge curves every 5 min. Beginning at about 1 microM, cocaine inhibited baroreceptor function; threshold increased, the maximum discharge decreased, and at 100 microM cocaine, all discharge ceased. The vasodilator nitroprusside or the alpha 1-adrenoreceptor antagonist prazosin did not affect baroreceptor responses to cocaine. In in vivo tests in rabbits, cocaine that perfused through a vascularly isolated carotid sinus reduced the slope of the baroreflex relationship between carotid sinus pressure and systemic mean arterial pressure. Significant depression of baroreceptor function was found at concentrations similar to the plasma cocaine levels measured in clinical studies. The local anesthetic properties of cocaine may be involved in baroreceptor effects. Our studies suggest a possible contributing role of a new site of action of cocaine outside the central nervous system. Compromise of baroreceptor reflexes could facilitate the development of serious cardiovascular complications associated with cocaine abuse.
cAMP attenuates autacoid release from endothelial cells: relation to internal calcium
Authors: Luckhoff A. , Mulsch A. , Busse R.
Published: December 2017

The effects of elevated levels of adenosine 3',5'-cyclic monophosphate (cAMP), in cultured endothelial cells from bovine aorta, on the ATP-induced increases in the intracellular free calcium concentration [( Ca2+]i) and the release of prostaglandin I2 (PGI2) and endothelium-derived relaxant factor (EDRF) were investigated. Endothelial cAMP production was assessed in terms of cAMP release in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine; this release was increased fivefold by isoproterenol (1 microM), 1.6-fold by isoproterenol (0.1 microM), and 1.5-fold by the stable PGI2 analogue iloprost (10 microM). [Ca2+]i, measured with the fluorescent probe indo-1, was increased by ATP (1 microM) from 150 +/- 20 (SE) to 410 +/- 50 nM. Neither isoproterenol nor iloprost changed [Ca2+]i in unstimulated cells, but they significantly reduced [Ca2+]i levels in the presence of ATP. Similar inhibitions of increases in [Ca2+]i as by iloprost and isoproterenol (0.1 microM) were evoked by dibutyryl-cAMP (100 microM). Release of PGI2 was enhanced from 3.9 +/- 0.5 to 34.6 +/- 6 ng.min-1.5 x 10(6) cells-1 by ATP (3 microM); in the presence of isoproterenol, the ATP-stimulated release was reversibly reduced to 18.1 +/- 4.9 ng/min. Release of EDRF was assayed in terms of its stimulatory action on purified soluble guanylate cyclase. EDRF release in the first minute after stimulation with ATP (10 microM) was significantly attenuated by isoproterenol from 32.3 +/- 4.8 to 23.0 +/- 4.6 nmol.min-1.mg-1 (activity of soluble guanylate cyclase).(ABSTRACT TRUNCATED AT 250 WORDS)
Prolonged renal sympathoinhibition following sustained elevation in arterial pressure
Authors: Kenney M. J. , Morgan D. A. , Mark A. L.
Published: December 2017

We tested the hypothesis that sustained elevations in mean arterial pressure (MAP) would produce an abbreviated suppression of renal sympathetic nerve activity (RSNA) in spontaneously hypertensive (SH) compared with Wistar-Kyoto (WKY) normotensive rats. For this purpose, we recorded RSNA during and after a 30-min elevation in MAP. Elevations in MAP (35-40 mmHg) induced by phenylephrine resulted in a suppression of RSNA in SH and WKY rats that persisted after MAP had returned to control levels. The prolonged suppression of RSNA was eliminated following sinoaortic denervation, indicating that this response was dependent on afferent baroreceptor mechanisms. The simultaneous recording of RSNA and aortic depressor nerve (ADN) activity provided additional evidence that baroreceptor afferents contribute to this prolonged suppression of RSNA in SH rats. Despite the return of MAP to control levels following the sustained pressure elevation in SH rats, there was a paradoxical increase in ADN activity (39 +/- 14%) compared with control values. In contrast, both ADN activity and MAP returned to control levels in WKY rats following the sustained pressure elevation. The sustained increase of ADN activity in SH rats did not account for the entire magnitude of the prolonged recovery of RSNA. In summary, both SH and WKY rats exhibit prolonged suppression of RSNA, whereas ADN activity is paradoxically elevated in only SH rats following a sustained elevation in MAP.
Redox changes in cat brain cytochrome-c oxidase after blood-fluorocarbon exchange
Authors: Ferrari M. , Hanley D. F. , Wilson D. A. , Traystman R. J.
Published: December 2017

Rapid scanning near-infrared spectroscopy (730-960 nm) was utilized to determine cat brain cytochrome-c oxidase copper band by blood-perfluorochemical emulsion (Oxypherol) exchange. Spectra were carried out before, during, and after the exchange transfusion on animals with preserved somatosensory-evoked potentials and microsphere-determined cerebral blood flow. Remaining hemoglobin (less than 4% of control) was converted to carboxyhemoglobin that does not absorb in this spectral region. Difference spectra, between an hypercapnic status (8% CO2-92% O2) and postmortem, demonstrated the presence of a broad absorption band centered around 820-845 nm that could be attributed to the oxidized low potential copper ion (CuA) of cytochrome-c oxidase. However, we were unable to further oxidize this band by adding CO2 to the inspired gas mixture, but this inconsistency may be due to the near-maximal cerebral blood flow levels present in this preparation. Cytochrome oxidation by CO2 is normally attributed to increased O2 delivery to the tissue, secondary to an increased cerebral perfusion. We were unable to induce further increases in cerebral blood flow. In contrast, the cytochrome band could be reduced both by lowering fractional O2 concentration and by inducing circulatory arrest. The spectral data support the hypothesis that it is possible to quantify the cytochrome-c oxidase copper band in the near-infrared spectral region.
Cardiac responses to acute insulin-induced hypoglycemia in humans
Authors: Fisher B. M. , Gillen G. , Hepburn D. A. , Dargie H. J. , Frier B. M.
Published: December 2017

The effects of acute hypoglycemia on the heart and cardiovascular system were examined in humans using radioisotopic techniques, complemented by measurement of heart rate and blood pressure. The heart rate increased from 62 +/- 3 to 87 +/- 3 beats/min in response to hypoglycemia; this increase was accompanied by a significant increase in systolic blood pressure, a fall in diastolic blood pressure, with no change in the mean arterial blood pressure. The left ventricular ejection fraction increased from 47 +/- 3 (SE) to 72 +/- 5% in response to hypoglycemia. The increases in heart rate and ejection fraction were abolished during parenteral nonselective beta-adrenergic blockade with propranolol but were unaffected by either alpha-adrenergic blockade with phentolamine or cholinergic blockade with atropine. During beta-adrenergic blockade, there were significant increases in diastolic and mean arterial blood pressure in response to hypoglycemia. During alpha-adrenergic blockade the systolic, diastolic, and mean arterial pressures fell significantly after hypoglycemia. The blood pressure responses to hypoglycemia were unaffected by cholinergic blockade. Thus the increases in ejection fraction and in heart rate in response to hypoglycemia are mediated by beta-adrenoreceptors, whereas the blood pressure responses to hypoglycemia are mediated by alpha- and by beta-adrenoreceptors.
Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure
Authors: Krams R. , Sipkema P. , Westerhof N.
Published: December 2017

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.
Biaxial mechanical behavior of excised ventricular epicardium
Authors: Humphrey J. D. , Strumpf R. K. , Yin F. C.
Published: December 2017

We present results from in vitro biaxial stress-strain experiments on epicardium excised from the right and left ventricular free walls of canine hearts. These data reveal that the biomechanical behavior of ventricular epicardium is qualitatively similar to atrial epicardium and parietal pericardium but different from noncontracting myocardium. In particular, ventricular epicardium exhibits a highly nonlinear stress-stretch behavior, being initially compliant but then very stiff near the limits of its extensibility. In addition, the epicardium appears to be initially isotropic but becomes markedly anisotropic upon rapid stiffening. Finally, specimens taken from the right and left ventricular free walls behaved similarly. We submit that excised ventricular epicardium is capable of carrying significant in-plane loads and that there is a need to investigate further its role in local and global cardiac mechanics and physiology.
Tone regulates opposing endothelium-dependent and -independent forces: resistance brain vessels in vivo
Authors: Rosenblum W. I. , Nelson G. H.
Published: December 2017

Pial arterioles on the surface of the mouse brain were observed with television microscopy and measured with an image-splitting technique. Previous studies showed that, in this vascular bed, serotonin (5-HT) and high-dose histamine produced endothelium-dependent constriction that masked and overwhelmed an endothelium-independent relaxation produced by the same agonists. Low-dose histamine produced relaxation. In the present studies we compared the responses to these agonists before and after alterations in tone. Preconstriction with uridine 5'-triphosphate caused reversal of the responses to 5-HT or high-dose histamine. These agonists now relaxed the arterioles to diameters greater than their original base line. Prerelaxation by nitroprusside caused reversal of the response to low-dose histamine. The agonist now constricted the arterioles to diameters smaller than their original base line. The data show, in vivo, in resistance vessels, that initial tone is an important determinant of the final effect or relative strengths of competing, opposing, endothelium-dependent and -independent forces triggered by a single agonist.
Enhanced norepinephrine sensitivity in renal arteries at elevated transmural pressure
Authors: Lombard J. H. , Eskinder H. , Kauser K. , Osborn J. L. , Harder D. R.
Published: December 2017

The electrical and mechanical responses of vascular smooth muscle to norepinephrine were compared at three different levels of transmural pressure (60, 100, and 140 mmHg) in cannulated small arteries that were isolated from dog kidneys. Elevation of transmural pressure caused depolarization of the vascular smooth muscle and a significant increase in vessel sensitivity to norepinephrine. Norepinephrine produced less depolarization as transmural pressure was elevated. Comparison of the relationship between transmembrane potential and norepinephrine concentration at these different transmural pressures suggests that membrane depolarization contributes to, but is not the sole explanation of, the increased norepinephrine sensitivity at higher transmural pressures. The results of this study suggest that transmural pressure in a blood vessel may be an important determinant of its sensitivity to vasoactive agonists.
Angiotensin and alpha-adrenoceptor activation play a role in hemodynamic response to aortic cross-clamping
Authors: Gelman S. , Bredle D. L. , Bradley W. E. , Cain S. M.
Published: December 2017

This study was designed to identify the possible role of vasoconstricting compounds released from ischemic tissues in the hemodynamic response to cross-clamping of the thoracic aorta. Twenty-one dogs were anesthetized with pentobarbital sodium. The left hindlimb was denervated, vascularly isolated, and pump perfused at a constant rate with blood drained from the inferior vena cava after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were maintained within normal limits. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 33-45% increase in limb vascular resistance in denervated control animals (n = 6). In animals pretreated with Enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change significantly. In animals pretreated with phenoxybenzamine (3 mg/kg, n = 6), an alpha-adrenoceptor antagonist, limb vascular resistance significantly decreased to 43% of preclamped level. The study demonstrated that vasoconstrictive compounds, such as angiotensin and catecholamines, play a role in systemic hemodynamic changes, including arterial hypertension, observed during cross-clamping of the thoracic aorta.
Cerebral blood flow and energy metabolism during stress
Authors: Bryan R. M.
Published: December 2017

Many, but not all, stressful events are accompanied by increases in cerebral blood flow and/or energy metabolism. The stressful events include pharmacological paralysis, footshock, conditioned fear, hypotension, hypoglycemia, hypoxia, noise, and ethanol withdrawal. These increases are significant because 1) all brain regions are often affected, i.e., certain stressful events have global effects on cerebral blood flow and energy metabolism; and 2) various stressful events appear to have a common adrenergic mechanism for increasing cerebral blood flow and energy metabolism. The adrenergic mechanism involves beta-adrenergic receptor stimulation by either epinephrine secreted from the adrenal medulla or possibly norepinephrine endogenous to the brain. While adrenergic mechanisms are not the only mechanism controlling flow and metabolism for a given stressful condition, they do appear to be common to many situations. At least part of the increase in cerebral blood flow and energy metabolism during many conditions appears to be the result of the stress response and not directly a result of the condition itself.
Age-related changes in myocardial relaxation and sarcoplasmic reticulum function
Authors: Kaufman T. M. , Horton J. W. , White D. J. , Mahony L.
Published: December 2017

Rapid regulation of relaxation is essential to allow the heart to alter stroke volume in response to stress. Inasmuch as Ca2+ transport by the sarcoplasmic reticulum (SR) is an important determinant of relaxation, the purpose of this study was to examine developmental differences in the ability of isoproterenol to alter relaxation time and to determine if these differences were associated with age-related changes in Ca2+ transport by the SR in isolated, perfused adult and newborn guinea pig hearts. Control values of the time constant of isovolumic relaxation (tau) were 37.8 +/- 5.9 ms in adult hearts (n = 8) and 31.6 +/- 5.3 ms in newborn hearts (n = 6). With maximum isoproterenol stimulation, the decrease in tau was significantly greater in adult (51.1 +/- 8.8%, mean +/- SD) compared with that in newborn (26.3 +/- 3.1%, P less than or equal to 0.0001) hearts. Ca2+ uptake, Ca2(+)-dependent adenosinetriphosphatase activity, and Ca2+ pump density were all significantly greater in SR vesicles isolated from adult hearts compared with values measured in SR vesicles from newborn hearts. We conclude that developmental differences in the capacity of the SR to sequester Ca2+ may contribute to age-related differences in the functional response of the heart to isoproterenol.
Acquisition and decay of heat-shock-enhanced postischemic ventricular recovery
Authors: Karmazyn M. , Mailer K. , Currie R. W.
Published: December 2017

Hyperthermia induces the synthesis of the 71-kDa heat-shock protein (heat-shock response) in all rat tissues, including heart. We examined whether induction of the heat-shock response alters the response of isolated hearts to ischemia and reperfusion. Anesthetized male rats were pretreated with 15 min of hyperthermia (42 degrees C) and then recovered for 0, 24, 48, 96, or 192 h. Hearts were isolated from control and hyperthermia-treated rats and retrogradely perfused. Greatest recovery occurred in 48-h postheat-shock hearts; after 30 min of reperfusion there was a 38, 62, and 62% recovery of force, +dF/dt, and -dF/dt, respectively, and 17, 36, and 30% recovery, respectively, for the control hearts. Creatine kinase efflux during reperfusion was reduced by 75% for 24-h postheat-shock hearts. The antioxidative enzyme catalase was increased 24, 48, and 96 h posthyperthermia. Treatment of rats with 3-amino-1,2,4-triazole (1 g/kg body wt), which irreversibly inactivates catalase, 30 min before isolation of hearts, abolished the hyperthermia-induced enhancement of postischemic recovery. These results show a strong relationship between the acquisition and decay of the enhanced postischemic ventricular recovery and the hyperthermic induction of the heat-shock response indicated by the accumulation of heat-shock protein HSP71 (mol mass 71 kDa) and the increase in catalase activity.
Exercise training alters Ca release from coronary smooth muscle sarcoplasmic reticulum
Authors: Stehno-Bittel L. , Laughlin M. H. , Sturek M.
Published: December 2017

We examined intracellular free calcium (Cai) buffering by the sarcoplasmic reticulum (SR) of porcine coronary artery smooth muscle cells (SMC) and the effects of chronic exercise training (ET) on this phenomenon. Cai was measured with fura-2. Depolarization of single SMC via high extracellular K induced the entry of Ca, a fraction of which was sequestered (buffered) by the SR. Endurance ET of Yucatan minipigs for 16-20 wk increased exercise tolerance, heart-to-body weight ratios, and skeletal muscle oxidative capacity. Caffeine-induced Ca release from the SR after a short (2 min) recovery time from depolarization to caffeine exposure was equal in SMC from both ET and sedentary pigs. With a longer (11 min) recovery period after depolarization, caffeine-induced Ca release from the SR of sedentary pigs was equal to that after the short recovery time. However, after the long recovery, caffeine-induced Ca release in SMC of ET pigs was 60% less (P less than 0.05) than in the other protocols. These results indicate that chronic ET increased Cai buffering in SMC of the coronary artery by increasing the rate of spontaneous Ca extrusion from the SR.
Negative inotropy of halogenated anesthetics in ferret ventricular myocardium
Authors: Housmans P. R.
Published: December 2017

The effects of the volatile anesthetics halothane, enflurane, and isoflurane on amplitude and time variables of contraction and relaxation in isometric, isotonic, and zero-load clamped twitches of isolated right ventricular ferret papillary muscles (n = 24) were compared with those of changing extracellular Ca2+ concentration [( Ca2+]o). Contraction and relaxation variables were compared at equal contraction amplitudes to determine whether the studied anesthetics exert specific effects on contraction and relaxation other than those that may exist as a consequence of their negative inotropic effect. Both changes in [Ca2+]o and anesthetic concentrations had quantitatively and qualitatively similar effects on the following variables of contraction amplitude: peak isometric developed force (DF), maximal extent of shortening (DL), and maximal unloaded velocity of shortening (MUVS). Analysis of anesthetic concentration-effect curves normalized for effects to changes in [Ca2+]o demonstrated that anesthetic effects relative to those of changes in [Ca2+]o were greater on DF greater than DL greater than MUVS. When compared with twitches of equal amplitude in low [Ca2+]o, halothane, enflurane, and isoflurane accelerated isometric and isotonic relaxation. These data are consistent with the hypothesis that the negative inotropic effects of halothane, enflurane, and isoflurane are mostly a consequence of a reduction of intracellular Ca2+ availability and that anesthetic-induced decreases in myofibrillar Ca2+ responsiveness play only a minor role.
Effects of sex hormones on development of physiological and pathological cardiac hypertrophy in male and female rats
Authors: Malhotra A. , Buttrick P. , Scheuer J.
Published: December 2017

Previous studies have demonstrated a role for sex hormones in maintaining normal heart weight and myosin isoenzyme balance in the rat. To determine if sex hormones were necessary to elicit cardiac adaptations to the chronic loads of swimming or hypertension, female rats were gonadectomized (X) and then exposed either to a chronic swimming program (Sw) or to renal hypertension for 8-10 wk. Because gonadectomy in females increased heart and body weight, separate groups of food-restricted sedentary and Sw gonadectomized females (XFR) were included. Swimming resulted in significant increases in both heart weight and in the percent ventricular V1 isomyosin in female controls (C), X, and XFR. Hypertension was studied in C, X, and X with estrogen replacement. Cardiac hypertrophy developed in all groups, but estrogen therapy attenuated the decline in percent V1 isomyosin in both normotensive and hypertensive X animals. Swimming, which is generally not associated with cardiac hypertrophy in males, was also studied in that sex. Gonadectomy did not alter either the heart weight or the myosin isoenzyme response to Sw, although testosterone replacement in gonadectomized males restored ventricular V1 myosin levels to or above normal. Measures of serum thyroid levels and of myocardial catecholamines failed to demonstrate a causal relationship between these hormones and the various results. Therefore, although sex hormones are important for maintaining normal heart weights and myosin isoenzyme balance in rats, they do not appear to be important in the adaptations hearts exhibit when exposed to physiological or pathological loads.
In situ calibration of fura-2 and BCECF fluorescence in adult rat ventricular myocytes
Authors: Borzak S. , Kelly R. A. , Kramer B. K. , Matoba Y. , Marsh J. D. , Reers M.
Published: December 2017

Quantitation of Ca+ and H+ activities within cells using presently available fluorescent probes is optimal when the fluorescence signal is calibrated in situ after each experiment. Fura-2 and 2',7'-bis(2-carboxy-ethyl)-5,6-carboxyfluoroscein (BCECF) are difficult to calibrate in freshly dissociated adult cardiac myocytes because calibration procedures produce cellular hypercontracture. In situ calibration was accomplished in rat ventricular cells by saturating fura-2 with La3+, an agent known to produce myocardial relaxation. Since fura-2 has different spectral properties when complexed with La3+ than with Ca2+, scaling factors were defined in vitro and then verified by experiments in cultured neonatal myocytes. In adult rat myocytes using the La3+ method, intracellular Ca2+ concentration ([Ca2+]i) was 131 +/- 47 nM (n = 14) in quiescent cells; diastolic [Ca2+]i and systolic [Ca2+]i in myocytes stimulated at 1 Hz were 140 +/- 56 and 1,088 +/- 211 nM (n = 5), respectively. BCECF fluorescence was calibrated in situ by a method that prevented cellular hypercontracture and reported a pH value of 7.10 +/- 0.10 in cells stimulated at 1.5 Hz. An additional advantage of both methods is that the buffers employed prevented large changes in the redox state of intracellular pyridine nucleotides, thus preventing a change in cellular autofluorescence during the calibration procedure.
Possible modulation of release of atrial natriuretic factor by endothelium-derived relaxing factor
Authors: Sanchez-Ferrer C. F. , Burnett J. C. , Lorenz R. R. , Vanhoutte P. M.
Published: December 2017

The aim of the present study was to investigate the influence of inhibitors of endothelium-dependent relaxing factor on the release of atrial natriuretic factor from isolated rat atria. Electrical stimulation of the tissue produced a frequency-dependent increase in secretion of atriopeptide from basal levels. Saponin (0.3 mg/ml for 45 min) augmented the basal release of the peptide. Methylene blue (10(-5)M), oxyhemoglobin (10(-6)M), or hydroquinone (10(-5)M), agents that inhibit the effects of endothelium-derived relaxing factor by different mechanisms, caused an increase in the basal secretion of atrial natriuretic factor. Blockade of cyclooxygenase with indomethacin (10(-5)M) did not alter the release of atriopeptide, suggesting that it is not controlled by endogenous prostaglandins. These results would be explained if the inhibitors tested were to interfere with a factor released continuously from either endocardial cells or endothelial cells of the atrial blood vessels and having the same nature as endothelium-derived relaxing factor. Such release may exert a tonic negative modulatory influence on the secretion of atrial natriuretic factor.
Selective interaction of alpha-adrenoceptors with myogenic regulation of microvascular smooth muscle
Authors: Faber J. E. , Meininger G. A.
Published: December 2017

The interaction of alpha 1- and alpha 2-adrenoceptor constriction of arterioles with the myogenic mechanism was examined in rat cremaster skeletal muscle using intravital microscopy. Intravascular pressure was increased or decreased by changing pressure from 0 to +30 and 0 to -20 mmHg in a chamber that surrounded the animal but not the cremaster. Arterioles of 110 microns in diameter were constricted by approximately 30% with the alpha 1-agonist, phenylephrine, or the alpha 2-agonist, UK-14304. Increases in microvascular (box) pressure caused stepwise constrictions of similar magnitude (10-30%) regardless of the prevailing type of alpha-adrenergic tone. In contrast, during alpha 2 tone, decreases in pressure caused a three- to fourfold greater dilation (myogenic inhibition) than during alpha 1 tone. Thus myogenic constriction, normally minimal in these large arterioles, was amplified similarly during either alpha 1 or alpha 2 tone; however, alpha 2 tone was much more susceptible than alpha 1 tone to myogenic inhibition. Similar results were obtained with tone produced by thromboxane A2 vs. the Ca2+ channel agonist, BAY K 8644. Thus the particular sensitivity of alpha 2 constriction to myogenic inhibition may relate to interactions between these stimuli at the postreceptor level. The degree and type of alpha-adrenoceptor tone at different microvasculature levels may be important in myogenic autoregulatory blood flow adjustments during changes in perfusion pressure.