bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac adjustments to left-side inotropic stimulation of in situ pig hearts
Authors: Vengen O. A. , Lande K. , Ellingsen O. , Ilebekk A.
Published: December 2017

Cardiac adjustments to inotropic stimulation of the left side of the heart by continuous infusions of isoproterenol (0.6-0.8 microgram/min) and calcium chloride (240 mumol/min) into the left coronary artery were examined in open-chest pigs (17-36 kg) anesthetized with pentobarbital sodium. Both agents caused a reduction in the left ventricular (LV) preload and preejection segment length (PESL). Stroke volume (SV) rose by only 1.2 ml from 15.9 ml (P less than 0.01) during isoproterenol infusion, but when the reduction in LV PESL of 3.2% (P less than 0.01) was restored by saline infusion, SV increased by 27%. The LV PESL reduction was less at hypervolemia than at normovolemia. A computer-based model of the circulation predicted most of these changes and suggested redistribution of blood from the pulmonary to the systemic circulation. During isoproterenol infusion, the pulmonary arterial pressure fell, and the right ventricular end-ejection segment length declined. Reduced right ventricular afterload thus appears to be an important mechanism by which right ventricular output is increased during a selective increase in LV inotropy.
Transfer of nonelectrolytes from blood into peripheral nerve endoneurium
Authors: Rechthand E. , Smith Q. R. , Rapoport S. I.
Published: December 2017

Permeability-surface area (PA) products were determined for the transfer of seven nonelectrolytes across the blood-nerve barrier (BNB) of rat tibial nerve using a quantitative in vivo injection technique. PA values at the BNB for slowly penetrating nonelectrolytes such as urea, mannitol, L-glucose, and sucrose differed by less than threefold from values at the blood-brain barrier in the same animals. Permeability coefficients for transfer across the BNB were calculated assuming both endoneurial capillaries and perineurium contribute to solute flux into endoneurium. Total BNB surface area was determined as 175 cm2/g with morphometric techniques. Calculated permeability coefficients for slowly penetrating nonelectrolytes ranged from 7 X 10(-8) cm/s for sucrose to 4 X 10(-7) cm/s for urea and were directly proportional to solute lipid solubility as measured by the octanol-water partition coefficient. BNB permeability coefficients for sucrose, mannitol, L-glucose, and urea were within 60% of values at cerebral capillaries, of the same order of magnitude as values at aporous lipid membranes, and 100-1,000 times less than values at most nonneural capillaries, such as in skeletal muscle. These results demonstrate that the BNB markedly restricts the transfer of hydrophilic nonelectrolytes between plasma and endoneurium and that diffusion restriction of the BNB is comparable to that of the blood-brain barrier.
Perivascular and tissue PO2 in contracting rat spinotrapezius muscle
Authors: Lash J. M. , Bohlen H. G.
Published: December 2017

This study evaluated the possibility that during skeletal muscle contractions tissue O2 tension (Po2) around arterioles and venules decreases substantially more than in the middle of the capillary bed and thereby influences functional hyperemia. Periarteriolar [H+] and [K+] were also measured because most large arterioles are in close proximity to venules such that the biochemical status of the periarteriolar tissue could be influenced by a large decrease in O2 availability in the annulet of tissue surrounding the venules. Stimulation frequencies in the range of 2-12 Hz were used to activate the rat spinotrapezius muscle. Periarteriolar and capillary bed Po2, [H+], and [K+] changed during the first few minutes of stimulation but were restored to near resting concentrations as the functional hyperemia developed. However, perivenular Po2 decreased rapidly to approximately 50-60% of the resting gas tension as contractions began, and only minor recovery occurred. Elevation of tissue and periarteriolar Po2 with an O2-enriched superfusion solution did not prevent dilation during contractions to the same diameter as during the response at very low superfusion Po2. Therefore, the extent to which O2 influences arteriolar dilation and exercise hyperemia in the spinotrapezius muscle of the rat may depend less on periarteriolar and capillary bed Po2 than on the release of vasoactive materials from the nearby perivenular tissues as the availability of O2 decreases.
Primary resetting of left atrial sensory endings in Dahl salt-sensitive rats fed a low-salt diet
Authors: Thoren P. , Morgan D. A. , Mark A. L.
Published: December 2017

Vagal afferent pathways contribute to vasomotor inhibition and renal sodium handling by modulating sympathetic nerve activity in rats. Low pressure or cardiopulmonary baroreflex inhibition of sympathetic nerve activity is attenuated in normotensive Dahl salt-sensitive (S) rats fed a low-salt diet. The aim of the study was to record activity in single-fiber vagal filaments from left atrial endings in Dahl S and resistant (R) rats to evaluate the mechanism for the attenuated low pressure baroreflex. Rats were fed a low-salt diet (0.1% NaCl) for 5–7 wk. Seven Dahl R and six S rats were anesthetized with urethan, and catheters were placed in the aorta and left atrium. Single-fiber recordings were obtained from the right cervical vagus. The relationship between left atrial pressure and receptor discharge was obtained during graded aortic snaring. Mean threshold for increased activation of the vagal afferents during volume expansion was 10.4 +/- 0.6 mmHg (means +/- SE) in S and 6.0 +/- 0.4 mmHg in R rats (P less than 0.002). Pressure-discharge curves were significantly shifted to the right in S rats. Maximal sensitivity of the endings expressed as delta discharge/delta LAP was not significantly different in R vs. S, but the right shift in threshold reduced the discharge of endings over a physiological range of filling pressures. We also measured left ventricular end-diastolic pressure (LVEDP) in conscious S and R rats to determine if the resetting of left atrial sensory endings could be explained by elevated left heart filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Reflectance measurements of hematocrit and oxyhemoglobin saturation
Authors: Steinke J. M. , Shepherd A. P.
Published: December 2017

Fiberoptic oximeters measure oxyhemoglobin saturation from the optical reflectance of whole blood, but the calibration of such oximeters is hematocrit dependent. Therefore, using photon-diffusion theory and an empirical approach, we have developed a new reflectance method that determines hematocrit and correspondingly corrects the oxyhemoglobin-saturation measurement. Our method employs four fiber-optic light guides, a photodetector, and three inexpensive light-emitting diodes (one with emissions at 660 nm and two at 813 nm). Hematocrit is determined from the ratio of reflectances from the differently spaced emitting fibers at 813 nm and is used to correct the 813-660 nm measurement of oxyhemoglobin saturation. In red cell suspensions, the mean difference between reflectance measurements of hematocrit and conventional determinations was only 2.09% (r = 0.99), and when compared with conventional gasometric measurements of oxyhemoglobin saturation, the reflectance method yielded the same calibration curve for different hematocrits and gave a mean difference of only 2.67%. Although the technique is demonstrated with a cuvette appropriate for an extracorporeal circulation in animal experiments, it could possibly be further developed for fiber-optic catheter oximeters.
Validity of microsphere depositions for regional myocardial flows
Authors: Bassingthwaighte J. B. , Malone M. A. , Moffett T. C. , King R. B. , Little S. E. , Link J. M. , Krohn K. A.
Published: December 2017

Due to the particulate nature of microspheres, their deposition in small-tissue regions may not be strictly flow dependent. To evaluate the importance of rheological and geometric factors and random error, their deposition densities in small regions of rabbit hearts were examined in comparison with those of a new “molecular microsphere,” 2-iododesmethylimipramine (IDMI), whose high lipid solubility allows it to be delivered into tissue in proportion to flow, and whose binding in tissue prevents rapid washout. 141Ce- and 103Ru-labeled 16.5-micron spheres in one syringe and [125I]- and [131I]DMI in another syringe were injected simultaneously into the left atrium of open-chest rabbits, while obtaining reference blood samples from the femoral artery. Hearts were removed 1 min after injection, cut into approximately 100 pieces averaging 54 mg, and the regional deposition densities calculated for each tracer from the isotopic counts. Correlations between the differently labeled microspheres were r greater than 0.95 and for the two IDMIs were greater than 0.98. Scatter plots of sphere densities vs. IDMI densities showed that differences between microspheres and IDMI had substantial scatter, 0.87 less than r less than 0.96 and were not random. Microsphere depositions tended to be lower than IDMI depositions at low flows and higher at high flows. The tendency for spheres to be deposited preferentially in high-flow regions may be explained by a bias at bifurcations toward entering the branch with higher flow and secondarily toward entering those branches that are straighter. We conclude that microspheres are generally adequate for estimating regional flows but suffer systematic error when the regions of interest are supplied via arteries of diameters only a few times those of the microspheres.
Free and conjugated catecholamines in dog pulmonary artery: presence and pharmacological action
Authors: Rorie D. K. , Tyce G. M.
Published: December 2017

Free and conjugated forms of norepinephrine (NE) and dopamine (DA) were detected in dog pulmonary artery, and small amounts were released during 2-Hz electrical stimulation. Hydrolysis of the conjugates by acid boiling and by enzymes indicated that they were primarily sulfates, but traces of glucuronide may also have been present. After isolation by column chromatography, free and conjugated amines were quantitated using liquid chromatography with electrochemical detection. Pulmonary artery tissue contained (in ng) 1,240 +/- 100 free NE, 15 +/- 5 conjugated NE, 47 +/- 6 free DA, and 2 +/- 0.3 conjugated DA/g tissue (means +/- SE). When strips of pulmonary artery were immersed in [3H]NE small amounts of [3H]NE sulfate were synthesized. The release of conjugated NE was not calcium dependent but release was attenuated somewhat by tetrodotoxin. Removal of endothelium did not change tissue content of conjugated or of free NE nor the amounts measured in superfusate. Small amounts of free DA were also detected in tissues and in superfusate during stimulation, but only when calcium was present in the superfusion fluid. Norepinephrine sulfate was not a potent agonist at either pre- or postsynaptic alpha-receptors; the agonist activity seen with high concentrations of norepinephrine sulfate seems likely to have been due at least in part to trace contamination by free NE.
Description of LV pressure-volume relations by time-varying elastance and source resistance
Authors: Little W. C. , Freeman G. L.
Published: December 2017

If the left ventricle (LV) behaves as a time-varying elastance [E(t)] that is independent of load, then definition of E(t) during normal ejecting beats should permit accurate prediction of LV pressure (LVP) during a maximally afterloaded (isovolumic) beat. We tested this hypothesis in six dogs preinstrumented to measure LVP and aortic flow (Q) and to determine LV volume (V) from three dimensions. LVP and V were varied by caval occlusions. These data were used to determine E(t) and minimal volume required to generate pressure (Vo) at 10-ms intervals during systole using a simple E(t) model, P(t) = E(t) [V(t)-Vo], where P(t) is LVP at any time after the onset of contraction, and V(t) is the LV volume at t. LVP was measured during isovolumic beats generated by sudden balloon occlusion of the ascending aorta. The simple E(t) model accurately predicted isovolumic LVP during the first 70 ms of systole (r = 0.99) and also the end-systolic LVP but underestimated LVP during midsystole by 48 +/- 5 (SD) mmHg (P less than 0.05). When a pressure-dependent source resistance (K = 0.0015 s/ml) was added to the model to reduce LVP in proportion to Q, such that P(t) = E(t) [V(t)-Vo] X [1 - KQ]), LVP during the isovolumic beat was accurately predicted throughout systole (r = 0.99). However, the time to develop peak isovolumic pressure was 22 +/- 7 ms less than predicted. Similar results were obtained during inotropic stimulation with dobutamine in five animals.
Inhibition of renal sympathetic nervous activity by area postrema stimulation in rabbits
Authors: Hasser E. M. , Nelson D. O. , Haywood J. R. , Bishop V. S.
Published: December 2017

This study investigated the effect of chemical and electrical stimulation of the area postrema on renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate in urethan-anesthetized rabbits. Electrical stimulation of the area postrema at 2, 5, 10, 20, 40, and 80 Hz using constant currents of 7.5, 15, and 30 microA (pulse duration = 0.3 ms, train duration = 5 s) produced progressive decreases in RSNA and heart rate, with no consistent change in arterial pressure. To control for electrical activation of fibers of passage in or near the area postrema, L-glutamate was injected into the area postrema using glass micropipettes. Micropressure injection of L-glutamate (10 mM) in volumes of 5-10 nl produced rapid decreases in RSNA averaging 27 +/- 5% (P less than 0.05) accompanied by a small bradycardia. The effects of electrical stimulation of the area postrema, but not the adjacent nucleus tractus solitarius, were totally eliminated by micropressure injection of kainic acid (40 ng in 40 nl) into the area postrema. During continuous electrical stimulation of the area postrema using parameters that produced small decrements in RSNA and heart rate, the slope of the line relating baroreflex inhibition of RSNA to increases in arterial pressure during graded infusions of phenylephrine was significantly enhanced (-6.77 +/- 1.30 vs. -3.81 +/- 0.66% RSNA/mmHg). These data are consistent with the hypothesis that activation of neurons in the area postrema results in an inhibition of RSNA. Furthermore, stimulation of the area postrema augments baroreflex inhibition of RSNA during increases in arterial pressure with phenylephrine.
Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo
Authors: Pohl U. , Dezsi L. , Simon B. , Busse R.
Published: December 2017

In vivo experiments were performed in autoperfused hindlimbs of rabbits to investigate the role of endothelium-mediated vasomotion in resistance-sized vessels. The flow responses to the vasodilators acetylcholine (ACh), ATP, and substance P (SP), all of which have been shown to act in an endothelium-dependent manner in large conduit arteries, were studied before and after exposure of the hindleg vasculature to gossypol (a potent inhibitor of endothelium-mediated vasodilation in vitro). The flow responses to adenosine (ADO), nitroglycerin (GTN), and prostaglandin E2 (PGE2), which induce relaxation by a direct effect on vascular smooth muscle, were tested in the same manner. All vasodilators induced dose-dependent increases in femoral flow up to two- to threefold when administered intra-arterially. After gossypol, the flow responses to the endothelium-dependent compounds (ACh, ATP, and SP) were severely reduced (by 88 +/- 3%, P less than 0.01) or sometimes were converted to constrictions (ATP). The flow increases induced by ADO, PGE2, and GTN remained largely unaffected. Sham treatment (gossypol solute only), exposure to indomethacin (10 microM), and ganglionic blockade had no differential effect on the flow responses. The selective action of gossypol in suppressing the flow responses to the endothelium-dependent compounds ACh, ATP, and SP is consistent with a vasomotor role for endothelial cells in resistance-sized vessels in vivo.
Mg inhibits voltage and tension oscillation but potentiates twitch in depolarized myocardium
Authors: Ito T. , Ehara T.
Published: December 2017

In the presence of 1-5 X 10(-8) M isoproterenol, guinea pig ventricular muscle, depolarized by K-rich (27 mM) solution, exhibits a biphasic twitch tension, after contraction (AC), and oscillatory afterpotentials (OAP) in response to 1-Hz stimulation. We obtained data suggesting that OAP and AC are due to a spontaneous oscillatory release of Ca from the sarcoplasmic reticulum (SR) and that the initial component (C1) of the biphasic twitch, which produces a large and early peak in tension, reflects the excitation-coupled Ca release from SR. Elevation of extracellular Mg concentration ([Mg]o) to 3–6 mM suppressed AC and OAP. However, C1 was markedly potentiated by high [Mg]o. When single extrasystoles with various coupling intervals were interposed during a regular stimulation at 0.2 Hz, C1 in the extrasystole, which was large with a short coupling interval, gradually decreased with lengthening of the coupling interval. Elevation of [Mg]o markedly reduced the rate of this decrease suggesting that the decrease in available Ca in the SR during diastole was slowed by high [Mg]o. Thus, in depolarized ventricle, high Mg solution seems to depress the spontaneous oscillatory Ca release from SR and subsequently enhances the Ca release coupled to membrane excitation. The latter enhancement may be related to stabilization of the Ca in SR during diastole.
Red blood cell catecholamine levels in normotensive and DOCA-salt hypertensive rats
Authors: Bouvier M. , Farley L. , de Champlain J.
Published: December 2017

Under basal conditions in anesthetized rats, significant concentrations of free norepinephrine (NE), epinephrine (E), and dopamine (DA) were detected in red blood cell (RBC) lysate. These concentrations were not proportional to their respective plasma concentrations and thus RBC-to-plasma concentration ratios were different for each catecholamine (CA). DA was by far the most concentrated amine inside the RBC. An acute increase in plasma NE and E levels, induced by hemorrhagic hypotension in normotensive (NT) rats, did not result in any modification of the RBC CA content. However, chronic elevation of the NE plasma levels in bilaterally adrenalectomized rats and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (DOCA-salt HT) were associated with increased NE levels in the RBC. In addition, the large elevation in plasma E concentrations following hemorrhagic hypotension in DOCA-salt HT rats, as well as the greater plasma NE response to hypotension in adrenalectomized animals, were accompanied by increases in the respective RBC amine concentrations. During a steady-state intravenous infusion of tritiated NE, we observed a slow accumulation of radioactivity inside the RBC, indicating that CA can enter the RBC from the plasma. Moreover, catechol methyltransferase activity was measured in the cytosolic fraction of the RBC of both NT and DOCA-salt HT rats suggesting that, once inside the RBC, the catecholamines can be metabolized.
Coronary vasodilator reserve persists despite tachycardia and myocardial ischemia
Authors: Bristow J. D. , McFalls E. O. , Anselone C. G. , Pantely G. A.
Published: December 2017

During myocardial ischemia, we tested whether coronary blood flow would increase in response to tachycardia, thereby employing known coronary flow reserve. We instrumented the left anterior descending (LAD) coronary circulation in anesthetized pigs and performed three sets of experiments while coronary pressure was controlled and several heart rate increases were produced. Pacing-induced tachycardia at normal LAD pressure was characterized by increased LAD flow and myocardial oxygen consumption, without production of lactate. Tachycardia at a mean LAD pressure of 38 mmHg was associated with a lower, fixed coronary flow and oxygen consumption. At average heart rates of 90 and 150 beats/min, LAD flow was 19.6 and 19.4 ml/min and corresponding myocardial blood flows were 0.59 and 0.54 ml X g-1 X min-1. Lactate was produced at all rates and local myocardial function declined progressively. Coronary flow at low LAD pressure doubled during tachycardia when intracoronary adenosine was added. The increase to the subepicardium was greater than 100%, whereas subendocardial flow changed little. There is persistent coronary flow reserve during moderately severe myocardial ischemia, even when metabolic demand is increased by tachycardia. This reserve, however, is predominantly subepicardial.
Myocardial adaptation to chronic propranolol therapy in normal rats
Authors: Fein F. S. , Zola B. , Miller B. , Malhotra A. , Sonnenblick E. H.
Published: December 2017

The intrinsic myocardial adaptation to chronic beta-blockade was explored in normal male Wistar rats. Propranolol was administered by subcutaneous infusion using osmotic minipumps for 3–4 wk (P group). Heart rate fell by approximately 100 beats/min. A second group of animals was similarly treated but had their pumps removed several days before study (P-R group). Heart rate rose, but remained below base line. Study of isolated ventricular papillary muscle from P, P-R, and age-matched controls (C group) revealed prolonged contraction duration in P and P-R groups, but no change in shortening velocity. A greater shortening of time to peak tension and time to one-half relaxation in response to norepinephrine was demonstrated in P and P-R groups. Acute in vivo or in vitro administration of propranolol had no effect on base-line mechanical performance. No changes in the Ca2+, actin-activated Mg2+ myosin adenosine triphosphatase (ATPase) activity, or myosin isoenzyme distribution were found. Free thyroxine levels were decreased in P but not P-R groups. These findings indicate that chronic propranolol therapy in normal rats slows contraction and relaxation without altering contractility. The greater shortening of contraction duration in response to norepinephrine is partly offset by the prolongation of the base-line contraction.
Effects of elevation of phosphocreatine on force and metabolism in rabbit aorta
Authors: Scott D. P. , Davidheiser S. , Coburn R. F.
Published: December 2017

Rings of rabbit thoracic aorta were incubated in 40 mM creatine; both intracellular free creatine (Cr) and phosphocreatine (PCr) content increased 300% in 4 h, whereas tissue ATP content and PCr-to-Cr ratio remained constant. Exogenous Cr was taken up and metabolized by creatine kinase; the newly formed PCr was available for tissue metabolism. Compared with control tissue, muscle rings with markedly increased Cr and PCr content showed no difference in either the rate of contraction with norepinephrine or the amplitude of contraction. ATP production rates, computed from mitochondrial and glycolytic metabolism during rest and during maintained contractions, were similar for creatine-loaded and control rings. Under conditions where muscle was developing force, creatine-loaded rings showed a threefold larger decrease in PCr content than untreated rings but no difference in the decrease in PCr/Cr. A similar pattern of PCr depletion was seen when creatine-loaded or untreated NE-contracted muscle was exposed to hypoxia plus zero-glucose medium. In addition, loaded rings showed smaller rates of efflux of lactate than did unloaded rings when exposed to hypoxia in normal glucose medium.
Regulation of arterial pressure lability in rats with chronic sinoaortic deafferentation
Authors: Alper R. H. , Jacob H. J. , Brody M. J.
Published: December 2017

After chronic (2-6 wk) sinoaortic deafferentation (SAD), rats exhibit slight increases in mean arterial pressure (MAP) and heart rate and marked increases in arterial pressure lability. Neither antagonists of humoral vasoconstrictors angiotensin and vasopressin nor acute hypophysectomy altered MAP or lability after chronic SAD. Ganglionic blockade produced hypotension and significantly reduced lability in SAD rats but decreased MAP and increased lability in normal rats. Although chlorisondamine reduced lability in rats with SAD to levels observed in similarly treated sham-operated rats, lability was significantly greater in both groups than in saline-treated sham-operated rats. When intact or SAD rats were administered chlorisondamine plus either captopril or a vasopressin antagonist, pressure lability was returned to levels seen in intact untreated animals. Selective antagonism of alpha 1- or alpha 2-adrenergic receptors did not markedly alter lability in SAD rats. Combined alpha-adrenergic blockade reduced lability in SAD rats and increased lability in intact rats, similar to chlorisondamine treatment. These data suggest that chronic SAD establishes arterial pressure variability that is maintained or generated in large part by the sympathetic nervous system through mechanisms dependent on higher central structures or descending efferent sympathetic nerves. The data further suggest that peripheral mechanisms may also be involved in arterial pressure regulation in baroreceptor-deficient rats.
AVP-induced pulmonary vasodilation during specific V1 receptor block in conscious dogs
Authors: Nyhan D. P. , Clougherty P. W. , Murray P. A.
Published: December 2017

Our objectives were 1) to determine whether exogenously administered arginine vasopressin (AVP) can exert a vasoactive influence on the pulmonary circulation of conscious dogs during specific vasopressinergic-1 (V1) receptor block, and 2) to assess the extent to which the pulmonary vascular response to AVP during V1 receptor block is mediated by either sympathetic beta-adrenergic or cholinergic receptor activation or by cyclooxygenase pathway activation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. In dogs pretreated with a specific V1 receptor antagonist [d(CH2)5 AVP, 10 micrograms/kg iv], AVP infusion (7.6 ng.kg-1 X min-1 iv) increased (P less than 0.01) Q from 139 +/- 6 to 175 +/- 8 ml.min-1 X kg-1, and decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure: PAP-PCWP) over the entire range of Q studied (140 to 80 ml.min-1 X kg-1). This pulmonary vasodilator response to AVP during V1 block was also observed following sympathetic beta-adrenergic block alone, following combined sympathetic beta-adrenergic and cholinergic block, and following cyclooxygenase pathway inhibition. Thus exogenous administration of AVP during specific V1 receptor block results in active, nonflow-dependent pulmonary vasodilation. This pulmonary vasodilator response is not mediated by reflex activation of sympathetic beta-adrenergic or cholinergic receptors or by metabolites of the cyclooxygenase pathway over a broad range of Q.
Coordinated diameter oscillations at arteriolar bifurcations in skeletal muscle
Authors: Meyer J. U. , Lindbom L. , Intaglietta M.
Published: December 2017

The spontaneous rhythmical luminal changes (vasomotion) at bifurcations in the microvasculature of the rabbit tenuissimus muscle were investigated by means of a microscope video photometric system. Video scenes, containing two terminal arterioles originating from one transverse arteriole, showed that adjacent terminal arterioles constricted synchronously in 26 out of 31 contraction cycles. The onset of 60 constrictions in the parent transverse vessels was synchronized with the activity in terminal arterioles in 75% of the cycles and delayed in 25%. Vasomotion in the parent transverse vessels was notably smaller than in the terminal vessels. All the terminal arterioles in the different animals oscillated at the fundamental frequency of 18.9 +/- 3.5 cycles/min. We conclude that in the skeletal muscle microcirculation 1) coordinated spontaneous diameter oscillations occur in arterioles that are in proximity, 2) diameter changes are most pronounced in the terminal arterioles, and 3) coordinated vasomotion in this tissue exhibits a characteristic narrow band frequency. The presence of a microvascular pacemaker is hypothesized.
Calcium channel blockers induce preferential coronary vasodilation by an alpha 1-mechanism
Authors: Knight D. R. , Vatner S. F.
Published: December 2017

The effects of nitrendipine were evaluated on coronary and systemic dynamics in conscious dogs. Nitrendipine (8 micrograms X kg-1 X min-1) decreased late diastolic left circumflex coronary resistance (62 +/- 1.3%) significantly more (P less than 0.01) than total peripheral resistance (54 +/- 1.8%). After propranolol (1 mg/kg) and atropine methyl bromide (0.1 mg/kg) to eliminate reflex increases in myocardial metabolic demand, nitrendipine still reduced late diastolic coronary resistance (56 +/- 1.5%) significantly more (P less than 0.01) than total peripheral resistance (46 +/- 1.4%). However, after adding alpha 1-adrenergic receptor blockade with prazosin (1 mg/kg) to beta-adrenergic and cholinergic receptor blockades, nitrendipine no longer reduced late diastolic coronary resistance (40 +/- 2.7%) more than total peripheral resistance (45 +/- 2.1%) and, in fact, reduced late diastolic coronary resistance less than prior to prazosin. Nifedipine and diltiazem also reduced late diastolic coronary resistance more than total peripheral resistance prior to, but not after, alpha 1-adrenergic receptor blockade. In contrast, sodium nitroprusside reduced late diastolic coronary resistance more (P less than 0.01) than total peripheral resistance both before and after alpha 1-adrenergic receptor blockade. Thus calcium channel blockers preferentially dilate the coronary bed in comparison with the systemic circulation. Since the preferential effects were abolished by prazosin, an alpha 1-adrenergic mechanism is implicated.
Lung morphological and permeability changes induced by intravascular coagulation in dogs
Authors: Minnear F. L. , Martin D. , Hill L. , Taylor A. E. , Malik A. B.
Published: December 2017

The objectives of this study were to describe the morphological alterations of the pulmonary microvasculature in anesthetized dogs infused intravenously with alpha-thrombin (111-233 NIH U/kg) and to measure the protein reflection coefficient (sigma d), an index of pulmonary vascular permeability to proteins. Quantitative electron microscopy of lung biopsies from a group of four dogs showed an increase in the volume density of the alveolar interstitium and an increase in intravascular fibrin at 30 min after the thrombin infusion. The pulmonary microvascular endothelium was often swollen, blistered, highly vacuolized, or rarefied when close to or in contact with fibrin but appeared normal when not closely associated with fibrin. Fibrin-endothelial interactions often included projections of endothelium surrounding fibrin, the presence of fibrin within endothelial cells, 10- to 15-nm bridges connecting fibrin and endothelium, and disruption of the endothelial plasmalemma in contact with fibrin. Alveolar epithelial cells were unaffected by the thrombin infusion. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node in a second group of five dogs anesthetized with pentobarbital sodium intravenously. Thrombin increased pulmonary lymph flow by sevenfold and also increased the extravascular lung water-to-bloodless dry lung weight ratio. Left atrial pressure was elevated after thrombin infusion until a filtration-independent state was approached for the calculation of sigma d. Thrombin decreased sigma d from a normal value of 0.62 +/- 0.02 to 0.53 +/- 0.02. Thus thrombin-induced intravascular coagulation in dogs produced focal disruptions of the microvascular endothelium associated with intravascular fibrin and increased the pulmonary vascular permeability to proteins.
Baroreflex mechanisms buffering alpha-adrenergic agonists in conscious dogs
Authors: Fujii A. M. , Vatner S. F.
Published: December 2017

To determine the relative importance of the mechanisms utilized by the arterial baroreflex in buffering the pressor and vasoconstrictor responses to alpha-adrenergic receptor agonists, we studied responses to norepinephrine and phenylephrine in conscious dogs. The dogs were studied 2-8 wk after instrumentation with aortic catheters and aortic electromagnetic flow probes to measure arterial pressure and cardiac output. Total peripheral resistance was calculated on-line by a digital computer. The dogs were studied after beta-adrenergic receptor blockade (propranolol 1.0 mg/kg) to eliminate the complicating inotropic effects of the agonists studied. Norepinephrine (0.2 microgram/kg bolus) increased mean arterial pressure by 30 +/- 3 mmHg, total peripheral resistance by 51 +/- 4 mmHg . l-1 . min-1, and decreased heart rate by 26 +/- 3 beats/min. After arterial baroreceptor denervation, norepinephrine increased mean arterial pressure by 69 +/- 8 mmHg, total peripheral resistance by 48 +/- 6 mmHg . l-1 . min-1, and heart rate did not change. After ganglionic blockade (hexamethonium 40 mg/kg), norepinephrine increased mean arterial pressure by 76 +/- 3 mmHg, total peripheral resistance by 47 +/- 4 mmHg X l-1 X min-1, and heart rate did not change. Only after elimination of the buffering by heart rate by use of cholinergic receptor blockade (atropine 0.1 mg/kg) or ventricular pacing could buffering of the vasoconstrictor responses to alpha-adrenergic receptor agonists be demonstrated. Thus in conscious dogs the primary mechanism for buffering increases in arterial pressure induced by alpha-adrenergic receptor agonists is compensatory changes in heart rate and cardiac output with little buffering of total peripheral resistance.
Twitch contractions during low Na+-induced [Ca2+]i overload in rat ventricular muscle
Authors: Watanabe H. , Ishide N. , Takishima T.
Published: December 2017

To elucidate the mechanisms of the negative inotropism induced by excessive intracellular Ca2+ ([Ca2+]i), we observed detailed characteristics of twitch contractions during low Na+-induced [Ca2+]i overload. Rat right ventricular trabecular muscles were superfused with a low-Na+ solution ([Na+]o:50, 25, 18, and 14 mM), obtained by substituting choline-Cl for NaCl at 30 degrees C on the stage of an inverted microscope and electrically stimulated at the rate of 12 pulses/min (n = 6). Each low-Na+ perfusion decreased developed tension with the increase in resting tension (Ca2+ overload). As [Na+]o decreased below 50 mM, peak contracture tension increased and developed tension at peak contracture decreased. The decrease in developed tension coincided with the appearance of the marked aftercontractions and with the increase in fluctuating intracellular contractile activities during the resting period, which have been ascribed to [Ca2+]i oscillations. Neither maximum rate of tension development nor minimum rate of relaxation showed significant changes during the phase of Ca2+ overload. These results suggest that the decrease in developed tension during Ca2+ overload is due to [Ca2+]i oscillations, rather than due to depressed contractility and relaxation.
Vasoconstrictor role for vasopressin in conscious, sodium-depleted rats
Authors: Jover B. , Dupont M. , Mimran A. , Woods R. , McGrath B.
Published: December 2017

To define the role of vasopressin as a vasoconstrictor hormone in sodium depletion, systemic hemodynamics and regional blood flow distribution were examined in conscious Sprague-Dawley rats after 6 days of a low-sodium diet. Studies were performed after selective or combined blockade with the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP (AVPA), enalaprilat (CEI), and phentolamine (PHENTOL). Plasma levels of vasopressin were increased significantly after CEI and increased further after PHENTOL and CEI plus PHENTOL. AVPA had no effect on blood pressure, whether given alone or in the presence of PHENTOL, CEI, or CEI plus PHENTOL. Significant falls in peripheral vascular resistance associated with reflex increases in cardiac output were observed when AVPA was given to animals pretreated with either CEI or PHENTOL but not both. AVPA alone produced no significant changes in regional blood flow distribution, but a vasoconstrictor action of vasopressin in the renal vascular bed was revealed after prior treatment with CEI or PHENTOL. Muscle blood flow was also increased in the PHENTOL plus AVPA group compared with the PHENTOL group. No significant additional effects of AVPA were revealed by pretreatment with CEI, PHENTOL, or CEI plus PHENTOL for mesenteric, hepatic, splenic, or cerebral vascular beds. It is suggested that vasopressin acts as a vasoconstrictor hormone in conscious sodium-depleted rats when either the renin-angiotensin system or alpha-adrenergic system is inhibited but not when both systems are blocked. The renal vascular bed is an important site for vasopressin-induced vasoconstriction under these circumstances.
Carotid and aortic baroreceptor control of heart rate in conscious monkey
Authors: Barazanji M. W. , Cornish K. G.
Published: December 2017

This study looks at the difference between the aortic and the carotid baroreceptors in controlling the heart rate of conscious monkeys in the cage vs. the laboratory. Macaca mulatta and M. radiata underwent sequential baroreceptor denervation by first stripping the aortic arch, then one carotid sinus, and finally the second carotid sinus [sinoaortic denervation (SAD)]. Four monkeys had the carotid sinuses denervated before denervation of the aortic arch. Mean arterial blood pressure (MABP)-heart rate (HR) curves were determined by infusing nitroprusside and phenylephrine hydrochloride. The peak sensitivity (PS) was significantly less for all animals (control and denervated) in the laboratory than in the cage (P less than 0.05) with the exception of the SAD animals, which showed no difference. There was no significant difference in sensitivity between control and aortic-denervated animals in the cage. The PS decreased significantly after denervation of aortic arch and one carotid sinus. Monkeys with only the aortic baroreceptors intact had gains for the baroreflex curves that were similar to that of the SAD animals. After complete SAD the PS were essentially zero. We concluded that 1) the maximum slope of the MABP-HR reflex is greater when the monkey is in the cage than it is in the laboratory, probably resulting from an increase in the sympathetic tone; and 2) the carotid baroreceptors exert a greater influence on the HR component of the baroreflex in the conscious monkey than do the aortic baroreceptors.
Arterial pressure after chronic reductions in suprarenal aortic flow in fetal lambs
Authors: Anderson D. F. , Parks C. M. , Faber J. J.
Published: December 2017

Experiments were performed on 13 fetal lambs of 126 days gestational age. Seven days after surgery, suprarenal aortic blood flow was reduced to 70% of control with an inflatable occluder for a period of at least 4 days. This produced an almost constant aortic pressure difference of 35 mmHg across the occluder. Plasma renin activity (PRA) rose in the next hour from 6 to 42 ng.ml-1.h-1 (P less than 0.01) but decreased to a level that was statistically insignificantly above normal by the next day. PRA as a function of lower body arterial blood pressure showed rapid adaptation. Upper body arterial blood pressure was statistically significantly elevated by 5 mmHg within 5 min and continued to rise while plasma renin activity was falling. Femoral artery blood pressure dropped immediately but returned to near normal within 1 h and remained there. The long-term upper body hypertension was irreversible with a 30-min infusion of saralasin. Subrenal aortic flow reduction caused none of these changes. We conclude that the fetal kidneys can regulate arterial blood pressure upward but that the long-term effect does not depend solely on a direct vasoconstrictive action of angiotensin.
Alterations in the microvasculature of one-kidney, one-clip hypertensive rats
Authors: Hashimoto H. , Prewitt R. L. , Efaw C. W.
Published: December 2017

The microcirculation was studied in the cremaster muscle of one-kidney, one-clip (1K-1C) hypertensive rats and uninephrectomized controls under chloralose-urethan anesthesia 1-2, 4-5, or 8-9 wk following renal artery stenosis. With the use of television microscopy, inside and outside diameters of first (1A) through fourth-order (4A) arterioles were measured before and after vasodilation with 10(-4) M adenosine. Mean arterial blood pressure was significantly elevated in the 1K-1C rats, rising to 170 +/- 6 mmHg by 8-9 wks vs. 93 +/- 2 mmHg in controls. Enhanced vasoconstriction, resulting in closure of arterioles, appeared only in the smaller arterioles of 1K-1C and diminished throughout the development of hypertension. Structural rarefaction appeared later and increased with the development of hypertension. Vasodilated inside diameters of control, but not 1K-1C, 1A, 2A, and 3As, increased with increasing age, leaving the hypertensive arterioles with structurally reduced lumens and increased wall-to-lumen ratios, but without increases in wall cross-sectional areas. Structural lumen reduction appeared first in the 1A and advanced downstream as hypertension developed. Thus vasoconstriction of the smallest arterioles is important initially in renal hypertension, but structural alterations become more important later.
Expression of single calcium channels in Xenopus oocytes after injection of mRNA from rat heart
Authors: Moorman J. R. , Zhou Z. , Kirsch G. E. , Lacerda A. E. , Caffrey J. M. , Lam D. M. , Joho R. H. , Brown A. M.
Published: December 2017

Oocytes of Xenopus laevis, after microinjection with mRNA from rat heart, display typical high-threshold calcium (Ca) whole cell currents. To prepare to study structure-function relationships of the cardiac Ca channel molecule, we examined the fidelity of expression of biophysical and pharmacological properties at the molecular level. Cell-attached gigaseal recordings in five K-depolarized oocytes injected with adult rat heart mRNA showed single channel Ba currents with mean amplitude 1.3-1.5 pA at 0 mV, slope conductance 18-25 pS, and extrapolated reversal potential 57-68 mV. Openings were predominantly brief (mean 1.2 ms) but longer openings (mean 9 ms) were greatly enhanced in 10(-6) M BAY-K 8644, increasing the ensemble average current at 0 mV by more than fivefold. These features are typical of high-threshold cardiac Ca channels. In two patches from one injected oocyte, we saw multiple Ca channel conductances, as recently observed in other preparations. We conclude that X. laevis oocytes injected with adult rat heart mRNA produce high-threshold cardiac Ca channels with molecular properties identical to native cells.
Fibrin has larger pores when formed in the presence of erythrocytes
Authors: Carr M. E. , Hardin C. L.
Published: December 2017

Due to difficulties caused by the presence of hemoglobin-containing erythrocytes, the structures of whole blood clots have not been reported. A perfusion technique described herein allowed the study of plasma and blood clots. Gel fiber diameter, fiber mass-to-length ratio, and average pore diameter were calculated from measurements of solvent flow through gels. When perfused with saline, intact erythrocytes washed from clots of whole blood. Subsequent perfusion with water resulted in rapid hemolyzing of remaining erythrocytes and flushing of hemoglobin from the network. The minimal impact of erythrocytes on fibrin fiber structure was indicated by similar fiber mass-to-length ratios, 7.4 vs. 9.3 X 10(13) Da/cm, for plasma and blood clots, respectively. Pore sizes were larger in gels formed in the presence of erythrocytes, increasing from 3.3 X 10(-4) cm for plasma gels to 5.1 X 10(-4) for gels containing 20% erythrocytes. The washing of red cells from clots confirmed calculated clot pore sizes (approximately 5 microns) and was testimony to the size of the spaces within the gel. Egress of cells and macromolecules to the site of injury during wound healing may be a function of the size of these spaces. The demonstrated applicability of this technique should allow study of this question.
Monophasic action potentials during induced hypothermia in hedgehog and guinea pig hearts
Authors: Duker G. , Sjoquist P. O. , Johansson B. W.
Published: December 2017

To evaluate mechanisms behind the difference in susceptibility to ventricular fibrillation (VF) between the guinea pig and hedgehog heart, the cardiac electrophysiology of the two species was studied at normal body temperature and at different hypothermic levels by simultaneous recording of the monophasic action potential (MAP) and the external electrocardiogram (ECG). At normal body temperature, the duration of the ventricular MAP was significantly shorter in the hedgehog (93 +/- 8.1 ms) than in the guinea pig (138 +/- 2.6 ms). There was a distinct plateau phase in the guinea pig, whereas no such phase could be detected in the hedgehog. During hypothermia, a similar increase in MAP duration at full repolarization was noticed for both species. However, the prolongation of the MAP at lower repolarization levels was much less in the hedgehog. Besides, hypothermia-induced slow conduction and dispersion of ventricular repolarization was much more apparent in the guinea pig heart compared with the hedgehog heart. These differences may be important factors in the resistance to VF in the hedgehog, at normal body temperature and during hypothermia.
Relationship of myocardial metabolism and coronary flow: dependence on extracellular calcium
Authors: Rumsey W. L. , Wilson D. F. , Erecinska M.
Published: December 2017

The hypothesis that extracellular [Ca2+] ([Ca2+]e) influences the transmission of vasoregulatory information from the heart to coronary smooth muscle was examined. The isolated, retrogradely perfused rat heart was used to evaluate vascular reactivity to transient infusion of either 0.88 mM Amytal (amobarbital), hypoxia (95% N2-5% CO2), or 12 microM adenosine in the presence and absence of 2.5 microM verapamil. Amytal alone enhanced coronary flow by 78% and lactate efflux by 10-fold, whereas it decreased O2 consumption by 40% and the ratio of the free cytosolic concentrations of ATP-to-ADP times the intracellular concentration of inorganic phosphate ([ATP]f/[ADP]f[Pi]) by 10-fold. These responses were attenuated by preperfusion with verapamil, i.e., flow and lactate efflux increased by 4% and fourfold, respectively, and O2 consumption and [ATP]f/[ADP]f/[Pi] decreased by 8% and threefold, respectively, as compared with values attained with verapamil at steady state. Washout of the calcium channel antagonist by perfusion for 55 min with a verapamil-free medium resulted in a return of metabolic variables to control levels. Subsequent infusion of Amytal induced metabolic changes that were similar to those obtained before exposure to the calcium antagonist, but flow rose only by 26%. Vascular responses to hypoxia were similarly modified, whereas those to adenosine were unaffected. Hearts perfused with media containing either low [Ca2+]e or 10 microM diltiazem and exposed to Amytal produced flow patterns analogous to those perfused with verapamil. These data, in part, distinguish changes in vascular resistance that occur in response to cardiac metabolism from those which result from agents with direct action on smooth muscle, in particular, adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)