bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue-type plasminogen activator release in response to epinephrine in perfused rat hindlegs
Authors: Zhu G. J. , Abbadini M. , Donati M. B. , Mussoni L.
Published: December 2017

We have studied the mechanism of release of plasminogen activator (PA) activity induced by epinephrine in the perfused rat hindleg model. Epinephrine perfusion at the dose of 12.5 microM caused a slighter effect on PA activity but an immediate increase in the perfusion pressure. At 25 microM, epinephrine induced a marked increase in PA activity that reached the maximum level at the end of the drug perfusion. The same response was induced by repeated stimulations with epinephrine (25 microM) only if the second stimulus was given 20-25 min apart from the first one. PA release could be blocked by propranolol (300 microM), a nonspecific beta-blocker, and not by phentolamine, a nonspecific alpha-blocker, unless used at very high concentrations (1,250 microM). Perfusion with dibutyryl adenosine 3',5'-cyclic monophosphate (DbcAMP) alone induces an immediate and transient increase in PA activity, but no potentiation could be demonstrated if theophylline was perfused together with epinephrine. The released PA has been characterized on the basis of molecular weight and immunological criteria as t-PA- and u-PA-like molecules in basal conditions. Epinephrine perfusion induced an increase only in the t-PA-like protein. These data indicate that the release of t-PA-like activity observed after epinephrine perfusion is mainly mediated by beta-receptors and is independent from its vasoactive action.
Vagal stimulation decreases rate of left ventricular relaxation
Authors: Henning R. J. , Cheng J. , Levy M. N.
Published: December 2017

We determined the effects of vagal stimulation on the time constant (tau) of left ventricular isovolumic pressure decay and on the maximum rates of left ventricular pressure change (dP/dt) during contraction and relaxation in anesthetized dogs. In each dog, the atria were paced at a constant rate of 150 beats/min. We recorded left ventricular pressure waveforms in the absence (control) and in the presence of vagal stimulation at frequencies of 1, 2, and 3 Hz. During the control periods and during vagal stimulation at each frequency, we determined tau, the maximal rate of contraction, and the maximal rate of relaxation from left ventricular pressure waveforms recorded at medium (100 mmHg), high (130 mmHg), and low (73 mmHg) afterloads. Vagal stimulation at a frequency of 3 Hz increased tau by 23%. This effect of vagal stimulation on tau was most pronounced at the high afterload. Vagal stimulation at 3 Hz decreased the maximal rate of relaxation by 19%, but it decreased the maximal rate of contraction by only 8%. Thus vagal stimulation significantly decreased the rate of left ventricular relaxation and had a greater depressant effect on ventricular relaxation than on contraction.
Effect of sinoaortic denervation on arousal responses to hypotension in newborn lambs
Authors: Horne R. S. , Berger P. J. , Bowes G. , Walker A. M.
Published: December 2017

To examine whether hypotension reflexly initiates arousal from sleep and the mechanisms involved, we subjected sleeping lambs to hypotensive stimuli of 1-min duration, before and after sinoaortic denervation (SAD). In intact lambs, hypotension increased the probability of arousal from both quiet sleep (QS) and rapid-eye-movement (REM) sleep. Hypotension resulted in nonarousal in 42% (QS) and 47% (REM) of tests. Arousal time was significantly longer in REM (34.9 +/- 1.8 s, means +/- SE) than in QS (26.0 +/- 1.8 s). Arterial saturation of O2 (SO2) and PO2 measured at the point of arousal were unchanged from control values in those tests in which arousal occurred. In nonarousal tests, there was a significant fall in both SO2 (4.9 +/- 1.2%) and PO2 (21.6 +/- 4.2 mmHg). After SAD, hypotension did not increase the probability of arousal. Nonarousals significantly increased to 75% (QS and REM, P less than 0.02). We conclude that acute hypotension is a potent stimulus for arousal from sleep in newborn lambs. As the arousal response is abolished by SAD and is not correlated with arterial oxygenation, hypotensive arousal appears to be mediated via arterial baroreceptors.
Pressure-flow characteristics of coronary collaterals in dogs
Authors: Scheel K. W. , Mass H. , Williams S. E.
Published: December 2017

In this study we utilized two methods to investigate the pressure-flow, P-F, relationship of the coronary collateral vessels in a beating, blood-perfused, isolated heart preparation. In the first method (free-flow method), 12 dog hearts were perfused at pressures ranging from 100 to 0 mmHg, whereas the retrograde flow (index of collateral flow) was measured on the circumflex coronary artery, LCA, against atmospheric pressure, first during autoregulation and then after maximum vasodilation. In the second method (back-pressure method), the back pressure to retrograde flow was varied from 0 to 100 mmHg, whereas the perfusion pressure to the remaining vessels was maintained constant at 100 mmHg. This procedure was performed on four hearts with and without embolization of the LCA by 25-microns spheres. The free-flow method demonstrated a linear P-F relationship with an average correlation coefficient, r, of 0.98. The pressure intercept was 1.7 +/- 1.2 mmHg. The back-pressure method yielded a relationship that was more curvilinear with an average pressure intercept of 13 mmHg without embolization and 38 mmHg with embolization. An analog of the coronary and collateral circulation was used to illustrate that, in the back-pressure method, changes in the coronary resistance at low pressures contributed to the nonlinearity of the collateral P-F characteristics and that the network formed between the collateral and coronary resistances was responsible for the higher pressure intercept value.
Lipoxins A4 and B4 dilate cerebral arterioles of newborn pigs
Authors: Busija D. W. , Armstead W. , Leffler C. W. , Mirro R.
Published: December 2017

We determined the effects of lipoxins A4 and B4 on the cerebral microcirculation of neonatal pigs and whether vascular responses were modulated by prostanoids. Pial arteriolar diameters were determined using a closed cranial window and intravital microscopy. Before lipoxin A4 application, arteriolar diameter was 143 +/- 6 microns (means +/- SE). Topical application of lipoxin A4 increased the diameter to 160 +/- 7 microns at 0.1 ng/ml, 167 +/- 7 microns at 1 ng/ml, and 173 +/- 7 microns at 10 ng/ml (n = 9). Before application of lipoxin B4, arteriolar diameter was 146 +/- 7 microns. Topical application of lipoxin B4 increased the diameter to 165 +/- 7, 169 +/- 6, and 175 +/- 6 microns at 0.1, 1, and 10 ng/ml (n = 9), respectively. Intravenous injection of indomethacin (5 mg/kg) or vehicle did not affect these responses. Levels of prostaglandins E2 and F2 alpha in cerebrospinal fluid (measured by radioimmunoassay) did not increase in response to lipoxins. We conclude that lipoxins are dilator stimuli in the cerebral circulation and that prostanoids do not mediate these responses.
d-Propranolol prevents adenosine formation associated with myocardial hypoperfusion
Authors: Wangler R. D. , Peterson W. P. , Sparks H. V.
Published: December 2017

d-Propranolol eliminates the increased adenine nucleoside release from hypoperfused hearts [R. D. Wangler, D. F. DeWitt, and H. V. Sparks, Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H330-H336, 1984]. To determine whether d-propranolol reduces adenosine formation or adenosine release into the vascular compartment, we measured myocardial tissue adenosine (TADO). Decreased formation would lower TADO, whereas decreased release would elevate TADO. Reduction of perfusion pressure by 50% reduced coronary flow (CF), venous oxygen tension (PVO2), and myocardial oxygen consumption (MVO2) by approximately 40, 25, and 35%, respectively. Total adenosine and inosine released during 30 min of hypoperfusion increased 10- and 5-fold, respectively. Also, TADO increased from 2.68 +/- 0.37 to 5.17 +/- 0.67 nmol/g (P less than 0.05). In the presence of d-propranolol, the same reduction in perfusion pressure caused a similar decrease in CF and MVO2. d-Propranolol eliminated the release of adenosine and inosine associated with hypoperfusion. TADO after 30 min of hypoperfusion plus d-propranolol was not significantly increased (3.27 +/- 0.40 nmol/g) and was significantly less than hypoperfused hearts. When severe hypoperfusion was created by reducing perfusion pressure 75%, adenosine release still did not increase if d-propranolol was present. When adenosine release was plotted as a function of oxygen supply-consumption, they were related in a hyperbolic fashion. Despite the severity of hypoperfusion, in the presence of d-propranolol the supply-to-consumption ratio was similar to that of the control perfusion group (no drug). We conclude that d-propranolol blocks nucleoside formation during hypoperfusion by reducing oxygen demand such that a reduction of oxygen supply no longer stimulates adenosine formation.
Conduction of vasomotor responses in arterioles: a role for cell-to-cell coupling?
Authors: Segal S. S. , Duling B. R.
Published: December 2017

Vasomotor responses of arterioles triggered by the iontophoretic application of acetylcholine (ACh) or norepinephrine (NE) are conducted along the vessel wall. The present experiments focus on elucidating the mechanism of conduction in arterioles of the superfused cheek pouch preparation in pentobarbital-anesthetized hamsters. Localized muscarinic or adrenergic receptor blockade on an arteriolar segment produced by atropine or phentolamine, respectively, did not affect propagation through the region of blockade but did block vasomotor responses to ACh or NE applied to the segment. Thus muscarinic and alpha-adrenergic receptors can trigger the propagation of vasomotor responses, but these receptors are not involved in their conduction. Tetrodotoxin did not affect either local or propagated responses to ACh or NE. Treatment of arteriolar segments with calcium antagonists (verapamil, diltiazem, nifedipine, or manganese) caused maximal dilation locally but did not affect propagation through the dilated region. The preceding findings argue against a neural pathway for propagation. A depolarizing solution (137 mM KCl) applied by micropipette to arteriolar segments caused both local and propagated vasoconstriction and significantly attenuated propagated vasodilation induced with ACh (P less than 0.05). Putative antagonists of gap-junctional communication (hypertonic sucrose solution, octanol, CO2) reversibly attenuated or abolished propagated responses. We hypothesize that propagation of vasomotor responses along arterioles is initiated via a local change in membrane potential secondary to receptor occupation and that changes in potential spread electrotonically through gap junctions coupling smooth muscle cells, endothelial cells, or both.
Leukocyte effects on microcirculation in artificially perfused rat lungs
Authors: Braide M. , Sonander H. , Johansson B. R. , Bagge U.
Published: December 2017

Evidence indicates that leukocyte microvascular flow obstructions play an important role in no-reflow phenomena after ischemia and that leukocytes may cause significant disturbances of capillary perfusion in low flow states. In the present study, a cell-free colloid perfusion (20-60 ml.kg-1.min-1) of isolated ventilated rat lungs was interrupted by bolus injections of leukocytes in varying numbers. Leukocyte effects on flow resistance, tracer gas exchange, and micromorphology were evaluated. The vast majority of the infused leukocytes remained trapped in the lungs after repeated infusions regardless of the number of leukocytes given, although leukocyte trapping decreased at the higher flow rates. The functional and morphological analyses showed that the polymorphonuclear granulocytes had a greater tendency than the mononuclear cells to become permanently trapped in the pulmonary capillaries. The tracer gas analyses indicated that the trapped leukocytes were scattered in the alveolar capillary networks and did not cause complete exclusion of flow from the affected alveoli. This was probably due to the anatomy of the pulmonary microvasculature, with its abundancy in interconnecting pathways.
Rabbit myocardial 82Rb kinetics and a compartmental model for blood flow estimation
Authors: Huang S. C. , Williams B. A. , Krivokapich J. , Araujo L. , Phelps M. E. , Schelbert H. R.
Published: December 2017

Quantification of regional myocardial blood flow (MBF) with rubidium-82 (82Rb) and positron emission tomography (PET) requires the validation of a tracer kinetic model that adequately describes the kinetics of 82Rb in tissue. We performed 134 82Rb kinetic experiments in 24 isolated, arterially perfused rabbit interventricular septa at different flow rates (0.5-4.5 ml.min-1.g-1) and under the following conditions: varied concentrations of glucose (2.8-11 mM), insulin (0-5 mU/ml), and potassium (5-8 mM); varied pH (7.2-7.8); varied workload; and the addition of acetylstrophanthidin (1.0 microM). The measured 82Rb tissue time-activity curves consisted of two exponential components, with half times inversely related to MBF. The size of the slow component decreased as MBF increased (from 70% at 0.3 ml.min-1.g-1 to 30% at 2.0 ml. min-1.g-1). The kinetics were not strongly dependent on the conditions studied and were consistent with a compartmental model containing two communicating compartments. The volume of the fast exchangeable compartment and the transport rate constant from the fast to the slow compartment were found to be independent of MBF. Values of MBF were estimated with the compartmental model from 82Rb kinetics, and they correlated well with the directly measured MBF (r = 0.91; slope = 1.03).
Preservation of coronary flow reserve in stunned myocardium
Authors: Jeremy R. W. , Stahl L. , Gillinov M. , Litt M. , Aversano T. R. , Becker L. C.
Published: December 2017

Microvascular obstruction and persistent focal ischemia have been suggested as a possible cause of myocardial dysfunction (stunning) after brief coronary occlusion. Microvascular occlusion should result in a reduction in maximal coronary flow reserve, although resting transmural coronary flow may be maintained by release of local vasodilators, such as adenosine. To test the microvascular occlusion hypothesis, coronary flow reserve was measured in 14 anesthetized dogs, before and after myocardial stunning produced by 10 min of ischemia. Intracoronary adenosine infusion (5,900 microM/min) increased coronary flow to the same degree in normal [195 +/- 20 (SE) ml/min] and stunned (212 +/- 23 ml/min) myocardium. Peak hyperemic flow after 100 s of coronary occlusion was also similar in normal (205 +/- 25 ml/min) and stunned (218 +/- 23 ml/min) myocardium. The adenosine antagonist 8-phenyltheophylline (5 mg/kg) reduced the flow response to exogenous adenosine, but neither resting coronary flow nor peak hyperemic flow in stunned myocardium was altered. In stunned myocardium, myocardial shortening at rest (0.2 +/- 2.0%) increased during reactive hyperemia (to 13.8 +/- 2.5%, P less than 0.01), but shortening promptly returned to basal levels after each hyperemia. These findings indicate that fixed microvascular occlusion is unlikely to be an important factor in the pathogenesis of stunned myocardium and that local adenosine release does not appear to have a compensatory role in coronary vasoregulation in stunned myocardium.
Diabetes alters postischemic response to a prostacyclin mimetic
Authors: Pieper G. M. , Gross G. J.
Published: December 2017

Eicosanoid metabolism is altered by diabetes. However, postischemic responses of diabetic hearts (DH) to eicosanoids such as prostacyclin are unknown. a prostacyclin analogue iloprost (Ilo) was given to isovolumically beating rat hearts during 20 min of total global ischemia and 30 min of reperfusion. Acute DH (48 h) but not chronic DH (2 mo) had pronounced postischemic dysfunction (developed pressure = 22 +/- 11%), which was completely reversed by 3 X 10(-8) M Ilo (developed pressure = 113 +/- 15%). Ilo also stimulated endogenous prostacyclin release in postischemic control hearts (CH) but not acute or chronic DH. Ilo significantly decreased postischemic recovery in CH (from 67 +/- 11 to 15 +/- 4%), which was partially blocked by the coadministration of the calcium-entry blocker diltiazem or almost completely reversed by the free radical scavengers superoxide dismutase plus catalase (100 U/ml). These data suggest that Ilo may promote functional recovery in DH at concentrations that produce dysfunction in CH. Furthermore, Ilo may induce dysfunction in CH by a calcium ionophoretic action, which appears depressed in diabetes, and by concomitant free radical production (presumably via prostaglandin hydroperoxidases) during Ilo-stimulated endogenous prostacyclin synthesis.
Hydraulic conductivity of endothelial cell monolayers cultured on human amnion
Authors: Luckett P. M. , Fischbarg J. , Bhattacharya J. , Silverstein S. C.
Published: December 2017

Hydraulic conductivity (Lp) of endothelial cell monolayers cultured on a supporting matrix of human amnion was measured. Bovine aortic (Baec), bovine microvascular (Bmec), and human umbilical vein endothelial cell (Huvec) monolayers were mounted in a water-jacketed chamber maintained at 37 degrees C. The lower compartment of the chamber was connected to an electronic sensor-aspiration system that served to volume clamp the lower compartment. The aspirated volume was displayed on a chart recorder, providing continuous measurements of volume flow per unit area (Jv). In 36 monolayers, Jv was linearly related to hydrostatic pressure. The average slope of this relationship (Lp) was 1.14 +/- 0.8 X 10(-6), 1.67 +/- 1.49 X 10(-6), and 2.9 +/- 0.85 X 10(-6) cm.s-1.cmH2O-1 for Baec, Bmec, and Huvec, respectively. The effect of increased luminal oncotic pressure was studied in seven monolayers. The oncotic pressure difference (delta pi) ranged from 3.1 to 7.1 cmH2O (measured with a Wescor oncometer). In all cases, there was an immediate fall in Jv and a displacement to the right of the x-intercept of the line Jv vs. change in pressure (delta P) without a change in the slope (Lp). These results indicate that the Lp of endothelial cell monolayers cultured on amnion is within the range of values previously reported for single capillaries in vivo and that these monolayers appear to sustain delta pi sufficient to generate an osmotically driven water flow.
Pulsatile activation of baroreceptors causes central facilitation of baroreflex
Authors: Chapleau M. W. , Hajduczok G. , Abboud F. M.
Published: December 2017

The reflex decrease in arterial pressure is greater and more sustained with elevated pulsatile than with elevated static carotid sinus pressure. The purpose of this study was to relate afferent baroreceptor activity (BRA) and efferent sympathetic nerve activity (SNA) during static and pulsatile pressure to evaluate the influence of pulsatile pressure on the central mediation of the baroreflex. The carotid sinuses were isolated in 11 dogs anesthetized with chloralose. Both vagosympathetic trunks were cut and both carotid sinuses exposed to static and pulsatile pressures over a range of mean carotid sinus pressures (40-180 mmHg). BRA was recorded from one carotid sinus nerve, and the other intact carotid sinus served to initiate reflex changes in lumbar or renal SNA and arterial pressure. For the same mean carotid sinus pressure, pulsatile pressure caused significantly greater inhibition of SNA than static pressure. More importantly, for the same or lesser levels of baroreceptor activity per second, pulsatile pressure caused significantly greater inhibition of SNA than static pressure. The inhibition of SNA was not sustained (i.e., there was "adaptation") with continuous baroreceptor input during static pressure, whereas the inhibition of SNA was sustained (i.e., there was no significant adaptation) with the phasic input during pulsatile pressure. Increases in pulse frequency from 1.4 to 2.5 and 3.7 Hz caused progressively less inhibition of SNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemorrhagic shock complicated by chronic ethanolism
Authors: Horton J. W.
Published: December 2017

To evaluate the effects of chronic ethanolism on responses to hemorrhagic shock (HS), 24 dogs were fed a diet mixed with 3 g/kg ethanol (ETOH) for 3 mo (group 1, n = 12) and 9 mo (group 2, n = 12); 12 dogs were fed a regular diet with no alcohol. Blood alcohol level 2-3 h after food consumption was 116 +/- 10 mg/100 ml. On the experimental day, both ETOH-treated and ETOH-free dogs were divided into two subgroups, one for HS [mean arterial pressure (MAP) of 30 mmHg for 2 h] and one for observation during anesthesia. Chronic ethanolism altered cardiocirculatory function (increased MAP, arterial lactate, and hematocrit and decreased cardiac output, stroke work, and pancreatic blood flow) regardless of the length of time ETOH was consumed. HS impaired cardiovascular performance regardless of ETOH consumption. However, coronary blood flow, myocardial oxygen delivery, extraction, and consumption were significantly higher in the ETOH-treated compared with ETOH-free dogs after 2 h of shock. Cardiocirculatory dysfunction after fluid resuscitation from shock in the ETOH group was not related to inadequate coronary perfusion, metabolic acidosis, or cardiac hypertrophy. An increased total myocardial tissue calcium content in the ETOH group suggests that ETOH-mediated changes in calcium homeostasis contribute to cardiac contractile dysfunction in the trauma subject who chronically consumes alcohol.
Cerebral ischemia alters cerebral microvascular reactivity in newborn pigs
Authors: Leffler C. W. , Beasley D. G. , Busija D. W.
Published: December 2017

The effects of cerebral ischemia on cerebral microvascular reactivity and prostanoid synthesis were examined in chloralose-anesthetized newborn pigs. Microvascular responses and periarachnoid cerebrospinal fluid (CSF) prostanoid concentrations were determined between 10 and 140 min after a 20-min period of total cerebral ischemia, as well as in sham-control piglets without cerebral ischemia. After cerebral ischemia, the decrease in pial arteriolar diameter in response to topical norepinephrine (10(-4) M) was similar in sham (-27 +/- 6%) and postischemic (-25 +/- 5%) piglets. However, the increase in pial arteriolar diameter in response to hypercapnia (10% CO2 ventilation) that was observed in sham piglets (+21 +/- 5%) was absent after ischemia (-2 +/- 3%). In contrast, dilations of pial arterioles in response to topical prostaglandin (PG)E2 (at 100 ng PGE2/ml: sham, +13 +/- 3%; postischemia, +21 +/- 4%) and topical isoproterenol (10(-6) M) (sham, +29 +/- 4%; postischemia, +23 +/- 3%) were not decreased by prior cerebral ischemia. In sham piglets, norepinephrine and hypercapnia produced increases in cortical periarachnoid prostanoid concentrations, whereas after cerebral ischemia, neither stimulus increased cortical periarachnoid prostanoid concentrations. The results are consistent with the hypothesis that failure of hypercapnia to dilate pial arterioles after cerebral ischemia results from the inability of this stimulus to increase cerebral vasodilator prostanoid synthesis.
Calf sweat lactate in peripheral arterial occlusive disease
Authors: Fellmann N. , Fabry R. , Coudert J.
Published: December 2017

The energy metabolism of sweat glands was studied to evaluate the reduction in oxygen delivery in the tissue of patients with peripheral arterial occlusive disease. We compared lactate concentration in pilocarpine-iontophoresis sweat collected from the middle calf area ([ L]sw) of 10 healthy subjects (group 1) and 84 patients suffering from intermittent claudications (group 2, n = 49), from rest pain (group 3, n = 21), and from severe ischemic skin changes (group 4, n = 14). In addition, the effect of a vasoactive drug (naftidrofuryl, 600 mg) or placebo infusion on [L]sw was investigated (n = 30). Results (means +/- SE) showed that 1) [L]sw (mmol/l) increased significantly with the severity of the symptoms: group 1 = 16.5 +/- 0.4, group 2 = 18.7 +/- 0.4, group 3 = 22.8 +/- 0.9, and group 4 = 27.5 +/- 2.0; and 2) [L]sw was reduced by 10% (P less than 0.01) after naftidrofuryl infusion, whereas there was no change after placebo infusion. We suggest that lactate in calf sweat is a good indicator in the evaluation of the severity of peripheral occlusive arterial disease and in assessing the efficiency of vasoactive drug treatment.
Cardiac adaptations to aortic constriction in adult and aged rats
Authors: Boluyt M. O. , Opiteck J. A. , Esser K. A. , White T. P.
Published: December 2017

Myocardial function in vitro and myosin heavy chains (MHCs) were studied in control and hypertrophied hearts of adult (9-10 mo) and aged (25-28 mo) female Fischer 344 rats 7 days after aortic constriction. Aortic constriction increased left ventricular mass to 110 and 112% of the control values of 484 +/- 12 and 617 +/- 18 (SE) mg in adult and aged rats, respectively. After aortic constriction, there was a significant age-related difference in the adaptation of peak pressure development in vitro, as peak left ventricular systolic pressure increased and decreased in hearts of adult and aged rats. The maximum rate of pressure development in control hearts of aged rats was 79% of the adult value of 11,264 +/- 1,527 mmHg/s; hypertrophy did not alter values of either age group. alpha-MHC accounted for 82 +/- 1 and 48 +/- 3% of the total left ventricular MHC for the adult and aged control groups, respectively, and values were not altered by aortic constriction. With hypertrophy 7 days after aortic constriction, there is an impairment in the adaptation of left ventricular function in hearts of aged compared with adult rats. This impairment is not explained by alterations in MHC isoform.
Validation of laser-Doppler flowmetry in measurement of spinal cord blood flow
Authors: Lindsberg P. J. , O'Neill J. T. , Paakkari I. A. , Hallenbeck J. M. , Feuerstein G.
Published: December 2017

Laser-Doppler flowmetry (LDF) is a non-invasive method for continuous on-line monitoring of microvascular blood flow. LDF has previously been validated with established methods in various tissues, yet its validity and resolution in the central nervous system (CNS) remain unclear. We compared LDF with the microsphere method (MS) using two independent laser probes placed on the dorsal lumbar spinal cord (L5 laminectomy) of anesthetized rabbits (n = 9). After base-line flow measurements, spinal cord blood flow (SCBF) was increased (up to 50%) with phenylephrine (10-80 micrograms.kg-1.min-1 iv) and decreased (up to 50%) with chlorisondamine (10 mg/kg iv) or other stimuli. The percentage changes of lumbar SCBF and vascular resistance (VR) from the base line obtained by LDF and MS excellently agreed (rBF = 0.86, rVR = 0.94, P less than 0.0001). LDF estimated also the absolute SCBF values parallel to MS (r = 0.77, P less than 0.001). In conclusion, the validity of LDF in estimating the SCBF and dynamic changes of BF and VR is confirmed. Therefore, LDF may prove useful for monitoring CNS microcirculation in normal or pathophysiological states.
Effect of enkephalins on cardiac output and regional blood flow in conscious dogs
Authors: Rosen C. L. , Cote A. , Haddad G. G.
Published: December 2017

Page H1656: C. L. Rosen, A. Cote, and G. G. Haddad. “Effect of enkephalins on cardiac output and regional blood flow in conscious dogs.” Figures 5 and 6 should appear as follows.

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Estimation of capillary reflection coefficients and unique PS products in dog paw
Authors: Reed R. K. , Townsley M. I. , Taylor A. E.
Published: December 2017

Lymphatic protein flux (Js) obtained in canine hindpaws at low lymph flows were used to determine the capillary osmotic reflection coefficients (sigma d) and unique permeability surface area (PS) products for total proteins, albumin, immunoglobulin (Ig)G, and IgM. This new analysis is based on the phenomenon that when maximal diffusion occurs across the capillary membrane, the Peclet number [x = Jv(1 - sigma d)/PS] attains a unique value defined only by sigma d. The diffusive flux is maximal when the relationship between protein flux and transcapillary fluid flux (Jv) changes from a curvilinear to a linear relationship. The slope of the linear portion of this protein flux relationship was used to determine sigma d as (1 - sigma d) = delta Js/(delta JvCp), where Cp is the plasma protein concentration. With the use of sigma d, the Jv at which the maximal diffusion occurred, and the corresponding Peclet number, a unique value is obtained for the PS product. Experiments performed using lymph from canine hindpaws (n = 6) yielded sigma d's (mean +/- SD) of 0.91 +/- 0.03, 0.83 +/- 0.11, 0.96 +/- 0.03, and virtually 1 for total protein, albumin, IgG, and IgM, respectively. The corresponding PS products for total protein, albumin, and IgG were 25.0 +/- 13.2, 28.4 +/- 6.6, and 14.0 +/- 7.9 microliters.min-1.100 g-1, respectively; PS for IgM was almost zero.(ABSTRACT TRUNCATED AT 250 WORDS)
Collateral influence on pressure-flow characteristics of coronary circulation
Authors: Scheel K. W. , Mass H. , Williams S. E.
Published: December 2017

The purpose of this study was to determine the role of the coronary collateral circulation on the shape of the coronary pressure-flow (P-F) relationship and its effects on the pressure at zero flow (PZF) or pressure intercept. We investigated the P-F characteristics of the coronary circulation under two conditions. 1) To minimize the influence of collaterals, we measured coronary flow by timed collections of coronary sinus outflow in 15 dog hearts, as perfusion pressure to all vessels was varied; 2) to maximize the effect of collaterals, we measured circumflex artery flow in six dog hearts, as perfusion pressure to only the circumflex coronary artery was varied and the pressure in the remaining vessels was maintained constant. We used an isolated heart preparation in which ventricular chamber and venous outflow pressures equalled atmospheric pressure and the vessels were maximally dilated with adenosine. In the first condition, the P-F relationship was curvilinear with a PZF of 0 mmHg; in the second condition, the P-F relationship was curvilinear with a PZF of 16 +/- 2 mmHg, and flow was retrograde at pressures below PZF. We conclude that in both conditions the curvilinearity of the coronary P-F relationship was the result of nonlinear elastic properties of blood vessels, not requiring the “waterfall” concept to be invoked, and that in the second condition the influence of collateral vessels produced the positive pressure intercept.
Acidosis depresses delayed afterdepolarization in guinea pig myocardium
Authors: Yano T. , Hotokebuchi N. , Morioka T. , Nishi K.
Published: December 2017

We examined the relationship among intracellular sodium activity (aiNa), intracellular pH (pHi), and delayed afterdepolarization (DAD) in guinea pig ventricular papillary muscle fibers exposed to K-free solution in vitro, using Na+- and H+-selective microelectrodes. In unstimulated papillary muscles, exposure to K-free solution caused a rapid increase in aiNa of 16.2–22 mM at the end of a 20-min superfusion period with rates of 0.51–0.73 mM/min. This was paralleled by a decrease in intracellular pH of 0.10–0.15 units. DADs were induced after a train of driven action potentials 5–15 min after superfusion with K-free solution at the elevated aiNa from the steady-state level. Prevention of intracellular acidosis associated with the increased aiNa in K-free solution by external alkalosis at pH 8.0 enhanced the amplitude of the DAD, whereas restoration of external pH to 7.4 and a further acidification of external pH to 6.4 suppressed DADs. We concluded that intracellular acidosis associated with the increased aiNa per se increased the likelihood for inhibition of sarcoplasmic reticulum Ca2+ release in spite of increased cytosolic Ca2+.
Effects of antiserum against alpha-rat atrial natriuretic polypeptide in spontaneously hypertensive rats
Authors: Sasaki A. , Kida O. , Kita T. , Kato J. , Nakamura S. , Kodama K. , Miyata A. , Kangawa K. , Matsuo H. , Tanaka K.
Published: December 2017

To clarify the physiological role of endogenous atrial natriuretic polypeptide (ANP), we investigated the effects of specific rabbit antiserum against alpha-rat ANP (alpha-rANP) on hemodynamics, diuresis, and natriuresis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous administration of anti-alpha-rANP antiserum caused an obvious rise of mean blood pressure and cardiac output in both SHR and WKY compared with rats administered with normal rabbit serum. Although there was no significant difference in increments of mean blood pressure between SHR and WKY, the increment of cardiac output in SHR was significantly higher than that in WKY. On the other hand, significant reductions in urine output and urinary sodium and potassium excretion lasted for approximately 20 min after administration of the antiserum in both SHR and WKY compared with rats administered with normal rabbit serum. There was no significant difference in these initial maximal decrements between SHR and WKY. These results indicate that endogenous ANP has an important physiological role in the regulation of hemodynamics and water-electrolyte balance in both SHR and WKY. The greater increment of cardiac output in SHR in response to the antiserum suggests that endogenous ANP in SHR may have a stronger cardiosuppressive action that it does in WKY.
Mechanism of Wenckebach periods: hypothesis based on computer modeling experiments
Authors: Malik M. , Camm A. J.
Published: December 2017

Wenckebach periodicity is characterized by progressive lengthening of conduction intervals and by progressive shortening of the intervals between conducted excitations. Although different hypotheses have been suggested to explain the mechanisms of Wenckebach periods, no serious proposition explaining both components of the phenomenon has yet been reported. A computer model simulating detailed mechanisms of excitation transmission and electrotonic interactions between neighboring cardiac cells has been employed to investigate the conduction properties of a one-dimensional cable composed of simulated cells. When introducing gradual prolongation of the recovery phase for the elements in the center of the cable and when incorporating physiologically realistic shapes of premature action potential curves into the simulation experiments, the model was able to reproduce all aspects of Wenckebach periodicity. Systematic evaluation with simulation experiments showed that a shorter duration of premature action potentials (i.e., of action potentials resulting from excitation of a cell before it has been fully repolarized) produced shortening of intervals between conducted excitations during a Wenckebach period.
Analysis of myocardial isometric dynamics using parameters of a global model
Authors: Nwasokwa O. N. , Bodenheimer M. M.
Published: December 2017

Despite previous efforts, a global empirical relation has not been described for the myocardial isometric curve, F(t). We propose here that a useful relation is F(t) = CtB-1e-AtB. A, B, and C are global parameters. We evaluated this model and the effect of change in muscle length (L) and dobutamine on the parameters in nine in situ canine papillary muscles. A servo-system clamped muscle length to produce isometric twitches. For each twitch, the parameters were determined by curve fitting. The model fit the observed curves of F(t) closely; the correlation coefficient was 0.997 +/- 0.001. Whereas C changed with L, A and especially B varied little with L averaging 28.6 +/- 5.2 and 2.42 +/- 0.08, respectively. Our predictions that A reflects chronotropic state, B lusitropic, and C heterometric and inotropic states, were verified with dobutamine. We also derived relations for various attributes of the F(t) curve in terms of A, B, and C only. An excellent correlation was noted between the calculated and the observed values of these attributes. The empirical relation F(t) = CtB-1e-AtB therefore provides a valid cohesive reference frame for analysis of myocardial dynamics.
Rapid cooling contractures as an index of sarcoplasmic reticulum calcium content in rabbit ventricular myocytes
Authors: Hryshko L. V. , Stiffel V. , Bers D. M.
Published: December 2017

Rapid cooling contractures (RCCs) were used to assess changes in sarcoplasmic reticulum (SR) Ca content in both isolated rabbit ventricular myocytes and multicellular preparations. The main difference observed between these preparations was the magnitude of RCCs relative to twitches, apparently due to differences in measured parameters, i.e., unloaded shortening vs. isometric tension. When multicellular preparations were unloaded, RCC shortening was similar to that observed in myocytes. RCC magnitude decreased as the time between the last electrical stimulation and the RCC was increased (rest decay). RCC rest decay closely paralleled that of postrest twitches, suggesting that SR Ca loss is responsible for this process. Paired RCC experiments were used to investigate RCC relaxation and rest decay. When a second RCC (RCC2) was induced immediately after the first (RCC1), a large contracture was still observed (RCC2/RCC1 x 100 = 77.8 +/- 7.3%, mean +/- SD), indicating that the SR resequestered the majority of Ca on rewarming. This fraction was increased (to 92.9 +/- 5.5%) if Na and Ca-free solution was used during RCCs and rewarming, indicating that Na-Ca exchange also contributes to RCC relaxation. Increasing the interval between paired RCCs led to a decrease in RCC2, analogous to rest decay. This rest decay was abolished by inhibiting Na-Ca exchange, indicating that SR Ca loss during rest is mediated primarily by this process. RCCs were abolished by 10 mM caffeine. Ryanodine (1 microM) greatly accelerated RCC rest decay but had less effect on RCCs generated immediately after a train of stimulation. This accelerated rest decay was also dependent on Na-Ca exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Maternal environment and development of high blood pressure in Dahl hypertensive rats
Authors: Murphy C. A. , McCarty R.
Published: December 2017

The contribution of the preweanling maternal environment to the development of hypertension was examined using the technique of reciprocal cross-fostering between two inbred rat strains, the Dahl hypertension-sensitive (SS/Jr) rat and the Dahl hypertension-resistant (SR/Jr) rat. Litters of SS/Jr and SR/Jr pups were reared by their natural mother, in-fostered to a dam of the same strain, or cross-fostered to a dam of the opposite strain for the entire preweanling period from postnatal days 1 to 30. At 60 and 100 days of age, one rat from each litter was surgically prepared with an indwelling catheter in the ventral tail artery. One day after surgery, measures of resting mean arterial pressure and heart rate were taken as the animals were resting and undisturbed in their home cages. Body weights were also obtained at 30, 60, and 100 days of age as a measure of general somatic development. Our findings indicate that SS/Jr rats fostered to SR/Jr dams exhibited a significant reduction in resting mean arterial pressure compared with naturally reared or in-fostered SS/Jr rats (P less than 0.01 at 60 days and P less than 0.03 at 100 days). Conversely, arterial pressure of SR/Jr rats did not differ across rearing conditions at either age. Body weights were not significantly affected by cross-fostering in either strain. We conclude from these results that characteristics of the SS/Jr maternal environment interact with the inbred genetic susceptibility of the SS/Jr pup to elicit the full expression of the SS/Jr hypertensive phenotype.
Varying elastance concept may explain coronary systolic flow impediment
Authors: Krams R. , Sipkema P. , Westerhof N.
Published: December 2017

We measured phasic arterial coronary inflow in the blood-perfused isolated cat heart (n = 5) with a balloon in the left ventricle under well-defined conditions, i.e., constant perfusion pressure, constant vasomotor tone (maximal vasodilation), and heart rate. The normalized amplitude (A) between systolic flow (Fs) and diastolic flow (Fd) [A = (Fd - Fs)/Fd] was related to systolic left ventricular pressure (Ps, range 1.6-17 kPa, 1 kPa = 7.5 mmHg) for different isovolumic beats obtained by changes in balloon volume and for low load isobarically ejecting beats (pressure 0.2 kPa). The data were fitted to A = a + bPs with a = 0.70 +/- 0.15 (SD) and b = 0.005 +/- 0.005 kPa-1. This relation indicates a very weak effect of left ventricular systolic pressure on normalized flow amplitude. Thus the hypothesis that left ventricular pressure is the sole determinant impeding coronary flow could not be confirmed. However, our data could be explained on basis of the time-varying elastance concept (H. Suga, K. Sagawa, and A. A. Shoukas. Circ. Res. 32: 314-322, 1973). The intravascular and luminal (cavity) compartments both are assumed to be subject to a time-varying elastance. The time-varying luminal elastance is similar for isovolumic and isobaric beats. We assume that the elastance of the vascular compartment also behaves the same for these beats, and therefore coronary flow is affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of G proteins in the acetylcholine-induced potassium current of canine atrial cells
Authors: Sorota S. , Hoffman B. F.
Published: December 2017

The acetylcholine-induced opening of potassium channels depends on GTP-binding proteins in the chick, guinea pig, frog, and rat. In contrast, Bubien and Woods (Biochem. Biophys. Res. Commun. 142: 1039-1045, 1987) have recently postulated that the acetylcholine response in cultured canine atrial cells may be independent of GTP-binding proteins. In whole cell patch-clamp experiments using cultured canine atrial cells, we did not detect an effect of GTP (10(-4) M) in the pipette solution on the acetylcholine-induced potassium current. However, 500 microM guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) in the pipette diminished the response to acetylcholine. Pertussis toxin (30 ng/ml for 24 h) blocked the response to acetylcholine. With guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 3 microM) in the patch pipette, acetylcholine irreversibly increased membrane conductance. The current-voltage relationship for the persistently activated current was similar to that induced by acetylcholine. We conclude that the acetylcholine-induced potassium current in canine atrial cells behaves like that seen in other species and depends on GTP-binding proteins.
Stimulus-specific changes in mechanical properties of vascular smooth muscle
Authors: Brozovich F. V. , Morgan K. G.
Published: December 2017

To determine whether the mechanical properties of vascular smooth muscle are stimulus specific, force, stiffness, and the unloaded shortening velocity (Vmax) were measured during contractions of aortic smooth muscle strips stimulated with phenylephrine or KCl. After activation, muscle force and stiffness rose to a steady-state plateau where they were maintained. In phenylephrine contractions, Vmax peaked during force development and then fell to a lower steady-state level during force maintenance, whereas in the KCl contractions, Vmax did not decline during sustained contractions. Stimulation with KCl, compared with phenylephrine, produced lower steady-state forces. One possible interpretation is that the muscle formed latch cross-bridges during phenylephrine contractions, but not during KCl depolarizations. The slope of the plot of relative muscle force vs. stiffness for phenylephrine contractions, compared with KCl depolarizations, was reduced. This may imply tht the relative force per attached latch crossbridge could be reduced.
Neural regulation of canine skeletal muscle blood flow during hypoxic hypoxia
Authors: Kubes P. , Cain S. M. , Chapler C. K.
Published: December 2017

Vascular resistance in canine limb skeletal muscle first increases and then decreases with prolonged arterial hypoxia, but whether neural sympathetic activity decreases with time is unknown. To assess the effectiveness of neurally mediated vasoconstrictor tone, we periodically cooled and rewarmed the sciatic nerve while nine anesthetized, paralyzed, pump-ventilated dogs were made hypoxic for 60 min by ventilation with 9.1% O2 in N2 (PaO2 = 24 +/- 2 mmHg). Before hypoxia, limb blood flow (QL) increased to a mean peak value of 111 ml.kg-1.min-1 with nerve cooling. With hypoxic hypoxia (HH), cardiac output increased but mean arterial pressure and limb blood flow remained the same. Nerve cooling at 15, 30, and 60 min of HH resulted in a pattern of progressively increasing mean peak QL values of 137, 151, and 160 ml.kg-1.min-1, respectively (P less than 0.05). Stimulation of the cut sciatic nerve at the end of the experiment established the maximum vasoconstriction that was possible and, thereby, the potential range that was available. The results showed that not only was neurally mediated vasoconstriction to skeletal muscle maintained throughout the hypoxic period, but that its intensity must have been increasing to overcome the local vasodilatory forces that were responsible for flow increasing even further with nerve cooling in prolonged hypoxia.
Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium
Authors: Kellogg D. L. , Johnson J. M. , Kosiba W. A.
Published: December 2017

Skin blood flow (SkBF) in humans is controlled by a noradrenergic active vasoconstrictor system and an active vasodilator system of an uncertain neurotransmitter. Understanding how these systems interact would be aided if the vasodilator system could be studied in the absence of effects of the vasoconstrictor system. To accomplish this we combined laser-Doppler velocimetry (LDV) with the local iontophoresis of bretylium in 10 studies with eight healthy subjects. Each subject had two forearm sites (0.64 cm2) treated with bretylium to block local norepinephrine release. LDV was monitored at those sites and at two untreated sites during 3-4 min of cold stress, 35-45 min of heat stress, and a final cold stress to verify blockade. In five studies, local temperature was raised to 39 degrees C at the LDV sites before the final cold stress. Whole body skin temperature was controlled by water-perfused suits. Mean arterial pressure (MAP) was measured noninvasively. Heart rate and internal temperature were also recorded. Cutaneous vascular conductance (CVC) was calculated as LDV/MAP. During the initial cold stress, performed 130 min after bretylium treatment, CVC at treated sites fell by an average of 0.3 +/- 3.2% (P greater than 0.10) and at untreated sites by 29.2 +/- 4.1% (P less than 0.001 between sites). During heat stress, CVC at treated sites rose by 419 +/- 66% and at control sites, by 517 +/- 90% (P greater than 0.10 between sites). The internal temperature threshold for cutaneous vasodilation was not statistically different between sites (P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)