bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of reflex stimuli on blood flow to the adrenal medulla
Authors: Faraci F. M. , Chilian W. M. , Williams J. K. , Heistad D. D.
Published: December 2017

The goal of this study was to examine changes in blood flow to the adrenal medulla during reflex stimuli that release catecholamines. Adrenal blood flow was measured with microspheres during exercise in conscious dogs and during bicuculline-induced seizures in anesthetized dogs. In awake dogs, blood flow to the adrenal cortex and adrenal medulla was 310 +/- 48 and 1,613 +/- 258 (SE) ml.min-1.100 g-1, respectively. Blood flow to the cortex and medulla was not affected by moderate exercise. Anesthesia (pentobarbital sodium) reduced blood flow to the adrenal cortex and medulla to 158 +/- 12 and 243 +/- 24 ml.min-1.100 g-1, respectively. In anesthetized dogs, seizures markedly increased blood flow to the adrenal medulla (282 +/- 68 to 1,257 +/- 128 ml.min-1.100 g-1), and this response was blocked by sectioning the greater splanchnic nerve. Vasodilator responses of the adrenal medulla to adenosine were not impaired by adrenal denervation. Blood flow to the adrenal cortex was not affected by seizures but increased in response to intravenous adenosine. These findings suggest that 1) anesthesia decreases adrenal blood flow, particularly to the adrenal medulla, and 2) reflex stimuli that release catecholamines can produce selective increases in blood flow to the adrenal medulla.
Phosphocreatine and oxidative metabolism-contraction coupling in rabbit aorta
Authors: Scott D. P. , Coburn R. F.
Published: December 2017

Oxidative metabolism-contraction coupling was studied in single rabbit aortic rings by measuring changes in phosphocreatine (PCr) and ATP content, the ratio of PCr to free creatine (Cr), and changes in muscle force under conditions in which cellular energy production was inhibited. We compared rings with markedly different total PCr content by using rings loaded with creatine, control (unloaded) rings, and rings exposed for 30 min to zero-glucose solution. Creatine loading resulted in increases in PCr content to 300% of control. Maintained muscle force generated by 30 microM norepinephrine was decreased by hypoxia, 0.05 and 0.1 mM cyanide, removal of glucose from the bathing media, or glucose removal plus hypoxia. There was no difference between creatine-loaded and unloaded rings in the mechanical effects of these perturbations. Changes in muscle force induced by inhibition of energy production using the various perturbations correlated with changes in PCr/Cr. Data are consistent with oxidative metabolism-contraction coupling being regulated by energy delivery to a reaction or reactions controlling muscle force. Metabolism-contraction coupling is not controlled by total energy stores or by PCr or Cr concentration.
Characteristics of canine coronary resistance arteries: importance of endothelium
Authors: Myers P. R. , Banitt P. F. , Guerra R. , Harrison D. G.
Published: December 2017

Canine coronary resistance vessels were studied in vitro to examine the role of the endothelium in modulating responses to acetylcholine, vasopressin, and thrombin and to compare these responses to those found in large epicardial vessels. Acetylcholine had no effect on passively distended microvessels; however, after preconstriction with the thromboxane analogue, U 46619 caused dose-dependent vasodilation [50% effective concentration (EC50), 0.05 microM; maximum response, 97.9 +/- 2.1% relaxation]. Large epicardial arterial rings studied in organ chambers similarly relaxed to acetylcholine (EC50, 0.07 microM; maximum response, 79 +/- 5% relaxation). Hemoglobin was utilized to inactivate endothelium-derived relaxing factor (EDRF), resulting in reversal of acetylcholine vasodilation in both the microvessels (92 +/- 3.2% reversal) and the large epicardial vessels (117 +/- 9%). Hemoglobin had no effect on passively distended or preconstricted microvessels. Vasopressin constricted resistance vessels by 22.3 +/- 5.9 microns at 500 microU/ml. Hemoglobin potentiated this response by 100%, suggesting that vasopressin elicited EDRF release. In large coronary arteries, however, vasopressin elicited endothelium-dependent dilation with maximal relaxation of 36 +/- 9% at 3,000 microU/ml. Thrombin produced endothelium-dependent relaxation of large epicardial arterial rings but only constricted coronary microvessels. The response to thrombin was not altered by hemoglobin. This study demonstrates that the endothelium of coronary microvessels, like that of larger vessels, importantly modulates vascular reactivity to selected agents. Furthermore, major differences exist between large and small coronary arteries in their response to vasopressin and thrombin.
[Ca2+]i and contraction of ear artery in response to rapid stimulation by NE: measurements with quin2 and fura-2
Authors: Vonderlage M. , Schreiner V.
Published: December 2017

The relationship between the quin2 and fura-2 fluorescence and isovolumetric contraction of smooth muscle cells of everted segments of the rabbit ear artery in response to rapid stimulation by norepinephrine (NE) was investigated. The resting level measured with quin2 (91 +/- 10 nM, n = 4) and with fura-2 (87 +/- 9 nM, n = 5) did not significantly differ. After addition of NE, an initial slow increase (ISI) in emission could be measured with quin2; however, Ca2+ buffering by this indicator slowed the increase of intracellular Ca2+ concentration ([Ca2+]i) and of contraction. When using fura-2, no ISI could be measured, but this indicator did not significantly interfere with the normal time course of contraction. Maximal response in [Ca2+]i to 1 microM NE was 424 +/- 30 nM (with quin2) and 337 +/- 46 nM (with fura-2). Mechanical latency depended not only on the onset but also on the initial rate of the increase in [Ca2+]i. Contractile response was quickest around 0.1 s after the onset of the fura-2 signal. During its rising phase, the rate of pressure development was linearly correlated with the -log molar Ca2+ concentration (pCa) of the cytoplasm (pCai), whereas during slow relaxation, pressure was linearly related to the pCai. These results suggest that contraction may depend not only on [Ca2+]i but also depend on its rate of change.
Beyond pure parasystole: promises and problems in modeling complex arrhythmias
Authors: Courtemanche M. , Glass L. , Rosengarten M. D. , Goldberger A. L.
Published: December 2017

The dynamics of pure parasystole, a cardiac arrhythmia in which two competing pacemakers fire independently, have recently been fully characterized. This model is now extended in an attempt to account for the more complex dynamics occurring with modulated parasystole, in which there exists nonlinear interaction between the sinus node and the ectopic ventricular focus. Theoretical analysis of modulated parasystole reveals three types of dynamics: entrainment, quasiperiodicity, and chaos. Rhythms associated with quasiperiodicity obey a set of rules derived from pure parasystole. This model is applied to the interpretation of continuous electrocardiographic data sets from three patients with complicated patterns of ventricular ectopic activity. We describe several new statistical properties of these records, related to the number of intervening sinus beats between ectopic events, that are essential in characterizing the dynamics and testing mathematical models. Detailed comparison between data and theory in these cases show substantial areas of agreement as well as potentially important discrepancies. These findings have implications for understanding the dynamics of the heartbeat in normal and pathological conditions.
Fetal neuromuscular blockade: effect on oxygen demand and placental transport
Authors: Wilkening R. B. , Boyle D. W. , Meschia G.
Published: December 2017

To study mechanisms by which variations in fetal oxygen demand alter fetal oxygen saturation and PO2, we measured uterine and umbilical blood flow and transplacental oxygen diffusion rate in eight chronically prepared pregnant ewes before and during fetal neuromuscular blockade with pancuronium bromide (0.2 mg/kg). Uterine and umbilical blood flows were measured by applying the steady-state method using ethanol as the test substance. Fetal oxygen uptake decreased 7.5% (P less than 0.05). Umbilical blood flow increased 6% (P less than 0.05), whereas uterine blood flow did not change significantly. Fetal arterial oxygen saturation increased markedly (54.8–60.9%; P less than 0.001). There were also significant increases in umbilical vein oxygen saturation (83.6–86.9%; P less than 0.01), uterine vein oxygen saturation (70.7–72.2%; P less than 0.01), umbilical vein PO2 (29.4–32.1 Torr; P less than 0.001), and uterine vein PO2 (49.4–50.7 Torr; P less than 0.01). The uterine-umbilical venous PO2 difference decreased significantly (20.0–18.6 Torr; P less than 0.001), whereas there was no significant change in the uterine-umbilical venous PCO2 difference or in the umbilical ethanol shunt. The data indicate that follows a small decrease in fetal oxygen demand is caused by two aspects of placental oxygen transport: 1) umbilical and uterine blood flow do not react homeostatically to prevent the rise of PO2 in the placental circulation, and 2) the decrease in oxygen flux from placenta to fetus is associated with a decrease in the transplacental PO2 gradient.
Regional blood flow in the brain and spinal cord of hypothermic rats
Authors: Sakamoto T. , Monafo W. W.
Published: December 2017

[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.
Effects of endothelin and vasopressin on cerebral blood vessels
Authors: Faraci F. M.
Published: December 2017

Endothelin is a recently described peptide which has been suggested to be one type of endothelium-derived contracting factor. The goals of the present study were to examine the effects of endothelin and vasopressin on diameter of cerebral vessels and on permeability of the blood-brain barrier to fluorescein sodium (mol wt of 376). In anesthetized rats, topical suffusion of arginine vasopressin (10(-10) to 10(-7) M) decreased the diameter of pial arterioles, with a reduction of 27 +/- 1% at 10(-7) M in cerebrum and 35 +/- 2% at 10(-8) M for the basilar artery. A low concentration of endothelin (10(-10) M) produced modest (5 +/- 1%) dilatation of pial arterioles. Higher concentrations of endothelin (10(-8) and 10(-7) M) constricted pial arterioles with a reduction in diameter of 22 +/- 5% at 10(-7) M. Dilatation to endothelin was not observed in the basilar artery. The basilar artery constricted to lower doses of vasopressin than endothelin, but vasoconstriction to 10(-7) M endothelin (56 +/- 4%) was greater (P less than 0.05) than that for the same dose of vasopressin. Permeability of the blood-brain barrier to fluorescein sodium was not increased by vasopressin or endothelin. Thus 1) vasopressin produces constriction of brain blood vessels; 2) endothelin produces dilatation of pial arterioles at low doses but constriction at high doses; 3) constrictor responses to both peptides appear to be greater in the brain stem than in the cerebrum; and 4) vasopressin and endothelin do not increase permeability of the blood-brain barrier.
Pentobarbital attenuates pulmonary vasoconstriction in isolated sheep lungs
Authors: Wetzel R. C. , Martin L. D.
Published: December 2017

Pentobarbital sodium is a widely used anesthetic agent that has been demonstrated to attenuate systemic vascular responses to multiple pressors. To determine whether pentobarbital affected pulmonary vasoreactivity we determined the pulmonary vascular response to hypoxia and potassium in isolated in situ perfused sheep lungs. The flow resistive characteristics of the pulmonary vasculature were assessed by determining mean instantaneous pressure-flow relationships over a wide range of flows (20–120 ml.min-1.kg body wt-1) with PIO2 of 200 and 30 Torr, with and without pentobarbital. Pentobarbital attenuated hypoxic pulmonary vasoconstriction (P less than 0.001) in a concentration-dependent fashion (50% effective concentration = 0.42 mM). In addition, the pulmonary constrictor response to potassium was markedly blunted by pentobarbital (P less than 0.001). We conclude that pentobarbital inhibits hypoxic pulmonary vasoconstriction in a concentration-dependent fashion and that this inhibition of pulmonary vasoconstriction in isolated sheep lungs is not specific for hypoxia.
Pentobarbital augments pulmonary vasoconstrictor response to cyclooxygenase inhibition
Authors: Nyhan D. P. , Chen B. B. , Fehr D. M. , Goll H. M. , Murray P. A.
Published: December 2017

We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to investigate the effects of pentobarbital sodium anesthesia on regulation of the pulmonary circulation by endogenous metabolites of the cyclooxygenase pathway. Our specific objective was to characterize the effects of two chemically dissimilar inhibitors of the cyclooxygenase pathway, indomethacin and sodium meclofenamate, on the pulmonary vascular P/Q relationship measured in conscious and pentobarbital-anesthetized dogs. P/Q plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Controlled ventilation during pentobarbital anesthesia (30 mg/kg iv) allowed the matching of systemic arterial and mixed venous blood gases to conscious values. Pentobarbital had no net effect on the base-line P/Q relationship compared with that measured in conscious dogs. Cyclooxygenase pathway inhibition with either indomethacin (5 mg/kg iv) or meclofenamate (2.5 mg/kg iv) resulted in active, flow-independent pulmonary vasoconstriction (P less than 0.01) in both conscious and pentobarbital-anesthetized dogs. However, the magnitude of the pulmonary vasoconstrictor response to indomethacin was increased (P less than 0.05) over a broad range of Q, and the pulmonary vasoconstrictor response to meclofenamate was increased (P less than 0.05) over the entire range of Q in pentobarbital-anesthetized compared with conscious dogs. Thus regulation of the base-line pulmonary vascular P/Q relationship by endogenous metabolites of the cyclooxygenase pathway in conscious dogs is altered during pentobarbital anesthesia.
Myogenic response and wall mechanics of arterioles
Authors: Jackson P. A. , Duling B. R.
Published: December 2017

The magnitude of the arteriolar response to altered intraluminal pressure was assessed in isolated, cannulated vessels of the hamster cheek pouch. Microvessels were studied during various levels of smooth muscle activation, either occurring spontaneously, or resulting from the application of exogenous agonists including potassium (35 or 70 mM) and phenylephrine (1.25 or 2.50 x 10(-6) M). Diameter-pressure curves were obtained by lowering intraluminal pressure from 60 to 0 mmHg in seven steps at 3-min intervals. At an intraluminal pressure of 40 mmHg, spontaneous tone produced an average constriction to 34 +/- 2% of the maximum diameter. Step reductions in pressure typically led to reductions in the level of activation of the muscle, which resulted in a net dilation over a significant pressure range. This “myogenic response” was more effective in modifying spontaneous tone than in modifying exogenous tone. In fact, the data suggest that reduction of the intraluminal pressure to zero can result in complete inactivation of spontaneous tone. Complete inactivation was not observed when contractions were induced by exogenous agonists, however. The magnitude of the myogenic response in arterioles was consistent with a role in autoregulation, which is 2.5-fold greater than that previously reported for small arteries. The data demonstrate that in the analysis of the mechanics of submaximally activated blood vessels one must include considerations of two phenomenon: the classical stress-length behavior as determined under conditions of maximal activation, and a superimposed modification of the activation level induced by stress- or length-dependent processes. Furthermore, the findings indicate substantial differences in response when tone is spontaneous compared with the case when tone is induced by exogenous agonists.
Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet
Authors: Morganroth M. L. , Schoeneich S. O. , Till G. O. , Pickett W. , Ward P. A.
Published: December 2017

Arachidonate metabolites appear to be involved in lung injury caused by cobra venom factor (CVF)-induced complement and polymorphonuclear leukocyte (PMN) activation. These studies were designed to assess the effects of a dietary-induced deficiency of arachidonic acid on CVF-induced lung injury. Rats raised on an essential fatty acid-deficient (EFAD) diet exhibited the expected changes in fatty acid composition including decreased plasma levels of arachidonic acid and increased levels of 5,8,11-eicosatrienoic acid. In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury, as evidenced by increased 125I-labeled bovine serum albumin accumulation in lung parenchyma and alveolar lavage fluid. The CVF-induced pulmonary artery pressor response and lung injury were reduced when blood perfusate or blood perfusate and excised lungs were obtained from rats raised on the EFAD diet. The pulmonary vascular constriction and lung injury were not attenuated when the blood perfusate was obtained from rats raised on the normal diet, irrespective of whether the excised lungs were obtained from rats raised on the normal or EFAD diet. PMNs obtained from rats raised on the EFAD diet demonstrated decreased superoxide production as well as impaired random migration and chemotaxis in vitro. In contrast, beta-glucuronidase release was quantitatively similar to PMNs from control rats. These data indicate that the EFAD diet-induced attenuation of CVF-induced pulmonary hypertension and acute lung injury is due to defective effector cells in blood rather than modified pulmonary target tissue.
Similar responsiveness of smooth muscle of the canine basilar artery to EDRF and nitric oxide
Authors: Katusic Z. S. , Marshall J. J. , Kontos H. A. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to compare the reactivity of canine basilar arteries to endothelium-derived relaxing factor (EDRF) and nitric oxide. Preparations with endothelium activated by bradykinin were used to study relaxations induced with EDRF, whereas the inhibitory effect of nitric oxide was studied in preparations without endothelium. All experiments were performed in the presence of indomethacin. EDRF- and nitric oxide-induced relaxations were significantly augmented in the presence of superoxide dismutase plus catalase but were reduced in the presence of methylene blue, LY 83583, and hemoglobin. M & B 22984 did not affect relaxations to either EDRF or nitric oxide. These results indicate that in the canine basilar artery EDRF is not an oxygen-derived free radical. The similar responsiveness of the basilar artery to EDRF and nitric oxide is consistent with the proposal that in the canine basilar artery nitric oxide is the factor.
Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A
Authors: Mehta J. L. , Lawson D. L. , Nichols W. W.
Published: December 2017

Previous studies demonstrate endothelium-dependent leukotriene D4 (LTD4)-induced relaxation of canine coronary arterial rings in vitro. We now show that coronary occlusion followed by reperfusion attenuates (P less than 0.01) the relaxation of canine coronary artery rings in response to LTD4 as well as acetylcholine (ACh), suggesting loss of endothelium-dependent coronary reactivity (n = 6 dogs). Since superoxide anions have been shown to cause breakdown of endothelium-derived relaxing factor (EDRF), we wondered whether treatment of dogs with superoxide anion scavenger superoxide dismutase (SOD) would modulate the effects of LTD4 and ACh on reperfused coronary artery rings. Indeed, treatment of dogs (n = 5) with SOD before coronary reperfusion resulted in preservation of LTD4- and ACh-induced relaxation of coronary rings. Treatment of another five dogs with selective thromboxane-synthetase blocker U 63557A before coronary reperfusion also resulted in preservation of coronary ring relaxation in response to LTD4 and ACh. To determine the mechanism of U 63557A-induced preservation of coronary reactivity, canine neutrophil superoxide anion generation in the presence of U 63557A was measured. Although U 63557A had no effect on superoxide anion generation in neutrophils alone, it markedly (P less than 0.02) inhibited superoxide anion generation in neutrophils in the presence of platelets, most likely via shunting of accumulated cyclic endoperoxide in platelets toward formation of prostacyclin, which inhibits neutrophil superoxide anion production. Thus SOD and U 63557A protect against loss of endothelium-mediated vascular relaxation by LTD4 and ACh after coronary occlusion and reperfusion.
Coronary hemodynamic effects of intravenous vasoactive intestinal peptide in humans
Authors: Smitherman T. C. , Popma J. J. , Said S. I. , Krejs G. J. , Dehmer G. J.
Published: December 2017

Vasoactive intestinal polypeptide (VIP), a probable neurotransmitter, is present in the hearts of experimental animals and is a coronary vasodilator in dogs. We evaluated the coronary hemodynamic effects of intravenously infused VIP in 11 men at two rates that modestly raised circulating VIP concentrations. The decreases in coronary and systemic vascular resistances during the second infusion, 33 and 31%, respectively, were slightly but insignificantly greater than the 24% decrease in pulmonary vascular resistance. Coronary sinus levels of 6-keto-prostaglandin F1 alpha were not elevated during the infusions, and cyclooxygenase inhibition did not significantly blunt coronary vasodilation. However, myocardial oxygen uptake rose significantly during both infusions. To test for a direct coronary vasodilator effect, we infused VIP into the left coronary artery of four other men at four levels. The maximum decline in coronary vascular resistance was 46% and was not associated with an increase in myocardial oxygen uptake. We conclude that 1) intravenous administration of low to intermediate doses of VIP in humans is associated with substantial coronary vasodilation, 2) the coronary bed appears to be at least as responsive as other vascular beds, 3) the coronary vasodilation is due to both direct and indirect effects, and 4) the coronary vasodilation does not appear to be mediated by prostaglandins.
An optical hemoglobinometer for whole blood
Authors: Schmalzel J. L. , Steinke J. M. , Randal V. T. , Shepherd A. P.
Published: December 2017

To overcome the disadvantages of the presently available hemoglobinometers, we have developed an optical instrument that measures the total hemoglobin (Hb) concentration in whole, undiluted blood. The device uses an infrared light-emitting diode to illuminate a capillary tube filled with a sample of whole blood. Light scattered in the blood travels a short distance down the length of the capillary tube, passes through a second light path, and reaches a photodetector, the output of which is amplified, digitized, and fed into a microprocessor. The microprocessor computes the Hb concentration as a nonlinear function of the light intensity. The optical device yielded Hb content measurements that correlated well with standard methods (r = 0.99, slope = 0.94, mean absolute difference = 0.75 g Hb/dl). Thus the accuracy appears to be less than 1 g Hb/dl. The advantages of the present device are as follows: 1) no chemical reaction is required (hence neither accurate dilutions nor toxic reagents are necessary); 2) it reads Hb concentration within a few seconds; 3) it can be operated by unskilled personnel; 4) it could be made portable and thus could be operated in the field, in rural settings, or at accident sites; 5) sample size is small (25-70 microliters); and 6) the same capillary tube can be centrifuged if a measure of hematocrit is also desired. A detailed parts list and circuit diagram are presented, and sources of error are discussed.
Modulation of vascular tone by neutrophils: dependence on endothelial integrity
Authors: Mehta J. L. , Lawson D. L. , Nichols W. W. , Mehta P.
Published: December 2017

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)–10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.
Cardiac and peripheral vascular contributions to hypotension in spinal cats
Authors: Yardley C. P. , Fitzsimons C. L. , Weaver L. C.
Published: December 2017

On transection of the cervical spinal cord, substantial decreases in systemic arterial pressure and in discharge of many sympathetic nerves suggest the absence of sympathetic support to the cardiovascular system. However, discharge of mesenteric and splenic nerves is well maintained in spinal cats (R. L. Meckler and L. C. Weaver. J. Physiol. Lond. 396: 139-153, 1988; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155-172, 1988). We proposed that the low arterial pressure in spinal animals was caused predominantly by decreased cardiac output and vasodilation in muscle and some visceral vascular beds but that sustained mesenteric and splenic discharge was causing significant splanchnic vasoconstriction and partial support of arterial pressure. Therefore, changes in cardiac output, total peripheral resistance, and resistance of constant-flow-perfused mesenteric visceral and hindlimb skeletal muscle vascular beds caused by interruption of cervical spinal pathways were assessed. Blockade of cervical pathways decreased arterial pressure as much by decreasing cardiac output as by decreasing total peripheral resistance. Resistances of the muscle and mesenteric vascular beds decreased equally. In conclusion, hypotension in spinal cats is caused by decreased cardiac output and by vasodilation, which is as prominent in mesenteric as it is in muscle vascular beds. The maintained mesenteric sympathetic discharge in spinal cats appears unable to produce significant support of vascular arterial resistance.
Effect of lysophosphatidylcholine on the filtration coefficient in intact dog lungs
Authors: Butler B. D. , Davies I. , Drake R. E.
Published: December 2017

Lysophosphatidylcholine (lyso-Pc) is a lysophospholipid normally found in low concentrations in the lung. At high concentrations lyso-Pc, instilled into the airways, causes pulmonary edema. We tested the hypothesis that the edema caused by lyso-Pc was due to an increase in pulmonary microvascular membrane permeability. In 11 anesthetized dogs we continuously weighed the left lower lobes (LLL) while instilling lyso-Pc (20 mM) into the LLL airways. After 30 min we determined the microvascular membrane fluid filtration coefficient (Kf) from the relationship between the rate of LLL weight gain and the pulmonary microvascular pressure. Kf was not significantly different between the lyso-Pc-treated lobes (0.048 +/- 0.018 ml.min-1.mmHg-1) vs. control lobes (0.067 +/- 0.031 ml.min-1.mmHg-1). Our data do not support the hypothesis that lyso-Pc, instilled into the airways, causes an increase in pulmonary microvascular permeability.
Effects of endothelial impairment on arteriolar dilator responses in vivo
Authors: Koller A. , Messina E. J. , Wolin M. S. , Kaley G.
Published: December 2017

In pentobarbital-anesthetized rats we investigated the role of the endothelium in the dilation of third-order arterioles of cremaster muscle to acetylcholine, adenosine, and sodium nitroprusside in vivo. Responses to the topical administration of these agents were measured with image shearing and recorded with video microscopy before and after light-dye (L-D) treatment of a 50- to 100-microns segment of the arteriole under study. L-D treatment consisted of intravascular administration of sodium fluorescein and the illumination of a discrete area of the arteriole under study with its excitation light from a mercury lamp. Before L-D treatment, acetylcholine (10(-7) to 10(-5) M) and adenosine (10(-6) to 10(-4) M) produced dose-dependent increases in arteriolar diameter (vasodilation). After L-D treatment of the arteriolar segment, administration of 10(-7) M acetylcholine evoked a vasoconstriction (-19% from control), and the dilator responses to 10(-6) and 10(-5) M were inhibited by 91 and 77%, respectively. In contrast, the arteriolar dilator responses to all doses of adenosine and sodium nitroprusside (2 x 10(-7) M) were not altered by this treatment. In addition, the dilator responses to acetylcholine were not changed in the nonilluminated, distal, and proximal segments of the arterioles. These findings suggest that L-D treatment selectively alters the function of the endothelium resulting in the loss of vasodilation to acetylcholine, whereas arteriolar smooth muscle function does not appear to be affected.
Peripheral baroreceptor control of neurohypophysial blood flow during hemorrhage
Authors: Vella L. M. , Hanley D. F. , Wilson D. A. , Traystman R. J.
Published: December 2017

We measured neurohypophysial blood flow (NHBF) in dogs made hypotensive to study the time course of neurohypophysial autoregulation. We found that the neurohypophysis has a unique autoregulatory response in which blood flow increases transiently before establishing a stable perfusion level. During the "hyperemic" phase, the time course of the flow transient correlates with an increased plasma arginine vasopressin (pAVP) neurosecretory transient. However, unlike pAVP, blood flow does not remain elevated. The transitory nature of the flow response led us to evaluate the hypothesis that peripheral baroreceptor activity may be responsible for the hyperemic phase. Bilateral vagotomy and carotid sinus nerve denervation attenuated the increase in neural lobe blood flow (NLBF) to a standardized step to 80 mmHg mean arterial pressure. The pAVP response was enhanced both by vagotomy and carotid sinus denervation. Combined denervation abolished both the pAVP and the NLBF responses. We conclude that NHBF is autoregulated; however, control may be exerted at multiple levels, i.e., via nerves as well as local metabolic mechanisms. The peripheral baroreceptors influence NHBF primarily during periods of changing blood pressure. When blood pressure is stable, local mechanisms appear to be dominant.
Effect of voltage and charge of electrical ablation pulses on canine myocardium
Authors: Bardy G. H. , Sawyer P. L. , Johnson G. W. , Ivey T. D. , Reichenbach D. D.
Published: December 2017

Multiple paired lesions produced by a train of high-voltage low-charge rectangular pulses (20 A, 30 microsecond) and a train of low-voltage high-charge rectangular pulses (2 A, 300 microsecond) were made to the left ventricular epicardium of 23 dogs to determine the relative influence of voltage and charge delivery on injury of canine myocardium. Both pulsing methods contained equal amounts of energy (15 J) delivered over equal periods of time (100 ms), and both pulsing methods were nonarcing and therefore nonbarotraumatic. The volume of cardiac tissue injury resulting from both types of pulses was then evaluated from planimetered serial histological sections after 1, 10, and 30 days. Over the 30-day period, lesion size progressively decreased to 56% of its original value for the high-voltage low-charge pulse. In contrast, lesion size from the low-voltage high-charge pulse remained relatively constant, decreasing only 12% of its original value. These results indicate that when energy delivery is held constant, voltage, not charge, is the dominant mediator of cell injury. Also, cells subjected to high voltages appear to recover partially over time with significantly less constancy of tissue injury than that seen with low-voltage high-charge pulses.
Intracellular magnesium affects I(K) in single frog atrial cells
Authors: Tarr M. , Trank J. W. , Goertz K. K.
Published: December 2017

Voltage-clamp experiments on single frog (Rana pipiens) atrial cells using whole cell recording techniques revealed that the addition of MgCl2 to the 150 mM KCl patch pipette solution influenced the voltage- and time-dependent potassium current (IK). After rupture of the membrane patch under the tip of the pipette, IK increased with time when the pipette solution was magnesium free, but decreased slightly when the solution contained 1.5 mM MgCl2. More dramatic decreases in IK occurred when the solution contained 3.0 or 10 mM MgCl2. In addition to suppressing the magnitude of IK, the activation rate of this current was enhanced by 10 mM MgCl2 but was not affected by 1.5 or 3 mM MgCl2. Other chloride salts containing mono-, di-, or trivalent cations were used to demonstrate that the effects of MgCl2 on IK were not related to alterations in ionic strength, osmolality, or chloride concentration produced by adding MgCl2 to the pipette solution. Our results suggest that changes in the intracellular magnesium concentration influence IK as the pipette solution exchanges with the intracellular fluid.
Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles
Authors: Uemura N. , Knight D. R. , Shen Y. T. , Nejima J. , Cohen M. V. , Thomas J. X. , Vatner S. F.
Published: December 2017

Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 +/- 5.1%) than mongrels (42.5 +/- 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO.
Effects of isoflurane and halothane on rapid cooling contractures in myocardial tissue
Authors: Komai H. , Redon D. , Rusy B. F.
Published: December 2017

The effects of isoflurane and halothane on the availability of Ca2+ stored in and released from the sarcoplasmic reticulum (SR) were studied in isolated rabbit papillary muscles by measuring the effects of the anesthetics on rapid cooling contractures, which are known to be activated by Ca2+ released from the SR. Isoflurane (0.3%) reduced the force of the rapid cooling contracture to 57% of control with a marked slowing of the average rate of contracture development and increased the force of the first contraction after rewarming to 133% of control. In contrast, 1.7% halothane, which reduced the rapid cooling contracture to 51% of control (comparable to the value in the presence of 0.3% isoflurane), had little effect on the rate of contracture development and strongly inhibited the first contraction after rewarming to 5% of control. Halothane, but not isoflurane, strongly inhibited postrest potentiated-state contractions, which are also known to be activated by Ca2+ released from the SR. These results suggest that 1) isoflurane inhibits rapid cooling-induced Ca2+ release from the SR without inhibiting Ca2+ release triggered by rapid depolarization as occurs in the potentiated-state contraction, and 2) halothane inhibits contractile activity dependent on Ca2+ released from the SR regardless of mechanism involved.
Norepinephrine spillover from skeletal muscle during exercise in humans: role of muscle mass
Authors: Savard G. K. , Richter E. A. , Strange S. , Kiens B. , Christensen N. J. , Saltin B.
Published: December 2017

The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one-legged knee extension either alone or in combination with the knee extensors of the other leg and/or with the arms. The range of work intensities varied between 24 and 71% (mean) of subjects' maximal aerobic capacity (% VO2max). Leg blood flow, measured in the femoral vein by thermodilution, was determined in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise in sympathetic nervous activity to skeletal muscle, either resting or working at a constant load, is not associated with any significant neurogenic vasoconstriction and reduction in flow or conductance through the muscle vascular bed, during whole body exercise demanding up to 71% VO2max.
Dialysate to blood transport of macromolecules during peritoneal dialysis
Authors: Leypoldt J. K. , Chiu A. S. , Frigon R. P. , Henderson L. W.
Published: December 2017

Asymmetrical transport of macromolecules between plasma and the peritoneal cavity results primarily from unidirectional lymphatic removal from the peritoneal cavity. Recent work suggests, however, that macromolecular transport across the peritoneal-plasma barrier via the capillary wall (i.e., the peritoneal membrane) may also be asymmetrical. We determined the diffusive and convective transport properties for creatinine, p-aminohippurate, and neutral dextran (13-40 A) across the peritoneal membrane in the dialysate to blood direction during peritoneal dialysis using isotonic and hypotonic solutions in awake New Zealand White rabbits. Values of the diffusive permeability-area product that were calculated during the isotonic exchange were similar to, yet somewhat smaller than, those previously determined in the blood to dialysate direction for all test solutes. Solute reflection coefficients that were calculated during the hypotonic exchange were variable, yet the resulting mean solute reflection coefficient values for all the test solutes were similar to those previously determined in the blood to dialysate direction. We conclude that asymmetrical peritoneal transport of macromolecules with radii less than 40 A is not due to asymmetrical transport across the peritoneal membrane.
The endothelium inhibits activation by calcium of vascular neurotransmission
Authors: Tesfamariam B. , Weisbrod R. M. , Cohen R. A.
Published: December 2017

The role of calcium in the inhibition by the endothelium of adrenergic neurotransmission was studied in isolated rabbit carotid artery. Contractions induced by transmural electrical field stimulation (0.5-8 Hz), norepinephrine (10(-8)-3 X 10(-5) M), potassium depolarization (15-30 mM), or by readdition of calcium (0.15-2.4 mM) to a calcium-free medium containing potassium (15 mM) were significantly smaller in rings with compared with rings without endothelium. The voltage-dependent calcium channel activator, BAY K 8644 (10(-6) M), increased contractions to all contractile stimuli in rings with more than in rings without endothelium and thereby abolished the inhibitory influence of the endothelium. The inhibition of neurogenic contractions by the endothelium was also, in part, prejunctional, as indicated by decreased overflow of endogenous norepinephrine from superfused segments with compared with segments without endothelium evoked by electrical stimulation (2 Hz) or by reinfusion of calcium (2.5 mM) to calcium-free medium containing potassium (80 mM). BAY K 8644 (10(-6) M) enhanced the overflow of norepinephrine evoked by electrical stimulation or calcium from segments with more than from segments without endothelium and abolished the difference. Thus the endothelium inhibits activation by extracellular calcium of adrenergic nerves and vascular smooth muscle. The action of the endothelium is overcome by BAY K 8644, suggesting that voltage-dependent calcium channels are important in the inhibitory role of the endothelium in both adrenergic nerves and smooth muscle cells.
Autonomic response to coronary occlusion in animals susceptible to ventricular fibrillation
Authors: Collins M. N. , Billman G. E.
Published: December 2017

Disturbances in autonomic control during myocardial ischemia may contribute significantly to the development of malignant cardiac arrhythmias. Therefore acute ischemia was induced in 29 mongrel dogs with healed myocardial infarctions during an exercise test. Seventeen animals developed ventricular fibrillation (susceptible, S), whereas 12 dogs did not (resistant, R). Before the exercise plus ischemia test a coronary occlusion was made at rest. The amplitude of respiratory sinus arrhythmia (0.24- to 1.04-Hz component of R-R interval fluctuation) was used as an index of cardiac vagal tone. Acute ischemia elicited a significantly larger heart rate increase in susceptible animals (S: control 115.6 +/- 0.8, occlusion 176.4 +/- 8.2 beats/min vs. R: control 114.6 +/- 8.9, occlusion 145.7 +/- 7.5 beats/min). Accompanying the heart rate increase were significantly greater reductions in the cardiac vagal tone index in the susceptible animals. (S: control 6.4 +/- 0.3, occlusion 2.2 +/- 0.6 ln ms2 vs. R: control 6.6 +/- 0.4, occlusion 5.1 +/- 0.5 ln ms2). beta-Adrenergic receptor blockade reduced the heart rate increases but exacerbated the reductions in the cardiac vagal tone index. These data suggest that coronary artery occlusion elicits a significantly greater increase in sympathetic activity coupled with a greater reduction in parasympathetic activity in animals subsequently shown to be susceptible to ventricular fibrillation.
Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?
Authors: Miller V. M. , Vanhoutte P. M.
Published: December 2017

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.
Effects of elevated venous pressure on capillary permeability in cat hindlimbs
Authors: Wolf M. B. , Porter L. P. , Watson P. D.
Published: December 2017

We investigated the effects of elevated venous pressure, Pv, (up to 140 mmHg) on the solvent drag reflection coefficient, sigma f, for protein and on the capillary filtration coefficient, CFC, in the isolated cat hindlimb perfused at constant flow. The perfusate contained 30% cat plasma and the remainder was a dialyzed albumin-electrolyte mixture. Cat red cells were added to a hematocrit of approximately 2%. sigma f was measured from the changes in hematocrit and plasma protein concentration (Integral-Mass Balance method) resulting from the fluid filtration caused by the Pv elevation. CFC was measured from the slope of the limb weight recording 2-4 min after the Pv elevation. sigma f decreased linearly from 0.807 (Pv less than 50 mmHg) to approximately 0.2 at 140 mmHg. CFC increased linearly from 0.0086 ml.min-1.mmHg-1.100 g-1 to about 0.04 over the same pressure range. A weight-independent filtration coefficient calculated from the change in hematocrit and a measurement of the initial perfusate volume gave comparable results, except at the very highest of pressures, where this coefficient was sometimes 20-40% less than CFC. Successive sigma f determinations at Pv at about 40 mmHg did not return to control after an initial measurement in which Pv was approximately 110 mmHg. Pore-theory analysis of the data suggests that the elevated Pv causes large pores to open as opposed to the stretching of small pores. Also, these large pores may remain open for a period of hours.