bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of stimulation of fastigial nucleus on cerebral blood flow in cats
Authors: Williams J. L. , Heistad D. D. , Siems J. L. , Talman W. T.
Published: December 2017

The goal of this study was to examine effects of electrical stimulation of the rostral fastigial nucleus on cerebral blood flow. Anesthetized cats were studied, and arterial pressure and blood gases were maintained at control levels during fastigial stimulation. In one group, we measured vessel diameter and velocity of blood flow through a pial artery with a Doppler probe and calculated blood flow as the product of cross-sectional area and velocity. Electrical stimulation of the fastigial nucleus produced a small increase in pial arterial flow of 16 +/- 6% (means +/- SE, P less than 0.05). Pial vascular resistance increased during moderate hypertension and decreased during decreases in arterial pressure, which indicates that cerebral vascular responses were not impaired. In a second group, cerebral blood flow was measured with microspheres. Blood flow to the pons and medulla increased 25 +/- 11 and 21 +/- 11%, respectively, during stimulation of the fastigial nucleus, but blood flow to the cerebral cortex did not increase significantly. Stimulation produced decreases in flow to the renal cortex and duodenum of 39 +/- 10 and 39 +/- 15%, respectively, and flow to the heart increased 48 +/- 22%, which indicates that the stimulus was efficacious. Thus electrical stimulation of the rostral fastigial nucleus in cats elicits only a small increase in cerebral blood flow.
Baroreceptor denervation profoundly enhances cardiovascular responses to central angiotensin II
Authors: Barron K. W. , Trapani A. J. , Gordon F. J. , Brody M. J.
Published: December 2017

The purpose of this study was to examine the influence of arterial baroreflexes on the pressor and regional hemodynamic responses to centrally administered angiotensin II (ANG II) in the conscious rat. Fourteen days after sinoaortic baroreceptor denervation (SAD) or the equivalent sham surgery, the pressor and hindquarters vascular resistance responses to intravenous administration of ANG II were augmented in the SAD group. The pressor and vasoconstrictor responses to intracerebroventricular ANG II were also augmented after SAD; however, the SAD animals were more than 1,000-fold more sensitive than the sham group to the pressor effects of intracerebroventricular ANG II. Further experiments demonstrated that 1) the enhanced pressor response to intracerebroventricular ANG II in the baroreceptor-denervated group was due to similar increases in sympathetic outflow and vasopressin mediated vasoconstriction, 2) the increased sensitivity to central ANG II occurs as soon as 1 h after SAD, and 3) the enhanced pressor effects to intracerebroventricular ANG II also occur with intracerebroventricular hypertonic saline. We conclude that arterial baroreflexes exert a potent central inhibitory effect on the central pressor actions of ANG II that are greater than can be accounted for by the peripheral reflex arc. Finally, because of the rapid onset of the increased responsiveness to central ANG II after SAD, we propose that baroreflex buffering of central pressor stimuli may be tonically involved in circulatory control.
Histamine's effect on pulmonary vascular resistance and compliance at elevated tone
Authors: Barman S. A. , Taylor A. E.
Published: December 2017

Histamine's effect on the longitudinal resistance and compliance distribution in the canine pulmonary circulation was determined under control and elevated vascular tone using the thromboxane analogue U46619. The arterial-, venous-, and double-occlusion techniques were used in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given the following treatments: 1) histamine; 2) histamine in lungs pretreated with the H1-receptor antagonist diphenhydramine, and 3) histamine in lungs pretreated with the H2-receptor antagonist cimetidine. The results of this study indicate that histamine constricts small and large veins through H1-receptor mediation at both normal and elevated vascular tone. When vascular tone was elevated, H2-receptor vasodilatation was also apparent in all blood vessel segments. Histamine decreased total, middle compartment, and large vessel vascular compliances by an H1-receptor effect. When vascular tone was elevated, histamine's H1-receptor-mediated vasoconstrictor effect on compliance vessels was less due to the presence of an H2-receptor-mediated vasodilatory system.
Sequential topographical portrayal of myocardial blood flow
Authors: Richeson J. F. , Waag R. C. , Zwierzynski D. , Schenk E. A.
Published: December 2017

Methods to portray myocardial blood flow in a two-dimensional continuum are advantageous in that they allow blood flow history to be overlaid on histological or histochemical descriptions of the consequences of ischemia. We describe here autoradiographic methods that allow such portrayals at three separate times during the evolution of ischemic injury. A computer-based image-analysis system was used to derive such flow maps by taking advantage of the physical characteristics of radioactive isotopes.
Compensatory hypertrophy and failure in gradual pressure-overloaded guinea pig heart
Authors: Siri F. M. , Nordin C. , Factor S. M. , Sonnenblick E. , Aronson R.
Published: December 2017

Left ventricular hypertrophy has been produced in the guinea pig by a procedure that gradually increases left ventricular afterload. A mildly constricting band was placed around the ascending aortas of very young guinea pigs (225–275 g). With growth to 500–1,000 g, left ventricular systolic pressure increased and left ventricular hypertrophy developed. In approximately 50% of these animals, the hypertrophy was associated with normal left ventricular function and with no unusual symptoms or evidence of heart failure. The other animals developed dyspnea, which appeared an average of 41 days after banding. Dyspneic animals had normal body weight, markedly increased right ventricular and lung weights, decreased left ventricular norepinephrine content, diminished maximum left ventricular pressure generating capacity, and a significantly higher incidence of left ventricular interstitial and perivascular fibrosis. These findings demonstrate that even when left ventricular overload is imposed gradually by banding the aortas of young animals, myocardial decompensation ultimately ensues in a significant proportion of such animals. The slow imposition of loading, the slow rate of decompensation, and the ability to identify animals in heart failure by clinical dyspnea make this model uniquely valuable for studies on the mechanisms of heart failure.
Dependence of delayed afterdepolarizations on diastolic potentials in ischemic Purkinje fibers
Authors: Gough W. B. , el-Sherif N.
Published: December 2017

The mechanism of focal rhythms 1 day after myocardial infarction has been ascribed to both abnormal automaticity and triggered activity arising from delayed after-depolarizations (DADs). During the course of superfusion in vitro, diastolic potentials repolarize to more negative resting potentials. The dependence of DADs and triggered activity on diastolic potentials was studied using extrinsic currents. During sustained activity (maximum diastolic potential = -61 +/- 7 mV), hyperpolarizing current decreased the DADs, rendered them subthreshold, and terminated triggered activity. During the quiescence caused by constant hyperpolarizing current, a stimulated train of action potentials produced DADs. Decreasing the current permitted augmented DADs. In quiescent preparations (resting potential = -68 +/- 7 mV), a train of stimulated action potentials was followed by subthreshold DADs. Depolarizing current increased the DAD amplitude. To exclude depolarization-induced automaticity, constant currents were applied without a previous train of stimuli. Neither DADs nor triggered activity were evoked. Therefore, DADs and triggered activity, postinfarction, depend on the diastolic potential. There is a continuity between subthreshold DADs and sustained activity. DADs may reach a magnitude in which extrinsic interventions may not adequately terminate sustained triggered activity.
Direct effects of graded hypoxia on intact and denuded rabbit cranial arteries
Authors: Pearce W. J. , Ashwal S. , Cuevas J.
Published: December 2017

In isolated rabbit common carotid, internal carotid, and basilar arteries denuded of endothelium, mounted for measurement of contractile activity, and contracted with 10 microM serotonin (common and internal carotid) or 100 microM uridine 5'-triphosphate (UTP; basilar), 20 min of severe (PO2 = 15 Torr) and moderate (PO2 = 35 Torr) hypoxia relaxed initial tensions to 17, 6, and 16% and 18, 7, and 61% of control, respectively. The corresponding values in arteries contracted with 120 mM potassium-Krebs solution were 42, 60, and 73% and 57, 72, and 88%. These data indicate that the main determinants of the responses to hypoxia were intrinsic to the vessel walls of these arteries and that complete depolarization attenuated but did not eliminate the effects of these mechanisms. Superimposed on these intrinsic mechanisms were the effects of the endothelium, which were evaluated by several methods, including integration of the area between the 20-min response time courses of corresponding intact and denuded segments. Positive and negative integrated area values indicated endothelial vasoconstrictor [endothelium-derived contracting factor (EDCF)] and vasodilator [endothelium-derived relaxing factor (EDRF)] influences, respectively. In common carotid, internal carotid, and basilar segments contracted with serotonin and/or UTP, these areas averaged 770, 354, and 44 min% during severe and 491, 189, and -411 min% during moderate hypoxia. Corresponding values during potassium contraction were 217, -271, and -356 min% and 52, -177, and -54 min%. Together, these findings suggest that 1) intrinsic vascular mechanisms contribute significantly to hypoxic cerebral vasodilation in the rabbit, 2) EDCF is more prominent but also may be more sensitive to depolarization than EDRF, 3) hypoxia promotes the simultaneous release of both EDCF and EDRF, and 4) the ratio of EDCF to EDRF released during hypoxia decreases as one moves from the rabbit common carotid to the internal carotid to the basilar arteries.
Effect of transit time on metabolism of a pulmonary endothelial enzyme substrate
Authors: Dawson C. A. , Bongard R. D. , Rickaby D. A. , Linehan J. H. , Roerig D. L.
Published: December 2017

Fractional hydrolysis (M) of the synthetic angiotensin-converting enzyme (ACE) substrate [3H]benzoyl-Phe-Ala-Pro (BPAP) on passage through the isolated dog lung lobe was found to be relatively independent of flow rate and transit time (t). The most commonly expressed explanation for this kind of observation is that recruitment of ACE-containing surface area occurs when flow is increased. To test this, as well as other hypotheses that might explain the behavior of this substrate, we compared M obtained after the first pass of a BPAP-containing bolus through isolated rabbit lungs with that obtained after two sequential passes through the lungs. In this way, we could double t with no change in flow or vascular pressure. We found that, when the second pass occurred within a few seconds of the first, M after both the first and second pass was only slightly larger than that after the first pass alone. If the time between passes was increased to a few minutes, M after the second pass was substantially increased. These results are contrary to the recruitment hypothesis and suggest that this substrate may exist in alternative forms that are in slow equilibrium relative to the capillary t. When albumin was present in the perfusate, an albumin-bound fraction appeared to be one such alternative form. However, experiments carried out using protein-free perfusate suggest the possibility that conformational variants of the substrate may also exist.
Thromboxane A2 and serotonin mediate coronary blood flow reductions in unsedated dogs
Authors: Eidt J. F. , Ashton J. , Golino P. , McNatt J. , Buja L. M. , Willerson J. T.
Published: December 2017

We have shown in anesthetized open-chest dogs that recurrent platelet aggregation at the site of coronary artery stenosis and endothelial injury results in a pattern of cyclical variations in coronary blood flow (CFVs) and that serotonin and thromboxane A2 are important mediators of CFVs. In the present study, we tested the following hypotheses: 1) severe spontaneous reductions in coronary blood flow occur in awake closed-chest dogs with coronary artery stenoses and endothelial injury; 2) there is a progression from CFVs to persistent low coronary blood flow; and 3) serotonin and thromboxane A2 are important mediators of coronary blood flow reductions in this model. In 17 of 20 awake closed-chest unsedated dogs with experimental coronary artery stenoses and endothelial injury, either intermittent CFVs (n = 3), persistent low flow (n = 4), or progression from CFVs to low flow (n = 10) occurred during the first postoperative week. A serotonin receptor antagonist (ketanserin or LY 53857) or a thromboxane synthesis inhibitor (dazoxiben) or receptor antagonist (SQ 29548) abolished platelet-dependent CFVs in 80% of dogs. Thus 1) severe spontaneous reductions in coronary blood flow occur in awake closed-chest unsedated dogs with coronary artery stenoses and endothelial injury; 2) there is a progression from CFVs to persistent low coronary blood flow and final coronary artery occlusion; and 3) serotonin and thromboxane A2 are important mediators of coronary blood flow reductions in this experimental model.
Canine coronary vasodepressor responses to hypoxia are abolished by 8-phenyltheophylline
Authors: Wei H. M. , Kang Y. H. , Merrill G. F.
Published: December 2017

Anesthetized randomsource mongrel dogs of either sex were instrumented to investigate the effects of 8-phenyltheophylline on changes in coronary perfusion pressure caused by systemic hypoxia under conditions of controlled constant coronary blood flow. In the absence of 8-phenyltheophylline, coronary perfusion pressure decreased from 98 +/- 10 to 69 +/- 4 mmHg (P less than 0.05) at the end of 3 min of systemic hypoxia [arterial partial pressure of oxygen (PO2) = 23 +/- 2 mmHg]. Calculated coronary vascular resistance decreased concomitantly by 30 +/- 5% (P less than 0.05). In the presence of continuously infused 8-phenyltheophylline, equally severe hypoxia increased coronary perfusion pressure from 112 +/- 10 to 129 +/- 13 mmHg (P less than 0.05). Under these conditions, calculated coronary vascular resistance increased 14 +/- 3% (P less than 0.05). Dose-dependent attenuation of the coronary vasodilator response to exogenous adenosine under normoxic conditions was produced by 8-phenyltheophylline. In vehicle-treated dogs, repeat bolus injections of adenosine consistently lowered coronary perfusion pressure by 45 +/- 15%. The vasodepressor response did not vary from one injection to the next. These data demonstrate that under conditions of controlled constant coronary blood flow, treatment with 8-phenytheophylline abolishes coronary vasodilation caused by systemic hypoxia.
Influence of verapamil on total and regional intravascular volume in dogs
Authors: Weinstock B. S. , Bell L. , Rutlen D. L.
Published: December 2017

Verapamil's influence on intravascular volume (IV) in the total capacitance circulation was examined in anesthetized dogs after mecamylamine or baroreceptor denervation. Blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that IV changes could be measured as reciprocal changes in reservoir volume. In 10 dogs, verapamil (50 micrograms/min) caused a decrease in total IV of 74 +/- 12 ml (P less than 0.0005) at 20 min and a decrease in arterial pressure from 79 +/- 5 to 66 +/- 3 mmHg (P less than 0.0005). After evisceration in nine animals, verapamil caused an extrasplanchnic (XSPL) IV decrease of 97 +/- 19 ml (P = 0.08). In 11 animals with separate perfusion and drainage of the splanchnic and XSPL circulations, verapamil caused an XSPL IV decrease of 74 +/- 20 ml (P less than 0.002) and a splanchnic IV increase of 19 +/- 9 ml (P = 0.06). In four animals on cardiopulmonary bypass, IV decreased 154 +/- 66 ml (P less than 0.002) during verapamil administration. Thus total IV decreases due to a decrease in systemic extrasplanchnic volume. Because pressure decreased while arterial flow and venous outflow pressure were constant, a decrease in the resistance to blood return to the central circulation mediates the XSPL volume decrement.
Contractile effects of cardiac neuropeptides in isolated canine atrial and ventricular muscles
Authors: Rigel D. F. , Grupp I. L. , Balasubramaniam A. , Grupp G.
Published: December 2017

Contractile effects of the cardiac neuropeptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and neurotensin (NT) were compared with those of l-isoproterenol (ISO) in isolated canine atrial and ventricular trabeculae muscles stimulated to contract at 1 Hz. In ventricular muscles, ISO, VIP, and PHI augmented developed isometric force by approximately 100%. VIP and PHI were three times and 1/10, respectively, as potent as ISO. VIP also exhibited positive inotropic effects in atrial trabeculae. The contractile responses to VIP were unchanged after beta-adrenergic blockade with nadolol at a concentration (10 microM) that shifted the ISO dose-response curve two to three orders of magnitude to the right. In atrial and ventricular trabeculae, NPY (1 microM) attenuated contractile force by 36 +/- 8 and 30 +/- 4%, respectively. Each peptide also caused comparable increases or decreases in the rate of development of force and the rate of relaxation. CGRP and NT caused no significant changes in developed force in either atrial or ventricular muscles in concentrations up to 1 microM. Our results indicate a potential positive inotropic action of endogenous VIP and PHI and a cardiodepressant effect of endogenous NPY in the canine heart.
Adenosine receptor coupling to adenylate cyclase of rat ventricular myocyte membranes
Authors: Romano F. D. , MacDonald S. G. , Dobson J. G.
Published: December 2017

The effects of adenosine analogues on beta-adrenergic receptor and receptor-independent elicited increases in adenylate cyclase activity were investigated using membranes obtained from primary cultures of adult rat ventricular myocytes. Phenylisopropyladenosine, an A1-receptor agonist, at concentrations of 0.1, 1.0, and 10 microM, maximally inhibited isoproterenol-stimulated adenylate cyclase activity by 35, 55, and 41%, respectively. The inhibition by phenylisopropyladenosine was antagonized by 10 microM theophylline. One micromolar phenylisopropyladenosine was much less effective at attenuating forskolin-stimulated activity, such that the maximum inhibition was 26%. Phenylisopropyladenosine had no effect on adenylate cyclase stimulation by 5'-guanylylimidodiphosphate. Phenylaminoadenosine, an A2 agonist, at 10 microM or greater stimulated adenylate cyclase activity. This effect was not significantly inhibited by theophylline or 0.1 microM 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), which antagonized phenylisopropyladenosine inhibition of isoproterenol-stimulated adenylate cyclase activity. Additionally, N-ethylcarboxamidoadenosine, a nonselective adenosine-receptor agonist, had no effect on adenylate cyclase activity in the absence of DPCPX but stimulated adenylate cyclase activity in the presence of DPCPX. These results indicate that both A1 and A2 receptors exist on the ventricular myocyte sarcolemma. More importantly, the findings suggest that adenosine inhibition of catecholamine-stimulated adenylate cyclase activity is primarily due to an alteration in beta-adrenergic receptor-mediated transduction and perhaps in part by a direct inhibition of the catalytic component.
Mechanisms responsible for decline in transthoracic impedance after DC shocks
Authors: Sirna S. J. , Kieso R. A. , Fox-Eastham K. J. , Seabold J. , Charbonnier F. , Kerber R. E.
Published: December 2017

To test the hypothesis that tissue hyperemia and edema in the current pathway cause a decrease in transthoracic impedance (TTI) following direct current (DC) shock, the thoracic-skin and skeletal blood flow and blood volume were measured in anesthetized dogs after three 100-J shocks. TTI declined 11% (P less than 0.01) after DC shocks. Blood flow increased 10-fold in skeletal muscle from 0.9 +/- 0.2 to 11.3 +/- 2.6 (SE) ml.100 g-1.min-1 (P less than 0.05). Blood flow did not change outside the current pathway. Blood volume increased in skin in the current pathway from 7.6 +/- 1.5 ml/100 g preshock to 17.5 +/- 2.0 ml/100 g (P less than 0.01) at 60 min after shock; skeletal muscle blood volume did not change. We also determined postshock tissue weight before and after 72 h of drying at 70 degrees C. The percentage decline from wet weight after drying was 68.4 +/- 3.4% in the current pathway vs. 64 +/- 3.8% outside the pathway (P less than 0.05), indicating the tissue in the current pathway was more edematous. Finally, hindlimb edema was induced by deliberate overperfusion. As hindlimb circumference (edema) increased, impedance declined. We conclude that increases in tissue blood flow or tissue blood volume or tissue edema contribute to the decline in transthoracic impedance after DC shock.
n-3 fatty acids increase postischemic blood flow but do not reduce myocardial necrosis
Authors: Force T. , Malis C. D. , Guerrero J. L. , Varadarajan G. S. , Bonventre J. V. , Weber P. C. , Leaf A.
Published: December 2017

The effects of a fish oil-supplemented diet on infarct size and regional myocardial blood flow were examined in a rat model of acute ischemia followed by reperfusion. Thirty-five rats were fed a diet containing 20% by weight: fish oil (FO), rich in n-3 polyunsaturated fatty acids; corn oil (CO), with predominantly n-6 polyunsaturated fatty acids; or beef tallow (BT), containing large amounts of saturated fatty acids. After 6-12 wk on the diet, animals underwent 40 min of left coronary artery occlusion followed by 2 h of reperfusion. Regional transmural myocardial blood flow was determined with radioactive microspheres at 30 min of occlusion and again 30 min after reperfusion. Infarct size was determined with triphenyltetrazolium chloride. Blood flow was virtually undetectable within the ischemic zone in all groups during occlusion. With reperfusion, however, ischemic zone absolute blood flow and relative flow (normalized to nonischemic zone flow) were significantly greater in the fish oil group [2.4 +/- 0.25 ml.min-1.g-1, 44 +/- 4% vs. 1.7 +/- 0.3, 29 +/- 5% for CO (P less than 0.05 vs. FO), and 1.4 +/- 0.3, 29 +/- 5% for BT (P less than 0.05 vs. FO)]. Despite differences in reperfusion blood flow, average percent transmural extent of infarction was nearly identical (68 +/- 4, 68 +/- 5, and 64 +/- 3%) and overall infarct size was similar (38 +/- 3, 36 +/- 4, and 29 +/- 3%) for FO, CO, and BT groups, respectively. In conclusion, dietary supplementation with fish oils increases postischemic blood flow but has no effect on extent of myocardial infarction in this ischemia-reperfusion model in rats.
Nonlinear mechanics of the heart's swinging during pericardial effusion
Authors: Rigney D. R. , Goldberger A. L.
Published: December 2017

When excessive fluid accumulates in the pericardial space, the heart, suspended by the great vessels, is then free to swing as a pendulum. The swinging may occur at either the same frequency as the heart rate (1:1 oscillation) or at half the heart rate (2:1 oscillation), the latter frequency often arising during cardiac tamponade. We show that these two frequencies of oscillation may be explained by the nonlinearity of Newton's equation of motion as applied to the heart. Terms in the equation correspond to gravitational and buoyancy forces, forces due to ejection of blood into the great vessels, and damping forces. A transition between the 1:1 and 2:1 swinging is found to occur when particular parameters of the model are changed, notably when there is an increase of heart rate. This finding is compatible with previous clinical reports.
Adrenal blood flow and secretory relationships during hypoxia in anesthetized dogs
Authors: Breslow M. J. , Ball T. D. , Miller C. F. , Raff H. , Traystman R. J.
Published: December 2017

To evaluate whether hypoxia-induced increases in adrenal cortical (CQ) and medullary (MQ) blood flow (radiolabeled microspheres) occur secondary to hypoxia-induced secretory activity, pentobarbital-anesthetized ventilated dogs were pretreated with dexamethasone (DEX) to prevent adrenocorticotropic hormone (ACTH) and corticosteroid secretory changes or underwent unilateral adrenal denervation to prevent adrenal catecholamine secretory responses. In nonsurgically stressed dogs, DEX completely prevented increases in ACTH or corticosteroid levels during reduction of arterial oxygen content to 8 vol% but had no effect on hypoxia-induced doubling of CQ. In dogs in which adrenal oxygen consumption (VO2) was measured, DEX reduced VO2 by 50% without altering CQ. Unilateral adrenal denervation prevented hypoxia-induced increases in adrenal catecholamine secretion and MQ but had no effect on the CQ response. These results suggest that hypoxia-induced medullary vasodilation is associated with adrenal catecholamine secretory activity but that increases in CQ occur independent of secretory activity and likely represent direct vascular effects of hypoxia.
Usefulness and limitations of regional cardiac sympathectomy by phenol
Authors: Mori H. , Pisarri T. E. , Aldea G. S. , Husseini W. K. , Dae M. W. , Stevens M. B. , Hill A. C. , Coleridge J. C. , Coleridge H. M. , Hoffman J. I.
Published: December 2017

We evaluated the completeness and extent of regional sympathetic denervation of the left ventricle after epicardial painting with phenol in anesthetized dogs. In a region encircled by phenol, the effect of electrical stimulation of efferent sympathetic fibers on myocardial contractility and coronary vascular resistance was completely abolished within 30 min. Denervation extended to untreated regions innervated by sympathetic fibers crossing the phenol line. For at least 4 h after phenol application, intravenous infusion of isoproterenol or coronary arterial infusion of tyramine increased myocardial contractility in the denervated region; norepinephrine content and neurotransmitter uptake were normal, indicating that nerve terminals, postjunctional receptors, and myocardium remained functional. However, after 3-14 days, tissue catecholamine content and transmitter uptake in the encircled area were markedly reduced. The results suggest that careful evaluation is necessary in selecting a fully innervated control region in studies employing regional sympathetic denervation with phenol.
Arteriolar oxygen reactivity is inhibited by leukotriene antagonists
Authors: Jackson W. F.
Published: December 2017

Experiments were performed to test the hypothesis that the arteriolar constriction produced by elevated oxygen tensions in the hamster cheek pouch is mediated by a leukotriene. To test this hypothesis, the diameter response of arterioles in superfused hamster cheek pouch preparations to stepwise increases in superfusion solution oxygen content was measured by video microscopy in the absence and 30 min after superfusion with solutions containing inhibitors of the synthesis or actions of leukotrienes. Oxygen-induced constrictions were inhibited in a dose-dependent fashion by two structurally distinct 5-lipoxygenase inhibitors (U 60257 and SC 43251) and two different leukotriene receptor antagonists (SKF 102922 and FPL 55712). Also, all four inhibitors tended to dilate the arterioles under low PO2 conditions. The inhibition of oxygen reactivity appeared to be selective in that arteriolar constrictions induced by topical application of phenylephrine were unaffected (SC 43251, SKF 102922, FPL 55717, and 30 microM U 60257) or only modestly reduced (100 microM U 60257) by the inhibitors. These data are consistent with the hypothesis that a leukotriene, or related compound, mediates arteriolar oxygen reactivity in the hamster cheek pouch.
Kinetics of ATP-sensitive K+ channel revealed with oil-gate concentration jump method
Authors: Qin D. Y. , Takano M. , Noma A.
Published: December 2017

Kinetics for gating the ATP-sensitive K+ channel was studied by exposing the inside-out patch to instantaneous changes in the intracellular concentration of ATP ( [ATP]i) using the oil-gate concentration jump technique in guinea pig ventricular cells. The closing time course of the channel after increasing [ATP]i was exponential with a time constant (tau), which decreased with increasing [ATP]i. The linear 1/tau - [ATP]i relation revealed two different binding (closing) rate constants (mu) of 51.7 and 5.6 mM-1.s-1 and predicted a common unbinding (opening) rate constant (lambda) of 3.2 s-1. A variable latent period was observed before channel opening when [ATP]i was decreased. The mechanism of latency is not clear. Once the channel started to open at the change lowering [ATP]i, the opening time course was exponential. Measurements of the exponential tau obtained at 0 mM [ATP]i were divided into two groups with corresponding lambda of 2.8 and 20.1 s-1, respectively. The former agrees with the predicted value of 3.2 s-1, but in the latter case, tau for opening increased as [ATP]i was increased. This increase in tau was attributed to a decrease of lambda, which approached an asymptotic value of 3.2 s-1. We conclude that binding and unbinding of one molecule of ATP determine the gating of ATP-sensitive K+ channel. Different pairs of mu and lambda result in four types of gating patterns and practically two states of sensitivities to ATP.
Postocclusive cerebral hyperemia is markedly attenuated by chronic trigeminal ganglionectomy
Authors: Moskowitz M. A. , Sakas D. E. , Wei E. P. , Kano M. , Buzzi M. G. , Ogilvy C. , Kontos H. A.
Published: December 2017

Marked hyperemia may develop in brain following temporary cessation of blood flow and is associated with the morbidity following cardiac arrest, stroke, and head injury. Regional cerebral blood flow was measured using radiolabeled microspheres and compared in 10 symmetrical regions after chronic unilateral trigeminal ganglionectomy (n = 8), trigeminal rhizotomy (n = 4), or sham operation (n = 4) following 10 min of combined brachiocephalic-left subclavian occlusion and hypotension (mean arterial blood pressure less than 50 mmHg) in cats. Blood flow was symmetrical at rest in the three groups and was undetectable during the ischemic period. Within 30 min after re-establishing flow, values in cortical gray matter increased symmetrically to approximately 250 ml.100 g-1.min-1 in the rhizotomy and the sham groups. Increases of similar magnitude were measured on the intact side following trigeminal ganglionectomy but flow was attenuated by greater than 50% ipsilateral to the ganglionectomy. Marked hyperemia developed during reperfusion in thalamus, caudate, deep cortical white matter, midbrain, and pons, but no asymmetries were present in the three groups. These data suggest that cortical hyperemia is mediated by trigeminal neurogenic mechanisms via axonal reflexlike mechanisms and suggest the importance of therapeutic strategies based on blockade of this nerve or its constituent neuropeptides.
Postischemic recovery rate of cerebral ATP, phosphocreatine, pH, and evoked potentials
Authors: Nishijima M. K. , Koehler R. C. , Hurn P. D. , Eleff S. M. , Norris S. , Jacobus W. E. , Traystman R. J.
Published: December 2017

We tested the hypotheses that after complete cerebral ischemia, first, rate of recovery of ATP, phosphocreatine (PCr), and intracellular pH (pHi) varies with ischemic duration and second, rate of metabolic recovery is a more sensitive predictor of consequent electrophysiological deficit than steady-state metabolic recovery. With the use of transient intracranial hypertension in anesthetized dogs, ischemic duration was set for either 3, 12, or 30 min, which depressed somatosensory-evoked potential (SEP) recovery amplitude by 30, 59, and 88%, respectively. In contrast, ATP, PCr, and pHi, measured by 31P magnetic resonance spectroscopy, fully recovered. When ischemic duration was increased from 3 to 12 min, mean recovery time of ATP (6 min) remained rapid but that of pHi (12-28 min) was prolonged. After 30 min of ischemia, pHi recovery was not slowed further (25 min) but that of ATP was now markedly prolonged (36 min). PCr recovery time increased progressively with ischemic duration (5, 11, and 21 min, respectively) and correlated best with SEP recovery (r = 0.74). We conclude that the brain's ability to rapidly normalize pH is a sensitive predictor of electrophysiological recovery after short ischemia but that ATP regeneration becomes important with prolonged ischemia. PCr recovery rate was the best overall predictor, probably because it depends on both pHi and the ratio of ATP to ADP by the creatine kinase reaction.
Effects of left ventricular pressure reductions on right ventricular systolic performance
Authors: Chow E. , Farrar D. J.
Published: December 2017

Reductions in left ventricular pressure (LVP) have been shown to produce a leftward shift of the interventricular septum and to reduce left ventricular contribution to right ventricular performance. To evaluate the magnitude of this contribution in the intact heart, five anesthetized pigs were implanted with a left prosthetic ventricle to gradually decrease LVP while maintaining arterial systemic pressure. Three descriptors of RV global and regional systolic function were studied in the septum to free wall (RVSFW) and anterior to posterior (RVAP) dimensions and in an outflow tract segment length (RVSL), during both steady state and transient inferior vena cava occlusion. LVP gradual reduction from 102 +/- 4 to 11 +/- 3 mmHg (90% decrease in peak systolic pressure) produced no changes in the RV global stroke work curve or in the RVAP and RVSL pressure-dimension relationships. However, the reduction in LVP resulted in parallel shifts in the RVSFW dimension, with 16.6 +/- 6.7% increase in the intercept D(o) of the end-systolic relationship and 16.5 +/- 2.5% increase in D(o) of the dimensional stroke work relationship, with no significant changes in their respective slopes as calculated by linear regression. Therefore, in the normal intact heart, large reductions in left ventricular pressure affect the geometry of the right ventricle because of septal shifting, but there is a negligible net effect of this anatomic ventricular interaction on overall right ventricular performance.
Dihydroxyphenylglycol as an index of neuronal uptake in dog saphenous vein
Authors: Rorie D. K. , Hunter L. W. , Tyce G. M.
Published: December 2017

Dihydroxyphenylglycol (DOPEG), the metabolite of norepinephrine (NE) that arises intraneuronally, was measured together with NE in superfusates collected before, during, and after nerve stimulation and in extracts of dog saphenous vein after superfusion and electrical stimulation (ES). Different concentrations of NE in the synaptic clefts were achieved by treating tissues with corticosterone, corticosterone and yohimbine, corticosterone and cocaine, or by omitting drugs from the superfusate. NE and DOPEG were quantitated by liquid chromatography with electrochemical detection. The time courses of NE overflow and DOPEG efflux into superfusate were followed. The amounts of DOPEG in superfusates under basal conditions were two to four times higher than the amounts of NE and progressively increased during ES except in tissues with neuronal uptake inhibited. NE overflow reached a steady state within the first 6 min of ES. Increased NE concentrations in synaptic clefts resulted in increased DOPEG production except where neuronal uptake was inhibited. The increased DOPEG production during ES appears to reflect the increased rate of neuronal uptake, which results in more NE being available for intraneuronal metabolism. No evidence was found that newly formed DOPEG was delayed in leaving the tissue. Thus the increase in DOPEG production that occurs during ES may be useful as an index of neuronal uptake of NE in dog saphenous vein.
Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors
Authors: Wyatt D. A. , Edmunds M. C. , Rubio R. , Berne R. M. , Lasley R. D. , Mentzer R. M.
Published: December 2017

This study was designed to assess the role of adenosine in the regulation of exogenous glucose utilization by myocardium. Perfusion of isolated rat hearts with buffer containing D-[3-3H]glucose and analysis of the coronary effluent for 3H2O production was used as an indicator of glycolytic flux. Initially, glycolytic flux was determined during five different conditions: 1) normoxia; 2) normoxia plus 100 microM adenosine; 3) normoxia plus 100 microM adenosine and 10 microM 8-(sulfophenyl)-theophylline (SPT), an adenosine receptor antagonist; 4) hypoxia; and 5) hypoxia plus 10 microM SPT. Both adenosine and hypoxia produced an approximate threefold increase in glycolytic flux that was attenuated by adenosine receptor blockade with SPT. Next, hearts were perfused during normoxic conditions with various concentrations of either R-phenylisopropyladenosine (PIA), an A1-adenosine receptor agonist, or 5'-N-ethylcarboxamidoadenosine (NECA), an A2-adenosine receptor agonist. Significant increases in glycolytic flux occurred with PIA, whereas NECA treatment resulted in only a marginal stimulation of glycolytic flux. These data provide evidence that: 1) exogenous adenosine stimulated glycolytic flux in the normoxic myocardium; 2) endogenous adenosine stimulated glycolytic flux during hypoxia; and 3) the effect of adenosine on glycolytic flux was mediated by interaction with A1-adenosine receptors.
Endothelial impairment inhibits prostaglandin and EDRF-mediated arteriolar dilation in vivo
Authors: Koller A. , Messina E. J. , Wolin M. S. , Kaley G.
Published: December 2017

The role of endothelium in the vasodilation of third order arterioles of cremaster muscle to a variety of vasoactive agents was investigated in pentobarbital-anesthetized rats. Changes in diameter to topical administration of agents were measured with image shearing, before and after mercury light/sodium fluorescein (light/dye) treatment of a 50- to 100-microns segment of the arteriole under study and were recorded with video microscopy. Before light/dye treatment, arachidonic acid (10(-5) M), prostaglandin E2 (5 x 10(-6) M), A23187 (2 x 10(-6) M), acetylcholine (10(-5) M), and adenosine (10(-4) M) elicited dilation between 75 and 106% of basal diameter. After light/dye treatment, dilations to arachidonic acid, A23187, and acetylcholine were completely eliminated; however, the responses to prostaglandin E2 and adenosine were not altered. These results indicate that light/dye treatment interferes with the production of or response to prostaglandins as well as other endothelial mediators, like endothelium-derived relaxing factor (EDRF). In a second series of experiments, bradykinin, in concentrations of 10(-9), 10(-8), and 10(-7) M elicited dose-dependent dilations, which were partially inhibited by indomethacin and completely abolished after additional light/dye treatment. Dilation of arterioles to adenosine was maintained throughout these experiments. These data suggest that vasodilation to bradykinin is mediated partly via prostaglandin production and partly via other endothelium-derived factor(s).
Posterior hypothalamic influences on cardiovascular effects of aortic nerve stimulation
Authors: Smith J. K. , Barron K. W.
Published: December 2017

The purpose of this study was to examine the influence of stimulation of the posterior hypothalamus on the baroreflex responses produced by stimulation of the aortic depressor nerve. Animals were initially anesthetized and implanted with a bipolar electrode in the posterior hypothalamus. Three to 5 days later, animals were anesthetized with urethan, and the left aortic depressor nerve was dissected and placed on a bipolar platinum-iridium electrode. The effects of electrical stimulation of the posterior hypothalamus (0, 160, and 280 microA) were examined in baroreflex-intact and acutely sinoaortic baroreceptor-denervated animals, and the responses to aortic nerve stimulation (2, 8, 16, and 32 Hz) were examined during each level of hypothalamic stimulation. The first set of experiments was performed in baroreceptor-intact animals; e.g., in animals with arterial baroreceptor inputs intact from both carotid sinus regions in addition to intact right aortic baroreceptor afferent pathways. In that group, stimulation of the posterior hypothalamus attenuated the bradycardia and depressor effects of aortic nerve stimulation. When influences from other baroreceptor inputs were removed with acute sinoaortic baroreceptor denervation, posterior hypothalamic stimulation interrupted the reflex bradycardia due to aortic nerve stimulation; however, the depressor response to aortic nerve stimulation was not attenuated. Similar to the arterial pressure response, hypothalamic stimulation did not attenuate the decreases in mesenteric and iliac vascular resistance produced by aortic nerve stimulation in the baroreflex-denervated group. We conclude that posterior hypothalamic stimulation attenuates baroreflex-mediated bradycardia but does not alter baroreflex control of arterial pressure and peripheral vascular resistance.
Hydrolysis of a synthetic angiotensin-converting enzyme substrate in dog lungs
Authors: Linehan J. H. , Bronikowski T. A. , Rickaby D. A. , Dawson C. A.
Published: December 2017

The present study was carried out to begin to evaluate the saturable kinetics of the hydrolysis of a synthetic substrate, benzoyl-phenylalanyl-alanyl-proline (BPAP), for angiotensin-converting enzyme (ACE), by the pulmonary endothelium of the dog using a multiple indicator dilution method. In the experiments, isolated dog lung lobes were perfused with a salt solution containing 5% bovine serum albumin. Boluses containing [3H]BPAP, and various amounts of unlabeled BPAP were injected into the lobar artery, and timed samples of venous effluent were collected. The samples were analyzed to determine the fractional hydrolysis of the injected BPAP. The BPAP hydrolysis on passage through the lungs exhibited the saturable behavior and the relative insensitivity to changing flow rate previously described. Since we have described previously that BPAP behaves as if it exists in two forms, one of which is virtually unhydrolyzable on a single pass through the lungs, a model was formulated to include the influence of the unhydrolyzable form, as well as the saturable hydrolysis of the hydrolyzable form, on the fractional hydrolysis of the injected BPAP. This model provides a new method for estimating the kinetic parameters of BPAP hydrolysis by pulmonary endothelial ACE, and it explains the observation that the fractional BPAP hydrolysis does not vary with flow rate and transit time to the extent predicted by previous models.
Analysis of the interval-force relationship in rat and canine ventricular myocardium
Authors: Bouchard R. A. , Bose D.
Published: December 2017

The mechanism of the negative force staircase in thin rat ventricular trabeculae was investigated and compared with the positive force staircase in dog ventricular muscles of comparable diameter. Increasing stimulus frequency from 0.2 to 0.5 and 1 Hz resulted in a stepwise reduction of twitch amplitude that was demonstrated in both 1.25 and 2.5 mM external calcium concentration ([Ca]o). The negative staircase was associated with no change in the amplitude of postrest contraction or rapid-cooling contracture at either [Ca]o investigated. Hence, neither decreased loading nor overloading of the rat sarcoplasmic reticulum with calcium during the steady state can be invoked as a likely explanation for the negative staircase. The results are consistent with a frequency-dependent increase in the refractoriness of the sarcoplasmic reticular calcium release process or a decrease in the amount of trigger for calcium release, assuming that the amount of calcium present in the release pool is constant from one frequency to the next. In contrast to the rat, canine ventricular muscle exhibited a positive force staircase, the slope of which depended on [Ca]o, as well as a frequency-dependent increase in postrest contraction and rapid-cooling contracture. Data obtained from this series of experiments suggests that increased filling of the release pool within the sarcoplasmic reticulum with calcium underlies the inotropic effect of high-frequency stimulation in canine ventricular muscle.
Characterization of intact mesenteric lymphatic pump and its responsiveness to acute edemagenic stress
Authors: Benoit J. N. , Zawieja D. C. , Goodman A. H. , Granger H. J.
Published: December 2017

The contractile properties of the mesenteric collecting lymphatics of the rat were analyzed under control conditions and during periods of enhanced lymph formation using in vivo microscopic techniques. Pressure and diameter were simultaneously monitored in microscopic collecting lymphatics, and lymphatic pump function was analyzed in accordance with basic principles of cardiac mechanics. The lymphatic contractile cycle was divided into two phases of systole and four phases of diastole. Under control conditions, lymphatics contracted with a frequency of 6.4 +/- 0.61 beats/min and ejected approximately 67% of their end-diastolic volume. Ten minutes after the rate of lymph formation was elevated by plasma dilution, end-diastolic diameter, contraction frequency, ejection fraction, and stroke volume increased. Pressure in the lymphatic network became less pulsatile in high lymph flow states. Contractility, an index of inotropic changes in lymphatic pump, was unaltered when lymph flow was increased by plasma dilution. Furthermore, the maximal shortening velocity of lymphatic smooth muscle did not change during periods of enhanced lymph flow. Thus it appears that passive increases in the rate of lymph formation exert few, if any, inotropic effects on the lymphatic pump. The augmented stroke volume and contraction frequency appear to result mainly from intrinsic stretch-dependent mechanisms set in motion by elevated preload. These data represent the first comprehensive characterization of both the flow-generating and muscle characteristics of intact collecting lymphatics and provide a basis for future studies on the physiological regulation of lymphatic contraction.
Albumin improves stability and longevity of perfluorochemical-perfused hearts
Authors: Segel L. D. , Ensunsa J. L.
Published: December 2017

Page H1107: L. D. Segel and J. L. Ensunsa. “Albumin improves stability and longevity of perfluorochemical-perfused hearts.” The stroke work data and CVR units in Table 2 should appear as follows.

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Characterization of pulmonary arterial input impedance with lumped parameter models
Authors: Grant B. J. B. , Paradowski L. J.
Published: December 2017

Page H587: B. J. B. Grant and L. J. Paradowski. “Characterization of pulmonary arterial input impedance with lumped parameter models.” Equations 5 and 6 should appear as the following.

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