ACTA PHYSIOLOGICA, Issue 2 2010
K. F. Nilsson
Abstract Aim:, Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations. Methods:, Plexus-containing guinea-pig ileum longitudinal smooth muscle preparations were made to contract intermittently by electrical field stimulation in organ baths. Schild plot regressions were constructed with 2-chloroadenosine (agonist) and 8-(p -sulfophenyl)theophylline (8-PST; antagonist). In separate experiments the reversing or enhancing effect of 8-PST and the inhibiting effect of 2-chloroadenosine (CADO) were analysed in the absence or presence of an adenosine uptake inhibitor (dilazep), and nucleoside overflow was measured by HPLC. Results:, Using the obtained DR, baseline adenosine concentration was calculated to 28 nm expressed as CADO activity, which increased dose dependently after addition of 10,6 m dilazep to 150 nm (P < 0.05). HPLC measurements yielded a lower fractional increment (80%) in adenosine during dilazep, than found in the pharmacological determination (440%). Conclusion:, Endogenous adenosine is an important modulator of intestinal neuro-effector activity, operating in the linear part of the dose,response curve. Other adenosine-like agonists might contribute to neuromodulation and the derived formulas can be used to calculate endogenous agonist activity, which is markedly affected by nucleoside uptake inhibition. The method described should be suitable for other endogenous signalling molecules in many biological systems. [source]

Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteers

ACTA PHYSIOLOGICA, Issue 1 2009
A. Soop
Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source]

Adenosine induces prolonged anti-,-adrenergic effects in guinea-pig papillary muscle

ACTA PHYSIOLOGICA, Issue 1 2002
L. ARVOLA
ABSTRACT A sustained anti- , -adrenergic effect of adenosine has been reported. This study was initiated to investigate this topic and especially elucidate the role of protein kinase C (PKC). Contractile force amplitude and action potential duration at 90% repolarization (APD90) were measured in guinea-pig papillary muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols contained 30 min exposure to the test agents adenosine 33 ,m (ado), adenosine + PKC-inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC-activator 1,2-dioctanoyl-sn-glycerol 10 ,m (DOG) and , -agonist phenylephrine 5 ,m (phe). Isoproterenol was given at the end of test exposure and after 15 min washout. Results are mean ± SEM of percentage-change, P , 0.05 considered significant and labelled *. The first isoproterenol challenge significantly increased contractile force (27 ± 7%*) in the control group. Responses in the test groups were 2 ± 4 (ado), 1 ± 5 (ado + BIM), 14 ± 4* (DOG), 0 ± 2% (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3 ± 8 (ado), 23 ± 5* (ado + BIM), 13 ± 5* (DOG), 15 ± 7% (phe) increase in test groups compared with 22 ± 5%* increase in contractile force in the control group. After 45 min washout of adenosine the inotropic response was still significantly reduced compared with control (29 ± 4 vs. 79 ± 8%*). Isoproterenol stimulation shortened APD90 in controls at both time points (5 ± 1%* and 4 ± 1%*), with no significant shortening in test groups. Adenosine induces sustained anti- , -adrenergic effects on contractile force as well as APD90. A role for PKC in signal transduction is supported with respect to contractile force. [source]

Peripheral sensitization in migraine,role for P2X purinergic receptors in the dura,vascular sensory pathway

DRUG DEVELOPMENT RESEARCH, Issue 6 2007
Ernest A. Jennings
Abstract Peripheral sensitization is still considered a prime contributor underlying the mechanisms of migraine. Trigeminal primary afferent neurons are the first neurons in the dural nociceptive pathway, and activation results in conscious perception of pain. Peripheral sensitization can lower the activation threshold of primary afferent neurons, rendering them more excitable, allowing for increases in release of neurotransmitter from both central and peripheral terminals. Increase in neurotransmitter release from central terminals contributes to excitation of second-order neurons, while the release of peptides from peripheral terminals has been implicated in neurogenic inflammation. Adenosine 5,-triphosphate (ATP) causes pain in human studies, and depolarize sensory neurons. There is evidence of the action of ATP at many levels in the dura,vascular sensory pathway. Animal studies have shown that some P2X receptors are located in neurons innervating the dura, including the P2X3 receptor, which is most often shown to be involved in nociceptive pathways. In this article, we briefly review peripheral sensitization in relation to migraine and provide emphasis for P2X receptor involvement where it is available. Drug Dev Res 68:321,328, 2007. © 2007 Wiley-Liss, Inc. [source]

Adenosine downregulates cytokine-induced expression of intercellular adhesion molecule-1 on rheumatoid synovial fibroblasts independently of adenosine receptor signaling

DRUG DEVELOPMENT RESEARCH, Issue 4 2003
Takashi Nakazawa
Abstract Adhesion of fibroblast-like synoviocytes (FLSs) to T cells through the interaction of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). We therefore used flow cytometry and quantitative polymerase chain reaction (PCR) to examine the effect of adenosine and its derivatives on expression of ICAM-1 induced by tumor necrosis factor-alpha and interferon-gamma in primary rheumatoid FLSs (RA-FLSs) and E11 cells, an RA-FLS line. Exposing cells to adenosine (5,500 µM) for 24 h in the presence of coformycin, an adenosine deaminase inhibitor, concentration-dependently inhibited cytokine-induced transcription of ICAM-1 mRNA, as well as subsequent surface expression of the protein. Although transcription of all four adenosine receptor isoforms has been detected in FLSs, neither the A1 receptor agonist R-PIA, the A2A receptor agonist CGS21680 nor the A3 agonist Cl-IB-MECA had any effect on cytokine-induced ICAM-1 expression. Conversely, A1/A2 receptor antagonist xanthine amine congener and A2A antagonist ZM240385 both failed to suppress the effect of adenosine. Adenosine appears to inhibit cytokine-induced ICAM-1 expression in FLSs independently of adenosine receptor-mediated signaling. By contrast, the effect of adenosine was neutralized by nitrobenzylmercaptopurin, a nucleoside transporter inhibitor, or by ABT702, an adenosine kinase inhibitor. This suggests that adenosine taken up via the nucleoside transporter is phosphorylated by adenosine kinase, and the resultant phospho-adenosine interferes with the ICAM-1 transcription and cell surface expression. Downregulation of T cell,FLS interaction by adenosine may thus represent a novel approach to the treatment of RA. Drug Dev. Res. 58:368,376, 2003. © 2003 Wiley-Liss, Inc. [source]

Adenosine A3 receptors in the rat hippocampus: Lack of interaction with A1 receptors

DRUG DEVELOPMENT RESEARCH, Issue 4 2003
Luísa V. Lopes
Abstract Adenosine acts as a neuromodulator in the hippocampus essentially through activation of inhibitory A1 receptors. Using single-cell PCR analysis, we found that CA1 pyramidal cells coexpress A1 receptor mRNA together with that of another adenosine receptor, the A3 receptor. As occurs for the A1 receptor, Western blot analysis indicated that the A3 receptor is also located in hippocampal nerve terminals. However, activation of A3 receptors with its purportedly selective agonist Cl-IBMECA (0.1,10 µM) failed to affect hippocampal synaptic transmission or to modify the evoked release of glutamate or GABA. Also, blockade of A3 receptors with MRS 1191 (5 µM) failed to affect either hypoxia- or ischemia-induced depression of hippocampal synaptic transmission. Activation of A3 receptors also failed to control A1 receptor function, as Cl-IBMECA (100 nM) did not modify the ability of CPA to displace [3H]DPCPX binding to hippocampal membranes or the A1 receptor-mediated inhibition of hippocampal synaptic transmission. However, ligand binding studies revealed that Cl-IBMECA displaced the binding of an A1 receptor agonist ([3H]R-PIA, Ki=47 nM) or antagonist ([3H]DPCPX, Ki=130 nM), which suggests that A3 receptor ligands also act on native A1 receptors. We believe that A3 receptors are expressed in hippocampal neurons and are located in hippocampal nerve terminals, though their function remains elusive. Drug Dev. Res. 58:428,438, 2003. © 2003 Wiley-Liss, Inc. [source]

Pharmacological characterization of the rat brain P2Y1 receptor expressed in HEK293 cells: Ca2+ signaling and receptor regulation

DRUG DEVELOPMENT RESEARCH, Issue 2-3 2001
Christian Vöhringer
Abstract The increasing number of ATP- and UTP-sensitive membrane receptors identified by cloning represent either ligand-activated ion channels (P2X) or G-protein-coupled receptors (P2Y). Adenosine, ATP, and UTP have potential application in the management of pain, cancer, and some cardiovascular and pulmonary diseases and are also involved in inflammatory processes in the brain. Therefore, P2Y receptors seem to be promising therapeutic targets. Multiple P2Y receptor subtypes, classified pharmacologically, are mainly linked to activation of phospholipase C (PLC). The present study further characterizes the rat brain P2Y1 wild-type receptor (rP2Y1 -wt) and the eGFP-tagged receptor (rP2Y1 -eGFP) stably expressed in HEK293 cells, thus shedding light on receptor regulation. Both receptors were analyzed by measuring Ca2+ responses in single cells. The rP2Y1 -eGFP receptor was coupled to Ca2+ release like the rP2Y1 -wt receptor. Experiments using the PLC inhibitor U73122 confirm the functional activation of PLC, through rP2Y1 -eGFP activation. The P2Y1 -selective agonists 2-MeSADP and 2-MeSATP were most potent at the heterologously expressed receptors. We found a ligand selectivity typical for P2Y1 receptors (2-MeSADP = 2-MeSATP > ADP > ATP,S, ATP >> UTP). Fluorescence microscopy and Ca2+ measurements confirm that the rP2Y1-eGFP receptor during homologous desensitization is subjected to processes leading to agonist-induced internalization. The kinetics of receptor resensitization were also examined. Therefore, rP2Y1 -eGFP expressing cells are suitable to determine the physiological P2Y1 receptor signaling pathway and can be a helpful tool to identify drugs acting at P2Y1 receptors as possible therapeutic targets. Drug Dev. Res. 53:172,179, 2001. © 2001 Wiley-Liss, Inc. [source]

Characterization and expression of ATP P2X4 receptor from embryonic chick skeletal muscle

DRUG DEVELOPMENT RESEARCH, Issue 1 2001
Xuenong Bo
Abstract Previous pharmacological experiments have indicated the existence of ATP P2X receptors in chick embryonic skeletal muscles. In this study we cloned a P2X4 -like cDNA encoding a protein of 385 amino acids, which shares 75% and 76% identity with rat and human P2X4 receptors, respectively. Functional studies of this cP2X4 receptor expressed in Xenopus oocytes showed that ATP induced a fast inward current, which was partially desensitized upon prolonged application of ATP. The ATP-induced currents were concentration-dependent, with an EC50 of 9.5 ,M. Adenosine 5,- O -(thio)triphosphate and 2-methylthioATP very weak agonists. ,,,-methyleneATP was almost inactive. In contrast to their potentiating effects on recombinant rat P2X4 receptors, both suramin and pyridoxalphosphate-6-azophenyl-2,,4,-disulfonic acid partially blocked ATP-induced currents. TrinitrophenylATP was able to block ATP-induced response completely, with an IC50 of 4.7 ,M. Northern blot and RT-PCR analysis showed that cP2X4 mRNAs were mainly expressed in skeletal muscle, brain, and gizzard of day 10 chick embryos. Lower levels of expression were also detected in liver, heart, and retina. Whole-mount in situ hybridization showed that cP2X4 mRNAs were expressed in the brain, spinal cord, notochord, gizzard, and skeletal muscle. The physiological functions of cP2X4 receptors in embryonic skeletal muscle remain unclear at present. Drug Dev. Res. 53:22,28, 2001. © 2001 Wiley-Liss, Inc. [source]

Functional and molecular evidence of adenosine A2A receptor in coronary arteriolar dilation to adenosine

DRUG DEVELOPMENT RESEARCH, Issue 1-2 2001
Lih Kuo
Abstract Adenosine is a potent vasodilator implicated in the regulation of coronary microvascular diameter during metabolic stress. However, the specific adenosine receptors and underlying mechanism responsible for the dilation of coronary microvessels to adenosine remains to be elucidated. Thus, pig subepicardial coronary arterioles (<100 ,m) were isolated, cannulated, and pressurized without flow for in vitro study. All vessels developed basal tone and dilated concentration-dependently to adenosine. Disruption of endothelium and inhibition of nitric oxide (NO) synthase by L-NAME produced identical attenuation of adenosine-induced dilation. KATP channel inhibitor glibenclamide further reduced the dilation of denuded vessels. cAMP antagonist Rp-8-Br-cAMP blocked vasodilation to forskolin, but failed to inhibit vasodilation to adenosine. Coronary dilation to adenosine was blocked by a selective adenosine A2A receptor antagonist ZM241385, but was not altered by an A1 receptor antagonist, DPCPX. Reverse transcription-polymerase chain reaction study revealed that A2A receptor mRNA was expressed in microvessels but not in cardiac myocytes; A1 receptor expression was observed only in cardiac myocytes. These results suggest that adenosine-induced dilation of coronary arterioles is mediated predominantly by A2A receptors. Activation of these receptors elicits vasodilation by endothelial release of NO and by smooth muscle opening of KATP channels in a cAMP-independent manner. Drug Dev. Res. 52:350,356, 2001. © 2001 Wiley-Liss, Inc. [source]

Seizure Suppression by Adenosine-releasing Cells Is Independent of Seizure Frequency

EPILEPSIA, Issue 8 2002
Detlev Boison
Summary: ,Purpose: Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine-releasing grafts was independent of seizure frequency. Methods: Adenosine-releasing cells were encapsulated and grafted into the lateral brain ventricle of rats kindled in the hippocampus. During 4 weeks after grafting, electric test stimulations were delivered at a frequency of either once a week or 3 times per week. Seizure activity was evaluated by visual scoring of seizure severity and by the recording of EEGs. Results: Adenosine released from encapsulated cells exerted potent antiepileptic activity for ,2 weeks. One week after grafting, treated rats displayed a complete protection from clonic seizures, and a protection from focal seizures was observed in the majority of animals. Seizure suppression was accompanied by a reduction of afterdischarges in EEG recordings. The protective efficacy of the grafted cells was the same irrespective of whether electrical test stimulations were delivered 1 or 3 times per week. Rats receiving control grafts continued to display full clonic convulsions. Conclusions: This study demonstrated that the frequency of test stimulations did not influence the seizure-suppressive potential of adenosine-releasing grafts. Thus the local delivery of adenosine is likely to be effective in seizure control over a threefold range of seizure-discharge frequency. [source]

Adenosine drives recycled vesicles to a slow-release pool at the mouse neuromuscular junction

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010
Paula P. Perissinotti
Abstract The effects of adenosine on neurotransmission have been widely studied by monitoring transmitter release. However, the effects of adenosine on vesicle recycling are still unknown. We used fluorescence microscopy of FM2-10-labeled synaptic vesicles in combination with intracellular recordings to examine whether adenosine regulates vesicle recycling during high-frequency stimulation at mouse neuromuscular junctions. The A1 adenosine receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine) increased the quantal content released during the first endplate potential, suggesting that vesicle exocytosis can be restricted by endogenous adenosine, which accordingly decreases the size of the recycling vesicle pool. Staining protocols designed to label specific vesicle pools that differ in their kinetics of release showed that all vesicles retrieved in the presence of 8-cyclopentyl-1,3-dipropylxanthine were recycled towards the fast-release pool, favoring its loading with FM2-10 and suggesting that endogenous adenosine promotes vesicle recycling towards the slow-release pool. In accordance with this effect, exogenous applied adenosine prevented the replenishment of the fast-release vesicle pool and, thus, hindered its loading with the dye. We had found that, during high-frequency stimulation, Ca2+ influx through L-type channels directs newly formed vesicles to a fast-release pool (Perissinotti et al., 2008). We demonstrated that adenosine did not prevent the effect of the L-type blocker on transmitter release. Therefore, activation of the A1 receptor promotes vesicle recycling towards the slow-release pool without a direct effect on the L-type channel. Further studies are necessary to elucidate the molecular mechanisms involved in the regulation of vesicle recycling by adenosine. [source]

Adenosine and Caffeine-induced Paroxysmal Supraventricular Tachycardia

ACADEMIC EMERGENCY MEDICINE, Issue 5 2010
Harry C. Karydes DO
No abstract is available for this article. [source]

Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005
Eduardo D. Martín
Abstract The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 µm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal-5,-phosphate-azophenyl 2,,4,-disulphonate (PPADS) and reactive blue-2, and the P1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 µm ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases. [source]

Functional significance of hepatic arterial flow reserve in patients with cirrhosis

HEPATOLOGY, Issue 2 2003
Alexander Zipprich
In cirrhosis, hepatic arterial vasodilatation occurs in response to reduced portal venous blood flow. However, although the hepatic arterial flow reserve is high in patients with cirrhosis, its impact on hepatic function is unknown. This study investigated the effect of adenosine-induced hepatic arterial vasodilatation on different markers of liver function. In 20 patients with cirrhosis (Child-Pugh class A/B/C: n = 2/7/11) adenosine (2-30 ,g · min,1 · kg body wt,1) was infused into the hepatic artery and hepatic arterial average peak flow velocities (APV), pulsatility indices (PI), and blood flow volumes (HABF) were measured using digital angiography and intravascular Doppler sonography. Indocyanine green (ICG), lidocaine, and galactose were administered intravenously in doses of 0.5, 1.0, and 500 mg/kg body weight in the presence of adenosine-induced hepatic arterial vasodilatation and, on a separate study day, without adenosine. ICG disappearance, galactose elimination capacity (GEC), and formation of the lidocaine metabolite monoethylglycinxylidide (MEGX) were assessed. Adenosine markedly increased APV and HABF and markedly decreased PI. Serum MEGX concentrations were 63.7 ± 18.2 (median, 62; range, 36-107) and 99.0 ± 46.3 (82.5; 49-198) ng/mL in the absence and presence of adenosine infusion, respectively (P = .001). Adenosine-induced changes in MEGX concentrations were correlated inversely to changes in APV (r = ,0.5, P = .02) and PI (r = ,0.55, P = .01) and were more marked in Child-Pugh class C compared with Child-Pugh class A patients (57.4 ± 49.9 [44; ,14 to 140] vs. 8.4 ± 16.5 [13; ,11 to 35] ng/mL, P < .01). In conclusion, hepatic arterial vasodilatation provides substantial functional benefit in patients with cirrhosis. The effect does not depend directly on hepatic arterial macroperfusion and is observed preferentially in patients with decompensated disease. [source]

Adenosine reverses a preestablished CCl4 -induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats

HEPATOLOGY, Issue 4 2001
Rolando Hernández-Muñoz
Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl4 -induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl4 (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of ,-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl4 discontinuation (5 weeks), increased persitance of ,-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl4 withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl4 -induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery. [source]

Regulatory processes interacting to maintain hepatic blood flow constancy: Vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction

HEPATOLOGY RESEARCH, Issue 11 2007
W. Wayne Lautt
Constancy of hepatic blood flow (HBF) is crucial for several homeostatic roles. The present conceptual review focuses on interrelated mechanisms that act to maintain a constant HBF per liver mass. The liver cannot directly control portal blood flow (PF); therefore, these mechanisms largely operate to compensate for PF changes. A reduction in PF leads to reduced intrahepatic distending pressure, resulting in the highly compliant hepatic vasculature passively expelling up to 50% of its blood volume, thus adding to venous return, cardiac output and HBF. Also activated immediately upon reduction of PF are the hepatic arterial buffer response and an HBF-dependent hepatorenal reflex. Adenosine is secreted at a constant rate into the small fluid space of Mall which surrounds the terminal branches of the hepatic arterioles, portal venules and sensory nerves. The concentration of adenosine is regulated by washout into the portal venules. Reduced PFreduces the washout and the accumulated adenosine causes dilation of the hepatic artery, thus buffering the PF change. Adenosine also activates hepatic sensory nerves to cause reflex renal fluid retention, thus increasing circulating blood volume and maintaining cardiac output and PF. If these mechanisms are not able to maintain total HBF, the hemodynamic imbalance results in hepatocyte proliferation, or apoptosis, by a shear stress/nitric oxide-dependent mechanism, to adjust total liver mass to match the blood supply. These mechanisms are specific to this unique vascular bed and provide an excellent example of multiple integrative regulation of a major homeostatic organ. [source]

Short Atrioventricular Mahaim Fibers: Observations on Their Clinical, Electrocardiographic, and Electrophysiologic Profile

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2005
EDUARDO BACK STERNICK M.D.
Introduction: A short atrioventricular decrementally conducting accessory pathway is an uncommon variant of preexcitation. Available data from small series suggest that their decremental properties might not be caused by A-V nodal-like tissue. Methods: We compared clinical, electrocardiographic and electrophysiologic parameters in two groups of patients: 8 patients with a short A-V Mahaim pathway (Group A), and 33 patients with atriofascicular pathways (Group B). Radiofrequency catheter ablation was carried out guided by activation mapping at the annulus in Group A patients and targeting the "M" potential in Group B patients. Results: After ablation of all associated rapidly conducting bypass tracts, 7 of the 8 Group A patients showed clear preexcitation. In only 1 of 8 patients the short A-V Mahaim fiber was actively engaged in a reentrant tachycardia circuit. During radiofrequency catheter ablation an automatic rhythm occurred in 4 of 8 patients. Intravenous adenosine caused conduction a block in the Mahaim fiber in 3 of the 5 patients tested. In group B, no patient showed clear preexcitation (P < 00001) while 72% had a minimal preexcitation pattern. Twenty-nine of the 33 patients had a circus movement tachycardia with AV conduction over the atriofascicular fiber. During radiofrequency catheter ablation 30 of 33 patients showed accessory pathway automaticity. Adenosine caused transient block at the atriofascicular pathway in 11 (92%) of the 12 patients tested. Conclusions: While short decrementally conducting right-sided accessory pathways show a typical ECG pattern different from atriofascicular pathways, their electrophysiologic properties do not seem to be uniform. Those pathways can be successfully interrupted by catheter ablation. [source]

Mechanical loading stimulates ecto-ATPase activity in human tendon cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2005
M. Tsuzaki
Abstract Response to external stimuli such as mechanical signals is critical for normal function of cells, especially when subjected to repetitive motion. Tenocytes receive mechanical stimuli from the load-bearing matrix as tension, compression, and shear stress during tendon gliding. Overloading a tendon by high strain, shear, or repetitive motion can cause matrix damage. Injury may induce cytokine expression, matrix metalloproteinase (MMP) expression and activation resulting in loss of biomechanical properties. These changes may result in tendinosis or tendinopathy. Alternatively, an immediate effector molecule may exist that acts in a signal-dampening pathway. Adenosine 5,-triphosphate (ATP) is a candidate signal blocker of mechanical stimuli. ATP suppresses load-inducible inflammatory genes in human tendon cells in vitro. ATP and other extracellular nucleotide signaling are regulated efficiently by two distinct mechanisms: purinoceptors via specific receptor,ligand binding and ecto-nucleotidases via the hydrolysis of specific nucleotide substrates. ATP is released from tendon cells by mechanical loading or by uridine 5,-triphosphate (UTP) stimulation. We hypothesized that mechanical loading might stimulate ecto-ATPase activity. Human tendon cells of surface epitenon (TSC) and internal compartment (TIF) were cyclically stretched (1 Hz, 0.035 strain, 2 h) with or without ATP. Aliquots of the supernatant fluids were collected at various time points, and ATP concentration (ATP) was determined by a luciferin-luciferase bioluminescence assay. Total RNA was isolated from TSC and TIF (three patients) and mRNA expression for ecto-nucleotidase was analyzed by RT-PCR. Human tendon cells secreted ATP in vitro (0.5,1 nM). Exogenous ATP was hydrolyzed within minutes. Mechanical load stimulated ATPase activity. ATP was hydrolyzed in mechanically loaded cultures at a significantly greater rate compared to no load controls. Tenocytes (TSC and TIF) expressed ecto-nucleotidase mRNA (ENTPD3 and ENPP1, ENPP2). These data suggest that motion may release ATP from tendon cells in vivo, where ecto-ATPase may also be activated to hydrolyze ATP quickly. Ecto-ATPase may act as a co-modulator in ATP load-signal modulation by regulating the half-life of extracellular purine nucleotides. The extracellular ATP/ATPase system may be important for tendon homeostasis by protecting tendon cells from responding to excessive load signals and activating injurious pathways. © 2005 Wiley-Liss, Inc. [source]

Diazoxide, a KATP opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyamines

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001
M Rahgozar
Abstract Background and Aims: Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5,-triphosphate (ATP)-dependent potassium channels (KATP) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of KATP channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied. Methods: Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations. Results: Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU. Conclusion: The KATP channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU. [source]

Adenosine inhibits paraventricular pre-sympathetic neurons through ATP-dependent potassium channels

JOURNAL OF NEUROCHEMISTRY, Issue 2 2010
De-Pei Li
J. Neurochem. (2010) 113, 530,542. Abstract Adenosine produces cardiovascular depressor effects in various brain regions. However, the cellular mechanisms underlying these effects remain unclear. The pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) play an important role in regulating arterial blood pressure and sympathetic outflow through projections to the spinal cord and brainstem. In this study, we performed whole-cell patch-clamp recordings on retrogradely labeled PVN neurons projecting to the intermediolateral cell column of the spinal cord in rats. Adenosine (10,100 ,M) decreased the firing activity in a concentration-dependent manner, with a marked hyperpolarization in 12 of 26 neurons tested. Blockade of A1 receptors with the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or intracellular dialysis of guanosine 5,- O -(2-thodiphosphate) eliminated the inhibitory effect of adenosine on labeled PVN neurons. Immunocytochemical labeling revealed that A1 receptors were expressed on spinally projecting PVN neurons. Also, blocking ATP-dependent K+ (KATP) channels with 100 ,M glibenclamide or 200 ,M tolbutamide, but not the G protein-coupled inwardly rectifying K+ channels blocker tertiapin-Q, abolished the inhibitory effect of adenosine on the firing activity of PVN neurons. Furthermore, glibenclamide or tolbutamide significantly decreased the adenosine-induced outward currents in labeled neurons. The reversal potential of adenosine-induced currents was close to the K+ equilibrium potential. In addition, adenosine decreased the frequency of both spontaneous and miniature glutamatergic excitatory post-synaptic currents and GABAergic inhibitory post-synaptic currents in labeled neurons, and these effects were also blocked by 8-cyclopentyl-1,3-dipropylxanthine. Collectively, our findings suggest that adenosine inhibits the excitability of PVN pre-sympathetic neurons through A1 receptor-mediated opening of KATP channels. [source]

Adenosine in the central nervous system: release mechanisms and extracellular concentrations

JOURNAL OF NEUROCHEMISTRY, Issue 3 2001
Serena Latini
Adenosine has several functions within the CNS that involve an inhibitory tone of neurotransmission and neuroprotective actions in pathological conditions. The understanding of adenosine production and release in the brain is therefore of fundamental importance and has been extensively studied. Conflicting results are often obtained regarding the cellular source of adenosine, the stimulus that induces release and the mechanism for release, in relation to different experimental approaches used to study adenosine production and release. A neuronal origin of adenosine has been demonstrated through electrophysiological approaches showing that neurones can release significant quantities of adenosine, sufficient to activate adenosine receptors and to modulate synaptic functions. Specific actions of adenosine are mediated by different receptor subtypes (A1, A2A, A2B and A3), which are activated by various ranges of adenosine concentrations. Another important issue is the measurement of adenosine concentrations in the extracellular fluid under different conditions in order to know the degree of receptor stimulation and understand adenosine central actions. For this purpose, several experimental approaches have been used both in vivo and in vitro, which provide an estimation of basal adenosine levels in the range of 50,200 nm. The purpose of this review is to describe pathways of adenosine production and metabolism, and to summarize characteristics of adenosine release in the brain in response to different stimuli. Finally, studies performed to evaluate adenosine concentrations under physiological and hypoxic/ischemic conditions will be described to evaluate the degree of adenosine receptor activation. [source]

A novel transverse push,pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn

JOURNAL OF NEUROCHEMISTRY, Issue 1 2001
Shawnna L. Patterson
Adenosine produces analgesia in the spinal cord and can be formed extracellularly through enzymatic conversion of adenine nucleotides. A transverse push,pull microprobe was developed and characterized to sample extracellular adenosine concentrations of the dorsal horn of the rat spinal cord. Samples collected via this sampling technique reveal that AMP is converted to adenosine in the dorsal horn. This conversion is decreased by the ecto-5,-nucleotidase inhibitor, ,,,-methylene ADP. Related behavioral studies demonstrate that AMP administered directly to the spinal cord can reverse the secondary mechanical hyperalgesia characteristic of the intradermal capsaicin model of inflammatory pain. The specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) inhibits the antihyperalgesia produced by AMP. This research introduces a novel microprobe that can be used as an adjunct sampling technique to microdialysis and push,pull cannulas. Furthermore, we conclude that AMP is converted to adenosine in the dorsal horn of the spinal cord by ecto-5,-nucleotidase and subsequently may be one source of adenosine, acting through adenosine A1 receptors in the dorsal horn of the spinal cord, which produce antihyperalgesia. [source]

Activation of adenosine A1 receptor,induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2008
Hideyuki Migita
Abstract Adenosine, a modulator of neuronal function in the mammalian central nervous system, exerts a neuroprotective effect via the adenosine A1 receptor; however, its effect on neural stem cells (NSCs) remains unclear. Because adenosine is released in response to pathological conditions and NSCs play a key role in neuroregeneration, we tested the hypothesis that adenosine is capable of stimulating NSC proliferation. We demonstrated that NSCs dominantly express adenosine A1 and A2B receptors. Adenosine and the adenosine A1 receptor agonist cyclopentyladenosine (CPA) increased proliferation of NSCs, and this CPA-induced cell proliferation was attenuated by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPA). CPA also induced phosphorylation of extracellular signal,regulated kinase (ERK), mitogen-activated protein kinase/ERK kinase (MEK), and Akt, and their phosphorylation was inhibited by DPCPA. In addition, CPA-induced cell proliferation was inhibited by MEK and Akt inhibitors. These results suggest that activation of adenosine A1 receptor,stimulated proliferation of NSCs occurs via MEK/ERK and Akt signaling pathways. © 2008 Wiley-Liss, Inc. [source]

Role of Wake-Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep-Promoting Effects of Ethanol

ALCOHOLISM, Issue 6 2010
Mahesh M. Thakkar
Background:, Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake-promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol-induced sleep associated with the inhibition of the BF wake-promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep-promoting effects of ethanol? Methods:, To address these questions, we performed 3 experiments in Sprague,Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c-Fos expression (a marker of neuronal activation) in the BF wake-promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol-induced sleep. Results:, Significant increase in non-rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine into the BF significantly attenuated sleep-promoting effects of ethanol. Conclusion:, These results suggest that the inhibition of BF wake-promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol. [source]

Effects of Ethanol on Extracellular Levels of Adenosine in the Basal Forebrain: An In Vivo Microdialysis Study in Freely Behaving Rats

ALCOHOLISM, Issue 5 2010
Rishi Sharma
Background:, Adenosine is implicated to play a pivotal role in mediating many neuronal responses to ethanol. While in vitro studies performed in cell culture have demonstrated that acute ethanol exposure increases extracellular adenosine levels, this effect has not been demonstrated, in vivo, in the brain. We performed an in vivo microdialysis study to examine the effects of local ethanol perfusion on extracellular levels of adenosine in the basal forebrain (BF). Methods:, Under sterile conditions and using a standard surgical protocol, adult male Sprague,Dawley rats were implanted with unilateral microdialysis guide cannula targeted toward the BF. Following postoperative recovery, the microdialysis probe was inserted. After allowing at least 12 to 16 hours for probe insertion recovery, the experiment was begun. Artificial cerebrospinal fluid (aCSF) was perfused (0.7 ,l/min) for 80 minutes, and 4 × 20-minute pre-ethanol baseline samples were collected. Subsequently, 30, 100, and 300 mM doses of ethanol were perfused. Each ethanol dose was perfused for 80 minutes, and 4 × 20-minute samples were collected. Finally, aCSF was perfused, and 4 × 20 postethanol samples were collected. Adenosine in the microdialysate was separated and measured with HPLC coupled with an UV detector. On completion, the animals were euthanized, brain removed and processed for histology. Results:, Local ethanol perfusion in the BF produced a significant increase in extracellular adenosine with the highest dose of 300 mM ethanol producing a 4-fold increase. Cresyl violet (Nissl) staining did not indicate any toxic damage in the area surrounding the probe tip. Choline acetyltransferase immunohistochemistry revealed that all microdialysis probe sites were localized in the BF. Conclusion:, Our study is the first to demonstrate that ethanol acts directly in the brain to increase extracellular adenosine. [source]

Acute Ethanol Inhibits Extracellular Signal,Regulated Kinase, Protein Kinase B, and Adenosine 3,:5,-Cyclic Monophosphate Response Element Binding Protein Activity in an Age- and Brain Region,Specific Manner

ALCOHOLISM, Issue 4 2005
L Judson Chandler
Background: As little as a single episode of exposure of the developing brain to ethanol can result in developmental neuropathology and mental retardation. Extracellular signal,regulated kinases (ERKs), protein kinase B (PKB), and adenosine 3,:5,-cyclic monophosphate response element binding protein (CREB) are messenger molecules that play important roles in neuronal plasticity and survival. This study was undertaken to examine the effects of acute ethanol on ERK, PKB, and CREB activation in the brain. Methods: Immunoblot analysis was used to determine the effects of a 1-hr exposure of ethanol on levels of phospho-ERC in primary cortical cultures and in the cerebral cortex, hippocampus, and cerebellum of postnatal day 5 (PN5), postnatal day 21 (PN21), and adult rats. Results: In cortical cultures, ethanol (100 mM) significantly reduced activity-dependent activation of phospho-ERK, phospho-PKB, and phospho-CREB by approximately 50%. In PN5 rats, ethanol (3.5 g/kg) inhibited both phospho-ERK and phospho-PKB in the cerebral cortex and hippocampus but was without effect in the cerebellum. A similar brain region,specific inhibition of phospho-ERK was observed in PN21 rats, whereas in adult rats, ethanol inhibited phospho-ERK in all three brain regions. In contrast, ethanol had no effect on phospho-PKB in either PN21 or adult rats. Without exception, ethanol inhibited phospho-CREB in an identical brain region, and age-dependent manner as was observed for phospho-ERK. Finally, administration of the NMDA antagonist MK-801 (0.5 mg/kg) to PN5 rats had no effect on phospho-ERK or phospho-PKB levels in any brain region. Conclusion: The results demonstrate that acute ethanol inhibits ERK/PKB/CREB signaling in brain. This inhibition occurs in an age- and brain region,specific manner, with inhibition of PKB restricted to a time during the brain growth-spurt period. Furthermore, the lack of effect of MK-801 suggests that inhibition of NMDA receptors is unlikely to play a major role in binge ethanol inhibition of ERK/PKB/CREB signaling in vivo. [source]

Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2003
R. J. Scaramuzzi
Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age. [source]

A distinct nitric oxide and adenosine A1 receptor dependent hepatic artery vasodilatatory response in the CCl4 -cirrhotic liver

LIVER INTERNATIONAL, Issue 7 2010
Alexander Zipprich
Abstract Increase of portal venous vascular resistance is counteracted by decrease of hepatic arterial vascular resistance (hepatic arterial buffer response). This process is mediated by adenosine in normal livers. In cirrhosis, hepatic arterial vascular resistance is decreased but the involvement of adenosine in this process is unknown. The aim of our study was to identify the signalling pathway responsible for the decreased hepatic arterial resistance in cirrhotic livers. Methods: Cirrhosis was induced by CCl4. Using a bivascular liver perfusion dose,response curves to adenosine of the HA were performed in the presence and the absence of pan-adenosine blocker (8-SPT), A1 blocker (caffeine) or nitric oxide synthase-blocker (l -NMMA) after preconstriction with an ,1-agonist (methoxamine). Western blot of the HA were used to measure the density of the A1 and A2a receptors. Results: Adenosine caused a dose dependent relaxation of the hepatic artery of both cirrhotic and control animals that were blocked in both groups by 8-SPT (P<0.02). The response to adenosine was greater in cirrhotic rats (P=0.016). Both l -NMMA (P=0.003) and caffeine reduced the response to adenosine in cirrhotic but not in control animals. Western blot analysis showed a higher density of A1 and a lower density of A2a receptor in cirrhotic animals (P<0.05). Conclusion: The adenosine-induced vasodilatation of the HA is increased in cirrhotic rats suggesting a role for adenosine-NO in the decreased hepatic arterial vascular resistance found in cirrhosis. This significantly greater response in cirrhosis by the A1 receptor follows the same pathway that is seen in hypoxic conditions in extra-hepatic tissues. [source]

Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small-for-size syndrome,

LIVER TRANSPLANTATION, Issue 11 2009
Dympna M. Kelly
The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100g/min) were 29 ± 12 (mean ± SD) and 74 ± 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7-14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 ± 8 ml/100 g/min at 90 min and remained low out to POD 7-14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome. Liver Transpl 15:1448,1457, 2009. © 2009 AASLD. [source]

Adenosine Induced Atrial Fibrillation Precipitating Polymorphic Ventricular Tachycardia

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2000
ILYA V. KAPLAN
An 86-year-old female developed supraventricular tachycardia 36 hours after a myocardial infarction (MI). She developed atrial fibrillation and polymorphic ventricular tachycardia (PVT) following administration of 12 mg ofadenosine. The PVT caused hemodynamic instability with no response to cardioversion, but termination with procainamide. The heart is vulnerable to hemodynamically unstable, possibly lethal, PVT early after MI under some circumstances. This vulnerability may be exposed following administration of adenosine. Extra caution is warranted when using adenosine in the post-Mi period. [source]