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PubMed1997

Comparison of adenosine triphosphate and dipyridamole in diagnosis by thallium-201 myocardial scintigraphy.

UNLABELLED: We examined whether 201Tl myocardial scintigraphy with intravenous infusion of adenosine triphosphate (ATP) can be substituted for dipyridamole (DIP) in the diagnosis of coronary artery disease CAD). METHODS: The coronary flow reserve (CFR) during intravenous infusion of ATP (0.10-0.20 mg/kg/min) was compared with that during intravenous infusion of DIP (0.56 mg/kg) using a Doppler flow wire in 19 subjects with normal coronary arteries. The highest CFR level was found in the ATP dose range of 0.16-0.20 mg/kg/min. The CFR at the ATP dose of 0.16 mg/kg/min was significantly higher than that during DIP infusion (4.2 versus 3.6) (p < 0.01), for which reason we adopted this dose of ATP. According, 201Tl SPECT in 140 patients with suspected CAD was performed after infusion of 0.16 mg/kg/min of ATP in 70 of them and 0.56 mg/kg of DIP in the 70 others. RESULTS: ATP stress 201Tl SPECT showed no significant difference in sensitivity and accuracy from DIP stress 201Tl SPECT (87.0% versus 82.9, and 87.1% versus 78.6, respectively). Adverse effects occurred at higher frequency when ATP was used, but they were mild and disappeared rapidly after administration was stopped. CONCLUSION: ATP stress 201Tl SPECT is accurate and safe. The optimal ATP regimen for this purpose is considered to be a 5-min infusion at 0.16 mg/kg/min. However, our data in CAD patients suggest that ATP stress 201Tl SPECT is equivalent to DIP stress 201Tl SPECT in the detection of CAD.

Adenosine Triphosphate↗
PubMed2006

Lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous neurally mediated syncope.

AIMS: We prospectively correlated the results of tilt testing (TT) and adenosine triphosphate test (ATP) with the findings observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR) in patients with a clinical diagnosis of neurally mediated syncope. METHODS AND RESULTS: We included patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities. Patients with orthostatic hypotension and carotid sinus syncope were excluded. After ILR implantation, patients were followed until the first documented syncope. Among 392 enrolled patients, 343 underwent TT, which was positive in 164 (48%), and 180 ATP test, which was positive in 53 (29%). Syncope was documented by ILR in 106 (26%) patients after a median of 3 months. Patients with positive and negative TT had similar baseline characteristics, syncopal recurrence rate, and mechanism of syncope, but those with positive TT had more frequently no or slight rhythm variations during spontaneous syncope (45 vs. 21%, P=0.02). An asystolic pause was more frequently found during spontaneous syncope than during TT (45 vs. 21%, P=0.02), but there was a trend for those with an asystolic response during TT also to have an asystolic response during spontaneous syncope (75 vs. 37%, P=0.1). Patients with positive ATP test responses showed syncopal recurrence rates and mechanism of syncope similar to those with negative ATP tests. CONCLUSION: In patients with neurally mediated syncope, clinical characteristics, outcome, and mechanism of syncope are poorly correlated and not predicted by the results of TT and ATP test. Therefore, these tests are of little or no value in guiding specific therapy.

Adenosine Triphosphate↗
PubMed1995

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease.

OBJECTIVES: The purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease. BACKGROUND: Both ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy. METHODS: The study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography. RESULTS: Although 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification. CONCLUSIONS: Thallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Adenosine Triphosphate↗
PubMed2001

Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of isoflurane.

The adenosine triphosphate-dependent potassium (K(ATP)) channel has been proposed to play an important role in the cardioprotective effect of isoflurane (ISO). However, the question of whether the K(ATP) channel, sarcolemmal or mitochondrial is the main contributor to the effect has not been clarified. The major aim of the present study was to determine whether or not the mitochondrial potassium channel was a site of action for ISO. Whether there was an acute "memory phase", in which drugs were not detected in the tissues, but the protective effect still remained in the ischemic preconditioning (IP) -like effect of ISO was also investigated. Dangling participle isolated rat hearts, a 20-min normothermic nonperfused phase was maintained to produce a global ischemia. Under these ischemic conditions, the effects of ISO, sodium 5-hydroxydecanoate (5HD: a selective mitochondrial K(ATP) channel antagonist), and ISO combined with 5HD on cardiac performance were examined. To all these four groups, (non-treated group, ISO group, 5HD group and ISO plus 5HD group, n=6 each) drugs were given for 30 min. After 10 min of drug-free perfusion (pre-ischemia restabilization period), 20 min of ischemia followed. Then the cardiac performance and the creatine kinase (CK) release during the reperfusion period were tested. In the non treated group and 5HD group, cardiac performance was stable during the treated period and pre-ischemia the restabilization period. In the ISO group and ISO plus 5HD group, heart rate (HR), left ventricular (LV) systolic pressure, and LV maximum rate of development of tension (dP/dtMax) during the drug-treated period became gradually and linearly worse. However, these values were the same as in the non-treated group and 5HD group at the end of the pre-ischemia restabilization period. So 5HD itself had no hemodynamic effect; nor did it have any influence on the actions of ISO. At the end of the pre-ischemia restabilization period, the significant hemodynamic differences among the groups diminished and ISO was not detected in the solution. In the post-reperfusion period, except for the ISO group, (non treated group, 5HD group and ISO plus 5HD group) cardiac performances were drastically decreased. ISO significantly ameliorated the dysfunction of cardiac output, LV systolic pressure and LV+dP/dtMax. The CK level in the coronary effluent during reperfusion was also significantly reduced by ISO. 5HD completely inhibited these cardiac effects of ISO. Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of ISO, and the action of this agent has an acute"memory phase" like ischemic preconditioning.

Adenosine Triphosphate↗
PubMed1996

[99mTc-MIBI myocardial tomography with intravenous infusion of adenosine triphosphate in the diagnosis of coronary artery disease].

To evaluate its feasibility, safety and diagnostic accuracy, 99mTc-MIBI myocardial tomography with adenosine triphosphate (ATP) infusion (0.16 mg/kg/min for 5 min) was performed 100 consecutive patients using the stress/rest one day protocol. None of the patients required treatment with aminophylline during the study. The sensitivity and specificity for detecting patients with coronary artery disease were 97% and 71%, respectively. Those for detecting individual coronary lesion (> or = 75% stenosis) were 92% and 89%, respectively. The high hepatic uptake of 99mTc-MIBI causes artifactual perfusion defects in the inferior myocardial wall, particularly on ATP stress images. In order to reduce this artifactual phenomenon, the interval time between injection and stress imaging must be increased.

Adenosine Triphosphate↗
PubMed1994

Circadian rhythms of adenosine triphosphate contents in the suprachiasmatic nucleus, anterior hypothalamic area and caudate putamen of the rat--negative correlation with electrical activity.

Contents of adenosine triphosphate (ATP) in the suprachiasmatic nucleus (SCN), anterior hypothalamic area (AH) and caudate putamen (CPu) were determined every 4 h in rats kept under constant dark conditions. All tested regions of the brain exhibited circadian rhythms in ATP content. Among these, the amplitude of the rhythm was largest in the SCN. Peaks of the ATP content were observed at circadian time 18 in the SCN, 6 in the AH and 10 in the CPu. In view of the observation that at around these peak times electrical or glucose uptake activity of each brain region was lowest, the present result suggests that ATP content is negatively correlated with electrical or glucose uptake activity.

Adenosine Triphosphate↗
PubMed2003

Adenosine triphosphate as a stimulant for nociceptive and non-nociceptive muscle group IV receptors in the rat.

For cutaneous and articular nociceptors, adenosine triphosphate (ATP) has been shown to be an effective stimulant. The aim of present study was to find out if among muscle afferents ATP-sensitive group IV receptors are present, and if differences in ATP-responsiveness existed between nociceptive and non-nociceptive units. Single fibre activity was recorded from group IV afferents innervating the rat gastrocnemius-soleus muscle. Using mechanical stimuli the fibres were classified as nociceptive or non-nociceptive ones. ATP was injected intramuscularly into the receptive field of the fibre. Results were: (1) ATP at a concentration that is present in muscle cells elicited excitations in 67% of the fibres; (2) ATP excited both nociceptive and non-nociceptive receptors; and (3) the acidity of the ATP solution was not an important factor for the ATP effect.

Action Potentials↗
PubMed1995

[Effectiveness and safety of coronary vasodilation with adenosine triphosphate with thallium-201 for the diagnosis of coronary disease].

OBJECTIVE: To evaluate the accuracy and safety of pharmacologic stress testing with adenosine triphosphate (ATP) associated with thallium-201 scintigraphy for detection of coronary artery disease. PATIENTS: We studied 44 patients, 35 male and 9 female with a mean age of 59 + 9 years. Previous myocardial infarction was present in 15 patients. Thirty-two patients underwent coronariography that revealed coronary artery disease in 28 patients. METHODS: ATP (Stryadine) was infused at a rate of 140 micrograms/kg/min for 6 minutes and 2 mCi of thallium-201 was injected at the third minute. Stress and redistribution SPECT acquisitions were performed respectively 5-10 minutes and 4-6 hours after ATP infusion. RESULTS: The incidence of side effects was 77% and chest pain was the most frequent (45%). Dyspnea occurred in 2 patients and only one patient presented transient first degree AV block. No serious or severe side effect occurred. In patients without myocardial infarction 14 of 16 patients with significant coronary artery disease had reversible perfusion defects demonstrated by ATP thallium-201 scintigraphy (sensitivity 88%) and all of 4 patients without significant coronary artery disease had normal myocardial perfusion (specificity 100%). The overall accuracy for detecting the presence of coronary artery disease was 90%. The test demonstrated an overall accuracy of 88% for detecting left anterior descending artery disease, 91% for circumflex artery disease and 80% for right coronary artery disease. CONCLUSIONS: Pharmacologic stress with ATP associated with thallium-201 scintigraphy, is a safe and high accurate alternative to dipyridamole and adenosine for the diagnosis of coronary artery disease.

Adenosine Triphosphate↗
PubMedDate not supplied

Cellular adenosine triphosphate production and consumption in the descending thin limb of Henle's loop in the rat.

To characterize the properties of cellular adenosine triphosphate (ATP) production and consumption in the descending thin limb of Henle's loop (DTL) in rats, we measured the cellular ATP content by applying the microchemiluminescence method. For ATP production, isolated DTL from the short- and long-loop nephron (SDL and LDL, respectively) was incubated with several substrates such as alanine, glucose, glutamine, beta-hydroxybutyrate (beta-HBA), lactate, and pyruvate; for ATP production from each substrate indicated that glucose and pyruvate were the preferred substrates to maintain cellular ATP in both SDL and LDL. ATP production from glutamine, beta-HBA, and lactate was substantial in LDL. In SDL, glutamine was the preferred substrate, and beta-HBA and lactate were minimal. The utilization of alanine was minimal in both LDL and SDL. The cellular ATP was significantly restored by ouabain at concentrations of 1.5 x 10(-5) and 1.5 x 10(-3) M in LDL, but in SDL only at 1.5 x 10(-3) M. In both segments, the cellular ATP level was significantly decreased by monensin above the concentrations of 1 micrograms/ml in LDL and 5 micrograms/ml in SDL. From these observations, we conclude that there exist clear differences between LDL and SDL in ATP-supplying substrate specificities and ATP-consuming properties.

Adenosine Triphosphate↗
PubMed1997

Adenosine triphosphate treatment for meconium aspiration-induced pulmonary hypertension in pigs.

To investigate the pulmonary haemodynamic effects of meconium aspiration and subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline into the right heart in doses of 0.02 to 0.80 mumol kg-1 min-1 after intratracheal administration of 2 mL kg-1 of human meconium. Meconium instillation induced significant increases in pulmonary vascular pressures and total and postarterial resistances calculated from pulmonary artery occlusion studies, but did not affect the systemic haemodynamics, except for a fall in heart rate and increase in central venous pressure. Infusion of ATP at the lowest doses (0.02 and 0.08 mumol kg-1 min-1) selectively decreased the pulmonary arterial pressure and vascular resistance and at 0.32 and 0.80 mumol kg-1 min-1 reduced both the pulmonary and systemic resistances. In the lung circulation the increasing doses of ATP reduced preferably the arterial but also the postarterial resistance. Withdrawal of ATP infusion led to a significant rebound effect especially in the postarterial segment of the lung circulation. Meconium aspiration thus induces an acute, predominantly postarterial obstruction in the lung circulation and infusion of ATP at low doses selectively dilates the pulmonary vascular bed and may help to preclude elevation of capillary pressures in meconium aspiration-induced pulmonary hypertension.

Adenosine Triphosphate↗
PubMed2006

Epidemiology, clinical features, and follow-up of patients with syncope and a positive adenosine triphosphate test result.

OBJECTIVES: We sought to evaluate epidemiology, clinical features, and outcomes of patients with syncope and an abnormal response to adenosine triphosphate (ATP). BACKGROUND: Syncope remains of unknown origin in almost 30% of the patients. Injection of ATP induces in some of these patients, but not in control patients, a ventricular pause > or =6 s. METHODS: Patients with syncope of unknown origin had an intravenous injection of 20 mg of ATP. All patients had a tilt test. RESULTS: Among 214 patients, 19 (8.9%) had a positive ATP test result. The proportion of positive test results was higher (p < 0.002) in women (14.3%) than in men (2.2%). Ten patients (4.7%) had positive ATP and tilt test results. These patients (exclusively women) were older (p < 0.05) at the time of their fist syncope than the 67 patients with a negative ATP test result but a positive tilt test result. There was a trend for these two test results to be correlated (p = 0.07). Side effects were of short duration and benign. The mean duration of pauses was longer in women (p = 0.009). During a mean period of 31 +/- 14 months, recurrences of syncope were reported in 25% of patients. CONCLUSIONS: The ATP test is a safe test with an "abnormal" result in <10% of patients with syncope of unknown origin. The profile of these patients is characteristic.

Adenosine Triphosphate↗
PubMed1994

Channel active mammalian porin, purified from crude membrane fractions of human B lymphocytes and bovine skeletal muscle, reversibly binds adenosine triphosphate (ATP).

A new aspect of mammalian porin (mammalian VDAC = mammalian voltage-dependent anion channel) is presented: channel active VDAC binds adenosine triphosphate (ATP) in the absence of Ca2+. Channel active "Porin 31HL" or "Porin 31BM", enriched from crude membranes of human B lymphocytes or whole cell lysates of bovine skeletal muscle, respectively, was bound to a nine atoms spacer ATP-agarose at pH 7.4 or 5.0 and reeluted from the resin by 10 mM ATP disodium salt. Furthermore, channel active "Porin 31BM" was labelled by [32P]ATP in a 1:1 stoichiometric relation. Binding of ATP to human porin was confirmed by studying the interaction of the synthetic porin fragment Type-1/Ac-35, comprising the putative nucleotide binding site G Y G F G, with trinitrophenyl-ATP (TNT-ATP) by scanning fluorometry. Peptide/TNP-ATP complexes clearly show enhancement of fluorescence intensity and a spectral shift of the fluorescence maximum. In a control experiment, using a porin fragment lacking the putative nucleotide binding site, no change of fluorescence emission was observed. Further confirmation for ATP binding by human VDAC arose from an autoradiographic experimental approach: the porin fragment Type-1/Ac-35 could be labelled by [32P]ATP, while a second porin fragment ending immediately before the putative nucleotide binding site could not; nor could a synthetic non porin peptide.

Adenosine Triphosphate↗
PubMed1998

Purinergic receptors mediate cell proliferation and enhanced recovery from renal ischemia by adenosine triphosphate.

Kidney dysfunction after ischemia can be improved by either limiting the initial injury or by enhancing the subsequent proliferative repair process. Adenosine triphosphate (ATP) favorably affects kidney function when it is given shortly after ischemia. We tested whether ATP promotes the proliferative repair response. Rats were subjected to occlusion of the left renal artery for 40 minutes and received an infusion of ATP, 12.5 micromol intravenously over 30 minutes, beginning at reperfusion. Control animals received saline solution or the hydroxyl radical scavenger dimethylthiourea (DMTU). Despite comparable functional protection by DMTU and ATP, only ATP specifically increased DNA synthesis (renal incorporation of tritiated thymidine) to an extent greater than that produced by ischemia alone. In other animals, ribonucleic acid was extracted from kidneys for Northern analysis. Expression of the proto-oncogenes c-fos and c-jun was enhanced in ATP-treated animals as compared with controls. Expression of a histone protein gene (H2b) and thymidine kinase was increased by ischemia but was not additionally affected by ATP. In vitro studies of primary cultures of renal proximal tubule epithelial cells confirmed the ability of ATP to stimulate cellular proliferation as a consequence of stimulation of purinergic P2 receptors, possibly of the P2x subclass. In summary, ATP given after ischemia increased new DNA synthesis and augmented expression of genes critical to cellular proliferation. These beneficial effects were not merely a consequence of limiting initial cellular damage, and they suggest a novel mechanism of action for ATP and other purinergic receptor agonists in renal ischemia.

Adenosine Triphosphate↗
PubMed1995

Alteration of Na+ homeostasis as a critical step in the development of irreversible hepatocyte injury after adenosine triphosphate depletion.

The exposure of isolated hepatocytes to the redox-cycling quinone menadione caused an early loss of mitochondrial membrane potential, adenosine triphosphate (ATP) depletion, and decreased intracellular pH. These alterations were followed by an increase in intracellular Na+ and, ultimately, cell death. If HCO3- was omitted from the incubation buffer, or the hepatocytes were incubated in an acidic medium (pH 6.5) the accumulation of Na+ was markedly reduced. Inhibition of the Na+/H+ exchanger and of the Na+/HCO3- cotransporter by, respectively, amiloride and 4,4'-di-isothiocyano-2,2'-disulfonic acid stilbene (DIDS) suppressed the initial Na+ influx but did not prevent subsequent Na+ accumulation, because amiloride and DIDS inhibited the Na+/K+ pump. The omission of HCO3- from the extracellular medium or the incubation in acidic conditions also prevented menadione toxicity, without interfering with the loss of mitochondrial membrane potential and with ATP depletion. A similar protection was evident when hepatocytes were incubated with menadione in a medium without Na+. The preservation of adequate levels of ATP by supplementing hepatocytes with fructose allowed the initial Na+ load to be recovered and provided partial protection against menadione toxicity. These effects were suppressed if Na+/K(+)-ATPase was inhibited with ouabain. Taken together, these results indicated that the activation of the Na+/HCO3- cotransporter and of the Na+/H+ exchanger in response to the decrease of intracellular pH stimulated an enhanced influx of Na+. When the activity of the Na+/K+ pump was not able to control Na+ levels because of ATP depletion, such an uncontrolled Na+ influx precipitated irreversible injury and caused hepatocyte death.

Adenosine Triphosphate↗
PubMed1987

The mechanical response of rat myometrium to adenosine triphosphate in Ca-free solution.

The contractile response of the myometrial longitudinal muscle of pregnant and estrogen-treated rats to adenosine triphosphate (ATP) was investigated. ATP (10(-5)-4 X 10(-3) M) added to Krebs solution caused a generation of spontaneous activity consisting of phasic contractions and an elevation of muscle tone in a dose-dependent manner. Effects of the "test solution" consisting of isotonic K, 4(mM) ATP, 4 Mg, 1-20 EGTA, 20 tris(hydroxymethyl)aminomethan (Tris) maleate (pH 6.8) on the contractile response was then investigated. An initial phasic and a following tonic contraction was evoked by the application of the test solution, when applied after the equilibration of the muscle with Krebs solution. ATP was proved to be an agonist to evoke the Ca-free contraction. The phasic contraction was depressed when the muscle was incubated with Ca-free Krebs solution. The amplitude of the tonic contraction became progressively larger when application of the test solution was repeated. The amplitude was 15-70% as large as the tonic component of the K-contracture induced by 40 mM K. Theophylline (10 mM), 0.1 mM papaverine and 1 microM isoprenaline nearly abolished, and 1 mM cAMP partly depressed the tonic contraction of K-contracture, whereas the tonic contraction induced by the test solution was unaffected. A calmodulin antagonist, W-7 (100 microM) strongly suppressed both the K-contracture and the contraction induced by the test solution, whereas trifluoperazine (10-200 microM) preferentially depressed the K-contracture. The tonic contraction induced by the test solution was strongly depressed when Mg was removed and 20 mM EDTA was applied. From these results, it is discussed that some Ca-independent process is involved in the generation of tonic component of Ca-free contraction developed by the application of the test solution.

Adenosine Triphosphate↗
PubMed1995

Intravenous administration of large dosages of adenosine or adenosine triphosphate with minimal blood pressure fluctuation.

Hemodynamic responses, blood gas, and metabolic changes were assessed when large dosages of a pre-mixed solution of adenosine or adenosine triphosphate (ATP) with catecholamine were intravenously administered in the conscious, spontaneously breathing rabbit. The present study offers a simple and effective approach to enabling safe administration of large doses of the potent vasodilators, adenosine or ATP with minimal cardio-respiratory and metabolic changes.

Adenosine↗
PubMed1979

Effect of adenosine triphosphate and some derivatives on cerebral blood flow and metabolism.

1. Responses of cerebral blood vessels to peri- and intravascular doses of ATP (adenosine triphosphate) and some derivatives were studied in cat and baboon. 2. Perivascular application of ATP to cat pial arterioles gave a threshold dilatory effect at a concentration of 10(-11) M. This figure is comparable to the amount of ATP calculated to be released from electrically stimulated brain slices. 3. It is concluded that adenine nucleotides have a major role to play in the local control of cerebral blood flow. 4. Intracarotid injection of ATP showed a calculated threshold effect at 4 x 10(8) M in the cat and 4 x 10(-9) M in the baboon. 5. The threshold response of the vasculature to intracarotid adenosine lay between 4 x 10(-7) M and 4 x 10(-6) M in the baboon. Little effect was produced with AMP, pyrophosphate and inorganic phosphate. 6. Intracarotid ATP increased the oxygen consumption of the baboon brain parenchyma. This effect was attributed in part to an elevation of the cellular cyclic AMP levels. 7. Osmotic disruption of the blood-brain barrier in baboon did not affect the vasodilatory or metabolic effect of intracarotid ATP. 8. It is postulated that circulating purine compounds mediate a form of metabolic communication inthe body. Also, release of purine compounds from active local nerves might influence cerebral blood flow.

Adenosine Triphosphate↗