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[Comparative study between verapamil and adenosine triphosphate in the treatment of paroxysmal supraventricular tachycardia].

PURPOSE: To evaluate the efficacy and safety of intravenous (IV) adenosine-triphosphate (ATP) and verapamil to convert acute episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. METHODS: Fifty patients with PSVT were randomized in two groups: A) 25 treated with IV bolus of ATP (10 or 20mg), and V) 25 treated with IV verapamil, up to 15mg, during 3min. We evaluated the time delay necessary to convert the arrhytmia, doses, and side-effects. Patients with acute ischemic syndromes (< 3 weeks), severe congestive heart failure, and treatment with dipyridamole or methylxanthine were excluded. RESULTS: There were no differences between the two groups regarding to age, sex, and success rate. The average time till reversal were respectively, 30s and 248s for ATP and verapamil. Ventricular ectopy and general discomfort were observed in 33% of patients receiving ATP, whereas no side-effects occurred in group V. CONCLUSION: ATP is a good option to convert rapidly PSVT to sinus rhythm and, probably, could be the first choice to treat PSVT patients with ventricular dysfunction.

Adenosine Triphosphate↗

Adenosine triphosphate phosphoydrolase activity associated with purified parainfluenza type 3 virions.

An adenosine triphosphate phosphohydrolase associated with purified parainfluenza type 3 virions has been characterized. It hydrolyzed ATP to ADP and AMP when activated with Mg-2+ ions. Using Ca-2+ the production of ADP was inhibited but not that of AMP. Neither K+ NOR Na+ ions were required for the expression of maximal activity. Ouabain had no inhibitory effect on enzyme activity even at 10-3M. After exposure of virus preparations to Tween 20, enzyme activity was not affected. A linear relationship between enzyme activity and concentration of virus was observed.

Adenosine Diphosphate↗

The influence of adenosine triphosphate on left ventricular function and blood flow distribution during aortic crossclamping in dogs.

To evaluate the influence of adenosine triphosphate (ATP)-induced vasodilation on myocardial performance and blood flow during aortic crossclamping (XC), ten dogs were instrumented to measure left ventricular (LV) pressure and dimensions. Regional LV function was assessed from the percentage of systolic shortening, whereas the slope of the linear regression of the LV end-systolic pressure-diameter relationship was used as an index of overall contractility. The regional blood flow distribution was measured from sequential injections of radioactive microspheres. Following XC, systemic arterial pressure proximal to the clamp (SAPa), LV end-diastolic pressure (LVEDP), LV end-systolic meridional wall stress (WS), and central venous pressure (CVP) increased significantly, whereas the cardiac index (CI) and heart rate did not change. After 30 minutes of ATP infusion (1 mg/kg/min) SAPa, LVEDP, WS, and CVP returned to control levels, CI increased significantly compared with XC alone, and vascular resistance fell below the control level. ATP produced a threefold increase in myocardial blood flow and shifted the intramural distribution in favor of the endocardial layer. In conclusion, our investigation of the effect of ATP on aortic XC in a canine model showed the drug to produce a smooth, predictable, and rapid reduction in left ventricular preload and afterload. This was accomplished with minimal changes in distal organ perfusion, some improvement in measured cardiac performance, and a large increase in myocardial blood flow.

Adenosine Triphosphate↗

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog.

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.

Adenosine Triphosphate↗

Effects of a bolus injection of adenosine triphosphate on atrioventricular conduction and hemodynamics in patients undergoing coronary artery bypass grafting.

OBJECTIVE: To investigate the effects of adenosine triphosphate (ATP) on atrioventricular (A-V) conduction and hemodynamics in patients undergoing coronary artery surgery. DESIGN: A prospective study. SETTING: University teaching hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Anesthesia was induced with the same dose of intravenous fentanyl (300 microg) and midazolam (10 mg) for each patient. After the baseline measurement, a bolus dose of 10 mg of ATP (0.19+/-0.03 mg/kg, mean +/- SD) was rapidly injected through a central venous catheter. Right ventricular pacing was conducted at a rate of 40 beats/min during the development of complete A-V block. MEASUREMENTS AND MAIN RESULTS: ATP induced an A-V block in 10 of 12 patients (2:1 block in two patients and complete A-V block in eight patients). The onset of the A-V block was rapid (17.1+/-3.4 seconds) and the duration was short (12.1+/-7.0 seconds). Radial arterial pressure (AP) decreased with the appearance of the A-V block (p < 0.01). Heart rate (HR) returned to the baseline value quickly after the restoration of the A-V block, but recovery of radial AP was delayed. HR increased 1 minute after the ATP injection (p < 0.01). Both HR and radial AP returned to the baseline values 2 minutes after the ATP injection. ST segments on both leads II and V5 of electrocardiograms decreased more than 0.10 mV 1 minute after the ATP injection in one patient. CONCLUSION: A bolus injection of 10 mg of ATP successfully induced a transient A-V block in 83% of the 12 patients. The countermeasures, including ventricular pacing, are indispensable to cope with the subsequent hypotension that may lead to myocardial ischemia, especially in patients with ischemic heart disease.

Adenosine Triphosphate↗

Effect of caffeine intake on myocardial hyperemic flow induced by adenosine triphosphate and dipyridamole.

UNLABELLED: The aims of this study were (a). to compare absolute myocardial blood flow (MBF) during adenosine triphosphate (ATP) infusion with that after dipyridamole administration without caffeine intake and (b). to evaluate the effect of caffeine intake on the hyperemic flow induced by these coronary vasodilator agents. METHODS: MBF was quantified with (15)O-labeled water and PET at rest, during ATP infusion (0.16 mg/kg/min for 9 min), and after dipyridamole administration (0.56 mg/kg over 4 min) after a 24-h abstinence from caffeine (baseline evaluation) in 10 healthy volunteers. Within 2 wk, the same PET studies were repeated after caffeine intake to evaluate the effect of caffeine on the hyperemic flow induced by these pharmacologic agents (caffeine study). Myocardial flow reserve (MFR), defined as the ratio of hyperemic to resting blood flow, was also evaluated. RESULTS: Resting MBF in baseline and caffeine studies did not differ significantly (0.79 +/- 0.29 vs. 0.75 +/- 0.31 mL/min/g, P = 0.88). Without caffeine intake, MBF during ATP infusion was significantly higher than that after dipyridamole administration (3.70 +/- 0.67 vs. 3.00 +/- 0.79 mL/min/g, P = 0.003), whereas there was no significant difference in MFR between ATP and dipyridamole stress (5.15 +/- 1.64 vs. 4.11 +/- 1.44, P = 0.07). After caffeine intake, the hyperemic flows induced by ATP and dipyridamole were not significantly different (1.68 +/- 0.37 vs. 1.52 +/- 0.40 mL/min/g, P = 0.50). MFR estimated by ATP and dipyridamole also did not differ significantly in the caffeine studies (2.44 +/- 0.88 vs. 2.25 +/- 0.94, P = 0.73). MBF during ATP infusion and after dipyridamole administration were significantly lower in the caffeine studies than that in the baseline evaluation (1.68 +/- 0.37 vs. 3.70 +/- 0.67 mL/min/g, P < 0.0001, and 1.52 +/- 0.40 vs. 3.00 +/- 0.79 mL/min/g, P < 0.0001, respectively). CONCLUSION: This study demonstrates that ATP has the potential to induce greater hyperemia than dipyridamole, whereas hyperemic responses to ATP and dipyridamole are similarly attenuated after caffeine intake. These findings suggest that abstinence from caffeine before ATP stress testing may be needed.

Adenosine Triphosphate↗

Hereditary high-adenosine triphosphate syndrome: study of a new variant.

A new variant of hereditary hemolytic anemia in a family due to high adenosine triphosphate (ATP) is reported. The increase in ATP levels varied from 83 to 105% in the family members. Low 2,3-diphosphoglycerate levels and low 2,3-diphosphoglyceromutase activity were observed in three family members, with normal glucose-6-phosphate dehydrogenase and pyruvate kinase activity.

Adenosine Triphosphate↗

Regulation of the high affinity choline transport in locust synaptosomes by adenosine triphosphate.

The effect of various nucleotides on the high affinity choline accumulation by synaptosomes from locusts has been studied. Extracellular adenosine triphosphate (ATP) was found to inhibit the transport of choline, whereas the accumulation of gamma-aminobutyric acid was not affected. The ATP-effect could not be mimicked by other purine derivatives, and seems not be mediated by purinergic receptors, but rather hydrolysis of the phosphate appears to be essential.

Adenosine Triphosphate↗

Spin-label electron paramagnetic resonance and differential scanning calorimetry studies of the interaction between mitochondrial cytochrome c oxidase and adenosine triphosphate synthase complex.

The interaction between cytochrome c oxidase complex and adenosine triphosphate synthase (F1F0) complex in the purified, dispersed state and embedded in phospholipid vesicles was studied by differential scanning calorimetry and by spin-label electron paramagnetic resonance. The detergent-dispersed cytochrome oxidase and F1F0 complexes undergo endothermic thermodenaturation. However, when these complexes are embedded in phospholipid vesicles, they undergo exothermic thermodenaturation. The energy released is believed to result from the collapse of a strained interaction between unsaturated fatty acyl groups of phospholipids and an exposed area of the complex formed by the removal of interacting proteins. The exothermic enthalpy change of thermodenaturation of a protein-phospholipid exothermic enthalpy change of thermodenaturation of a protein-phospholipid vesicle containing both cytochrome oxidase complex and F1F0 was smaller than that of a mixture of protein-phospholipid vesicles formed from each individual electron transfer complex. This suggests specific interaction between cytochrome oxidase complex and F1F0 in the membrane. Further evidence for interaction between these two complexes is provided by saturation transfer EPR studies in which the rotational correlation time of spin-labeled cytochrome oxidase increases significantly when the complex is mixed with F1F0 prior to being embedded in phospholipid vesicles. From these results, it is concluded that at least a part of cytochrome oxidase and a part of F1F0 form a supermacromolecular complex in the inner mitochondrial membrane. No such supermacromolecular complex is detected between F1F0 and ubiquinol--cytochrome c reductase.

Animals↗

Evidence for adenosine triphosphate degradation in critically-ill patients.

Alterations of cellular energy metabolism may provide important markers during the clinical course of critically ill patients. To determine whether adenosine triphosphate (ATP) degradation occurs in critically ill patients, we measured levels of adenosine, inosine, hypoxanthine, and xanthine in 18 patients and seven control subjects. The mean concentration of hypoxanthine (3.8 microM) in the critically ill patients was elevated (p less than 0.01) compared to that of our control population (0.1 microM). A subgroup of seven critically ill patients had levels of hypoxanthine, xanthine, or inosine higher than those of any member of the control group. This subgroup was characterized by a lower systolic blood pressure, an increased requirement for vasopressors, and a markedly decreased survival rate when compared to the other critically ill patients. Arterial and mixed venous blood gas values were not helpful in predicting survival and did not correlate with levels of ATP degradation products. In two patients who showed subsequent clinical improvement, the initially elevated levels of hypoxanthine and xanthine returned to normal. This study indicates that critically ill patients have elevated levels of ATP degradation products. These increased levels may indicate cellular hypoxia.

Adenosine↗

Erythrocyte 2,3-diphosphoglycerate and adenosine-triphosphate in cretins living at high altitude.

A comparison of concentrations of 2,3-diphosphoglycerate (2,3-DPG) and adenosine-triphosphate (ATP) in the red cells of cretins and normal controls living at 3,700 m in the Nepal Himalayas has shown that 2,3-DPG and ATP levels were higher in the cretins. A negative correlation between hemoglobin and 2.3-DPG level was found. Chronic hypoxia appears to have provided the additional stress required to differentiate the significance of thyroid hormone deficiency in producing anemia from its effect on 2,3-DPG levels. If thyroid hormone is in fact one regulator of 2,3-DPG, the anemia of hypothyroidism appears to be more significant. This also suggest that the anemia of hypothyroidism, is at least in part, "pathologic" as opposed to "adaptive".

Adenosine Triphosphate↗

The value of adenosine triphosphate (ATP) measurements in assessing the fertilizing ability of human spermatozoa.

A study was undertaken to examine the relationship between adenosine triphosphate (ATP) levels and the fertilizing capacity of human spermatozoa in vitro and in vivo. The concentration of ATP in semen was found to be positively correlated with the ability of sperm to fuse with zona-free hamster oocytes. However, it was also demonstrated that a large part of this relationship depends upon the relationship between semen ATP concentrations and sperm number. Measurements of ATP levels in cryostored ejaculates used in an artificial insemination by donor program revealed that such measurements were not able to distinguish fertile from infertile ejaculates. However, among fertile donors, ATP levels did seem to contribute useful information on relative fertility. It is concluded that ATP measurement has a limited role in the laboratory evaluation of sperm function.

Adenosine Triphosphate↗

Evidence that release of adenosine triphosphate from endothelial cells during increased shear stress is vesicular.

In response to increased shear stress, vascular endothelial cells release adenosine triphosphate (ATP) by an unknown mechanism. We have investigated this mechanism using different approaches. First, we discovered that quinacrine, used to locate intracellular stores of ATP bound to peptides, displayed a granular fluorescence, typical of vesicular storage. Second, we found that two inhibitors of vesicular transport (monensin and N-ethylmaleimide) produced a highly significant reduction in the release of ATP from vascular endothelial cells in response to increased shear stress. Preliminary experiments using inhibitors of the cystic fibrosis transmembrane regulator, the sulfonylurea receptor, and the multidrug resistance protein showed no involvement of these ATP-binding cassette transporter proteins (previously characterized in endothelial cells) in the mechanism of release of ATP. We suggest, therefore, that the release of ATP from vascular endothelial cells, like that of nerve cells, is probably by vesicular exocytosis.

ATP-Binding Cassette Transporters↗

Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes.

Low red-cell concentrations of 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) with resulting increased oxygen affinity of hemoglobin is one of the mechanisms by which hypophosphatemia exerts clinically detrimental effects. The possibility that obligatory post-traumatic and/or glucose-induced hypophosphatemia leads to changes in red-cell 2,3-DPG and ATP concentrations was investigated in patients undergoing elective colonic surgery. In addition to standardized intravenous fluids postoperatively, one (randomized) patient group received continuous glucose-saline infusion, which is specially associated with hypophosphatemia, while another group was given the same amount of glucose/24 hours, but in a 5-hour infusion. Serum phosphate fell significantly in both groups, mainly in the former, but unaccompanied by change in red-cell 2,3-DPG or ATP concentration. During the 5-hour glucose infusions significant hypophosphatemia appeared, but without reduction of 2,3-DPG or ATP. Thus neither the obligatory hypophosphatemia after elective surgery nor the further fall during postoperative glucose infusion altered the red-cell concentration of 2,3-DPG or ATP.

2,3-Diphosphoglycerate↗

Increased Na+/K(+)-pump activity and adenosine triphosphate utilization after compound 48/80-induced histamine secretion from rat mast cells.

The Na+/K(+)-pump activity and the utilization of adenosine triphosphate (ATP) were studied in rat peritoneal mast cells after histamine secretion induced by compound 48/80. We measured the ouabain-sensitive K(+)-uptake by a radioactive technique (86Rb+). The ATP content and the glycolytic ATP-production were measured by the bioluminescence technique (firefly lantern) and by measurement of the lactate production under anaerobic conditions (antimycin A, oligomycin), respectively. There was an increased requirement for ATP after the secretory response associated with an increased activity of the Na+/K(+)-pump. The anaerobic, but not the aerobic, pathway for ATP-synthesis was able to respond to the increased ATP-requirement. The ATP-requirement of the Na+/K(+)-pump was only partly satisfied when ATP was supplied from either the glycolytic or the oxidative pathway. This may indicate that the availability of ATP was the limiting factor for the activity of the Na+/K(+)-pump following histamine secretion under these conditions. It is concluded that the large increase in Na+/K(+)-pump activity after a secretory response is a likely explanation for the long lasting ATP-decrease in mast cells that follows histamine secretion.

Adenosine Triphosphate↗

Effect of phosphoenolpyruvate and adenosine triphosphate on rabbit skeletal muscle after ischaemia: preliminary biochemical study.

The present study examined the effect of phosphoenolpyruvate (PEP) and adenosine triphosphate (ATP) on rabbit skeletal muscle flap survival after warm ischaemia. Two muscle flap models, rectus femoris pedicle flap and latissimus dorsi free flap, were subjected to a total ischaemia of 4 hours at 37 degrees C and 20 degrees C, respectively. Immediately prior to revascularisation, the muscles were infused with either Hanks' balanced salt solution (BSS) or Hanks' BSS containing 200 mumol PEP and 6.6 mumol ATP. Quantification of muscle damage was determined by measuring the plasma levels of creatinine kinase (CK), lactate dehydrogenase (LDH), lactate, potassium, and phosphate at 0, 2, 24, and 96 hours after revascularisation. Infusion of PEP/ATP compared with Hanks' BSS alone significantly decreased the efflux of CK in both rectus femoris (P less than 0.025) and latissimus dorsi muscles (P less than 0.05) and of LDH in the rectus femoris muscle (P less than 0.01). No significant changes were observed, however, for the plasma levels of lactate, potassium, and phosphate. From this study it was concluded that PEP and ATP partially protect skeletal muscle from ischaemia and reperfusion injury.

Adenosine Triphosphate↗

Intravenous injection of adenosine triphosphate for assessing sinus node dysfunction in patients with sick sinus syndrome.

The clinical value of rapid intravenous injection of adenosine triphosphate (ATP, Adephos Kowa # L3, CAS 56-65-5) for assessing sinus node function was examined in 5 patients with sick sinus syndrome (SSS) and 6 normal controls. All patients with SSS showed cardiac pauses longer than 3 s on a 24-h Holter ECG monitoring. First, after prophylactic insertion of a temporary pacemaker in the right ventricle, overdrive suppression test was conducted using the standard technique, and sinus node recovery time (SNRT) was observed to evaluate the sinus node function. Then, 10 min later, 10 mg of ATP was rapidly injected intravenously, and body surface and intracavitary ECG were continuously recorded until the basal state was regained. The rapid injection of ATP resulted in a slight inhibition of sinus node automaticity in normal subjects, but marked inhibition was in patients with SSS associated with suppression of AV conduction. The longest post ATP atrial cycle (AA interval in the intracavitary ECG showed a close inverse relationship with SNRT corrected for basal sinus length (CSNRT), according to the following formula: longest AA interval (ms) = 3.32 x CSRT (ms) +254.4 (r = 0.91, p < 0.001). The results suggest that rapid intravenous injection is a useful tool for the diagnosis of SSS.

Adenosine Triphosphate↗

Action of angiotensin II, 5-hydroxytryptamine and adenosine triphosphate on ionic currents in single ear artery cells of the rabbit.

1. Angiotensin II, 5-hydroxytryptamine (5-HT) and adenosine triphosphate (ATP) evoked a transient inward current in isolated single car artery cells of rabbit held at -60 mV by whole cell voltage clamp in physiological saline using a KCL-containing pipette solution. Under these conditions agonist did not activate a calcium-dependent potassium current. 2. Responses to each agonist were transient and desensitized rapidly. Inward current at -60 mV holding potential was not abolished by blockade of voltage-dependent calcium channels or by buffering intracellular calcium with BAPTA, a calcium chelator, or following depletion of intracellular calcium stores with ryanodine. 3. The shape of the current-voltage relationships and the reversal potentials of the current induced by angiotensin II, 5-HT and ATP were similar under a variety of ionic conditions. Agonist-induced current was unaffected by replacing intracellular chloride with citrate ions or by replacing intracellular sodium with caesium or extracellular sodium with barium or calcium. Replacement of extracellular sodium with Tris shifted the reversal potential in all cases by around 30 mV negatively. 4. These data suggest that angiotensin II, 5-HT and ATP activate similar cationic conductances which are relatively non-selective allowing mono- and divalent cations to cross the smooth muscle cell membrane. These channels may allow the influx of calcium under physiological conditions.

Adenosine Triphosphate↗