Intravenous Administration Of Adenosine Triphosphate Research Articles

ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ФУНКЦИОНАЛЬНОЙ ПРОБЫ МОЗГОВОГО КРОВОТОКА С АДЕНОЗИНТРИФОСФАТОМ ПО ДАННЫМ ОФЭКТ С 99mTc-ГМПАО У ПАЦИЕНТОВ С АТЕРОСКЛЕРОЗОМ СОННЫХ АРТЕРИЙ

Introduction: Previously, a functional test with intravenous administration of adenosine triphosphate (ATP) was proposed to assess the reactivity of cerebral circulation and the functional significance of internal carotid artery stenoses, with evaluation by brain SPECT (neuroSPECT) with 99mTc-HMPAO. The types of the reaction of the cerebral blood flow during it were identified, with different ratios of internal carotid artery stenoses and the degree of ischemic brain damage assessed according to brain MRI data. However, the prognostic value of the results of the ATP test of cerebral blood flow in relation to disorders of cerebral circulation (NMC) remains unknown. Purpose: In a retrospective study, we tried to study the prognostic value of the ATP test of cerebral blood flow in relation to the risk of subsequent disorders of cerebral circulation. Material and methods: The retrospective study included 37 patients with atherosclerotic stenosis of the carotid arteries, who in 2002–2005 underwent functional studies of cerebral blood flow with a sample with intravenous administration of ATP solution. Brain damage was quantified according to MRI data (Magnetom Open, Siemens) in a T2-weighted mode, according to a previously developed technique. Denoting Iliq – the intensity of the T2 signal from the cerebrospinal fluid in the ventricles of the brain, Iinsult – in the area affected by ischemia, and Inorm – in the area of the unaffected brain, the volume of the damaged tissue (VDT) was calculated as the sum taken from all sections i, where the area of brain damage is visible: VDT=Σid·Si∙[(Iinsult ‒ Inorm)/(Iliq ‒ Inorm)]i, where d is the thickness of the slice, and Si is the area of the ischemia area on the slice i. The quota of damaged tissue in the physical volume of the lesion area is then obviously eqal to : QD={Σid·Si∙[(Iinsult ‒ Inorm)/(Iliq ‒ Inorm)]i}/{Σid·Si}. NeuroSPECT with 99mTc-HMPAO (540 MBq) in each patient was carried out at rest and with intravenous administration of ATP solution (100 μg / kg of weight, intravenously slowly for 1 min under ECG control). The asymmetry of the cerebral blood flow was evaluated at rest and in a sample with ATP as the 99mTc-HMPAO accumulation asymmetry index (AI) – the interhemispheric ratio of the average 99mTc-HMPAO absorption score in the middle cerebral artery basin. Results: In accordance with the previously presented classification, patients were assigned to one of three groups – with different types of brain blood flow reaction to a stress test with ATP. In 14 individuals (type 1), a symmetrical distribution of blood flow at rest was noted (AI=0.98±0.01), while the ATP test caused an asymmetry in the uptake of 99mTc-HMPAO (AI=0.91±0.04), due to a decrease on the side of the stenosis-dependent hemisphere (unilateral stenosis of the common and/or internal carotid arteries, exceeding 55 %), without signs of damage to the cerebral cortex. In 11 patients with previous ischemic brain injuries (type 2), proven by MRI, the carotid arteries were patent, including after carotid endarterectomy (5 patients) or after correction of stenosis with a stent (three). Rest asymmetry of blood flow was present (AI=0.92±0.03). The ATP test increased blood supply on the side of injury if, according to T2-weighted MRI in the ischemic area, QD<0.35. Due to this, in general, there was a significant decrease in the absorption asymmetry of 99mTc-HMPAO (AI=0.96±0.03) during the ATP test. In 12 patients (type 3) with predominantly unilateral 50‒90 % carotid artery stenosis and ischemic stroke on the same side (group III), the hemispheric asymmetry of blood supply to the brain, noted already at rest (AI=0.96±0.03), increased (AI=0.93±0.03) with an adenosine test. When analyzing the results of a two-year follow-up, it turned out that frequent transient ishemic attacs, minor strokes and strokes developed only in patients in whom the adenosine test induced or increased the interhemispheric asymmetry of 99mTc-HMPAO accumulation by more than 5 % – four with type 1 reactivity, and three with type 3 reactivity Conclusions: Thus, perfusion neuroSPECT with 99mTc-HMPAO and ATP stress-test can be employed to identify patients with a reduced reserve of cerebral perfusion, who have an increased risk of ischemic stroke. Quantitative analysis of T2-weighted MRI gives an estimate of the proportion of viable brain tissue in the focus of the past ischemia, in which reactivity is preserved.

Characteristics of coronary flow velocity reserve on transthoracic Doppler echocardiography in patients with a history of Kawasaki disease.

The coronary flow velocity reserve of the left anterior descending artery was examined by transthoracic Doppler echocardiography in 189 patients (male 125, female 64) with a history of Kawasaki disease and 10 volunteers (control). Their ages ranged from 6 to 40 years (median 22 years). The patients were divided into nine groups based on the left anterior descending artery lesions. The coronary flow velocity reserve was measured by intravenous administration of adenosine triphosphate (0.15 mg/kg/minute) while fasting. The coronary flow velocity reserve was calculated as the ratio of hyperaemic to basal mean diastolic flow velocities. The respective groups were as follows: control, no coronary artery lesions (n = 39), no coronary artery lesions in the right coronary artery (n = 29), regression (n = 11), aneurysm at the bifurcation of the left coronary artery (n = 26), aneurysm of the left anterior descending artery (n = 15), localised stenosis <75% (n = 12), localised stenosis ≥75% (n = 17), segmental stenosis (n = 5) and coronary artery bypass grafting (n = 36). One-factor ANOVA followed by Tukey's test was used to compare the coronary flow velocity reserve among the groups. The coronary flow velocity reserve was significantly lower in the localised stenosis ≥75%, segmental stenosis and coronary artery grafting groups than in the other groups (p < 0.05). The endothelial function in the epicoronary artery was preserved in patients with a history of Kawasaki disease and dilated coronary artery lesions.

Discordance predictor between fractional flow reserve and resting full-cycle ratio in clinical characteristics

Abstract Introduction Fractional flow reserve (FFR) is a gold standard method to evaluate functional lesion severity in daily clinical practice. Recently, the resting full-cycle ratio (RFR) which was newly developed resting indices was launched. Unlike other resting indices evaluated in diastolic phase, RFR is evaluated during entire cardiac phase. Previous studies showed discordance predictors between FFR and instantaneous wave-free ratio. However, it is previously unreported what predictor cause discordant outcome between FFR and RFR. Purpose The purpose of this study was to evaluate clinical predictors of discordance between FFR and RFR. Methods A total of 156 patients with 220 lesions were prospectively enrolled in this study. RFR was evaluated before inducing hyperemia. FFR was measured after intravenous adenosine triphosphate administration (180 mcg/kg/min). According to FFR and RFR values, the patients and lesions were classified into 4 groups: Concordant negative (Group-1 [n=114]: FFR &amp;gt;0.80, RFR &amp;gt;0.89); negative FFR and positive RFR (Group-2 [n=18]: FFR &amp;gt;0.80, RFR ≤0.89); positive FFR and negative RFR (Group-3 [n=25]: FFR ≤0.80, RFR &amp;gt;0.89); Concordant positive (Group-4 [n=63]: FFR ≤0.80, RFR ≤0.89). Among them, discordance predictors with clinical characteristics between RFR and FFR were compared using by two separate logistic regression analyses. (Group-1 vs. Group-2, Group-3 vs. Group-4, respectively). Age, sex and those predictors with a p value ≤0.10 were included in a multivariate regression analysis using by forward stepwise selection to identify independent predictors of discordance. Results On multiple regression analysis, hemodialysis (HD) (OR:6.072 [1.090–33.836]), peripheral artery disease (PAD) (OR:9.053 [1.776–46.162]) and left anterior descending artery (LAD) (OR:9.264 [2.092–41.031]) were significantly associated with positive RFR among negative FFR groups (Groupe 2 discordance). Conversely, diabetes mellitus (DM) (OR:0.212 [0.062–0.721]) and Hb (OR:1.480 [1.102–1.987]) were significantly associated with negative RFR among positive FFR groups (Groupe 3 discordance) Conclusions Since the clinical characteristics with HD, PAD, LAD, DM and Hb may influence concordant with FFR during RFR evaluation, it should be considered when interpreting RFR. Distribution and independent predictors Funding Acknowledgement Type of funding source: None

Intravenous administration of adenosine triphosphate and phosphocreatine combined with fluoxetine in major depressive disorder: protocol for a randomized, double-blind, placebo-controlled pilot study

BackgroundMajor depressive disorder (MDD) is a common psychiatric disorder. With systematic antidepressant treatment, 50–75% of patients have a treatment response but require 4–6 weeks to have their symptoms alleviated. Therefore, researchers anticipate the development of novel fast-acting antidepressants. Previous studies have revealed that the decrease of bio-energetic metabolism may contribute to the occurrence of depression, while our team has found adenosine triphosphate (ATP) and phosphocreatine (PCr) to be fast-acting antidepressants in the depressed-animal model. ATP and PCr have already been widely prescribed clinically as energy supplements for cells. This will be the first clinical attempt of the intravenous administration of ATP and PCr combined with orally administered fluoxetine in MDD.MethodsThis is a single-center, randomized, double-blind, placebo-controlled pilot study. A total of 42 patients will be divided randomly into three groups. Patients will receive an intravenous administration of ATP or PCr or saline twice daily combined with orally administered fluoxetine (20 mg/day) for the first 2 weeks and fluoxetine monotherapy for the following 4 weeks. Follow-up assessment will be completed at week 10. Feasibility outcomes will include percentages of patient eligibility, intention to use medication, willingness to participate, drug adherence, completion of the scheduled assessment, retention, drop-out, etc. Physical examination results, Side Effect Rating Scale, adverse events, results from blood tests, electroencephalogram, and electrocardiograph will be recorded for safety evaluation of the augmentation therapy. The trends of efficacy will be evaluated by the reduction rate of the Hamilton Depression Rating Scale, the mean change of the Clinical Global Impression Scale, and the Patients Health Questionaire-9 items.DiscussionIn our study, ATP and PCr will be given by intravenous infusion. Thus patients will be hospitalized for the initial 2 weeks for safety concern. Hospitalization will be an impact factor for the recruitment, participation, drop-out, efficacy, results, etc. The evaluation of our feasibility outcomes, study setting, safety of augmentation therapy and possible efficacy trends among groups, will facilitate a full-scale trial design and sample size calculation.Trial registrationNCT03138681. Registered on 3 May 2017. First patient: 4 May 2017.

Abstract 10976: Diagnostic Ability of Contrast Media Induced Fractional Flow Reserve to Assess Functional Significance of Entire Coronary Artery Stenosis

Introduction: Although fractional flow reserve (FFR) is helpful to evaluate functional lesion severity, the need of adenosine limits the widespread adoption of FFR. Hypothesis: We hypothesized that contrast media induced FFR (cFFR) with submaximal hyperemic condition could assess functional lesion severity of coronary artery stenos. The aim of this study was to evaluate the diagnostic ability of cFFR compared to FFR in entire range of coronary artery stenosis. Methods: A total of 96 patients with 123 lesions were prospectively enrolled in this study. At first, we measured resting Pd/Pa ratio before inducing hyperemia. Then, cFFR was obtained after intracoronary injection of 6 ml of contrast media, while FFR was measured after intravenous adenosine triphosphate administration (180 mcg/kg/min). Lesions with FFR less than or equal 0.80 were considered functional significance of coronary artery stenosis. Results: In 123 lesions, reference diameter, diameter stenosis, resting Pd/Pa ratio, cFFR, and FFR were 2.7±0.8 mm, 47±12%, 0.91±0.10, 0.83±0.12, and 0.81±0.12, respectively. Functional significance was observed in 41% of all lesions. Both of resting Pd/Pa and cFFR showed strong correlations with FFR (r=0.861, p&lt;0.001, and r=0.930, p&lt;0.001, respectively). The correlation coefficient of cFFR was significantly superior to that of resting Pd/Pa ratio (p&lt;0.05). This strong correlation between cFFR and FFR was shown in every coronary artery (LAD; r=0.924, p&lt;0.001, LCX; r=0.923, p&lt;0.001, and RCA; r=0.926, p&lt;0.001, respectively). The Bland-Altman plot demonstrated a good agreement with a mean difference of -0.02 and a standard deviation of 0.05 between cFFR and FFR across entire range of coronary artery stenosis. ROC curve analysis showed an excellent accuracy of cFFR &lt;0.84 in predicting functional significance (AUC 0.96, sensitivity 90%, specificity 89%, and diagnostic accuracy 89%). Moreover, the cFFR &gt;0.89 was not corresponded to functional significance of entire coronary artery stenosis. Conclusions: The cFFR is an accurate, rapid and easy method in predicting functional significance of entire coronary artery stenosis. This physiology-based approach may be a possible alternative method for FFR measurements in daily practice.

Influence of microvascular resistance on fractional flow reserve after successful percutaneous coronary intervention

Background: There have been concerns that microvascular dysfunction could limit the maximal and constant microvascular vasodilation, which are the requisites of fractional flow reserve (FFR) measurement. Increased microvascular resistance may impair hyperemic coronary flow, resulting in an underestimation of the translesional pressure gradient with an increased FFR values compared with that without microvascular dysfunction. Aim: We assessed the hypothesis that increased microvascular resistance represented by an index of microcirculatory resistance (IMR) may lead to an increased FFR in patients with successful percutaneous coronary intervention (PCI). Methods and results: A total of 104 coronary arteries from 98 patients treated with successful stenting (less than 20% residual stenosis with TIMI 3 flow grade) underwent FFR and IMR measurements during maximal hyperemia induced after PCI by intravenous administration of adenosine triphosphate. FFR values were compared according to the quartiles of the IMR values. Coronary flow was assessed using the hyperemic mean transit time (Tmn). The median IMR values for the interquartile ranges of 8.5–11.3, 13.9–16.3, 20.9–24.5, and 34.2–61.6 were 10.2, 15.1, 22.8, and 38.2, respectively. Both FFR and Tmn values differed significantly across the IMR quartiles (p<0.001). The angiographic and intravascular ultrasound findings and post-PCI cardiac troponin levels showed no significant difference across the IMR quartiles. Multivariate logistic regression analysis revealed that the left anterior descending artery lesion location (odds ratio [OR] 0.17, 95% confidence interval [CI] 0.06–0.49, p=0.001), IMR (OR 1.05, 95% CI 1.01–1.09, p=0.012), and minimal cross-sectional lumen area (OR 1.49, 95% CI 1.03–2.17, p=0.036) were independent predictors of increased FFR values. Conclusions: IMR values after successful PCI were widely distributed, and increased IMR was not uncommon. Increased microvascular resistance may reduce coronary flow and increase FFR after successful elective PCI.

Dormant pulmonary vein conduction induced by adenosine in patients with atrial fibrillation who underwent catheter ablation

intravenous administration of adenosine triphosphate (ATP) is used to induce transient pulmonary vein (PV) reconduction (dormant PV conduction) following PV isolation. This study investigated the detailed characteristics of dormant PV conduction in patients with atrial fibrillation (AF) who underwent catheter ablation. two hundred sixty consecutive patients (235 men; mean age, 54 ± 10 years) who underwent catheter ablation of their AF were included in this study. ATP was injected following PV isolation to induce dormant PV conduction, which was then eliminated by radiofrequency application. dormant PV conduction was induced by ATP in 60.4% (157/260) of the patients and in 25.3% (258/1,021) of the isolated PVs. This transient PV reconduction was more frequently observed in the left superior PV in comparison with other PVs (P < .0001). There was no significant difference in the prevalence of the dormant PV conduction among patients with paroxysmal AF, persistent AF, and long-lasting AF (62%, 66%, and 48%, respectively; P = .13). During the follow-up period, repeat AF ablation was performed in 70 patients with recurrent AF. The dormant PV conduction was less frequently induced in the repeat procedure than in the initial procedure (60.4% vs 31.4%, P < .0001). dormant PV conduction was evenly induced among AF types. The repeat PV isolation led to the decrease in incidence of the ATP-induced acute transient pharmacological PV reconduction.

Electrophysiologic and electrocardiographic characteristics of focal atrial tachycardia arising from superior tricuspid annulus

This study describes the electrophysiologic and electrocardiographic characteristics of focal atrial tachycardia (AT) arising from superior tricuspid annulus in six (1.9%) patients of a consecutive series of 320 patients. Six patients (mean age 42 +/- 22 years) with a mean cycle length of 326 ms of a consecutive series of 320 patients undergoing radiofrequency ablation for focal AT were mapped. During electrophysiologic study, tachycardia could be induced in five patients with programmed atrial extrastimuli while a spontaneous onset and offset with 'warm-up and cool-down' phenomenon was seen in the other patient. During tachycardia, P-wave morphology in Lead I, II, III and aVF was upright in all the six patients. The precordial leads were dominantly negative or isoelectric in V(1)-V(2) and positive in V(5)-V(6) with a transition at V(3) or V(4). Moreover, the tachycardia was sensitive to intravenous administration of adenosine triphosphate in five of six patients. Radiofrequency ablation was performed successfully in all patients (mean 4.5 +/- 1.2 applications). No recurrence of AT was observed after a mean follow-up of 8 +/- 6 months. Thus, AT arising from superior tricuspid annulus is rare. Radiofrequency ablation of this kind of AT is safe and effective.

Participation of a concealed atriohisian tract in the reentrant circuit of the slow–fast type of atrioventricular nodal reentrant tachycardia

The retrograde fast pathway in typical atrioventricular nodal reentrant tachycardia (AVNRT) exhibits marked variation in its electrophysiologic properties. The purpose of this study was to characterize the retrograde fast pathway and localize the lower turnaround site of the reentrant circuit in typical AVNRT. Seventy-four patients with typical AVNRT were divided into two groups according to the response of the retrograde fast pathway to intravenous administration of adenosine triphosphate (ATP) during ventricular pacing: ATP-S [n = 47 (63.5%)] with and ATP-R without [n = 27 (36.5%)] His-atrial (H-A) block. H-A intervals were measured from the most proximal His-bundle electrogram to the earliest atrial activation during the tachycardia (HAt) and entrainment pacing from the parahisian right ventricular region (HAe). It was postulated that the HAt was the difference in conduction time between the lower common pathway (x) and retrograde fast pathway (y) (HAt = y - x), whereas HAe was the sum of the two (HAe = y + x). Hence, x = (HAe-HAt)/2. x >0 suggested the presence of a lower common pathway, whereas x <0 suggested the absence of a lower common pathway and lower turnaround site within the His bundle. x was significantly smaller in ATP-R than ATP-S (-6 +/- 5 vs 4 +/- 4 ms, P <.05) and was <0 in 23 (85%) of 27 ATP-R patients. The maximal increment in H-A interval during ventricular pacing was significantly longer in ATP-S than ATP-R (35 +/- 33 vs 2 +/- 2 ms, P <.05). A concealed atriohisian tract totally bypassing the atrioventricular node constituted the retrograde fast pathway in one third of all typical AVNRT cases.

Electrophysiologic characteristics and radiofrequency ablation of focal atrial tachycardia arising from para-Hisian region

This study describes the electrophysiologic characteristics and radiofrequency ablation of focal atrial tachycardia (AT) arising from para-Hisian region in 14 (6.0%) patients of a consecutive series of 224 patients patients. Inverted or biphasic P wave in V(1) and uncharacteristic P wave in inferior leads were observed during tachycardia, suggesting that there isn't a characteristic P-wave morphology for para-Hisian AT. During electrophysiological study, tachycardia could be induced with programmed atrial extrastimuli in 11 patients while a spontaneous onset and offset with "warm-up and cool-down" phenomenon were seen in other three patients. Moreover, the tachycardias were sensitive to intravenous administration of adenosine triphosphate in all patients. On the basis of these findings, the mechanism is suggestive of triggered activity or micro-reentry, but automaticity cannot be conclusively excluded. Radiofrequency energy was delivered to the earliest site of atrial activation during AT. Ablating energy was carefully titrated, starting at 5 W and increasing gradually upto a maximum of 40 W, to achieve the ceasing of tachycardia. The long-term outcome was a 100% success rate in these 14 patients and there were no irreversible complications associated with ablation. Thus, the mapping and ablation of focal AT arising from para-Hisian region is safe and effective, delivery of radiofrequency energy in a titrated manner and continuous monitoring of atrioventricular (AV) conduction advocated to minimise the risk of damage to the anterograde AV conduction.

Usefulness of an echo-contrast agent for assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery with transthoracic doppler scan echocardiography

Background This study assessed the feasibility of transthoracic Doppler scan echocardiography (TTDE) combined with echo-contrast agent in measuring coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending artery. Methods In 68 consecutive patients who underwent cardiac angiography, TTDE was recorded before and after induction of a hyperemic condition with intravenous administration of adenosine triphosphate (0.14 mg/kg/min). After CFV values returned to baseline, the same measurements were repeated while an echo-contrast agent was continuously infused. CFVR was assessed as the ratio of hyperemic to basal CFV. The pulsed wave Doppler scan quality was graded from 1 to 3 (TTDE score: 1, no signal detection; 2, poor definition of outline; 3, optimal outline definition). Results Before enhancement, CFVR could not be measured in 20 patients. Prevalence of delayed stenosis (Thrombolysis In Myocardial Infarction [TIMI] II grade flow) in these patients (30%) was significantly greater than in those whose CFVRs could be measured without enhancement (2%; P <.01). TTDE scores both at baseline and after hyperemia were significantly improved with contrast enhancement (before, 2.8 ± 0.6; after, 3.0 ± 0.3; P <.01; before, 2.6 ± 0.7; after, 3.0 ± 0.3; P <.01; respectively). Overall contrast enhancement increased the rate of successful CFVR measurement from 70% to 97% ( P <.01). Sensitivity and specificity of significant left anterior descending artery stenosis detection with CFVR of <2.0 were 94.4% and 87.8%, respectively. Conclusion These data suggest that administration of echo-contrast agent improves pulse wave Doppler scan quality and thus the feasibility of measuring CFVR. (Am Heart J 2002;143:668-75.)

Selective enhancement of intratumoral blood flow in malignant gliomas using intra-arterial adenosine triphosphate

The effect of intravenous and intracarotid administration of adenosine triphosphate (ATP) on the regional blood flow of glioma patients has been examined by means of positron emission tomography. Intracarotid administration of ATP at a dose of 0.52 to 1.3 micrograms/kg/min selectively increased the blood flow in the tumor by 26.2% +/- 10.5% (mean +/- standard deviation). The side effects observed were tolerable. In contrast, intravenous administration of ATP failed to increase tumor blood flow. It is suggested that intracarotid administration of ATP may serve to selectively enhance the delivery of anticancer agents to malignant brain tumors.

Unmasking of ventricular preexcitation by adenosine triphosphate: Its usefulness in the assessment of ajmaline test

We herein report the usefulness of the intravenous administration of adenosine triphosphate (ATP), a potent AV nodal depressant agent, in unmasking preexcitation and assessing the results of the ajmaline test in two patients with inapparent ventricular preexcitation in sinus rythm