Injection Of Adenosine Triphosphate Research Articles

Development of a rabbit model of Adenosine triphosphate-induced monocular retinal degeneration for optimization of retinal prostheses.

Optimization of retinal prostheses requires preclinical animal models that mimic features of human retinal disease, have appropriate eye sizes to accommodate implantable arrays, and provide options for unilateral degeneration so as to enable a contralateral, within-animal control eye. In absence of a suitable non-human primate model and shortcomings of our previous feline model generated through intravitreal injections of Adenosine Triphosphate (ATP), we aimed in the present study to develop an ATP induced degeneration model in the rabbit. Six normally sighted Dutch rabbits were monocularly blinded with this technique. Subsequent retinal degeneration was assessed with optical coherence tomography, electroretinography, and histological assays. Overall, there was a 42% and 26% reduction in a-wave and oscillatory potential amplitudes in the electroretinograms respectively, along with a global decrease in retinal thickness, with increased variability. Qualitative inspection also revealed that there were variable levels of retinal degeneration and remodeling both within and between treated eyes, mimicking the disease heterogeneity observed in retinitis pigmentosa. These findings confirm that ATP can be utilized to unilaterally induce blinding in rabbits and, potentially present an ideal model for future cortical recording experiments aimed at optimizing vision restoration strategies.Clinical Relevance- A rapid, unilaterally induced model of retinal degeneration in an animal with low binocular overlap and large eyes will allow for clinically valid recordings of downstream cortical activity following retinal stimulation. Such a model would be highly beneficial for the optimization of clinically appropriate vision restoration approaches.

Adenosine triphosphate (ATP): a safe and effective vasodilator for stress perfusion cardiac magnetic resonance imaging

To evaluate the efficiency and safety of adenosine triphosphate (ATP) as a stress agent in a cohort of patients undergoing stress perfusion cardiac magnetic resonance imaging (CMRI). This retrospective study was conducted between December 2019 and October 2021. The study recruited patients who underwent stress perfusion CMRI using ATP as a vasodilator. Adverse events, such as chest pain, flushing, dyspnoea, headache, and splenic switch-off (SSO) phenomenon, were evaluated in the patients who underwent stress perfusion CMRI. The study included 107 patients (age range: 53±11 years; male:female, 62%:38%). The haemodynamic response (heart rate increased by≥10 beats/min) was quick and observed within 2 minutes of ATP infusion. Scanning was stopped in three patients because of atrioventricular block. CMRI images of seven out of 104 patients were excluded from the final analysis because of inferior quality. During ATP infusion, 37/107 patients (35%) experienced mild adverse events, such as chest pain, flushing, dyspnoea, headache, and atrioventricular block. Myocardial infarction and bronchospasms were not observed during ATP infusion. SSO, a marker of adequate stress, was observed in 91% (94/103) of the patients who underwent stress perfusion CMRI. As a coronary vasodilator, ATP was safe for stress perfusion CMRI. In addition, the adverse events during ATP infusion were mild, which were relieved within 2 minutes of ATP injection cessation. SSO could serve as an indicator of stress success in ATP stress perfusion CMRI.

Impact of high frequency stimulation to confirm a complete box isolation in catheter ablation of non-paroxysmal atrial fibrillation.

Pulmonary vein (PV) isolation (PVI) including the left atrial posterior wall (LAPW) (Box-PVI) is proposed as an additional strategy for non-paroxysmal atrial fibrillation (NPAF), however, the efficacy remains controversial. The more reliable and durable the Box-PVI we can create, the better the rhythm outcomes might be than with a conventional PVI alone. This study focused on the potential exit conduction of the box lesion and investigated whether the conventional Box-PVI would be sufficient. We enrolled 350 consecutive patients with NPAF that underwent a conventional encircling Box-PVI and examined whether latent exit conduction and dormant "exit" conduction independently remained on the LAPW and in the PVs using high frequency stimulation (HFS) and an adenosine triphosphate (ATP) injection. All electrograms inside the box lesion were eliminated in all cases, however, HFS inside the box propagated outward in 23 cases (6.6%) without any exit conduction by conventional burst stimulation, and 24 cases (6.9%) exhibited only dormant "exit" conduction of the LAPW. Additional ablation where positive HFSs were observed created a complete bidirectional Box-PVI in 43 (41.3%) of the cases without a first pass Box-PVI. The recurrence rates depended on the groups classified according to the HFS response. HFS delivered with an ATP injection on the LAPW and in the PVs following a Box-PVI could not only elucidate true exit block but also identified possible incomplete lesions or connections outside the ablation line, whose elimination could achieve a complete Box-PVI leading to a better rhythm outcome.

Generation, breakdown and responses of ATP in the carotid body

Purinergic signaling involving adenosine triphosphate (ATP) acting on P2X2/3 receptors modulates physiological carotid body (CB) afferent discharge and chemoreflex activation however, the upregulation of P2X3 receptors on petrosal sensory neurons is partly responsible for aberrant CB tonicity and hyperreflexia, and the increase in blood pressure in the Spontaneously Hypertensive rat (SHR). The enhanced chemoreflex occurs prior to the onset of hypertension and elevated CB activity is thought to contribute to the underlying pathophysiology of the disease but the exact mechanisms remain unclear. We hypothesize that there is greater release of ATP and/or decreased ATP breakdown in the pre‐hypertensive SHR CB compared with that in the Wistar rat, and this evokes an increase in the chemoreflex response and subsequent activation of the sympathetic nervous system. We performed three studies. (i) Using digital droplet PCR (ddPCR), we measured mRNA expression levels of enzymes involved in the breakdown of ATP in CBs extracted from male 4‐week‐old prehypertensive SHR and Wistar rats; these included: ectonucleotide pyrophosphatase/phosphodiesterase 1‐3 (Enpp1‐3), ectonucleoside triphosphate diphosphohydrolase 2‐3 (Entpd2‐3), and ecto‐5’‐nucleotidase (Nt5e). (ii) We quantified ATP release from CBs in vitro during baseline conditions and during cyanide‐evoked ATP release using a colorimetric assay (213‐579‐1 ‐ Millipore), comparing between male 4‐week‐old pre‐hypertensive SHR and Wistar rats. (iii) In an in situ working heart‐brainstem preparation of 4‐week‐old Wistar rats, simultaneous recordings were made from phrenic (PN), hypoglossal (HN), recurrent laryngeal (RLN), abdominal (ABN), and thoracic sympathetic nerves (tSNA). The peripheral chemoreceptors were stimulated with either potassium cyanide (KCN 20‐100 μL, 0.04%) or ATP at varying concentrations (10‐100 µL, 50 µM ‐ 2 mM) delivered via the internal carotid artery. In whole CB extracts, ddPCR revealed increased Enpp2‐3 and Nt5e expression (p<0.05) in pre‐hypertensive SHRs relative to Wistar rats suggesting greater capacity to break down ATP in the pre‐hypertensive SHR CB. There were no differences in the expressions of Enpp1 or Entpd2‐3 between rat strains. However, the amount of ATP released from the CB in both baseline and during cyanide stimulation was two‐fold greater in the pre‐hypertensive SHR (P<0.05). Stimulation of the CB with KCN evoked hyperpnoea, bradycardia and sympathoexcitation at all doses. In contrast, CB injection of low dose ATP increased PN rate with little effect on tSNA, whereas higher doses induced apnea accompanied by repetitive burst discharge of post‐inspiratory activity in the RLN with tonic elevations in the discharge of both ABN and tSNA. In sum, despite the upregulation of several ATP degrading enzymes in the CBs of the SHR, CB release of ATP is higher in this species. We hypothesize that the increase in ATP release in the SHR CB drives the CB hyperexcitability and that the shift towards an upregulation of ATP degrading enzymes even prior to the development of hypertension is compensatory to oppose the increase in ATP signaling. The dose‐dependent effect of exogenous ATP at supraphysiological levels evoking greater CB‐mediated expiratory and sympathetic outflow in the Wistar rat mimics aspects of pathophysiological CB chemoreflex signaling in the SHR.

Electrophysiological manifestations of rare supra-ventricular tachycardias with concealed nodo-ventricular fibers.

To clarify the electrophysiological mechanism of supra-ventricular tachycardias (SVT) with concealed nodo-ventricular (NV) fibers. We studied the intra-cardiac electrograms during electrophysiological study (EPS) of three cases of SVT which concerned concealed NV fibers. Electrophysiological maneuvers including right ventricular apex entrainments, RS2 stimuli, adenosine triphosphate injection and so on were done for differential diagnosis before ablation. Among these patients, one had atrio-ventricular nodal reentrant tachycardia (AVNRT) with a bystander NV fiber; the other 2 had NV fiber mediated orthodromic reentrant tachycardias (NVRT). VA dissociation was observed during SVT in all 3 cases with an antegrade His bundle conduction sequence. Ventricular stimulation at His refractory period reset the H-H intervals and the V-V intervals sequentially, suggesting the existence of a retrogradely conductive accessory pathway. Adenosine injection could terminate these tachycardias. The cycle length of an NVRT prolonged during the status of functional right bundle branch block, suggesting that the fiber located on the right side. Multiple QRS fusion morphologies during ventricular entrainments or ventricular stimulation at His refractory period at a fixed position could be observed in these cases. Concealed NV fibers can either mediate orthodromic reentrant tachycardia or be a bystander of AVNRT. V-A dissociation usually occur during such SVTs. Dissociation of H and V due to entrainment of right ventricular apex is a newly discovered maneuver to differentiate AVNRT from NVRT.

Effect of intravenous adenosine triphosphate injection on chronic pain and fatigue in female patients with fibromyalgia

Effect of intravenous adenosine triphosphate injection on chronic pain and fatigue in female patients with fibromyalgia

Electrical Field Shaping Techniques in a Feline Model of Retinal Degeneration.

The majority of preclinical studies investigating multi-electrode field shaping stimulation strategies for retinal prostheses, have been conducted in normally-sighted animals. This study aimed to reassess the effectiveness of two electrical field shaping techniques that have been shown to work in healthy retinae, in a more clinically relevant animal model of photoreceptor degeneration. Four cats were unilaterally blinded via intravitreal injections of adenosine triphosphate. Cortical responses to traditional monopolar (MP) stimulation, focused multipolar (FMP) stimulation and two-dimensional current steering were recorded. Contrary to our previous work, we found no significant difference between the spread of cortical activation elicited by FMP and MP stimulation, and we were not able to reproduce cortical responses to singleelectrode retinal stimulation using two-dimensional current steering. These findings suggest that while shown to be effective in normally-sighted animals, these techniques may not be readily translatable to patients with retinal degeneration and require further optimization.

Latest technologies and techniques to improve pulmonary vein isolation

Pulmonary vein isolation (PVI) is the established cornerstone in catheter ablation for atrial fibrillation (AF). The traditional point-to-point ablation by focal radiofrequency (RF) catheter to achieve PVI was technically challenging, and the outcome remained suboptimal despite advancement in three-dimensional electroanatomical mapping systems and steerable sheaths. Different catheter designs including contact force, balloon-based catheters with other energy sources (cryothermal and laser energies), and circular RF catheters have been developed to make the ablation procedure more user-friendly and PVI more durable. Adjunctive techniques including detection of dormant conduction by adenosine triphosphate injection and pace-capture-guided ablation have also been studied to improve the durability of PVI and thus reduce the AF recurrence rate.

Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration.

Retinal prostheses have emerged as a promising technology to restore vision in patients with severe photoreceptor degeneration. To better understand how neural degeneration affects the efficacy of electronic implants, we investigated the function of a suprachoroidal retinal implant in a feline model. Unilateral retinal degeneration was induced in four adult felines by intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post injection, animals received suprachoroidal electrode array implants in each eye, and responses to electrical stimulation were obtained using multiunit recordings from the visual cortex. Histologic measurements of neural and glial changes in the retina at the implant site were correlated with cortical thresholds from individual stimulating electrodes. Adenosine triphosphate-injected eyes displayed changes consistent with mid-to-late stage retinal degeneration and remodeling. A significant increase in electrical charge was required to induce a cortical response from stimulation of the degenerated retina compared to that in the fellow control eye. Spatial and temporal characteristics of the electrically evoked cortical responses were no different between eyes. Individual electrode thresholds varied in both the control and the ATP-injected eyes and were correlated with ganglion cell density. In ATP-injected eyes, cortical threshold was also independently correlated with an increase in the extent of retinal gliosis. These data suggest that even when ganglion cell density remains unaffected, glial changes in the retina following degeneration can influence the efficacy of suprachoroidal electrical stimulation. A better understanding of how glial change impacts retinal prosthesis function may help to further the optimization of retinal implants.

Retinal Changes in an ATP-Induced Model of Retinal Degeneration.

In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration.

Abstract 10199: Right Atrial Fibrillation in Humans - Evidence for A Right Atrial Driver Activated by Right Atrial Ectopies

Background: A left-to-right dominant frequency (DF) gradient exists in acute atrial fibrillation (AF) in animals and in paroxysmal AF (PAF) in humans. PAF initiated by right atrial ectopy (PAF-RAE) is rare. Adenosine triphosphate (ATP) can be effective to unmask such a rare non-pulmonary vein (PV) ectopy and accelerate the frequency of a reentrant source of AF (driver). Objective: This study aimed to investigate characteristics of patients with PAF-RAE using pharmacological maneuvers and spectral analysis. Methods: Enrolled were 111 consecutive patients referred for catheter ablation of lone PAF. Infusions of isoproterenol and ATP were used to induce AF. Patients with PAF initiated only by PV ectopies and with PAF-RAE were classified into the PV-ectopy group (N=32) and RA-ectopy group (N=6), respectively. ATP was also injected during ongoing AF to unmask the AF driver. High RA, coronary sinus (CS), and PV-left atrial junction (PV-LAJ) electrograms underwent spectral analyses. Results: RA-ectopy group patients were younger (49±13 vs. 63±7 years, p<0.001), more commonly had a family history of AF (67% vs. 9%, p<0.001), and had a higher RA appendage/RA volume ratio (0.22±0.022 vs. 0.15±0.055, p=0.002) than PV-ectopygroup patients. The most common origin of RA ectopy was the base of the RA appendage (67%). There was a baseline right-to-left DF gradient in the RA-ectopy group (PV-LAJ: 6.0±0.4, CS: 5.7±0.7, RA: 7.4±0.8 Hz, p<0.05), in contrast to a left-to-right DF gradient in the PV-ectopy group (PV-LAJ: 5.9±0.8, CS: 5.3±0.7, RA: 5.2±0.8 Hz, p<0.01). ATP injection mainly increased the DF of the high RA, augmenting a right-to-left DF gradient in the RA ectopy group (PV-LAJ: 8.0±2.0, CS: 7.8±1.0, RA: 10.7±0.7 Hz, p<0.05), whereas it augmented a left-to-right DF gradient in the PV-ectopy group (PV-LAJ: 7.9±1.0, CS: 6.4±0.5, RA: 6.6±1.2 Hz, p<0.05). Conclusions: PAF-RAE may be maintained by a reentrant driver localized in the RA (so-called right atrial fibrillation).

Right-to-left frequency gradient during atrial fibrillation initiated by right atrial ectopies and its augmentation by adenosine triphosphate: Implications of right atrial fibrillation

A left-to-right dominant frequency (DF) gradient commonly exists in paroxysmal atrial fibrillation (AF). AF initiated by right atrial (RA) ectopy (AF-RAE) is rare. This study aimed to investigate characteristics of AF-RAE using pharmacological maneuvers and spectral analysis. Seventy-nine consecutive patients referred for catheter ablation of paroxysmal AF were enrolled. Infusions of isoproterenol and adenosine triphosphate (ATP) were used to induce AF. Patients with AF-RAE and patients with AF initiated only by pulmonary vein (PV) ectopies were classified into the RA-ectopy group (n = 7[9%]) and PV-ectopy group (n = 32[41%]), respectively. ATP was also injected during ongoing AF to unmask the driver of AF. High RA, coronary sinus, and PV-left atrial junction electrograms and electrocardiogram lead V1 underwent spectral analyses. Patients in the RA-ectopy group were younger (51 ± 13 years vs 63 ± 7 years; P = .01) and more commonly had a family history of AF (71% vs 9%; P < .001) than patients in the PV-ectopy group. There was a baseline right-to-left DF gradient in the RA-ectopy group (PV-left atrial junction: 6.0 ± 0.4 Hz; coronary sinus: 5.7 ± 0.6 Hz; RA: 7.3 ± 0.8 Hz; P < .05) in contrast to a left-to-right DF gradient in the PV-ectopy group (5.9 ± 0.8, 5.3 ± 0.7, 5.2 ± 0.8 Hz; P < .01). ATP injection predominantly increased the DF of the high RA in the RA-ectopy group and augmented a right-to-left DF gradient (7.9 ± 1.8, 7.6 ± 1.0, 10.7 ± 0.7 Hz; P < .001), whereas it augmented a left-to-right DF gradient in the PV-ectopy group (7.9 ± 1.0, 6.4 ± 0.5, 6.6 ± 1.2 Hz; P < .05). A rare type of paroxysmal AF initiated by RA ectopy may be maintained by a reentrant driver localized in the RA (so-called RA fibrillation).

ATP-induced photoreceptor death in a feline model of retinal degeneration.

To develop and characterize a feline model of retinal degeneration induced by intravitreal injection of adenosine triphosphate (ATP). Nineteen normally sighted adult cats received 100 μL intravitreal injections of ATP with a final concentration of 11, 22, or 55 mM at the retina. Four animals were euthanized 30 hours after injection and retinal sections examined for apoptosis using a TUNEL cell death assay. In the remaining animals, structural and functional changes were characterized over a 3-month period using a combination of electroretinography (ERG) and optical coherence tomography (OCT). Using a TUNEL cell death assay, we detected widespread photoreceptor death 30 hours after injection with 55 mM intravitreal ATP. All concentrations of ATP caused loss of retinal function and gross changes in retinal structure within 2 weeks of injection. Intravitreal injection of ATP led to a rapid loss of rod photoreceptor function and a gradual loss of cone photoreceptor function within 3 months. Outer nuclear layer thickness was globally reduced by 3 months, with the inner nuclear layer including the retinal nerve fiber layer remaining intact. Structural abnormalities were observed, including focal retinal detachment with evidence of both intravitreal and intraretinal inflammation in some eyes. Development of an ATP-induced feline model of retinal degeneration provides a rapid and effective large-eyed animal model for research into vision restoration.

English

The effects of puerarin on acute nociception mediated by the P2X3 receptor in rat dorsal root ganglia (DRG) were studied. Intrathecal injection of adenosine triphosphate (ATP) or &alpha;,&beta;-methylene-ATP (&alpha;,&beta;-meATP) could potentiate acute nociceptive responses induced by intraplantar injection of ATP or &alpha;,&beta;-meATP in rat hindpaw. Intraplantar injection of formalin increased the expression of P2X3 in rat DRG and induced acute nociceptive responses. These induced nociceptive responses were inhibited by intrathecal injection of puerarin, which also decreased the up-regulated expression of P2X3 mRNA and protein in DRG induced by intraplantar injection of formalin. Molecular docking studies revealed that puerarin could interact perfectly with homology-modeled rat P2X3 receptor (rP2X3). rP2X3 can be restricted to binding ATP because of its combination with puerarin (increasing the concentration of free ATP), therefore blocking the rP2X3 channel. Whole cell patch clamp recording showed that puerarin inhibited the potentiation of P2X3 receptor-mediated currents induced by lipopolysaccharide. These results demonstrated that puerarin inhibited nociceptive responses induced by ATP, &alpha;,&beta;-meATP, or formalin and its inhibitory effect was mediated by reduction of inflammatory pain-induced up-regulation of P2X3 receptor expression and blockade of ATP binding sites on the P2X3 receptor. Our results suggest that puerarin could decrease acute pain mediated by the P2X3 receptor in the DRG. Key words: Puerarin, acute nociceptive response, P2X3 receptor, dorsal root ganglia, whole cell patch clamp.

Utility of nicorandil for the measurement of coronary fractional flow reserve

Nicorandil, an adenosine triphosphate (ATP)-sensitive potassium channel opener, has been used as an anti-angina drug that causes coronary vasodilation of both epicardial and resistance vessels. We assessed the hyperaemic efficacy of nicorandil for the measurement of coronary fractional flow reserve (FFR). In this prospective, single-centre study, we enrolled 20 consecutive patients (20 lesions) with intermediate coronary artery stenosis. Hyperaemic efficacy of intracoronary bolus injection of nicorandil (2mg) was compared with that of continuous intravenous infusion of adenosine triphosphate (ATP, 150μg/kg/min). The intra-patient difference of FFR value between the two hyperaemic stimuli was evaluated using a non-inferiority design with the margin of 0.03. Among study patients, no serious event occurred with administration of either stimulus. A strong and linear correlation of FFR with ATP and nicorandil was observed (r (2)=0.98, P<0.0001). The intra-patient difference of the FFR between nicorandil and ATP was 0.003 (95% confidence interval -0.004 to 0.011), and the probability for the non-inferiority margin of 0.03 was <0.0001. In conclusion, bolus intracoronary injection of nicorandil was non-inferior to continuous intravenous injection of ATP in achieving maximal hyperaemia. Nicorandil could be considered as an alternative option for achieving maximal coronary and myocardial hyperaemia for the assessment of FFR.

Time Courses and Time‐Resolved Spectra of Firefly Bioluminescence Initiated by Two Methods of ATP Injection and Photolysis of Caged ATP

The time-dependent characteristics of firefly bioluminescence initiated by manual injection of adenosine triphosphate (ATP) into buffer solution containing luciferin (Ln), luciferase (Luc) and Mg(2+) were measured with a resolution of 10 ms, and compared with those obtained by photolysis of caged ATP. The time course depends on pH; both rise and decay rates decrease when pH is lowered from 7.8 to 6.8. In contrast, the parameter λ in the kinetic formula related to diffusion of ATP is almost independent of pH. The pH dependence of the time course of bioluminescence can be explained by the same pH tendency as the rate of ATP binding at the active site of Luc. The time-resolved spectra can be decomposed into two Gaussian components with maxima at 2.2 and 2.0 eV. At pH 7.8, the band at 2.2 eV is more intense than that at 2.0 eV for all three concentration conditions. At lower pH, the band at 2.2 eV becomes weaker than that at 2.0 eV. The intensity ratio of the 2.0 and 2.2 eV bands is constant for duration time of 600 s for both injection and photolysis experiments, and the above conclusions are unaffected by the concentration ratio [Ln]/[Luc].

Clinical Impact of Adenosine Triphosphate Injection on Arrhythmogenic Superior Vena Cava in the Context of Atrial Fibrillation Ablation

Superior vena cava (SVC) is an infrequent yet an important source of atrial fibrillation. The clinical impact of ATP injection on arrhythmogenic SVC has not been evaluated. A total of 43 patients (59±11 years; men, 32) who underwent ATP test for arrhythmogenic SVC after the electric isolation at either initial procedure or repeat procedure were included. Pulmonary vein antrum isolation was performed at index procedure in all patients. SVC was isolated after identifying the arrhythmogenicity at index and repeat atrial fibrillation ablation procedure in 34 (79.1%) and 9 (20.9%) patients, respectively. Atrial fibrillation originated from the SVC spontaneously and under isoproterenol infusion in 30 (75.0%) patients, and immediately after ATP injection in 10 (25.0%) patients. Tachycardia persistently confined to SVC was recorded after electric isolation in 13 (30.2%) patients. SVC reconnection was provoked by ATP test in 7 of 36 (19.4%) patients at acute phase. At median 4.0 (2.25-7.5) months after SVC isolation, reconnection was observed in 12 of 15 (80.0%) patients at repeat procedure. Among 12 patients with reconnection at baseline, SVC reconnection was provoked by ATP test after reisolation in 1 (8.3%) patient. Among 3 patients without SVC reconnection at baseline, reconnection was provoked by ATP test at chronic phase in 1 patient. Dormant conduction between an arrhythmogenic SVC and the right atrium can be exposed by ATP administration both immediately and late after isolation, potentially facilitating detection and ablation for isolation.

Evaluation of coronary microvascular function in patients with vasospastic angina

To investigate endothelium-dependent and -independent coronary microvascular functions in patients with vasospastic angina (VSA). Thirty-six patients with VSA (30 men and 6 women; mean age, 58 years) were enrolled in this study. VSA was defined as ≥ 90% narrowing of the epicardial coronary arteries on angiography performed during a spasm provocation test, presence of chest pain, and/or ST-segment deviation on an electrocardiogram (ECG). Patients (n = 36) with negative spasm provocation test results and those matched for age and sex were enrolled as a control group (nonVSA group). Low-dose acetylcholine (ACh; 3 μg/min) was infused into the left coronary ostium for 2 min during the spasm provocation test. Following the spasm provocation test, nitroglycerin (0.2 mg) was administered intracoronally. Coronary blood flow (was calculated from quantitative angiography and Doppler flow velocity measurements, and the coronary flow reserve was calculated as the ratio of coronary flow velocity after injection of adenosine triphosphate (20 μg) to the baseline value. Changes in the coronary artery diameter in response to ACh and nitroglycerin infusion were expressed as percentage changes from baseline measurements. Body mass index was significantly lower in the VSA group than in the nonVSA group. The frequency of conventional coronary risk factors and the rate of statin use were similar between the 2 groups. The left ventricular ejection fraction as evaluated by echocardiography was similar between the 2 groups. The duration of angina was 9 ± 2 mo. The results of blood chemistry analysis were similar between the 2 groups. Low-dose ACh did not cause coronary spasms. The change in coronary artery diameter in response to ACh was lower in the VSA group (-1.4% ± 9.3%) than in the nonVSA group (3.1% ± 6.5%, P < 0.05), whereas nitroglycerin-induced coronary artery dilatation and coronary blood flow increase in response to ACh or coronary flow reserve did not differ significantly between the 2 groups. These findings suggest that microvascular coronary function may be preserved despite endothelial dysfunction of the epicardial coronary arteries in patients with VSA.

Distribution of the Origin of Adenosine TriphosphateSensitive Atrial Tachycardias With the Earliest Activation Recorded in the His Bundle Catheter

The aim of this study was to assess the spatial distribution of the origins of adenosine triphosphate (ATP) sensitive focal atrial tachycardias (AT) that have their earliest activation recorded in the His bundle (HB) catheter. Catheters were placed according to the standard fashion for an electrophysiologic study of supraventricular arrhythmia, namely, high right atrium, HB, coronary sinus, and right ventricle. The ATs with their earliest activation recorded in the HB catheter and that were terminated by rapid injection of ATP (4.3 ± 2.5mg), formed the study group (n=12). After catheter ablation of these ATs, the distances between the successful ablation site and the HB area were measured. Only one successful site was near the HB and the other sites were at the noncoronary sinus of Valsalva (n=6), tricuspid annulus (n=3), right atrial septum (n=1), and left atrial septum (n=1). The average distance between the HB catheter and successful site was 10.4 ± 8.8mm. In 5 of the 12 cases (the 3 tricuspid and 2 septal foci), the distances were greater than 10mm. When ablating ATP-sensitive AT with the earliest activation recorded in the HB catheter, it is important to perform detailed mapping not only around the HB.

Differential Diagnosis of Supraventricular Tachycardia with Ventriculoatrial Dissociation during Ventricular Overdrive Pacing

Case Presentation A 72-year-old man with a history of multiple episodes of paroxysmal supraventricular tachycardia underwent electrophysiologic studies and a catheter ablation procedure. The 12-lead electrocardiogram during tachycardia showed long RP’ tachycardia with negative P waves in leads II, III, and aVF. Ventriculoatrial (VA) conduction with a shortest 1:1 pacing cycle length of 780 ms and earliest atrial activation at the ostium of coronary sinus was observed during ventricular overdrive pacing. A narrow QRS tachycardia documented previously was reproducibly induced by programmed atrial, though not ventricular, stimulation. During tachycardia, the His-atrial (HA) and atrial-His (AH) intervals were 381 and 156 ms, respectively. The atrial activation sequence during tachycardia seemed identical to that during ventricular pacing. A 2-mg bolus injection of adenosine triphosphate reproducibly terminated the tachycardia after a last ventricular event, following progressive prolongation of the atrial cycle length. Overdrive ventricular pacing for >30 seconds during tachycardia, at a cycle length 10‐30 ms shorter than the tachycardia cycle length, invariably caused VA dissociation without atrial capture or termination of the tachycardia (Fig. 1). What is the tachycardia mechanism? Comment