Biomedical subjects

H Tomoike

Publications and source records attributed to H Tomoike.

At least 55 records · Page 3Linked to original sources

PubMed1999

Canine model of ventricular fibrillation using programmed stimuli and localized myocardial warming or cooling.

The purpose of this study was to establish an animal model in which ventricular fibrillation (VF) can be induced reproducibly and defibrillation can be accomplished repeatedly. The left anterior descending artery (LAD) was cannulated and perfused with blood from the carotid artery in eleven open-chest dogs. Electrodes of the internal defibrillator were inserted in the cavities of the left atrium and left ventricle via incisions in the left atrial appendage and left ventricular apex. The perfused blood temperature was modulated to produce regional myocardial warming (42 degrees C) or cooling (28 degrees C). In all dogs, VF was repeatedly induced by the combination of warming and left ventricular extrastimuli and by the combination of cooling and right ventricular extrastimuli. The VF was quickly defibrillated by use of the internal defibrillator. The mechanism of VF was found to be reentry by the analysis of activation sequences. This VF model may be useful when evaluating the efficacy of antiarrhythmic drugs because of the high reproducibility.

Animals↗

PubMed1999

Angioplasty but not thrombolysis improves short-term mortality of acute myocardial infarction. A multicenter survey in Yamagata, Japan.

There are few district-based surveys to investigate the actual effects of thrombolytic therapy and percutaneous transluminal coronary angioplasty (PTCA) on short-term mortality in patients with acute myocardial infarction (AMI) in Japan. The study population comprised 974 patients (319 women and 655 men, aged 69 +/- 12 years) admitted with confirmed AMI to 41 hospitals in Yamagata Prefecture from January 1, 1994 to December 31, 1996. Thrombolysis and PTCA were performed in 262 (27%) and 428 (44%) patients, respectively, and 161 patients died within 28 days after the onset of AMI (short-term mortality 16.5%). Thirteen variables, including risk factors and clinical manifestations, were examined by bivariate and multiple logistic regression analyses to identify the predictors of short-term mortality. Multiple logistic regression analysis, incorporating variables with a p value < 0.05 in a bivariate analysis, demonstrated that advanced age, history of myocardial infarction and Killip class III or IV independently correlated with increased short-term mortality and treatment with PTCA independently correlated with decreased short-term mortality (odds ratio 0.21, 95% confidence interval [CI] 0.11-0.39). Thrombolytic therapy was not an independent predictor of short-term mortality (odds ratio 0.67, 95% CI 0.37-1.20). Treatment with PTCA but not thrombolysis significantly improved the short-term mortality in patients with AMI in our area-based study.

Aged↗

PubMed1999

Direct effects of class I antiarrhythmic drugs on epicardial electrograms in dogs.

The effects of class I antiarrhythmic drugs on epicardial electrograms during regular atrial pacing were investigated in anesthetized, open-chest dogs. Lidocaine, flecainide or disopyramide was infused selectively into the distal site of the left-anterior descending artery. Lidocaine produced a dose-dependent elevation of ST segment without changing the amplitude of R wave. Flecainide produced a dose-dependent increase of R-wave amplitude accompanied by the augmentation of negative T. The ST segment was elevated at the high dose. The QRST area did not change at the low dose but significantly increased at the high dose, indicating that the ST-T change at the low dose was secondary to changes in ventricular depolarization. The effects of disopyramide on R wave and ST segment were between those of lidocaine and flecainide. The major action of lidocaine was the acceleration of ventricular repolarization while that of flecainide was the deceleration of ventricular conduction. Disopyramide had an action that was intermediate between the two drugs.

Animals↗

PubMed1999

Simulation of late potentials and arrhythmias by use of a three-dimensional heart model: casuality of peri-infarctional slow conduction in ventricular fibrillation.

A three-dimensional heart model was constructed to simulate late potentials and ventricular fibrillation (VF). The model consisted of 50,000 discrete elements having a 1.5-mm spatial resolution. Each element represented excitable ventricular tissue, including a conduction system, and was characterized with classical features of the action potential, refractory period, and conduction velocity (theta). An infarcted area on the lateral wall was identified as dead (inexcitable) cells or scar tissue, and peri-infarctional (PI) cells with slow conduction. Body surface potentials were calculated by using the boundary element method. When theta of PI cells was reduced below 0.3 m/s, late potentials became evident after the J point of simulated electrocardiograms (ECGs), and VF was induced by applying four consecutive premature stimuli. However, when Purkinje fibers were removed, VF could not be initiated. Late potentials were induced when slow conduction was present. The presence of PI slow conduction and Purkinje fibers, which were normally contained in the model, was essential for the induction of VF.

Computer Simulation↗

PubMed1999

Fatty acid imaging with 123I-15-(p-iodophenyl)-9-R,S-methylpentadecanoic acid in acute coronary syndrome.

UNLABELLED: 123I-15-(p-iodophenyl)-9-R,S-methylpentadecanoic acid (9-MPA) has recently been developed as a tracer for myocardial fatty acid uptake. The aim of this study, which was performed as part of a phase III clinical trial of 9-MPA, was to test the usefulness of 9-MPA for the assessment of myocardial viability in patients with acute coronary syndrome (ACS). METHODS: Fifteen patients with ACS who had undergone direct percutaneous transluminal coronary angioplasty were examined. Myocardial SPECT with 9-MPA and 99mTc-sestamibi and low-dose dobutamine echocardiography were performed within 2 wk after onset. The 9-MPA images were obtained 10 and 60 min after tracer administration, and sestamibi imaging was begun 60 min after the injection. The left ventricle was divided into 9 segments, and 9-MPA and sestamibi uptake were scored from 0 (normal) to 3 (no activity) in each segment. Lower uptake of 9-MPA than of sestamibi was defined as a mismatch. Myocardial segments showing improvement in wall motion during low-dose dobutamine infusion (5-10 microg/kg/ min) were considered viable. RESULTS: The 9-MPA images were of high quality for all patients. Myocardial uptake of 9-MPA was lower in ischemic myocardium than in nonischemic myocardium (58.2%+/-14.2% versus 91.9%+/-6.5%, P<0.0001). Clearance of 9-MPA from ischemic myocardium was slower than that from nonischemic myocardium (10.2%+/-11.7% versus 19.1%+/-5.9%, P<0.01). A mismatch was seen in 10 of 15 patients, and 18 of 20 (90%) mismatched segments were defined as viable by dobutamine echocardiography. Conversely, 18 of 20 (90%) matched segments did not show any improvement in function during dobutamine stimulation (P<0.0001). Uptake of 9-MPA in nonviable segments was lower than that in dysfunctional but viable segments (P<0.05), and 9-MPA clearance from nonviable segments was slower than that from viable segments (P<0.05). CONCLUSION: The imaging characteristics of 9-MPA for SPECT are excellent, allowing noninvasive assessment of myocardial fatty acid uptake. Myocardial imaging with 9-MPA may reveal impaired fatty acid uptake in dysfunctional but viable myocardium and thus provide useful information for clinical decision making in ACS.

Aged↗

PubMed1998

Quantitative detection method of triglycerides in serum lipoproteins and serum-free glycerol by high-performance liquid chromatography.

We have developed a simple and reliable method for quantitative detection of triglycerides (TG) in serum lipoproteins and serum-free glycerol (FG) by high-performance liquid chromatography (HPLC). After separation of serum constituents using a new gel-permeation column (TSK gel Lipopropak XL, Tosoh) and a new eluent (TSK eluent LP-2, Tosoh), TG and FG were detected by on-line reaction using a modified reagent which contained glycerol kinase, glycerol-3-phosphate oxidase and lipoprotein lipase. HPLC patterns showed five peaks corresponding to chylomicrons, very-low-density, low-density, high-density lipoproteins and FG. Absolute concentrations of TG in each lipoprotein fraction and serum FG were calculated from the corresponding peak areas using standard FG as a calibrator. Due to its very high sensitivity of peak detection, this method has become desirable for the analyses of lipoproteins of very low concentrations such as in cell culture systems. This technique will contribute to a better understanding of lipoprotein TG and serum FG distribution in human and nonhuman subjects.

Animals↗

PubMed1998

Enhanced expression and shedding of tumor necrosis factor (TNF) receptors from mononuclear leukocytes in human heart failure.

TNFalpha exerts its functions by engaging two receptors (TNF-RI and TNF-RII). The extracellular parts of the receptors are proteolytically shed to the soluble forms by a matrix metalloproteinase-like enzyme (sTNF-RI and sTNF-RII). The soluble TNF receptors can neutralize TNFalpha activities. Circulating levels of both sTNF-RI and sTNF-RII are elevated in patients with congestive heart failure (CHF). It remains unclear how a large amount of sTNF-RI and sTNF-RII is mobilized into the circulation. Mononuclear leukocytes were obtained from 14 controls and 21 patients with CHF. TNF-RII of the cells from CHF patients was upregulated in the cell-surface expression and mRNA transcripts. Besides enhanced shedding of TNF-RII on the cells from CHF patients with phorbol myristate acetate (PMA), sera from CHF induced shedding of TNF-RII on the cells from normal volunteers. Thus, the enhancement of both expression and shedding of TNF-RII may be related to increased circulating levels of the soluble TNF receptor in patients with CHF. The presence of CHF may affect the regulation of TNF receptors, which may modulate the responsiveness to TNFalpha in the tissues of patients with CHF.

Adult↗

PubMed1998

Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome.

Familial long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur as a result of ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far, and mutations have been reported on the basis of partially characterized genomic organization. To optimize the search for HERG mutations, we have determined the genomic structure of HERG and investigated mutations in LQTS families. Human genomic clones containing the HERG gene were isolated from a human genomic library by using reverse-transcribed polymerase chain reaction (RT-PCR) products from this gene as probes. We determined exon/intron boundaries and flanking intronic sequences by using primers synthesized on the basis of the HERG cDNA sequence available in the DNA database. HERG was shown to consist of 15 exons spanning approximately 19 kb on chromosome 7q35. Subsequently, we synthesized oligonucleotide primers to cover the entire coding region and searched for mutations in 36 Japanese LQTS families. When genomic DNA from each proband was examined by the PCR/single-strand conformation polymorphism technique followed by direct DNA sequencing, five novel mutations were detected. Each mutation was present in affected relatives of the respective proband. This work should increase the efficiency of screening mutations associated with HERG.

Amino Acid Sequence↗

PubMed1998

Identification by differential display of eight known genes induced during in vivo intimal hyperplasia.

To achieve a better understanding of the mechanism of intimal thickening, we used a rabbit model in which aorta was denuded mechanically by a balloon catheter. Total RNA was prepared from each aorta 1, 2, 7, 14, 23, or 30 days after denudation, and from intact aorta of non-denuded control rabbits. Subsequently, using the differential display method, we identified eight genes that were expressed differently during the time course after injury. One of them, RESP18 (encoding regulated endocrine secretory protein 18), was suppressed during the acute reaction. The other seven showed increase in expression during the acute phase: the genes for hTAFII68 (human TATA-binding protein associated factor), NPAT (nuclear protein mapped to the AT locus), OSF2 (osteoblast-specific factor 2), Pyst1, casein kinase 1 alpha, integrin alpha 1, and XP-C complementing protein. Although hTAFII68, NPAT, OSF2, and Pyst1 are thought to be related to transcription, not all four are positive regulators. Considering that none of these genes had previously been reported as being implicated in intimal hyperplasia, we conclude that many known or unknown genes play roles in this process. We believe that differential display is an effective method for screening genes whose variations in expression can provide clues toward understanding the molecular mechanism of intimal hyperplasia.

Animals↗

PubMed1998

Cardiac sympathetic nervous disintegrity is related to exercise intolerance in patients with chronic heart failure.

The aim of this study was to clarify the relationship between cardiac sympathetic nervous activity assessed by 123I-MIBG imaging and exercise capacity in patients with congestive heart failure. The subjects were 24 patients with heart failure (NYHA class II to III) and 7 normal controls. A dose of 148 MBq of 123I-MIBG was administered intravenously, and 5-min anterior planar images were obtained 20 min (early) and 4 h (delayed) after the injection of 123I-MIBG. Regions of interest were placed over the left ventricle and mediastinum, and the heart-to-mediastinum ratio (H/M ratio) was calculated as a fraction of the mean counts per pixel in the heart divided by those in the mediastinum. The washout rate from the myocardium was determined by: (early counts delayed counts) x 100/early counts (%). Treadmill exercise tests were performed using a ramp method within 1 week of the 123I-MIBG studies. During exercise, expired gas was analysed, and peak VO2 and VO2 at the anaerobic threshold (ATVO2) were measured. A significant linear correlation was found between the H/M ratio on delayed 123I-MIBG images and exercise duration (r = 0.48, P < 0.05), peak VO2 (r = 0.49, P < 0.05) and ATVO2 (r = 0.56, P < 0.01). The washout rate of 123I-MIBG was inversely correlated with exercise duration (r = -0.45, P < 0.05), peak VO2 (r = -0.51, P < 0.01), and ATVO2 (r = -0.50, P < 0.05). In conclusion, enhanced cardiac sympathetic nervous activity relates to exercise intolerance in patients with congestive heart failure. The non-invasive assessment of cardiac sympathetic nervous activity by 123I-MIBG can predict exercise capacity in human heart failure.

3-Iodobenzylguanidine↗

PubMed1998

Discordant S-T alternans contributes to formation of reentry: a possible mechanism of reperfusion arrhythmia.

Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.

Animals↗

PubMed1998

Artificial surfactant (Surfactant TA) modulates adherence and superoxide production of neutrophils.

Neutrophils cause lung injuries by releasing proteases and active oxygen radicals in patients with acute respiratory distress syndrome (ARDS). Artificial surfactant is used to replace native surfactant whose functions are deteriorated by serum-derived inhibitors in these patients. We investigated potential interactions between exogenous surfactant (Surfactant TA) and neutrophils in in vivo and in vitro experimental models. Neutrophil alveolitis was induced in hamster lungs by the intratracheal administration of bleomycin (5 mg/kg) on Day 0. Some of the animals were followed by replacement with Surfactant TA (5 and 10 mg/100 g body weight) on Day 1. Alveolar cells were harvested by lung lavage on Day 2. The numbers of the neutrophils obtained from the lungs treated with bleomycin and Surfactant TA were unchanged, but the superoxide production from these cells was significantly decreased when compared with control animals (no Surfactant TA). From the in vitro experiments, Surfactant TA was shown to inhibit adherence and superoxide production of human neutrophils. These effects were derived from the heat-resistant components of Surfactant TA and were mimicked by treatment with liposomes of dipalmitoyl phosphatidylcholine. Surfactant-TA-treated neutrophils were demonstrated to have picnotic nuclei and to express Fas antigens, which were characteristic of apoptotic cells. These results suggest that exogenous Surfactant TA may play an important role not only in improving surfactant functions but in preventing neutrophils from further activation, probably through enhancing apoptosis.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1998

Brachial artery flow pattern and clinical backgrounds in patients with angina pectoris.

Blood flow velocity of the brachial artery was measured noninvasively by ultrasound pulsed Doppler technique under the guidance of a B-mode ultrasound image in 56 patients with angina pectoris. There was no significant stenosis along the brachial artery on a B-mode image. The authors investigated seven clinical backgrounds for each patient, ie, age, gender, absence or presence of smoking, hyperlipidemia, diabetes mellitus, hypertension, and the number of significantly stenosed (> or =50%) coronary arteries. Among these variables, the determinants of the brachial artery velocity profile were selected by stepwise multiple regression analysis. Selected variables were the presence of hypertension for peak systolic velocity (R=0.276), age and the number of diseased vessels for peak reverse velocity (R=0.624), and age for peak diastolic velocity (R=0.609). The peak systolic velocity was larger in patients with hypertension than in those without it (0.565+/-0.023 vs 0.490+/-0.013 m/see, P<0.05), and the peak reverse velocity was larger in patients with multivessel disease than those without it (-0.117+/-0.071 vs -0.053+/-0.081 m/sec, P<0.01). Thus, the level of flow velocity of the brachial artery in patients with angina pectoris was partly determined by age, hypertension, and severity of coronary artery disease. The simple measurement of brachial artery flow velocity suggests changes in peripheral vasculature related to atherosclerosis.

Adult↗

PubMed1998

Early mortality after acute myocardial infarction: observational study in Yamagata, 1993-1995.

Although considerable information is available regarding the prognosis after acute myocardial infarction (AMI) in Western populations, little is known about the fate of Japanese subjects after AMI. The purpose of this study was to assess short-term mortality and factors influencing it after AMI in Japan. From April 1993 to December 1995, 1,014 patients with AMI from 41 hospitals in Yamagata Prefecture were registered by cardiologists for the prospective survey. Among patients who died within 28 days after the onset of AMI, immediate causes of death were examined and the clinical profiles of these subjects were compared with those of patients that survived. Early death occurred in 184 patients (short-term mortality 18%). Patients who died were significantly older than survivors (76.1+/-9.4 vs 67.6+/-11.8 years, p<0.01). They were also more likely to be women (50% vs 31%, p<0.01), to have had hypertension (64% vs 54%, p<0.05), diabetes mellitus (29% vs 20%, p<0.02), prior MI (17% vs 12%, p<0.05), or Killip class III or IV disease (63% vs 15%, p<0.01), and were significantly less likely to be current smokers (26% vs 45%, p<0.01) or to have been treated with reperfusion therapy (27% vs 63%, p<0.01). Multivariate logistic analysis demonstrated that independent predictors of early death were Killip class III or IV and advanced age. Reperfusion therapy was a negative predictor of death. Patients who died had arrived at hospital earlier than patients who survived. Mortality as a result of heart failure, cardiac rupture, or arrhythmia fell exponentially after the onset of AMI. Thus, the predictors of short-term mortality were similar to those reported in Western populations. More deaths occurred just after the onset of disease, suggesting that early therapy is important in reducing short-term mortality.

Adult↗

PubMed1998

Quantitative assessment of myocardial 99mTc-sestamibi uptake during exercise: usefulness of response rate for assessing severity of coronary artery disease.

An increase of 99mTc-sestamibi uptake in the myocardium during exercise was defined as a response rate, and the feasibility of a response rate for detecting coronary artery disease (CAD) was tested. Eighty-seven patients with suspected CAD had myocardial perfusion imaging with 99mTc-sestamibi during exercise and at rest. A dose of 370 MBq of 99mTc-sestamibi was injected at the maximal level of exercise, and a myocardial image was obtained 90 min later (exercise image). Then, 740 MBq of 99mTc-sestamibi was administered at rest, and myocardial imaging was repeated (rest image). The exercise and rest images were corrected for physical decay and injected doses, and the exercise image was subtracted from the rest image to obtain the corrected rest image. A response rate was calculated as follows: (exercise image-corrected rest image)x100/corrected rest image (%). The global response rates of 20 patients without significant coronary stenosis (< or =50%) were higher than those of 67 patients with significant coronary stenosis (81+/-33% and 50+/-28%, p<0.01). Global response rates were correlated with the maximal rate pressure products during exercise (r=0.56, p<0.01) and delta rate pressure products (r=0.53, p<0.01). Regional response rates in myocardial areas perfused by stenotic coronary arteries of < or =50%, 75%, 90% and 99-100% were 60+/-24%,* 56+/-33%,* 40+/-23%* and 30+/-23%,* respectively, (*p<0.01 vs without significant coronary stenosis). The response rates decreased as the severity of coronary artery stenosis advanced, and distinguished between coronary stenoses of graded severity. Accordingly, the response rate from myocardial perfusion imaging with 99mTc-sestamibi may provide complementary information to the conventional inspection with myocardial tomography regarding the severity of CAD.

Coronary Disease↗

PubMed1998

Decrease in the high frequency QRS components depending on the local conduction delay.

The high frequency components contained in the QRS complex (HF-QRS) are a powerful indicator for the risk of sudden cardiac death. However, it is controversial whether conduction delay increases or decreases the HF-QRS. In 21 anesthetized, open-chest dogs, the right atrium was constantly paced. A cannula was inserted into the left anterior descending artery and flecainide, lidocaine or disopyramide was infused to slow the local conduction. Sixty unipolar electrograms were recorded from the entire ventricular surface and were signal-averaged. Data were filtered (30-250 Hz) by using fast-Fourier transform. The HF-QRS was calculated by integrating the filtered QRS signal. Activation time (AT; dV/dt minimum) was delayed and the HF-QRS was reduced in the area perfused by flecainide, lidocaine or disopyramide. The percent increase in AT closely correlated the percentage decrease in the HF-QRS; the correlation coefficients were 0.75, 0.83 and 0.76 for flecainide, lidocaine and disopyramide infusion, respectively, (p<0.001). Decrease in the HF-QRS linearly correlated with the local conduction delay. This study proved that conduction delay decreases the HF-QRS, and that the HF-QRS is a potent indicator of disturbed local conduction.

Animals↗

PubMed1998

Acute renal failure due to oxalate ingestion.

A 47-year-old man presented with acute renal failure following oxalate ingestion. Nausea and hematoemesis appeared four hours after attempted suicide and acute oliguric renal failure ensued the following day. The patient underwent four sessions of hemodialysis and then reverted to normal state. Histopathologic examination of renal biopsy specimen revealed the degeneration of the renal tubular epithelial cells associated with intracellular calcium oxalate crystal deposition. Most of the renal tubules were patent despite the intraluminar crystal deposition. These findings suggest that dysfunction of the renal tubular epithelial cell plays a more important role than tubular obstruction in developing acute renal failure.

Calcium Oxalate↗

PubMed1998

Myocardial tomography with technetium-99m-tetrofosmin during intravenous infusion of adenosine triphosphate.

UNLABELLED: The purpose of this study was to determine the biodistribution of 99mTc-tetrofosmin during intravenous infusion of adenosine triphosphate (ATP) and to evaluate the potential diagnostic value of myocardial tomography with 99mTc-tetrofosmin during ATP infusion for the detection of coronary artery disease. METHODS: Myocardial 99mTc-tetrofosmin imaging with ATP infusion and coronary arteriography were performed on 65 patients with suspected coronary artery disease. ATP was infused intravenously at a rate of 0.16 mg/kg/min for 5 min, and 370 MBq of 99mTc-tetrofosmin was injected 3 min after the start of ATP infusion. Myocardial SPECT imags were obtained 60 min later. Then, 740 MBq of 99mTc-tetrofosmin was administered at rest, and myocardial SPECT was repeated. Regional uptakes of 99mTc-tetrofosmin were scored from 4, normal, to 0, no activity. Serial 5-min planar images were obtained in the anterior projection at 15, 30, 45 and 60 min after the 99mTc-tetrofosmin injection in 10 patients. Heart-to-lung and heart-to-liver count ratios were defined from the serial planar images. RESULTS: Adverse effects of ATP infusion were mild and transient. A heart-to-lung ratio after ATP infusion was high even at 15 min (3.40 +/- 0.33) and gradually increased with time. A heart-to-liver ratio after ATP was 0.53 +/- 0.40 at 15 min and increased with time. A heart-to-liver ratio reached 0.99 +/- 0.25 (p < 0.01) after 45 min and 1.32 +/- 0.36 (p < 0.01) after 60 min. The sensitivity and specificity for detecting coronary artery disease by myocardial SPECT with ATP were 89% (39/44) and 86% (18/21), respectively. CONCLUSION: This study shows the favorable biodistribution of 99mTc-tetrofosmin after intravenous infusion of ATP. A one-day imaging protocol of 99mTc-tetrofosmin tomography with ATP is feasible and has high diagnostic accuracy for coronary artery disease.

Adenosine Triphosphate↗