Biomedical subjects

T Tsuchida

Publications and source records attributed to T Tsuchida.

At least 19 recordsLinked to original sources

PubMed2006

Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus.

Murine cytomegalovirus (MCMV) immediate-early (IE) 2 protein has been reported to be dispensable for growth and latency in mice. Therefore, its role in viral pathogenesis and tissue tropism is not known. Here we prepared specific antibodies to the IE2 and IE3 proteins by using fusion proteins expressed in Escherichia coli as antigens. Immunostaining of MCMV-infected cultured fibroblasts revealed IE2 protein to be expressed diffusely in the nucleoplasm similar to the IE1 protein. In contrast, expression of the IE3 protein, 88 kDa, exhibited a punctate pattern in the nucleus in the early phase of infection then diminished. In the brain of neonatal mice infected with MCMV, both IE2 and IE3 proteins were detected immunohistochemically in the cells of the ventricular walls early in infection. When the infection was prolonged, the IE2 protein was expressed in neurons of the cortex and hippocampus, while the IE3 protein was preferentially expressed in glial cells in the early phase of infection, and its levels declined during the infection. These results suggest that the IE2 protein may play a role in persistent infection in neurons, whereas the IE3 protein, expressed preferentially in glial cells, may play the main role in acute infection.

Animals↗

PubMed2005

Characterization of a facultative endosymbiotic bacterium of the pea aphid Acyrthosiphon pisum.

The pea aphid U-type symbiont (PAUS) was investigated to characterize its microbiological properties. Fluorescence in situ hybridization (FISH) and electron microscopy revealed that PAUS was a rod-shaped bacterium found in three different locations in the body of the pea aphid Acyrthosiphon pisum: sheath cells, secondary mycetocytes, and hemolymph. Artificial transfer experiments revealed that PAUS could establish stable infection and vertical transmission when introduced into uninfected pea aphids. When 28 aphid species collected in Japan were subjected to a diagnostic PCR assay, four species of the subfamily Aphidinae (Aphis citricola, Aphis nerii, Macrosiphum avenae, and Uroleucon giganteus) and a species of the subfamily Pemphiginae (Colopha kansugei) were identified to be PAUS-positive. The sporadic incidences of PAUS infection without reflecting the aphid phylogeny can be best explained by occasional horizontal transfers of the symbiont across aphid lineages.

Animals↗

PubMed2005

Development of a nosocomial outbreak investigation database.

A pilot web-based database was created to facilitate epidemiological investigation of nosocomial outbreaks. The database provides highly structured abstracts in a case study format to serve as a guide for investigations. Problems encountered in abstracting over 330 published reports included missing information and classification of study methods. The database offers a new way to review outbreaks, for example, in terms of their impact measured by various combinations of database fields, such as the number of cases, attack rate, pathogens, service/ward and mode of transmission. Feedback from users of the database suggests its usefulness. Creation of a large web-based database seems to be both desirable and feasible.

Abstracting and Indexing↗

PubMed2004

Antioxidant effect of MCI-186, a new Free-Radical scavenger, on ischemia-reperfusion injury in a rat hindlimb amputation model.

BACKGROUND: A newly synthesized free-radical scavenger, MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-1), was recently approved in Japan for treating acute brain infarction. The purpose of this study was to investigate whether or not MCI-186 is effective in reducing ischemia-reperfusion injury in the extremities. MATERIALS AND METHODS: Warm ischemia was sustained for 4 hours. The animals were divided into 4 groups: (1) sham group, (2) control group (saline injection), (3) MCI group (MCI-186 injection), and (4) EPC group (EPC-K1 [(l-ascorbic acid 2-[3,4-dihydro-2, 5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt], a hydroxyl-radical scavenger, injection). Wet and dry (W/D) weights of the gastrocnemius and tibialis anterior muscles, muscle contractile function, and serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), glutamic oxaloacetic transminase (GOT), and mitochondrial glutamic oxaloacetic transminase (GOT-m) were measured after 24 h of reperfusion. The cytotoxic aldehydes malondialdehyde and 4-hydroxy-2-nonenal as indices of lipid peroxidation (LPO), and neutrophil-specific enzyme myeloperoxidase (MPO) as an index of neutrophil infiltration, were measured in the gastrocnemius muscle. RESULTS: Contractile functions in the MCI and EPC groups were significantly better than in the control group. In the tibialis anterior muscle, the contractile function was better in the MCI group than in the EPC group. W/D ratios and serum levels of CPK, LDH, GOT, and GOT-m were lower in the sham and MCI groups than in the control group. Levels of LPO and MPO activity were significantly lower in the MCI and EPC groups than in the control group. Histological findings demonstrated that inflammatory tissue reactions rarely occurred in the MCI group. CONCLUSION: MCI-186 is effective in preventing ischemia-reperfusion injury in extremities. MCI-186 seems to have promise as a therapeutic agent, because it prevents ischemia-reperfusion injury even in the tibialis anterior muscle, which contains fast-twitch glycolytic fibers, known to be very susceptible to ischemic insult.

Amputation, Surgical↗

PubMed2004

Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy.

The purpose of this study was to determine whether h-PTH (1-34) treatment would recover cancellous bone connectivity and bone strength in ovariectomized (OVX) or ovariectomized and sciatic-neurectomized (OVX+NX) rats. Seven-month-old female Wistar rats were treated with h-PTH or vehicle (6.0 microg/kg, six times a week, subcutaneously) for four weeks beginning 4, 8, or 12 weeks after OVX or OVX+NX. These were compared to age-matched baseline and sham-operated groups. Right tibiae were used for bone histomorphometry and node-strut analysis, and left tibiae were used for mechanical testing. The bone formation rates in the OVX and OVX+NX rats treated with h-PTH were significantly higher than those in their baseline controls. h-PTH treatment increased the node numbers and failure energies in the OVX rats, compared to their baseline controls, at all time points. However, in the OVX+NX rats, the effects of h-PTH treatment on the node number and failure energy were observed only at four weeks after surgery, but not at eight weeks or 12 weeks after surgery. These results suggest that the lowest limit, at which trabecular connectivity and bone strength are able to be restored by h-PTH, occurred between four and eight weeks in OVX+NX rats, but not in OVX rats. h-PTH cannot recover trabecular connectivity and bone strength in advanced osteopenia.

Animals↗

PubMed2003

Effects of combined treatment of insulin and human parathyroid hormone(1-34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats.

The purpose of this study was to test the hypothesis that combined treatment with insulin and human parathyroid hormone (hPTH) is more effective than treatment with insulin or hPTH alone in improving cancellous bone mass, connectivity, and strength in insulin-dependent diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in 7-month-old female Wistar rats. The diabetic rats received insulin, hPTH, insulin and hPTH, or hPTH vehicle for 4 weeks, starting 8 weeks after STZ injection. They were compared with baseline controls and normal controls that received STZ alone and STZ vehicle alone, respectively. The rats' proximal right tibias were processed to serve as undecalcified Villanueva-stained bone sections for histomorphometry. Changes in trabecular connectivity were determined through node-strut analysis. The decreased cancellous bone volume (BV/TV) and bone formation in diabetic rats improved in all the drug-treated groups compared with baseline controls. Furthermore, recovery of BV/TV was greater in rats that received the combination of insulin and hPTH than in those that received insulin or hPTH alone. In node-strut analysis, the node-related parameter (N.Nd/TV) significantly increased in rats that received the combination of insulin and hPTH, but did not increase in those that received insulin or hPTH alone. In addition to these results, the combination treatment significantly increased bone mineral density of the femur and bone strength in the femoral metaphysis compared with treatment with insulin or hPTH alone. These results indicate that the doses of insulin and hPTH employed in the combination treatment were more effective in improving not only bone mass but also trabecular connectivity and bone strength than treatment with insulin or hPTH alone in insulin-dependent diabetic rats.

Animals↗

PubMed2002

Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression: 10 years' experience.

5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. In this study, we measured serum levels of 5-S-CD in 2648 samples taken from 218 patients in order to evaluate the usefulness of this parameter in following melanoma progression and prognosis. 5-S-CD levels were significantly elevated above the upper limit of the normal range (10 nmol/l) in stage IV melanoma patients. The sensitivity of elevated serum 5-S-CD levels in detecting distant metastasis was 73%, while the specificity was 98% and the positive predictive value 94%. The sensitivity was improved to 77% when cases of amelanotic melanoma were excluded. Patients without metastases had elevated 5-S-CD values in 5% of the 1480 serum samples. Changes in serum 5-S-CD levels were followed during disease progression until the end stage in 49 patients. In 33% of the patients, elevation of serum 5-S-CD levels preceded clinical detection of visceral metastases, and in 37% elevation of 5-S-CD levels occurred at the same time as visceral metastasis. Patients with elevated 5-S-CD levels before or after surgical treatment had significantly shorter survival times than those with normal levels. These results show that the level of 5-S-CD in the serum is a sensitive and specific marker in predicting distant metastases. Elevated serum levels of 5-S-CD, before or after surgical treatment, is associated with a poor prognosis.

Adolescent↗

PubMed2001

Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition.

Activin A induces growth arrest of rat hepatocytes in vitro and in vivo. The alpha(1)-adrenergic agonist, norepinephrine (NE), enhances epidermal growth factor-stimulated DNA synthesis and inhibits activin A-induced growth inhibition, but the mechanisms of these actions are unclear. Smad proteins have recently been identified as intracellular signaling mediators of transforming growth factor-beta family members. In the present study, we explored how NE modulates the Smad signaling pathway in rat cultured hepatocytes. We demonstrate that NE inhibits activin A-induced nuclear accumulation of Smad2/3 and that NE rapidly induces inhibitory Smad7 mRNA expression. Infection of Smad7 adenovirus into rat hepatocytes inhibited activin A-induced nuclear accumulation of Smad2/3, enhanced epidermal growth factor-stimulated DNA synthesis, and abolished the growth inhibitory effect of activin A. We also demonstrated that the induction of Smad7 by NE is dependent on nuclear factor-kappa B (NF-kappa B). The amount of active NF-kappa B complex rapidly increased after NE treatment. Preincubation of the cells with an NF-kappa B pathway inhibitor N-tosyl-l-phenylalanine chloromethyl ketone or infection of the cells with an adenovirus expressing an I kappa B super-repressor (Ad5I kappa B) abolished the NE-induced Smad7 expression. These results indicate a mechanism of transmodulation between the Smad and trimeric G protein signaling pathways in rat hepatocytes.

Activins↗

PubMed2001

Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis.

PDT has been reported to induce cancer cell expression of cytokines, such as IL-6 and TNF-alpha, but it has been unclear whether cytokine expression by cancer cells is directly related to the antitumor effect of PDT. We treated Lewis lung carcinoma (LLC) cells with a new photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) and light from a diode laser and found that expression of the mRNA of IL-2, IL-6, and TNF-alpha was increased by NPe6-mediated-PDT 6 hr later. To elucidate the mechanism of the direct anti-tumor effect of cytokine expression, we examined the photosensitivity of cytokine-gene-transfected cells, namely LLC-IL-2, LLC-IL-6, and LLC-TNF-alpha cells, by MTT assay. The IL-6 gene transfected, LLC-IL-6 cells were significantly more sensitive to cytotoxic effects than the parent LLC cells and other cytokine gene-transfected cells. This finding indicates that IL-6 expression modulates cellular sensitivity to PDT and that IL-2 and TNF-alpha expressions does not. In addition, the apoptosis of LLC-IL-6 cells induced by NPe6-PDT was greater than in the other cells as determined by DNA fragmentation and staining of apoptotic nuclei. Because IL-6 has been reported to induce apoptosis by downregulating expression of Bcl-2, we analyzed the expression of apoptosis-related Bcl-2, Bax, and cytochrome C by Western blot analysis. Decreased expression of Bcl-2 and cytochrome C was observed in both LLC cells and LLC-IL-6 cells. Bax protein increased in a time-dependent manner, and the ratio of Bax to Bcl-2 rose markedly after PDT in LLC-IL-6 cells. These results suggest that the increased sensitivity of LLC-IL-6 cells to PDT-induced cytotoxicity results from the high ratio of Bax to Bcl-2 in the IL-6-dependent apoptotic pathway. In conclusion, IL-6 expression plays a role in cellular sensitivity to PDT, and combination of IL-6 and PDT may provide a new strategy for cancer treatment.

Animals↗

PubMed2001

Application of gel microdroplet and flow cytometry techniques to selective enrichment of non-growing bacterial cells.

We describe an application of gel microdroplet (GMD) and flow cytometry techniques to selective enrichment of non-growing Leuconostoc mesenteroides cells, which are well culturable on other media, from a mixture with Bacillus subtilis cells in nutrient broth. After encapsulating cells of the mixed population within GMDs and a brief incubation in nutrient broth, the inability of L. mesenteroides cells to form microcolonies within GMDs allowed their discrimination from B. subtilis cells. After staining the GMD mixture with 6-carboxyfluorescein diacetate, which showed no influence on cell viability, the GMDs containing single cells of L. mesenteroides were selectively collected using flow cytometry sorting based on differences in fluorescence intensity. The cells of L. mesenteroides retained viability during the process.

Bacillus subtilis↗

PubMed2001

Increased ischemia-reperfusion blood flow impairs the skeletal muscle contractile function.

BACKGROUND: The ultimate aim of replantations and transplantations of skeletal muscle is to improve impaired function. The purpose of this study was to examine the contribution of varying durations of ischemia to postischemic blood flow in the skeletal muscle and the contribution of modulation of postischemic blood flow to skeletal muscle function and viability, using an ischemic revascularized hind limb model in rats. MATERIALS AND METHODS: Warm ischemia produced by vascular pedicle clamping was sustained for 90 min, 3 h, or 6 h. Postischemic blood flow was measured by a Doppler flowmeter or microsphere technique. In another series of experiments of 3-h ischemia, either saline or N(G)-methyl-l-arginine acetate (l-NMMA) was infused for the first 2 h of reperfusion. Postischemic blood flow was also measured. Muscle contractile function and viability were determined after 24 h of reperfusion. RESULTS: Postischemic blood flow was significantly increased during the first 10 min of reperfusion in the 90-minute ischemic group and during the first 2 h in the 3-h ischemic group compared with contralateral control blood flow. No significant increase in postischemic blood flow was noted in the 6-h ischemic group. Postischemic blood flow was significantly decreased by the l-NMMA infusion. Contractile function and viability of the tibialis anterior muscle and contractile function of the gastrocnemius muscle in the l-NMMA group were significantly increased. CONCLUSION: Reperfusion blood flow increased time dependently until 3 h of warm ischemia. Hyperemia deteriorated skeletal muscle contractile function, although it was well preserved by l-NMMA infusion to restrict the postischemic hyperemia.

Animals↗

PubMed2001

Effect of perfusion during ischemia on skeletal muscle.

BACKGROUND: Despite the established preservation method for major organs of perfusion followed by immersion at hypothermia, a standard preservation technique for skeletal muscle is still a matter of controversy. The purpose of this study is to examine the effect of perfusion on the preservation of skeletal muscle in amputated limbs. MATERIALS AND METHOD: The rat hindlimb was amputated for perfusion with Euro-Collins (EC) or University of Wisconsin (UW) solution at different perfusion pressures (40 or 100 cm-gravity). After certain ischemic periods (4 or 5 h), the skeletal muscle viability was determined by measuring the tissue content of adenosine triphosphate (ATP). RESULT: The UW solution perfusion group maintained better ATP levels than the EC solution group when the ischemic period was extended to 5 h. The perfusion pressure of 100 cm-gravity was more effective for preserving muscle viability than 40 cm-gravity with both EC and UW solutions. CONCLUSION: UW solution might be adequate to preserve muscle viability and perfusion pressure is recommended at 100 cm-gravity rather than at minimal pressure (40 cm-gravity), which washes out stagnant blood.

Adenosine↗

PubMed2001

Risk factors for sudden unexpected death among workers: a nested case-control study in central Japan.

UNLABELLED: BACKGROUND; Few studies have focused on sudden death among apparently healthy workers, and the risk factors have not been fully discussed. METHODS: A nested case-control study was conducted among 164,017 male employees receiving annual medical checkups in Japan. Most recent medical checkup data of 242 sudden death victims (mean age, 48.0 years) were compared with corresponding data of 505 age-, workplace-, and job-type-matched male controls. Odds ratios (ORs) and their 95% confidence intervals (CIs) for each variable were calculated by logistic regression. RESULTS: OR (95% CI) significantly increased with advancing blood pressure, reaching 6.6 (3.4-13.1) for systolic blood pressure > or =160 mm Hg relative to that <120 mm Hg. Hypo-HDL-cholesterolemia, hyperuricemia, increased aminotransferases, and abnormal urinary findings were associated with the risk in a dose-dependent manner. The presence of arrhythmias and ST-T abnormalities as well as abnormal Q waves on electrocardiograms yielded a 3.5 to 4.8 times greater risk of sudden death. As for lifestyles, heavy smoking was a positive, and light drinking was a negative risk factor. Multivariate analysis revealed that hypertension, proteinuria, glucosuria, arrhythmias, ST-T abnormalities, and light drinking were independent predictors for sudden death. CONCLUSION: These findings suggest that periodic medical checkups can help to predict and prevent employee sudden death.

Blood Pressure↗

PubMed2001

Copper-62 ATSM as a hypoxic tissue tracer in myocardial ischemia.

Copper-62 labeled diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) has been proposed as a generator produced positron-emitting tracer for hypoxic tissue imaging. To clarify the usefulness of 62Cu-ATSM for myocardial ischemia, 62Cu-ATSM PET was performed in 7 patients with coronary artery disease. Increased myocardial uptake of 62Cu-ATSM was observed (myocardium/blood ratio: 3.09) in one patient with unstable angina, who had increased 18F-fluorodeoxyglucose (18F-FDG) uptake under the fasting condition. The other 6 patients, who were clinically stable, did not have increased 62Cu-ATSM uptake, although abnormal 18F-FDG uptake was seen in 4 patients. This preliminary study suggests that 62Cu-ATSM is a promising PET tracer for hypoxic imaging in acute ischemia.

Aged↗

PubMed2001

Myocardial FDG-PET examination during fasting and glucose loading states by means of a one-day protocol.

We propose a new method to measure the myocardial FDG uptake during fasting and glucose loading in one day, a myocardial FDG-PET one-day protocol, with both 2- and 3-dimensional data acquisition (2D and 3D) without background activity subtraction. To confirm it, we evaluated the effect of scatter correction in the 2D and 3D modes of a PET scanner both in phantom and patient studies. In the phantom study, we used a cardiac phantom with six divided chambers and two cylindrical phantoms placed as the activity outside the field of view. Each chamber was filled with a different concentration of F- 18 solution. Regions of interest (ROI) were placed on a polar map generated from reconstructed images and were compared to the concentration of the solution in each chamber in both 2D and 3D. In the patient study, 10 non-diabetic patients with coronary artery disease were studied. Each patient received a myocardial FDG study during fasting (F) and glucose loading (L). L images with background subtraction (Lsub(+)) and without background subtraction (Lsub(-)) were compared by polar map analysis. The ROI counts for the true activity in 2D and 3D demonstrated a linear relationship, and quite similar slopes were observed (0.72 in 2D, 0.69 in 3D). The background fraction in Lsub(-) was 3.59+/-1.83%. There were significant differences between Lsub(-) or Lsub(+) and F in both normal and ischemic myocardium. Scatter correction was successfully performed in both 2D and 3D modes. Background activity is thought to be negligible and this proposed method is simple touse in measuring the myocardial FDG uptake in one day.

Aged↗

PubMed2001

Acute effects of stereotactic radiosurgery on the kinetics of glucose metabolism in metastatic brain tumors: FDG PET study.

UNLABELLED: Hyperacute changes in the expression of glycolysis-associate gene products as well as FDG uptake in tumor cells after high-dose irradiation reflect response of the cells to noxious intervention and may be a potential indicator of the outcome of treatment. To understand acute effects on the kinetics of glucose metabolism of tumors in vivo after high-dose irradiation, we analyzed dynamic FDG PET data in patients with metastatic brain tumors receiving stereotactic radiosurgery. MATERIALS AND METHODS: We studied 5 patients with metastatic brain tumors by means of dynamic FDG PET before and 4 hours after stereotactic radiosurgery. Rate constants of glucose metabolism (K1*- k3*) were determined in a total of 13 tumors by a non-linear least squares fitting method for dynamic PET and arterial blood sampling data. Rate constants after radiosurgery were compared with those before radiosurgery. Changes in the rate constants induced by the therapy were also correlated with changes in tumor size evaluated by CT and/or MRI 6 months later. RESULTS: Four hours after radiosurgery, the phosphorylation rate indicated by k3* was significantly higher (0.080 +/- 0.058) than that before radiosurgery (0.049 +/- 0.023) (p < 0.05, paired t test), but there was no significant change in the membrane transport rates indicated by K1* and k2*. Although increases in the net influx rate constant K* (= K1*k3*/(k2* + k3*)) were correlated with increases in k3*, K* after radiosurgery (0.027 +/- 0.011) was not significantly different from that before the therapy (0.024 +/- 0.012). The reduction in the tumor size was correlated with k3* after radiosurgery. CONCLUSION: Acceleration of the phosphorylation process was demonstrated in vivo in metastatic brain tumors as early as 4 hours after stereotactic radiosurgery, as shown experimentally in vitro in a previous report. The phenomenon may be a sensitive indicator of cell damage.

Aged↗

PubMed2001

Brain perfusion SPECT study with 99mTc-bicisate: clinical pitfalls and improved diagnostic accuracy with a combination of linearization and scatter-attenuation correction.

To evaluate the usefulness of a combination of linearization and scatter-attenuation correction on 99mTc-bicisate (ECD)-single photon emission tomographic (SPECT) images, both cerebral blood flow (CBF)-positron emission tomographic (PET) images and ECD-SPECT images from fifteen patients with chronic cerebral infarction were acquired. We measured radioactivity counts in regions of interest (ROIs) on all sets of both images and obtained a 2D scattered graph between ECD-SPECT and CBF-PET data. To evaluate diagnostic accuracy, the sensitivity, specificity and accuracy of ECD-SPECT images were calculated by means of discriminant analysis. The same analysis was also performed on the ECD-SPECT images corrected by a combination of linearization and scatter-attenuation correction. An overall nonlinear relationship was observed between ECD-SPECT and CBF-PET. The sensitivity, specificity, and accuracy of ECD-SPECT images were 69.6%, 91.4% and 73.0%, and those of ECD images corrected by the combination of linearization and scatter-attenuation correction were 79.5%, 95.7% and 82.0% respectively. The clinically diagnostic accuracy of ECD-SPECT images corrected by the combined method apparently increased. So that the linearization with the scatter-attenuation method is useful for improving the diagnostic accuracy of ECD-SPECT images.

Aged↗

PubMed2001

Clinical significance of reverse redistribution on resting thallium-201 imaging in patients with vasospastic angina.

To evaluate the clinical significance of reverse redistribution (RR) of resting 201Tl single photon emission computed tomography (SPECT) in patients with vasospastic angina (VSA), we performed left ventriculography, coronary angiography and resting 201Tl-SPECT in 22 patients with VSA. Left ventriculography showed abnormal wall motion in 17 of 22 patients (77%) and 37 of 154 segments. Thirty-one of these 37 segments (84%) were within the area perfused by coronary arteries showing acetylcholine-induced vasospasm. On 201Tl images, abnormal findings were observed in 11 of 22 patients (50%), and among them, 7 patients (32%) had RR. Seven of 37 segments (19%) having abnormal regional wall motion had RR of 201TI, and in 6 of these 7 segments (86%), accumulation of 123I-BMIPP was found to be reduced. We conclude that repetitive brief myocardial ischemia may cause myocardial injuries in patients with VSA, and that the presence of RR of 201Tl indicates the presence of myocardial injury in these patients.

Acetylcholine↗