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Biomedical subjects

L M Voipio-Pulkki

Publications and source records attributed to L M Voipio-Pulkki.

At least 19 recordsLinked to original sources

Thalidomide therapy and polyneuropathy in myeloma patients.

Thalidomide is today an increasingly used therapy in advanced and refractory myeloma patients, especially in patients relapsing after high dose therapy. One important and well-known side effect of thalidomide is polyneuropathy (PNP). The purpose of this study was to investigate 1) how severe the thalidomide-induced PNP is in patients treated for myeloma 2) which neurophysiological tests and parameters are most sensitive in detecting the thalidomide-induced PNP and 3) how neuropathic symptoms correlate with neurophysiological changes. Twelve patients received thalidomide for treatment of relapsed multiple myeloma for at least 5 months. Prior to the thalidomide treatment, all patients had been treated with chemotherapy including vincristine, and seven patients had also received cisplatin. PNP symptoms, clinical findings and neurophysiological tests before and after the therapy were evaluated. Prior to thalidomide treatment, 7 patients had minimal and one patient slight PNP. After thalidomide treatment, 4 patients had minimal, 4 patients slight, and 3 patients moderate PNP. Thalidomide-induced PNP mainly affected sensory myelinated axons, but also alpha motor neuron axons were affected to some extent. Thermal thresholds were not altered, indicating that thin myelinated and unmyelinated axons are spared. The most sensitive parameter for detecting thalidomide-induced PNP was the sensory nerve compound action potential amplitude. The neuropathic symptoms deteriorated significantly during the therapy, but clinically, no patient developed a disabling PNP that would have required interrupting the therapy. The neuropathic side effects of thalidomide seem to be acceptable in myeloma patients.

Action Potentials↗

Use of [11C]acetate and [15O]O2 PET for the assessment of myocardial oxygen utilization in patients with chronic myocardial infarction.

Carbon-11 acetate positron emission tomography (PET) has been widely used to assess regional oxidative metabolism of the heart. However, the accuracy of [11C]acetate PET in assessing oxidative metabolism in infarcted myocardium remains controversial. Thirteen patients with stable coronary artery disease and old myocardial infarction were studied. The 15O-based PET studies yielded regional blood flow (rMBF, ml/min/g) and oxygen consumption (rMMRO2, ml/min/g), which was compared with the myocardial clearance rate constant (kmono) of [11C]acetate in segments with rMBF > or = 75% (group A), 50%-74% (group B) or < 50% (group C) of the normal reference segment. Mean MBF was 0.96 +/- 0.08 ml/g/min in group A, 0.67 +/- 0.06 ml/g/min in group B and 0.42 +/- 0.07 ml/g/min in group C segments. The segmental rMMRO2 correlated linearly with kmono (r = 0.89, P < 0.001, y = 0.61x + 0.026). The kmono/rMMRO2 ratio was comparable in the group A and B segments (0.99 +/- 0.19 vs 1.07 +/- 0.21, P = NS). However, the ratio was significantly higher in the group C segments (1.28 +/- 0.35, P = 0.037). It is concluded that kmono of [11C]acetate correlates linearly with rMMRO2 determined by [15O]O2 inhalation. However, kmono appears to yield higher rMMRO2 estimates than the [15O]O2 method in low-flow areas.

Acetates↗

Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor prognosis in chronic heart failure.

Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35% +/- 8%) who had undergone carbon-11 hydroxyephedrine (11C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55 +/- 19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of 11C-HED retention (mean 0.184 +/- 0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with 11C-HED retention below the median and three in the group with 11C-HED retention above the median (P < 0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak VO2), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that 11C-HED PET provides independent prognostic information in patients with CHF.

Aged↗

Adenosine in myocardial protection given through three windows of opportunity. An experimental study with pigs.

OBJECTIVE: Adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischemia. However, the timing and dose of ADO administration have not been defined. This study was designed to determine the cardioprotective effect of exogenous ADO in an experimental open heart surgery model in pigs. DESIGN: The animals were openly divided into two groups both undergoing 30 min of total cardiac arrest. In the control group animals received cold crystalloid cardioplegic solution. In the ADO group ADO was added to cardioplegic solution and in addition ADO was infused to the superior vena cava for 2 h starting 30 min before cardiac arrest. The pumping function of the heart was measured with echocardiography and myocardial blood flow was measured with microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was detected and tumor necrosis factor (TNF) levels were measured. RESULTS: Better post-ischemic pumping function was found in the ADO group (relative decrease 43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased significantly from the baseline values (p < 0.05 in both groups). There was a temporary decrease in myocardial blood flow post-ischemically, followed by a compensatory increase during the later reperfusion period. The cardiomyocyte apoptosis was induced significantly in both groups. CONCLUSIONS: In this experiment two important details were noticed. Firstly, cardiomyocyte apoptosis is involved in ischemia-reperfusion injury associated with open heart surgery. Secondly, PET is a comparable method with the microsphere technique when coronary flow is studied. No significant effects of ADO against ischemia-reperfusion injury could be shown. However, there were some signsof positive outcome, even though statistical significance could not be reached.

Adenosine↗

Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats.

We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% (P < 0.01 vs. sham) at 4 wk and 0.10% at 12 wk in the border zones. In the remote myocardium, cardiomyocyte apoptosis increased to 0.07% (P = 0.03 vs. sham) on day 1 and remained on the same level up to 4 wk. The increase in diastolic diameter 1-4 wk after infarction correlated (r = 0.60, P < 0.01) with cardiomyocyte apoptosis in the noninfarcted myocardium, which quantitatively contributed most (>50%) to the apoptotic cell loss by 4 wk.

Animals↗

Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis.

Despite well-documented cardiotoxic effects, doxorubicin remains a major anticancer agent. To study the role of myocardial apoptosis following doxorubicin administration, male Wistar rats were exposed to 1.25, 2.5, and 5 mg/kg of i.p. doxorubicin and terminated on days 1-7 in groups of five. Doxorubicin caused a significant (P < 0.001) and dose-dependent induction of cardiomyocyte apoptosis at 24-48 h after the injection. Repeated injections of 2.5 mg/kg given every other day resulted in peaks of apoptosis at 24 h after each injection. However, no additive effect of repeated dosing was noted. In histological samples, alterations in the cytoskeletal apparatus with focal loss of contractile elements were seen after a single injection. Myocyte necrosis was absent. Thus, acute doxorubicin-induced cardiotoxicity involves cardiomyocyte apoptosis, a potentially preventable form of myocardial tissue loss.

Animals↗

Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition.

Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing abnormalities, arterial hypertension, and an increased number of cardiovascular events. Sympathetic activity is increased during nocturnal apneic episodes, which may mediate the cardiovascular complications of sleep apnea. We studied 15 male subjects with obstructive sleep apnea syndrome and associated hypertension, 54 subjects with mild to moderate essential hypertension, and 25 healthy normotensive men. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability (HRV) during a controlled breathing test and during orthostatic maneuver. Compared with normotensive and hypertensive groups, total power and low- and high-frequency components of HRV during controlled breathing were significantly (analysis of variance, p<0.0001) lower in the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change in total power of HRV was different between the 3 groups (analysis of variance, p = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/-12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/-1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome. According to multivariate regression analysis, age and sleep apnea were the major independent determinants of HRV. This study found that an abnormal response to autonomic nervous tests characterizes hypertension in overweight subjects with obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or supersaturation of the end-organ receptors by excessive and prolonged sympathetic stimulation. Our results also show the reduced response of orthostatic maneuver and controlled breathing in the hypertensive group compared with the normotensive group.

Autonomic Nervous System↗

Bactericidal/permeability-increasing protein (BPI) in sepsis correlates with the severity of sepsis and the outcome.

OBJECTIVE: To compare the prognostic significance of bactericidal/permeability-increasing protein (BPI), group II phospholipase A2 (PLA2-II), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF), interleukin-8 (IL-8) and interferon-gamma (IFN) in terms of predicting severity of sepsis and outcome. DESIGN: A prospective study. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: Thirty-four patients with severe sepsis requiring ICU treatment. MEASUREMENTS AND RESULTS: The levels of BPI, PLA2-II, CRP, TNF, IL-8 and IFN were measured in these 34 patients. High levels of BPI were associated particularly with Gram-negative sepsis. BPI and BPI/neutrophil ratios correlated positively with PLA2-II, CRP, TNF and IL-8 and negatively with blood pressure. At 24 h, BPI/neutrophil ratios, IL-8 and Simplified Acute Physiology Scores II (SAPS II) scores were higher in non-survivors than in survivors. No such associations were noted in the levels of CRP, PLA2-II, TNF or IFN. The areas under the curve (AUC(ROC)s) of SAPS II scores and IL-8 were higher than AUC(ROC) of BPI/neutrophil ratio. CONCLUSION: The BPI and BPI/neutrophil ratios may serve as adjunctive tools to illustrate the severity of sepsis. However, their predictive power for sepsis-related death was not comparable to that of SAPS II scores and IL-8.

Adult↗

Level of circulating phospholipase A2 in prediction of the prognosis of patients with suspected myocardial infarction.

OBJECTIVES: Atherosclerotic lesions result from inflammatory-proliferative responses of the endothelium and smooth muscle of the arterial wall. Poor prognosis of acute myocardial infarction (AMI) patients has been associated with elevated levels of acute phase proteins including C-reactive protein. We investigated the significance of circulating phospholipase A2 in the long-term prognosis of suspected AMI patients. METHODS: The concentration of phospholipase A2 was measured by an immunoassay in sera of 100 suspected AMI patients. Admission phospholipase A2 95 % fractile outliers were excluded to eliminate the effect of acute infectious diseases. The total and atherosclerotic mortalities were followed for a 4-year period. RESULTS: The most powerful prognostic limit for both admission (p = 0.02, RR = 2.6 and 95% CI = 1.2 to 5.6) and maximal (p = 0.06, RR = 2.4 and 95% CI = 0.96 to 5.9) phospholipase A2 groups was > or =8 microg/l. The admission phospholipase A2 level had an independent prognostic significance for atherosclerotic mortality (p = 0.04, RR = 2.4 and CI = 1.02 to 5.8) in multivariate analysis with CK-MB and age. CONCLUSIONS: The elevated serum phospholipase A2 level at admission is an independent predictor of long-term atherosclerotic mortality in patients with suspected AMI. The prognostic significance of phospholipase A2 weakens during hospitalisation concomitant to the onset of the acute inflammatory response to myocardial injury.

Aged↗

In vivo detection of vascular adhesion protein-1 in experimental inflammation.

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation.

Amine Oxidase (Copper-Containing)↗

Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans.

OBJECTIVES: The expression of endothelial adhesion molecules and their functional significance in leukocyte adhesion to human myocardial blood vessels in acute myocardial infarction (AMI) were studied. BACKGROUND: Leukocyte extravasation, mediated by specific adhesion molecules, exacerbates tissue injury after restoration of blood supply to an ischemic tissue. Experimental myocardial reperfusion injury can be alleviated with antibodies that block the function of adhesion molecules involved in leukocyte emigration, but the relevant molecules remain poorly characterized in human AMI. METHODS: Semiquantitative immunohistochemistry and in vitro adhesion assays were used to study the expression and granulocyte binding abilities of different endothelial adhesion molecules in human AMI. Changes in the molecular nature of vascular adhesion protein-1 (VAP-1) were evaluated using immunoblotting. RESULTS: Certain endothelial adhesion molecules (intercellular adhesion molecule [ICAM-2], CD31 and CD73) were expressed in myocardial blood vessels homogeneously in normal and ischemic hearts, whereas others (E-selectin and peripheral lymph node addressin) were completely absent from all specimens. The synthesis of ICAM-1 was locally, and that of P-selectin regionally, upregulated in the infarcted hearts when compared with nonischemic controls. Vascular adhesion protein-1 showed ventricular preponderance in expression and alterations in posttranslational modifications during ischemia-reperfusion. Importantly, P-selectin, ICAM-1 and VAP-1 mediated granulocyte binding to blood vessels in the ischemic human heart. CONCLUSIONS: Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising targets when antiadhesive interventions preventing leukocyte-mediated tissue destruction after myocardial ischemia are planned.

5'-Nucleotidase↗

Celiprolol augments the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure.

PURPOSE: Impaired insulin sensitivity has been linked with chronic heart failure (CHF). Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of randomized treatment with celiprolol, a vasodilating beta(1)-adrenoceptor antagonist, 200 mg once daily (n=20) or placebo (n=11) on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional beta(1)-adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test (diabetic subjects excluded, n=11 for the celiprolol group and n=8 for the placebo group). RESULTS: Insulin sensitivity index (ISI) increased by 33% (P<0.05) in the celiprolol group and by 17% (NS) in the control group. The mean increase in the whole group was 20% [from 68.2+/-11.5 to 81.7+/-10.7 ml/min/kg (mU/l), P<0.05]. No change was found in the total cholesterol level. HDL cholesterol levels increased by 12% (from 0.98+/-0.05 to 1.10+/-0.05 mmol/l, P<0. 005), and HDL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respectively (P<0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P<0.05). At baseline ISI correlated with maximal oxygen uptake (r=0. 65, P<0.0001) and body mass index (r=-0.55, P<0.001). The change in ISI correlated weakly with the improvement in muscle exercise capacity (r=0.53, P<0.05). CONCLUSIONS: Insulin sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating beta1- selective adrenoceptor antagonist, potentiates this effect.

Adrenergic beta-Antagonists↗

Myocardial efficiency during levosimendan infusion in congestive heart failure.

AIMS: Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure. METHODS AND RESULTS: Eight hospitalized patients with New York Heart Association functional class III or IV heart failure received levosimendan or placebo intravenously in a randomized double-blind cross-over study. During steady-state, dynamic positron emission tomography with [11C]acetate was used to assess myocardial oxygen consumption and [15O]H2O to measure myocardial blood flow. Cardiac performance and dimensions were assessed by pulmonary artery catheterization and echocardiography. Compared with healthy volunteers, myocardial oxygen consumption during placebo was elevated in the right ventricle but comparable in the left ventricle. During administration of levosimendan, cardiac output increased by 32% (P = .002) mainly because of higher stroke volume. Coronary, pulmonary, and systemic vascular resistance values were significantly reduced. Mean myocardial blood flow increased from 0.76 to 1.02 mL/min/g (P = .033). Levosimendan was neutral on myocardial oxygen consumption and left ventricular efficiency, but it improved right ventricular mechanical efficiency by 24% (P = .012). CONCLUSIONS: Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle.

Cardiotonic Agents↗

Feasibility of, and success in adopting a low-fat diet in coronary patients.

The aim of this study was to evaluate the feasibility of dietary counselling and the predictability of success in reducing fat intake to less than 20% of total energy in patients with symptomatic coronary heart disease. Forty-seven patients with coronary heart disease attended a 2-week in-house cardiac rehabilitation course with the main emphasis on individual dietary counselling by a nutritionist. Patients were followed up at 3 and 6 months. The dietary data were collected by means of 3-7 days food diaries. Mean fat intake decreased from 33.6 +/- 6.2% to 24.7 +/- 5.5% of total energy intake at 3 months and to 27.0 +/- 6.9% (p < 0.001) at 6 months. Only 13% of the patients were able to reduce their dietary fat intake as recommended. Thus, reduction of > or = 20% was considered a good response, while reduction of < 20% was classified as poor. Forty-seven percent (n = 22) of the patients were good and 53% (n = 25) poor responders. It was not possible to predict the success rate from the baseline data. After a 2-week intensive counselling period at the rehabilitation centre, half of the coronary patients were able to comply with a low-fat diet at home for 6 months. Long-term compliance requires further investigation.

Adult↗

Protein C substitution in sepsis-associated purpura fulminans.

OBJECTIVE: To assess the effect of protein C (PC) substitution on imminent peripheral necroses and overall outcome in patients with sepsis-associated purpura fulminans. DESIGN: Case series. SETTING: Intensive care units of two university hospitals. PATIENTS: A total of 12 patients with purpura fulminans, disseminated intravascular coagulation and imminent peripheral necroses in association with sepsis caused by Neisseria meningitidis (n = 5), Streptococcus pneumoniae (n = 2), Capnocytophaga canimorsus (n = 2), and Staphylococcus aureus (n = 1). In two patients, no pathogens were identified. INTERVENTIONS: Intravenous administration of PC concentrate (100 IU/kg every 6 hrs). In addition, antithrombin III substitution, antimicrobial therapy, hemodynamic support, and mechanical ventilation in all patients and hemodiafiltration in 10 patients. MAIN RESULTS: After the onset of PC, progressive peripheral ischemia was reversed irrespective of the etiology of infection. Laboratory variables reflecting disseminated intravascular coagulation improved rapidly, although the recovery of the platelet count was retarded in the patients who subsequently died. No drug-related adverse events were noted. Amputations were necessary in two patients, and necrotic tips of fingers and toes were macerated in a third. The hospital mortality was 42%. Of the five lethal cases, two were caused by S. pneumoniae, one by N. meningitidis, one by C. canimorsus, and one by an unknown pathogen. CONCLUSIONS: This article provides encouraging results on the use of PC substitution in meningococcal purpura and presents new data on the administration of this drug to patients with septic purpura caused by other bacterial species. By clinical judgment, PC limited the extent of tissue necrosis. The small number of patients does not allow for any conclusions on the potential effect of PC on mortality. A controlled and randomized study with a larger number of patients is needed before any recommendations can be given on the use of PC in sepsis-related purpura fulminans and shock.

APACHE↗

Multimodality MR imaging assessment of myocardial viability: combination of first-pass and late contrast enhancement to wall motion dynamics and comparison with FDG PET-initial experience.

PURPOSE: To combine three magnetic resonance (MR) imaging modalities-dobutamine stress cine, first pass, and late contrast material-enhanced T1-weighted imaging-and to compare the results with 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the assessment of unviable myocardium in coronary artery disease. MATERIALS AND METHODS: Ten patients with multivessel coronary artery disease underwent MR imaging before and 6 months after bypass surgery. Left ventricular cine MR imaging was performed at rest and during dobutamine infusion. Inversion-recovery gradient-echo images were obtained to study myocardial contrast enhancement at first pass and 5 minutes later. FDG PET was performed with orally administered acipimox before surgery. RESULTS: With dobutamine cine MR imaging, unviable myocardium was detected with a sensitivity of 79% and a specificity of 93%; postoperative wall thickening was the standard. First-pass analysis increased these values to 97% and 96%; analysis of late enhancement with T1-weighted imaging, to 62% and 98%. FDG PET had a sensitivity of 81% and a specificity of 86%. CONCLUSION: The combination of first-pass enhancement analysis and wall motion assessment with stress significantly increases the specificity of MR imaging in the detection of unviable sectors.

Aged↗

Prediction of short-term outcome in patients with suspected myocardial infarction.

STUDY OBJECTIVE: Although specific cardiac injury markers have enhanced early patient classification, the ECG remains a necessary investigation in the acute phase of chest pain. Combined use of both tests could further improve the diagnostic and prognostic accuracy. METHODS: We studied 311 consecutive patients who came to the emergency department of a regional referral hospital for the differential diagnosis of acute chest discomfort. The admission ECG was classified using an automated interpretation program and tested together with elevated admission creatine kinase isoform MB (CK-MB) and cardiac troponin I (TnI) concentration for prediction of final myocardial injury (44%) and in-hospital mortality (14%). RESULTS: Combining the information from the admission ECG and cardiac markers, the sensitivity for becoming final myocardial injury (maximal CK-MB >/=11 microg/L) was 90% and specificity 61%. The proportion of false-negative results (10%) was independent of symptom duration. Age, positive ECG findings, and increased admission TnI levels were predictive for in-hospital mortality. CONCLUSION: The commonly available biochemical and ECG criteria allow risk stratification of patients with a suspected acute ischemic event. The data analysis can easily be automated and is independent of patient delay.

Adult↗