Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Short-term effects of nicardipine and propranolol on ocular and systemic hemodynamics in healthy Japanese subjects.

Ocular perfusion is a critical factor in ischemic ocular diseases, and blood flow in the ophthalmic artery has a pronounced effect on perfusion. To evaluate the effects of dihydropyridine calcium channel blocker and nonselective beta-adrenergic antagonist on ocular perfusion, we investigated the short-term effects of single oral doses of nicardipine (40 mg) and propranolol (40 mg) on the blood flow velocity in the ophthalmic artery, intraocular pressure (IOP), systemic blood pressure, and heart rate in nine healthy Japanese male volunteers in a double-blind, placebo-controlled study using color Doppler imaging. Parameters were evaluated before and 60 and 120 minutes after administration. Nicardipine significantly increased the maximum systolic velocity and time-averaged blood flow velocity compared with placebo without significant increase in the resistance index. Propranolol had no significant effects on Doppler parameters. Propranolol exhibited a great reduction in IOP from placebo values. Systolic blood pressure and heart rate were significantly reduced by propranolol. Nicardipine significantly increased heart rate. These results suggest that nicardipine increased ophthalmic blood flow, but propranolol did not.

Ophthalmic artery flow velocity after physical exercise in healthy men.

This study was conducted to evaluate the effects of physical exercise on blood flow velocity in the ophthalmic artery of healthy men. Color Doppler imaging, which permits rapid noninvasive imaging of the ophthalmic artery, was performed in 11 healthy male adult volunteers to compare pre- and post-exercise measurements of blood flow velocity. After submaximal physical exercise, systolic blood flow velocity (Vmax) and time-averaged blood flow velocity (Vmean) increased significantly, but returned to pre-exercise levels 5-10 minutes after the completion of physical exercise. There were no significant changes in minimum end-diastolic blood flow velocity (Vmin), resistance index (RI) or pulsatility index (PI). The RI and PI parameters are considered to reflect vascular resistance. Our results indicate that submaximal physical exercise increased the blood flow velocity, but did not alter the resistance index of the ophthalmic artery.

[The variability of blood velocity in the ophthalmic artery with color Doppler imaging].

Non-invasive measurements of blood velocities of the ophthalmic artery (BVA) in color Doppler imaging (CDI) are increasingly used to assess the influence of disease on the hemodynamics of the eye. Such measurements are only valid when compared to spontaneous variability. Therefore, the aim of this study was to examine the variability of BVA in healthy subjects. Within-a-day short-term variability was assessed from measurements obtained during one day from 5 healthy young male subjects as the coefficient of variation (CV) of 10 consecutive measurements. Between-days variability was assessed by comparing measurements made on three different days at one month intervals. The left and right BVA were measured five consecutive times to evaluate the difference in BVA between left and right eyes in 5 healthy young male subjects. In the within-a-day variability, mean CV in maximum systolic BVA (V max), minimum end diastolic BVA (V min), time-averaged BVA (V mean), resistive index (RI), and pulsatility index (PI) were found to be 6.6%, 14.0%, 14.9%, 3.2%, and 17.4%, respectively. The between-days variability was just as high as the within-a-day variability. There was significant difference in BVA between left and right eyes in two of the five subjects. We concluded that the within-a-day variability and the between-days variability of BVA measured using CDI are reproducible. The CDI can be used to assess the influence of disease and drugs on the hemodynamics of the eye.

Electrical stimulation prolongs the survival days of leukemic mice treated with methotrexate.

To investigate effects of electrical stimulation on survival days of leukemic mice treated with methotrexate (MTX), L1210-bearing mice were treated by MTX and calcium folinate (leucovorin) rescue therapy (MTX: 400 mg/kg, followed by leucovorin at the dose of 7.5 mg/kg at 8, 15 and 24 hr after MTX) under electrical stimulation (foot shock: shock amplitude, 0.4 mA; voltage, 60-100 V/cm; shock duration, 5 sec; frequency, 0.5 Hz) of various lengths. The survival days were significantly prolonged by 6-hr electrical stimulation in combination with MTX, while plasma MTX concentrations and pharmacokinetic parameters such as the area under the curve (AUC-12 hr) and clearance (CL) were not significantly altered. Psychological stress did not alter the efficacy of MTX in the communication box paradigm. Amplified efficacy of MTX was shown in a length-dependent manner when electrical stimulation of various lengths were applied to L1210-bearing mice.