Highly Sensitive Cardiac Troponins: The Evidence Behind Sex-Specific Cutoffs.

Emergence of various highly sensitive cardiac troponin assays into clinical practice provides a new tool for clinicians diagnosing acute coronary syndrome. These assays also create a challenge for laboratories and clinicians who have yet to familiarize themselves with sex-specific cutoffs. Healthy men and women, studied across various age groups and geographic locations, have notable differences in baseline values of highly sensitive cardiac troponin I and T, leading to establishment of sex-specific upper reference limits and cutoffs. Several differences in cardiac physiology, size, and structure may account for baseline differences in highly sensitive cardiac troponins and outcomes between the sexes. The clinical utility of implementing sex-specific cutoffs for diagnosis and management of acute coronary syndrome remains unclear. Presently, the only prospective study failed to show improved outcomes for men or women with use of sex-specific cutoffs; however, a major limitation is the frequent lack of diagnostic, therapeutic, and preventive interventions prescribed to women with low-level troponin elevations. Based on the current literature, we posit that there may nonetheless be clinical value in the use of sex-specific cutoffs for evaluating suspected acute coronary syndrome, especially in select patient populations such as younger women who tend to have lower baseline values of highly sensitive cardiac troponins. Future studies should prospectively evaluate differences in diagnostic, pharmacologic, and interventional management in men and women using myocardial infarctions classified with sex-specific cutoffs of the highly sensitive cardiac troponin assays.

A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain Injury.

Blast-induced traumatic brain injury (bTBI) is the "signature" injury of the recent Iraq and Afghanistan wars. Here, we present a novel method to induce bTBI using shock wave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N = 70; 408.3 ± 93 g) received five SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into three study endpoints: 24 h (n = 25), 72 h (n = 19) and 168 h (n = 26). Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod, and elevated plus maze) were performed at the baseline, and further assessments followed at 3, 6, 24, 72, and 168 h post-injury, if applicable. We performed digital subtraction angiography (DSA) to assess presence of cerebral vasospasm due to induced bTBI. Damage to brain tissue was assessed by an overall histological severity (OHS) score based on depth of injury, area of hemorrhage, and extent of axonal injury. Except for beam walking, OHS was significantly correlated with the other three outcome measures with at least one of their assessments during the first 6 h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 h post-injury (r(baseline) = -0.75, r(6hrs) = 0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (p<0.01). In this study, we successfully established a preclinical rat model of bTBI with characteristics similar to those observed in clinical cases. This new method may be useful for future investigations aimed at understanding bTBI pathophysiology.

Elevated blood pressure causes larger hematoma in a rat model of intracerebral hemorrhage.

Hypertension has been recognized as an independent risk factor for intracerebral hemorrhage (ICH). The objective of this study was to assess the effect of chronically elevated blood pressure on amount of hematoma in a rat model of ICH. A total of 46 rats were divided into two groups-normotensive group (n = 18) and spontaneously hypertensive group (n = 28). To induce ICH, we delivered 2 µL of collagenase solution (0.1 U/1 µL normal saline) into the striatum. Each animal's brain was removed 24 h post-surgery for spectrophotometric hemoglobin assay. Equal or unequal variance t tests were performed to assess changes in variables between the hypertensive and normotensive groups. Tissue analysis revealed a statistically significant difference in optical density percent change at 540-nm wavelength for the hypertensive vs. the normotensive group (261.47 ± 103.68 and 133.33 ± 58.53, p < 0.0001, respectively). As compared to the normotensive rats, hypertensive rats exhibited a higher neurological deficit, loss of balance and coordination, and loss of motor function. Our results demonstrated that hypertensive rats had significantly higher amounts of hemorrhage in comparison to normotensive ones. These findings support the need for further adequately powered studies to investigate differences in amount of hematoma and corresponding functional impairments due to ICH among hypertensive vs. normotensive rats.