The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1 +/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end-systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although G(pi) can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate.
Transgenic mice offer a valuable way to relate gene products to phenotype, but the ability to assess the cardiovascular phenotype with pressure-volume analysis has lagged. Conductance measurement offers a method to generate an instantaneous left ventricular (LV) volume signal in the mouse but has been limited by the volume signal being a combination of blood and LV muscle. We hypothesized that by developing a mouse conductance system that operates at several simultaneous frequencies, we could identify and correct for the myocardial contribution to the instantaneous volume signal. This hypothesis is based on the assumption that mouse myocardial conductivity will vary with frequency, whereas mouse blood conductivity will not. Consistent with this hypothesis, we demonstrated that at higher excitation frequency, greater end-diastolic and end-systolic conductance are detected, as well as a smaller difference between the two. We then empirically solved for LV blood volume using two frequencies. We combined measured resistivity of mouse myocardium with an analytic approach and extracted an estimate of LV blood volume from the raw conductance signal. Development of a multifrequency catheter-based system to determine LV function could be a tool to assess cardiovascular phenotype in transgenic mice.
Background:
Recent randomized trials demonstrated the efficacy of endovascular therapy (EVT) in managing acute ischemic stroke (AIS), though EVT was initiated <6 hours from time last seen well in nearly all patients, and posterior circulation strokes were excluded. Current data is limited for patients receiving EVT >6 hours, and more so for those with posterior circulation strokes. We aim to assess safety and clinical outcome of EVT in patients presenting >6 hours, with anterior or posterior circulation strokes.
Methods:
We conducted a retrospective review of patients with AIS receiving EVT >6 hours between 2012-2015, including those with unknown time of onset and wake-up strokes. Outcomes observed include mRS at ≥90 days, rates of recanalization (TICI 2b-3), sICH and mortality.
Results:
A total of 34 patients were identified presenting with AIS and receiving EVT >6 hours, including 25 anterior and 9 posterior circulation strokes. See Table 1 for comparison with published data from recent EVT trials.
Conclusion:
Our results are not significantly different from some of the recent trials. MR CLEAN, the only trial that did not employ advanced imaging in patient selection, had similar outcomes. The IV-tPA only groups of recent trials (where data is available) also produced comparable results. It should be noted that the patients in our study all have large vessel occlusions and high NIHSS, are mostly ineligible for tPA, and thus would be expected to have very poor outcomes without treatment. Our data supports the possibility of expanding the EVT window to >6 hours, and with advanced imaging screening, better rates of functional outcome/mortality may still be achieved. DAWN and DEFUSE3 trials currently underway should provide further insight into this subject.
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