Distinguishing core from penumbra by lipid profiles using Mass Spectrometry Imaging in a transgenic mouse model of ischemic stroke.

Detecting different lipid profiles in early infarct development may give an insight on the fate of compromised tissue. Here we used Mass Spectrometry Imaging to identify lipids at 4, 8 and 24 hours after ischemic stroke in mice, induced by transient middle cerebral artery occlusion (tMCAO). Combining linear transparency overlay, a clustering pipeline and spatial segmentation, we identified three regions: infarct core, penumbra (i.e. comprised tissue that is not yet converted to core), and surrounding healthy tissue. Phosphatidylinositol 4-phosphate (m/z = 965.5) became visible in the penumbra 24 hours after tMCAO. Infarct evolution was shown by 2D-renderings of multiple phosphatidylcholine (PC) and Lyso-PC isoforms. High-resolution Secondary Ion Mass Spectrometry, to evaluate sodium/potassium ratios, revealed a significant increase in sodium and a decrease in potassium species in the ischemic area (core and penumbra) compared to healthy tissue at 24 hours after tMCAO. In a transgenic mouse model with an enhanced susceptibility to ischemic stroke, we found a more pronounced discrimination in sodium/potassium ratios between penumbra and healthy regions. Insight in changes in lipid profiles in the first hours of stroke may guide the development of new prognostic biomarkers and novel therapeutic targets to minimize infarct progression.

Left ventricular mass is associated with ventricular repolarization heterogeneity one year after renal transplantation.

Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR > or =60 mL/min/1.73 m(2) (248 +/- 61 g and 86% vs. 210 +/- 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R(2)= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R(2)= 0.10; p = 0.034), and QTRR (R = 0.55; R(2)= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function.

The responses of glabrous and nonglabrous skin microcirculation to graded dynamic exercise and its recovery.

This study investigated the responses of skin blood flow (SkBF) in glabrous and nonglabrous skin to graded submaximal dynamic exercise and its recovery. We enrolled eight healthy young men with comparable maximal oxygen uptake (VO2max). Laser-Doppler flux (LDF) was assessed on the finger pulp (glabrous site) and the volar forearm (nonglabrous site) simultaneously with skin temperature, heart rate and blood pressure; cutaneous vascular conductance (CVC) was calculated. Subjects were monitored before (baseline), during and 25 minutes after incremental cycling. CVC in the pulp decreased with the onset of exercise (0.53±0.09AUmmHg-1 vs. baseline 1.23±0.25AUmmHg-1, p = 0.006), and persisted low until exercise cessation, whereas CVC in the forearm started to increase at 60% of subjects' VO2max, attaining its maximum at the highest exercise load (0.44±0.11AUmmHg-1 vs. baseline 0.12±0,03AUmmHg-1, p = 0.017). In the recovery, CVC in the pulp attained a higher plateau value compared to baseline (1.51±0.22AUmmHg-1, p = 0.021), interrupted by abrupt transient falls of CVC. On the forearm, CVC subsequently returned to its baseline. SkBF of glabrous and nonglabrous sites adjust in an opposite manner to graded exercise load and also differ during recovery.

The reversible displacement of the passive diastolic p-V curve in the isolated guinea pig left ventricle.

We studied viscoelastic behaviour of the isolated diastolic guinea pig left ventricle (LV), manifested in changes of the hysteresis loop of the pressure-volume (p-V) diagram, produced by acute volume loading. Specifically, we investigated how the width of the hysteresis depends on the way LV volume loading, and whether changes in the hysteresis width are reversible. Each of 11 LV was instrumented with a catheter for injection and withdrawal of saline, and a micromanometer (Millar, 2F) to measure LV pressure. LV were loaded by the computer controlled injection of saline in 6-8 sequential injection steps of 100 microl each with a pause of 5 s, followed by a similar withdrawal pattern. In protocol A (N = 5), a 100 microl higher maximal LV volume (LVVmax) was reached during injection than in the control run, and in protocol B (N = 6), the time spent at LVVmax was longer (20 vs. 5 s pause). In both protocols a reproducible displacement of the passive p-V curve during volume unloading was observed, reflected in the increase of the hysteresis width by 23+/-8% in protocol A, and 12+/-3% in protocol B. Reversible displacement of the passive diastolic p-V curve after large aperiodic volume change suggests participation of reversible phenomena, like extracellular fluid filtration, and may in part provide an answer to the phenomenon of preconditioning.

Non-invasive beat-to-beat determination of changes in the small artery compliance after smoking.

We investigated the response of the small arterial compliance on smoking in 5 occasional smokers before, during and after inhaling the first cigarette in the day. For this purpose we used a non-invasive method based on interpretation of the oscillometric signal from the finger cuff coupled to the signal from photoplethysmograph. This system enables on-line determination of the finger artery compliance as function of transmural pressure (p(tm)) between 0 and 120 mm Hg, where each heart beat is presented by a set of compliance values in the range of the pulse pressure reduced by the cuff pressure. This procedure allowed construction of time course of the arterial compliance. When comparing the compliance value at ptm of 40 mm Hg, we found its fluctuations around the steady value during the rest and immediate lowering of the compliance after smoking, accompanied by the increase of blood pressure and heart rate.

Relaxation of epicardial strains after volume changes in the isolated guinea pig left ventricle.

Cardiac muscle is a porous viscoelastic material, exhibiting stress relaxation and hysteresis after being passively stretched. We investigated whether these material properties are also manifested in relaxation of epicardial segment lengths of the passive diastolic left ventricle (LV). For this purpose LV pressure and biaxial epicardial strains were measured simultaneously in isolated guinea pig hearts, arrested in diastole and instrumented to manipulate LV volume. Our study confirmed the existence of epicardial strain relaxation in both axial and circumferential directions, though it was much less expressed than LV pressure relaxation. Since the volume calculated from the segment lengths also revealed relaxation phenomena, our findings suggest that epicardial strain relaxation was connected with exchange of fluid from the LV cavity into the tightened epicardial vessels and back and not with the transformation of the LV shape.