Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotension, tissue hypoxia, and inflammation despite adequate resuscitation. There is a lack of information concerning the alteration of renal microcirculation and perfusion during shock and resuscitation. The aim of this study was to investigate the possible role of renal microcirculatory alterations on development of renal dysfunction in a pig model of non-traumatic hemorrhagic shock (HS) induced AKI. Fully instrumented female pigs were divided into the two groups as Control (n = 6) and HS (n = 11). HS was achieved by withdrawing blood until mean arterial pressure (MAP) reached around 50 mmHg. After an hour cessation period, fluid resuscitation with balanced crystalloid was started for the duration of 1 h. The systemic and renal hemodynamics, renal microcirculatory perfusion (contrast-enhanced ultrasound (CEUS)) and the sublingual microcirculation were measured. CEUS peak enhancement was significantly increased in HS during shock, early-, and late resuscitation indicating perfusion defects in the renal cortex (p < 0.05 vs. baseline, BL) despite a stable renal blood flow (RBF) and urine output. Following normalization of systemic hemodynamics, we observed persistent hypoxia (high lactate) and high red blood cell (RBC) velocity just after initiation of resuscitation resulting in further endothelial and renal damage as shown by increased plasma sialic acid (p < 0.05 vs. BL) and NGAL levels. We also showed that total vessel density (TVD) and functional capillary density (FCD) were depleted during resuscitation (p < 0.05). In this study, we showed that the correction of systemic hemodynamic variables may not be accompanied with the improvement of renal cortical perfusion, intra-renal blood volume and renal damage following fluid resuscitation. We suggest that the measurement of renal injury biomarkers, systemic and renal microcirculation can be used for guiding to the optimization of fluid therapies.

Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of blood and purposed to cause renal injury in perioperative setting. It is best accomplished in a perioperative setting by a colloid such as hydroxyl ethyl starch (HES) due its capacity to fill the vascular compartment and maintain colloidal pressure. However, alterations of intra renal microvascular perfusion, flow and its effects on renal function and damage during ANH has not been sufficiently clarified. Based on the extensive use of HES in the perioperative setting we tested the hypothesis that the use of HES during ANH is able to perfuse the kidney microcirculation adequately without causing renal dysfunction and injury in pigs. Hemodilution (n = 8) was performed by stepwise replacing blood with HES to hematocrit (Hct) levels of 20% (T1), 15% (T2), and 10% (T3). Seven control animals were investigated. Systemic and renal hemodynamics were monitored. Renal microcirculatory perfusion was visualized and quantified using contrast-enhanced ultrasound (CEUS) and laser speckle imaging (LSI). In addition, sublingual microcirculation was measured by handheld vital microscopy (HVM). Intrarenal mean transit time of ultrasound contrast agent (IRMTT-CEUS) was reduced in the renal cortex at Hct 10% in comparison to control at T3 (1.4 ± 0.6 vs. 2.2 ± 0.7 seconds, respectively, P < 0.05). Although renal function was preserved, the serum neutrophil gelatinase-associated lipocalin (NGAL) levels was higher at Hct 10% (0.033 ± 0.004 pg/μg protein) in comparison to control at T3 (0.021 ± 0.002 pg/μg protein. A mild correlation between CO and IRMTT (renal RBC velocity) (r -0.53; P = 0.001) and CO and NGAL levels (r 0.66; P = 0.001) was also found. Our results show that HES induced ANH is associated with a preserved intra renal blood volume, perfusion, and function in the clinical range of Hct (<15%). However, at severely low Hct (10%) ANH was associated with renal injury as indicated by increased NGAL levels. Changes in renal microcirculatory flow (CEUS and LSI) followed those seen in the sublingual microcirculation measured with HVM.

Objective: The speed of pressure pulses traveling through the blood, the pulse wave velocity (PWV), is a metric that provides substantial information about the passive and active elasticity of the blood vessels. Therefore, PWV is a valuable parameter in the diagnosis of cardiovascular and vessel-related neurological diseases. The purpose of this study was to investigate whether a novel, simple, easy-to-use, photoplethysmography-based Multi Photodiode Array (MPA) provides PWV measurements that agree with measurements done with more complicated and harder-to-use systems currently used in clinical practice. Methods: An often-used vascular perturbation that changes the conduit artery vasomotor tone during reactive hyperemia was imposed on thirty healthy volunteers. The MPA was used alongside and its results compared to those of a commonly used measurement device, the Biopac-system, during flow-mediated dilation (FMD). This way it was investigated if measurements with these systems, measuring over two different, but partly overlapping vessel trajectories agree. Results: The baseline absolute PWV values were significantly lower for the MPA as compared to the Biopac-system. Additionally, Bland-Altman plots and Pearson's correlation tests suggested good agreement between the two PWV measurement techniques during the FMD. Conclusion: Measuring PWV with the MPA in clinical practice is feasible and provides reliable data. Significance: The MPA may substantially simplify PWV measurements and may enable long-term PWV monitoring as long as one is aware of the relation between PWV and the vascular trajectory over which it is measured.

Arterial stiffness is a reliable prognostic parameter for cardiovascular diseases. The effect of change in arterial stiffness can be measured by the change of the pulse wave velocity (PWV). The Complior system is widely used to measure PWV between the carotid and radial arteries by means of piezoelectric clips placed around the neck and the wrist. The Biopac system is an easier to use alternative that uses ECG and simple optical sensors to measure the PWV between the heart and the fingertips, and thus extends a bit more to the peripheral vasculature compared to the Complior system. The goal of this study was to test under various conditions to what extent these systems provide comparable and correlating values. 25 Healthy volunteers, 20–30 years old, were measured in four sequential position: sitting, lying, standing and sitting. The results showed that the Biopac system measured consistently and significantly lower PWV values than the Complior system, for all positions. Correlation values and Bland–Altman plots showed that despite the difference in PWV magnitudes obtained by the two systems the measurements did agree well. Which implies that as long as the differences in PWV magnitudes are taken into account, either system could be used to measure PWV changes over time. However, when basing diagnosis on absolute PWV values, one should be very much aware of how the PWV was measured and with what system.

The multiphotodiode array (MPA) is a novel transmission photoplethysmography (PPG) sensor to measure pulse wave velocity (PWV) in the finger. To validate the MPA, a setup was built to generate a red laser dot traveling over the MPA with known and constant scanning velocities. These scanning velocities were chosen to include speeds at least twice as high as those found in the normal range of PWV in healthy populations and were set at 12.9, 25.8, 36, or 46.7 m/s. The aim of this study was to verify the functionality of the MPA: performing local noninvasive PWV measurements. To illustrate the applicability of the MPA in clinical practice, an in vivo pilot study was conducted using the flow-mediated dilation (FMD) technique. The in vitro accuracy of the MPA was ±0.2%, 0.3%, 0.5%, and 0.6% at the applied scanning velocities. The MPA can measure PWVs with a maximum deviation of 3.0%. The in vivo pilot study showed a PWV before the FMD of 1.1±0.2 m/s. These results suggest that this novel MPA can reliably and accurately measure PWV within clinically relevant ranges and even well beyond.

Photoplethysmography (PPG) is a widely available non-invasive optical technique to visualize pressure pulse waves (PWs). Pulse transit time (PTT) is a physiological parameter that is often derived from calculations on ECG and PPG signals and is based on tightly defined characteristics of the PW shape. PPG signals are sensitive to artefacts. Coughing or movement of the subject can affect PW shapes that much that the PWs become unsuitable for further analysis. The aim of this study was to develop an algorithm that automatically and objectively eliminates unsuitable PWs. In order to develop a proper algorithm for eliminating unsuitable PWs, a literature study was conducted. Next, a ‘7Step PW-Filter’ algorithm was developed that applies seven criteria to determine whether a PW matches the characteristics required to allow PTT calculation. To validate whether the ‘7Step PW-Filter’ eliminates only and all unsuitable PWs, its elimination results were compared to the outcome of manual elimination of unsuitable PWs. The ‘7Step PW-Filter’ had a sensitivity of 96.3% and a specificity of 99.3%. The overall accuracy of the ‘7Step PW-Filter’ for detection of unsuitable PWs was 99.3%. Compared to manual elimination, using the ‘7Step PW-Filter’ reduces PW elimination times from hours to minutes and helps to increase the validity, reliability and reproducibility of PTT data.