Role Of Pulsatility Research Articles

Loss of pulsatility with continuous-flow left ventricular assist devices and the significance of the arterial endothelium in von-Willebrand factor production and degradation.

Patients on continuous flow ventricular assist devices (CF-VADs) are at high risk for the development of Acquired von-Willebrand Syndrome (AVWS) and non-surgical bleeding. von Willebrand Factor (vWF) plays an essential role in maintaining hemostasis via platelet binding to the damaged endothelium to facilitate coagulation. In CF-VAD patients, degradation of vWF into low MW multimers that are inefficient in facilitating coagulation occurs and has been primarily attributed to the supraphysiological shear stress associated with the CF-VAD impeller. In this review, we evaluate information from the literature regarding the unraveling behavior of surface-immobilized vWF under pulsatile and continuous flow pertaining to: (A) the process of arterial endothelial vWF production and release into circulation, (B) the critical shear stress required to unravel surface bound versus soluble vWF which leads to degradation, and (C) the role of pulsatility in on the production and degradation of vWF. Taken together, these data suggests that the loss of pulsatility and its impact on arterial endothelial cells plays an important role in the production, release, unraveling, and proteolytic degradation of vWF into low MW multimers, contributing to the development of AVWS. Restoration of pulsatility can potentially mitigate this issue by preventing AVWS and minimizing the risk of non-surgical bleeding.

How well do we understand pulsatility in the context of modern ventricular assist devices?

Modern ventricular assist devices (VADs) use a continuous flow design. It has been suggested that a lack of pulsatility contributes to a range of adverse outcomes including pump thrombus, gastrointestinal bleeding and stroke. To better assess the role of pulsatility in these adverse events, we first require a clear definition of 'pulsatility' in the setting of a severely impaired ventricle and a modern continuous flow VAD. A literature review was conducted to elucidate the understanding of pulsatility in modern VAD literature. Search engines used included PUBMED, EMBASE and the Cochrane library. Articles were appraised on three aspects: Whether they mentioned pulsatility; whether they mentioned which pulsatility measure was used and finally which methodology was used to obtain the value. Of 354 articles reviewed, only 13 met our broad inclusion criteria. Of these articles, the most cited measure was pulsatility index (PI) - used by 11 of the publications. The methodology used to obtain the value was not uniform and five articles did not clearly state it. Other measures included pulse pressure and surplus haemodynamic energy. The majority of articles did not directly discuss pulsatility in the setting of patient-pump interaction. Most publications did not provide a definition for pulsatility. In those that did, the most common measure was PI. Measuring PI was not standardised. Few papers addressed the impact of intrinsic ventricular function and arterial compliance on pulsatility. We suggest that future publications adopt a uniform definition which encompasses both patient and pump characteristics.

Heart transplantation and mechanical circulatory support.

Dr. O.P. Yadava, CEO and Chief Cardiac Surgeon, National Heart Institute, New Delhi, India, and Editor-in-Chief, Indian Journal of Thoracic and Cardiovascular Surgery, in conversation with Dr. Vivek Rao, Chief of Cardiovascular Surgery, Peter Munk Cardiac Centre, University of Toronto, discusses donation after circulatory death, role of pulsatility in mechanical circulatory support (MCS) and current status of MCS versus heart transplant as a destination therapy.

Fluid structure interaction model analysis of cerebrospinal fluid circulation in patients with continuous-flow left ventricular assist devices.

The current 1-dimensional fluid structure interaction model (FSI) for understanding cerebrospinal fluid (CSF) circulation requires pulsatility as a precondition and has not been applied to patients with continuous-flow left ventricular assist devices (CF-LVAD) where pulsatility is chronically reduced. Our study aims to characterize the behavior of CSF pressure and flow in patients with CF-LVADs using a computational FSI model. Utilizing the computational FSI model, CSF production in choroid plexuses of the 4 ventricles was specified as a boundary condition for the model. The other source of production from capillary ultrafiltrate spaces was accounted for by the mass conservation equation. The primary CSF absorption sites (i.e., arachnoid granulations) were treated as the outlet boundary conditions. We established a low pulse wave to represent patients with a CF-LVAD. From the model, low pulse conditions resulted in a reduction in CSF pressure amplitude and velocity though the overall flow rate was unchanged. The existing FSI model is not a suitable representation of CSF flow in CF-LVAD patients. More studies are needed to elucidate the role of pulsatility in CSF flow and the compensatory changes in CSF production and absorption that occur in patients with CF-LVADs in whom pulsatility is diminished.

Role of Pulsatility in Hypothermic Reconditioning of Porcine Kidney Grafts by Machine Perfusion After Cold Storage

Brief in-house machine perfusion after cold storage (CS) (hypothermic reconditioning) has been proposed as a convenient tool to improve kidney graft function. The present study aimed to investigate the mechanistic role of vascular pulsatility in this context. Kidney function after cold preservation (4°C, 18 hr) and subsequent reconditioning by 90 min of pulsatile machine perfusion (PP) (30/20 mm Hg) or nonpulsatile machine perfusion (NPP) (30 mm Hg) was studied in an isolated kidney perfusion model in pigs (n=6 for both) and compared with simply CS grafts. Compared with CS, PP but not NPP significantly improved renal perfusate flow and urine production and significantly increased the reduction of perfusate levels of creatinine and urea during reperfusion. Perfusate levels of fatty acid binding protein, a marker of tubular cell injury, were dramatically reduced by PP but not NPP. PP and NPP lowered fractional excretion of sodium, but significance was only reached for PP. Molecular effects of PP comprised a significant (vs. CS) mRNA elevation of the endothelial anti-inflammatory transcription factor Krüppel-like factor 2 as well as endothelial nitric oxide synthase, along with significantly higher perfusate levels of the endogenous vasodilator nitric oxide. Functional efficiency of PP over CS was confirmed in additional porcine transplant experiments (n=5 for both) by, for example, up to threefold improved clearance of creatinine during the first days after transplantation. PP of 90 min shortly before transplantation seems to be an efficient mechanism to reduce proinflammatory endothelial phenotype and improve functional outcome of kidney grafts even after preceding static storage.

Numerical Evaluation and Experimental Validation of Pressure Drops Across a Patient-Specific Model of Vascular Access for Hemodialysis

In this work we investigated the possibility to predict the pressure drops across a patient-specific arterio-venous fistula (AVF) by means of an open-source hemodynamics solver aimed at convection-dominated incompressible flows. To account for the very high flow rates that develop in AVFs we considered a wide range of steady input flow conditions (corresponding to Reynolds numbers 100, 200, 550, 1000, 1500, and 2000), and compared with experiments for over 200 flow rates, up to Reynolds 2000. Three meshes for the numerical model, based on a micro-CT acquisition of the in vitro silicon model, were generated, in order to perform a h-refinement study and assess the mesh density allowing to correctly estimate the losses across the anastomosis. For the sake of validation, in addition to pressure assessment, the velocity solutions for Re 550 and 1000 were compared with particle image velocimetry (PIV) acquisitions. Once the solver was validated we also simulated pulsatile input flow conditions to investigate the role of pulsatility in predicting pressure drops. When the finer grid is considered almost all the experimental values for the pressure drop vs. flow measurements are within the standard deviation range of the numerical pressure drops. For the PIV validation, a good agreement is observed between in vitro data and numerical results. The ability to simulate unstable convection-dominated flows in complex 3D geometries is demonstrated and more insight is obtained about the non-common physiological flow conditions induced by fistula creation.

4D flow measurements in the superior cerebellar artery at 7 Tesla: feasibility and potential for applications in patients with trigeminal neuralgia

Background Trigeminal Neuralgia is characterized by episodic severe facial pain possibly the result of “pulsatile” compression of the nerve Root Entry Zone (REZ) of the Trigeminal Nerve (TN) by the adjacent superior cerebellar artery (SCA). The exact role of pulsatility of SCA remains unknown and currently no methods are available to measure the pulsatility of the SCA. Herein we investigate the feasibility of measuring blood flow and the Pulsatility Index (PI) within SCA and within the nearby posterior cerebral artery (PCA) using 4D-flow in a normal volunteer at 7T.

A nonpulsatile total artificial heart with 1/R control

A total artificial heart (TAH) using continuous flow pumps is promising for size reduction of the device; however, the role of pulsatility in TAHs has been a subject of great debate. Additionally, it is unclear whether, in a nonpulsatile TAH, a physiological control method such as 1/R control can keep the experimental animal in good condition. To realize a nonpulsatile TAH with 1/R control, the artificial valves were removed from undulation pump total artificial hearts (UPTAHs), which can produce both pulsatile and nonpulsatile flows using a single device. The UPTAHs were implanted into 18 goats, and 4 goats survived for more than 1 month. Three weeks of long-term nonpulsatile TAH operation could be tested in the goat that survived for 72 days, and it was proved that 1/R control is possible not only with a pulsatile TAH but also with a nonpulsatile TAH. The general condition of the goat and its organ function did not change on the application of nonpulsatile mode. Cardiac output and arterial pressure changed with the condition of the goat in pulsatile and also in nonpulsatile modes, and the changes seemed almost identical. However, the sucking effect of the atria was very significant in nonpulsatile mode, resulting in hemolysis. Therefore, nonpulsatile TAHs under 1/R control are considered to be inadequate unless some pulsatility can be introduced to avoid fatal sucking effects and to ensure sufficient inflow. During nonpulsatile operation, regular fluctuations were sometimes found in the aortic pressure, and these were caused by the periodic sucking effect in the left atrium that was possibly influenced by respiratory changes.

The role of pulsatility in end-organ microcirculation after cardiogenic shock.

To estimate the effectiveness of pulsatility in end-organ microcirculation after cardiogenic shock, experimental studies using swine were done. Cardiogenic shock was produced in 14 pigs by ligating the left anterior descending branches so that mean aortic pressure dropped to 60% of the control value. After inducing shock, left atrial to ascending Ao bypass was initiated. A pneumatic pulsatile pump (Zeon Medical Inc, Tokyo, Japan) was used in seven pigs (Group P) and a centrifugal pump (BP-80, BioMedicus Inc, Minneapolis, MN) in seven (Group NP). In both groups, about half the usual cardiac output was supported for 3 hr, maintaining mean aortic pressure at approximately 100 mm Hg. The pulse pressure was 36.6 +/- 4.6 mm Hg in Group P, and 14.3 +/- 1.5 mm Hg in Group NP. Epicardial and endocardial regional flows recovered after assist in both groups. There were no significant differences between the two groups. However, liver tissue flow, renal cortex flow, and stomach mucous flow in Group P was significantly higher than those of Group NP after support (p < 0.05). In addition, arterial blood ketone ratio in Group P was 0.61 +/- 0.13 vs 0.39 +/- 0.06 in Group NP, a significant difference (p < 0.05). These results suggest that in uneven blood flow distribution of end organs after cardiogenic shock, pulsatility was effective in improving and maintaining function and microcirculation of end organs, preventing multiorgan failure.

The Role of Pulsatility in End Organ Microcirculation after Cardiogenic Shock

The Role of Pulsatility in End Organ Microcirculation after Cardiogenic Shock

The Role of Pulsatility in End Organ Microcirculation after Cardiogenic Shock

The Role of Pulsatility in End Organ Microcirculation after Cardiogenic Shock

Pulsatile and steady flow induces c‐fos expression in human endothelial cells

The effects of pulsatile and steady fluid flow on the mRNA levels of proto-oncogenes c-fos, c-jun, and c-myc in cultured human umbilical vein endothelial cells (HUVEC) were investigated. c-fos mRNA levels in stationary cultures were very low. A 1 Hz pulsatile flow with an average shear stress of 16 dynes/cm2 induced a dramatic increase of c-fos mRNA levels in HUVEC 0.5 h after the onset of flow, which declined rapidly to basal levels within 1 h. Steady flow with a similar shear stress also induced a transient increase of c-fos mRNA levels, but to a lesser extent. In addition, increased c-fos mRNA levels were observed when low shear (2-6 dynes/cm2) was replaced by high shear (16-33 dynes/cm2). Pulsatile and steady flow caused a slight increase of c-jun and c-myc mRNA levels. The role of pulsatility was also investigated in platelet-derived growth factor (PDGF) expression. Pulsatile flow induced a transient increase of PDGF A- and B-chain mRNA levels with peaks at 1.5-2 h. Pulsatile flow, which was more stimulatory in mediating c-fos expression, however, was less stimulatory than steady flow in mediating PDGF expression. By using various inhibitors, protein kinase C was found to be an important mediator in flow-induced c-fos expression, with the involvement of G proteins, phospholipase C, and intracellular calcium. Protein kinase C was previously shown as a possible major mediator in flow-induced PDGF expression which, at least partly, appeared to follow the induction mechanism of c-fos, suggesting a possible connection between c-fos and PDGF induction. However, the c-fos antisense treatment, which significantly inhibited c-fos transcription, failed to block the flow-induced PDGF expression, suggesting that flow-induced c-fos expression may not play an important role in the mechanism of flow-induced PDGF expression. The difference in the induction of c-fos and PDGF expression under pulsatile as compared to steady flow indicates that a complex, flow-mediated regulatory mechanism of gene expression exists in HUVEC. The increased expression of these proto-oncogenes mediated by flow may be important in regulating long-term cellular responses.