Pulsatile Perfusion Research Articles

Complete Myogenic Differentiation of Adipogenic Stem Cells Requires Both Biochemical and Mechanical Stimulation.

Vascular tissue engineering of the middle layer of natural arteries requires contractile smooth muscle cells (SMC) which can be differentiated from adipose-derived mesenchymal stem cells (ASC) by treatment with transforming growth factor-β, sphingosylphosphorylcholine and bone morphogenetic protein-4 (TSB). Since mechanical stimulation may support or replace TSB-driven differentiation, we investigated its effect plus TSB-treatment on SMC orientation and contractile protein expression. Tubular fibrin scaffolds with incorporated ASC or pre-differentiated SMC were exposed to pulsatile perfusion for 10days with or without TSB. Statically incubated scaffolds served as controls. Pulsatile incubation resulted in collagen-I expression and orientation of either cell type circumferentially around the lumen as shown by alpha smooth muscle actin (αSMA), calponin and smoothelin staining as early, intermediate and late marker proteins. Semi-quantitative Westernblot analyses revealed strongly increased αSMA and calponin expression by either pulsatile (12.48-fold; p < 0.01 and 38.15-fold; p = 0.07) or static incubation plus TSB pre-treatment (8.91-fold; p < 0.05 and 37.69-fold; p < 0.05). In contrast, contractility and smoothelin expression required both mechanical and TSB stimulation since it was 2.57-fold increased (p < 0.05) only by combining pulsatile perfusion and TSB. Moreover, pre-differentiation of ASC prior to pulsatile perfusion was not necessary since it could not further increase the expression level of any marker.

Perioperative-, Recipient-, and Donor-Related Factors Affecting Delayed Graft Function in Kidney Transplantation.

Delayed graft function is a frequent complication in deceased-donor kidney transplant, with an incidence ranging from 10% to 50% among different centers; it is also associated with lower graft survival. In this study, we aimed to identify risk factors for delayed graft function, particularly those associated with perioperative management (including cold ischemia time) and nonmodifiable recipient- and donor-related factors. The effects of delayed graft function on graft and patient outcomes were also evaluated. Our retrospective analyses included 125 adult patients who underwent deceased-donor kidney transplant. Delayed graft function was diagnosed if at least 1 dialysis treatment was required during the first week posttransplant according to Perico's definition. Prevalence of delayed graft function was 30.4% (n = 38). Cold ischemia time was significantly prolonged in patients with delayed graft function compared with those without it. Multivariate regression showed that cold ischemia time was the only predictor of delayed graft function. A cutoff of 9 hours and 12 minutes was found as a limit beyond which delayed graft function occurred (sensitivity = 90%; specificity = 29%; area under the curve = 0.68). Greater donor and recipient age and longer pretransplant dialysis time in recipients were associated with occurrence of delayed graft function. In patients with delayed graft function, hospital stay duration was significantly greater and 1-year graft survival was significantly lower. Efforts should be focused on limiting cold ischemia time and associated injury to reduce occurrence of delayed graft function and consequently improve long-term graft survival in kidney transplant recipients. Optimization of posttransplant renal function with the help of new technologies, such as pulsatile perfusion, could be crucial for minimization of cold ischemia time.

A feasibility study of a multimodal stimulation bioreactor for the conditioning of stem cell seeded cardiac patches via electrical impulses and pulsatile perfusion.

Ischemic heart disease is a major cause of mortality worldwide. Myocardial tissue engineering aims to create transplantable units of myocardium for the treatment of myocardial necrosis caused by ischemic heart disease - bioreactors are used to condition these bioartificial tissues before application. Our group developed a multimodal bioreactor consisting of a linear drive motor for pulsatile flow generation (500ml/min) and an external pacemaker for electrical stimulation (10mA, 3V at 60Hz) using LinMot-Talk Software to synchronize these modes of stimulation. Polyurethane scaffolds were seeded with 0.750 × 106 mesenchymal stem cells from umbilical cord tissue per cm2 and stimulated in our system for 72h, then evaluated. After conditioning histology showed that the patches consisted of a cell multilayer surviving stimulation without major damage by the multimodal stimulation, scanning electron microscopy showed a confluent cell layer with no cell-cell interspaces visible. No cell viability issues could be identified via Syto9-Propidium Iodide staining. This bioreactor allows mechanical stimulation via pulsatile flow and electrical stimulation through a pacemaker. Our stem cell-polyurethane constructs displayed survival after conditioning. This system shows feasibility in preliminary tests.

Hemodynamic energy during pulsatile extracorporeal circulation using flexible and rigid arterial tubing: a reassessment

Pulsatile extracorporeal circulation may improve organ perfusion during cardiac surgery. Some minimally invasive extracorporeal circulation (MiECC) systems allow pulsatile perfusion. The present study investigated the influence of arterial tubing compliance on hemodynamic energy transfer into the patient. Aortic models with adult human geometry were perfused in a mock circulation. A MiECC system was connected using either high-compliance silicone tubing or standard kit tubing. Energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) were computed from flow and pressure data. Aortic models with physiological and sub-physiological compliance were tested to assess the influence of the pseudo-patient. Non-pulsatile flow did not generate SHE. SHE during pulsatile flow in the compliant aortic model was significantly higher with kit tubing compared to silicone tubing. Maximum SHE was achieved at 1.6 L/min with kit tubing (7.7% of mean arterial pressure) and with silicone tubing (4.9%). Using the low-compliance aortic model, SHE with kit tubing reached a higher maximum of 14.2% at 1.8 L/min compared to silicone tubing (11.8% at 1.5 L/min). Flexible arterial tubing did not preserve more hemodynamic energy from a pulsatile pump compared to standard kit tubing in a model of adult extracorporeal circulation. The pseudo-patient's compliance significantly affected the properties of the mock circulation.

A Comparative Study of Single and Dual Perfusion During End-ischemic Subnormothermic Liver Machine Preservation

BackgroundIt remains controversial if arterial perfusion in addition to portal vein perfusion during machine preservation improves liver graft quality. Comparative studies using both techniques are lacking. We studied the impact of using single or dual machine perfusion of donation after circulatory death rat livers. In addition, we analyzed the effect of pulsatile versus continuous arterial flow.MethodsDonation after circulatory death rat livers (n = 18) were preserved by 6 hours cold storage, followed by 1 hour subnormothermic machine perfusion (20°C, pressure of 40/5 mm Hg) and 2 hours ex vivo warm reperfusion (37°C, pressure of 80/11 mm Hg, 9% whole blood). Machine preservation was either through single portal vein perfusion (SP), dual pulsatile (DPP), or dual continuous perfusion (DCP) of the portal vein and hepatic artery. Hydrodynamics, liver function tests, histopathology, and expression of endothelial specific genes were assessed during 2 hours warm reperfusion.ResultsAt the end of reperfusion, arterial flow in DPP livers tended to be higher compared to DCP and SP grafts. However, this difference was not significant nor was better flow associated with better outcome. No differences in bile production or alanine aminotransferase levels were observed. SP livers had significantly lower lactate compared to DCP, but not DPP livers. Levels of Caspase-3 and tumor necrosis factor-α were similar between the groups. Expression of endothelial genes Krüppel-like-factor 2 and endothelial nitric oxide synthase tended to be higher in dual perfused livers, but no histological evidence of better preservation of the biliary endothelium or vasculature of the hepatic artery was observed.ConclusionsThis study shows comparable outcomes after using a dual or single perfusion approach during end-ischemic subnormothermic liver machine preservation.

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia-reperfusion autotransplant model.

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia-reperfusion autotransplant model. The left kidney of an approximately 40-kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22-hour static cold storage (SCS) (n = 6), (2) 22-hour hypothermic machine perfusion (HMP) (n = 6), (3) 22-hour oxygenated HMP (n = 7), (4) 20-hour HMP plus 2-hour normothermic perfusion (NP) (n = 6), (5) 20-hour SCS plus 2-hour oxygenated HMP (n = 7), and (6) 20-hour SCS plus 2-hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end-ischemic strategies. The active oxygenated 22-hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22-hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.

Hypothermic pulsatile perfusion of human pancreas: Preliminary technical feasibility study based on histology

BackgroundThere are currently two approaches to hypothermic preservation for most solid organs: static or dynamic. Cold storage is the main method used for static storage (SS), while hypothermic pulsatile perfusion (HPP) and other machine perfusion-based methods, such as normothermic machine perfusion and oxygen persufflation, are the methods used for dynamic preservation. HPP is currently approved for kidney transplantation. MethodsWe evaluated, for the first time, the feasibility of HPP on 11 human pancreases contraindicated for clinical transplantation because of advanced age and/or history of severe alcoholism and/or abnormal laboratory tests. Two pancreases were used as SS controls, pancreas splitting was performed on 2 other pancreases for SS and HPP and 7 pancreases were tested for HPP. HPP preservation lasted 24 h at 25 mmHg. Resistance index was continuously monitored and pancreas and duodenum histology was evaluated every 6 h. ResultsThe main finding was the complete absence of edema of the pancreas and duodenum at all time-points during HPP. Insulin, glucagon and somatostatin staining was normal. Resistance index decreased during the first 12 h and remained stable thereafter. Conclusion24 h hypothermic pulsatile perfusion of marginal human pancreas-duodenum organs was feasible with no deleterious parenchymal effect. These observations encourage us to further develop this technique and evaluate the safety of HPP after clinical transplantation.

Pulsatile Perfusion Bioreactor for Biomimetic Vascular Impedances

Pulsatile waves of blood pressure and flow are continuously augmented by the resistance, compliance, and inertance properties of the vasculature, resulting in unique wave characteristics at distinct anatomical locations. Hemodynamically generated loads, transduced as physical signals into resident vascular cells, are crucial to the maintenance and preservation of a healthy vascular physiology; thus, failure to recreate biomimetic loading in vitro can lead to pathological gene expression and aberrant remodeling. As a generalized approach to improve native and engineered blood vessels, we have designed, built, and tested a pulsatile perfusion bioreactor based on biomimetic impedances and a novel five-element electrohydraulic analog. Here, the elements of an incubator-based culture system were formulaically designed to match the vascular impedance of a brachial artery by incorporating both the inherent (systemic) and added elements of the physical system into the theoretical approach. Freshly harvested porcine saphenous veins were perfused within a physiological culture chamber for 6 h and the relative expression of seven known mechanically sensitive remodeling genes analyzed using the quantitative polymerase chain reaction (qPCR) method. Of these, we found plasminogen activator inhibitor-1 (SERPINE1) and fibronectin-1 (FN1) to be highly sensitive to differences between arterial- and venous-like culture conditions. The analytical approach and biological confirmation provide a framework toward the general design of long-term hemodynamic-mimetic vascular culture systems.

Analysis of blood flow energy characteristics of pulsatile and non-pulsatile flow during extracorporeal circulation

Objective: To analyze the magnitude of blood flow energy and characteristics of frequency domain between pulsatile flow and nonpulsatile flow during cardiopulmonary bypass and physiological flow. Methods: From January 2017 to December 2017, 60 cases of patients with mitral valve disease scheduled for mitral valve replacement or repair at Department of Cardiasurgery, Shanghai Chest Hospital, Shanghai Jiaotong University were randomly divided into 2 groups: pulsatile perfusion (PP) and non-pulsatile perfusion (NP). The magnitude of blood flow energy during pulsatile and non-pulsatile was calculated using energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) while fast Fourier transformation (FFT) was used to perform power spectral density analysis to identify the frequency domain characteristics between artificial and physiological flow (prior to CPB). The data was analyzed by analysis of variance or t test. Results: At the different time-points after occlusion, the EEP and SHE in PP group were respectively 1.52 to 1.62 and 2.03 to 2.22 times higher than NP at the distal of artery filter. The power density analysis revealed that the blood flow energy of physiological pulsatile flow patterns was within 40 Hz and the ratio of low frequency energy was more than 90% before clamp. The spectral energy ratio of low frequency decreased in both group compared with physiological flow was more obvious in NP group at the radial artery. The ratio of estimated value of power density of PP and NP groups analysis showed the corresponding 0 to 5 Hz, 0 to 10 Hz, 0 to 40 Hz frequency range values measured at the radial artery and filter were 9.51, 4.68, 3.59 and 3.87, 2.69, 2.38 respectively after occulusion. In each frequency range, the energy of PP is higher than that of NP, and the lower the frequency, the greater the difference. The ratio of estimated value of power density of PP and NP groups for the three frequencies measured at the radial artery before and after occlusion were 2.86, 2.83, 2.75 and 14.70, 12.74, 9.85 respectively, and decreased significantly in NP group and low frequency energy. The ratio of estimated value of power density of PP and NP groups under the three different frequencies measured at the radial artery and filter were 26.35, 33.15, 37.36 and 37.41, 54.18, 56.64 respectively, in the conduction process from filter to radial artery, energy exhaustion is significant, especially in group NP. Conclusions: The PP provides significantly more energy than the NP whereby the PP is closer to the physiological pulsatile on the energy frequency structure and attenuation characteristics, with mainly low frequency energy of 0 to 5 Hz and weak energy attenuation. The energy loss of non-pulsatile flow is obvious, especially the low frequency energy.

The outcome of pediatric patients undergoing congenital cardiac surgery under pulsatile cardiopulmonary bypass in different frequencies.

PurposeTo investigate the influence and possible pathophysiological mechanism of pulsatile cardiopulmonary bypass (CPB) in various frequencies in pediatric patients undergoing congenital cardiac surgery.Patients and methodsClinical data and hemodynamic parameters were collected in 80 patients who underwent congenital cardiac surgeries and were perfused in different settings: pulsatile perfusion (PP) in frequencies of 30 beats/min, PP 60 beats/min, PP 100 beats/min and non-pulsatile perfusion (NP). Serum proteins, plasma-free hemoglobin (PFH), endothelin-1 (ET-1) and nitric oxide (NO) were collected to study possible pathophysiological changes, possible hematological injury and oxidative status under different perfusing conditions.ResultsPatients in all groups had similar baseline characteristics, aortic cross-clamping time and CPB duration. More effective pulse gradient (PG), energy-equivalent pressure (EEP) and surplus hemodynamic energy (SHE) were observed in pulsatility with lower frequency setting, under which more patients achieved physiologically normal mean arterial pressure (MAP), without the support of inotropic agents during bypass. Significant between-group differences of serum proteins and PFH were absent the whole time during and after bypass, while a relatively lower percentage of perioperative requirement of diuretics was observed in the low frequency pulsatile group. A better performance to oxidative stress was seen in the low frequency group with higher levels of NO and lower concentration of ET-1, and both intergroup differences were found (P<0.01). Satisfactory clinical outcome was obtained on post procedure course in all groups.ConclusionPulsatile perfusion with low frequency setting in pediatric patients undergoing congenital cardiac surgery showed better hemodynamic profiles, potential protective effects on vital organs, better oxidative status and satisfactory clinical outcome.

Pancreas preservation by pulsatile hypothermic machine perfusion

Pancreas preservation by pulsatile hypothermic machine perfusion

BOP02-8 - The impact of non-pulsatile perfusion on cerebral blood flow and brain oxygenation

Pulsatile perfusion on cardiopulmonary bypass (CPB) is frequently recommended to enhance brain protection (1). Its impact on cerebral blood flow's (CBF) CO2 reactivity and brain oxygenation, however, has not been systematically investigated yet.

CORM-401 Reduces Ischemia Reperfusion Injury in an Ex Vivo Renal Porcine Model of the Donation After Circulatory Death.

Carbon monoxide (CO) inhalation protects organ by reducing inflammation and cell death during transplantation processes in animal model. However, using CO in clinical transplantation is difficult due to its delivery in a controlled manner. A manganese-containing CO releasing molecules (CORM)-401 has recently been synthesized which can efficiently deliver 3 molar equivalents of CO. We report the ability of this anti-inflammatory CORM-401 to reduce ischemia reperfusion injury associated with prolonged cold storage of renal allografts obtained from donation after circulatory death in a porcine model of transplantation. To stimulate donation after circulatory death condition, kidneys from large male Landrace pig were retrieved after 1 hour warm ischemia in situ by cross-clamping the renal pedicle. Procured kidneys, after a brief flushing with histidine-tryptophan-ketoglutarate solution were subjected to pulsatile perfusion at 4°C with University of Wisconsin solution for 4 hours and both kidneys were treated with either 200 μM CORM-401 or inactive CORM-401, respectively. Kidneys were then reperfused with normothermic isogeneic porcine blood through oxygenated pulsatile perfusion for 10 hours. Urine was collected, vascular flow was assessed during reperfusion and histopathology was assessed after 10 hours of reperfusion. We have found that CORM-401 administration reduced urinary protein excretion, attenuated kidney damage markers (kidney damage marker-1 and neutrophil gelatinase-associated lipocalin), and reduced ATN and dUTP nick end labeling staining in histopathologic sections. CORM-401 also prevented intrarenal hemorrhage and vascular clotting during reperfusion. Mechanistically, CORM-401 appeared to exert anti-inflammatory actions by suppressing Toll-like receptors 2, 4, and 6. Carbon monoxide releasing molecules-401 provides renal protection after cold storage of kidneys and provides a novel clinically relevant ex vivo organ preservation strategy.

Does Acute Kidney Injury Contraindicate Transplantation of Kidneys from very Small Pediatric Donors? Single-center Analysis of 68 en Bloc Kidney Transplants from Donors ≤15 kg

Background Kidneys from very small pediatric donors that have acute kidney injury (AKI) are frequently discarded due to concerns about the potentially negative effects of the AKI on short- and long-term outcomes. We tested the hypothesis that AKI does not adversely impact outcomes of en bloc kidney grafts from very small donors. Patients and Methods We defined AKI as terminal donor creatinine [mg/dL] ≥1.5 for donors 0-14 days old and ≥1.0 for donors >14 days old. Among 219 pediatric en bloc kidney transplants from donors ≤15 kg performed 11/2003-01/2015 at our institution, we identified 29 AKI grafts and pair-matched these (for donor weight, DCD setting [7%], and preservation time) with 29 no-AKI grafts (median overall recipient age, 50.3 [7-76] years). Our standard management protocol for en bloc grafts includes hypothermic pulsatile perfusion pre-implantation, rATG induction, and steroid-free maintenance with tacrolimus and mycophenolate mofetil. Results Donor and preservation characteristics are given in Table 1. Delayed graft function (dialysis during the first week posttransplant) was more frequent in AKI (48%) vs. no-AKI (14%) grafts (p=0.01). Early graft loss from graft thrombosis or primary non-function occurred for 3 (10%) AKI vs. 2 (7%) no-AKI grafts (p=n.s.). At 1 and 5 years, neither death-censored graft survival (Figure 1) nor graft function (Table 2) were significantly affected by donor AKI.Conclusions Despite the slower early function in the AKI group, long-term survival and function of en bloc grafts from small (≤15 kg) donors were were not impacted by donor AKI. Our outcomes suggest (i) that AKI in small pediatric donors should not be viewed as a contraindication to organ donation and (ii) that these donors can effectively expand the limited deceased organ donor pool.

Fabrication of Hydrogel Tubes with Vascular Mimicked Stiffness for Construction of in Vitro Vascular Models.

Stiffness of blood vessels is one of the most important parameters involving in vascular diseases. However, no vascular model well mimics the stiffness of native blood vessels, and thus, the effects of vascular stiffness on endothelial cells cannot be studied in vitro. For this purpose, we fabricated the gelatin/carboxybetaine (CBMA) interpenetrating network (IPN) hydrogel tubes to exactly present the stiffness of soft (i.e., physical) and stiff (i.e., pathological) arteries in human. The vascular models are then constructed via endothelial cell culture inside the gel tubes under a cardiac-like pulsatile perfusion. As found, the velocity magnitude and wall shear stress in the stiff gel tube are much higher than those in the soft one. Correspondingly, the endothelial cells in the soft gel tube (i.e., physical model) express higher vascular functions than those in the stiff one (i.e., pathological model). Moreover, a pathological model was more sensitive to ethanol-induced vascular injury than the physical model. Thus, the new vascular models with a tunable stiffness provide a useful tool to investigate the stiffness involved mechanism in vascular diseases under in vivo mimicked microenvironments.

Perfusion of a Kidney Graft From a Donor After Cardiac Death Based on Immediately Started Pulsatile Machine Perfusion—An Experimental Study on a Small Animal

IntroductionThere is still a lack of organs for kidney transplantation. The aim of our experimental animal study was to improve the quality of the kidney grafts from donors after cardiac death (DCD) using immediate start of machine perfusion instead of perfusion based on hydrostatic pressure. MethodsTen rabbits were used as an experimental model. In group A, 5 kidneys after ischemic injury were perfused in situ using hydrostatic pressure. In group B, 5 kidneys were perfused in situ using machine pulsatile perfusion. After nephrectomy kidney parenchyma was histologically analyzed. We have evaluated the maximum perfusion flow rate, temperature drop rate, and degree of parenchymal injury. ResultsThe flow rate in the group of machine-perfused animals (group B) was significantly higher than in the control group (group A), and temperature was significantly decreased in group B (P < .001). Qualitative histopathologic evaluation of the perfusion quality of the grafts was statistically significant, again in favor of machine perfusion in group B (P = .005). DiscussionAccording to our results, the immediate start of machine perfusion is a superior method of kidney graft preservation in DCDs. All observed modalities were superior in the group with machine perfusion compared with usual clinical practice.

Effect of pulsatile flow perfusion on decellularization

BackgroundDecellularized animal organs have been used as scaffolds for tissue engineering. To make a properly functioning scaffolds, the extracellular matrix (ECM) components must be preserved after decellularization. Because pulsatile flow is known to be beneficial for tissue perfusion, pulsatile perfusion of a detergent might decrease the exposure time of the tissues to the detergent used for decellularization. Using Energy Equivalent Pressure (EEP) as a pulsatility parameter, the effect of pulsatile flow in decellularization process is studied.ResultsTwelve rat hearts were decellularization with 1% sodium dodecyl sulfate (SDS) solution for 2 h. They are divided into two groups, one with pulsatile perfusion (n = 6), the other with non-pulsatile perfusion (n = 6) of SDS. The initial mean perfusion pressures were same in both group. The result indicated that the EEP and the perfusion flow were increased significantly in the pulsatile group compared to the non-pulsatile group. Photographs taken during the decellularization showed more profound decellularization in the pulsatile group. The residual DNA content in the scaffolds was significantly lower in the pulsatile group. However, the level of ECM components, collagen and GAG showed no significant differences between the groups.ConclusionsDecellularization is more efficient in pulsatile flow than in non-pulsatile flow but still preserves the ECM molecules.

Microvascular Responsiveness to Pulsatile and Nonpulsatile Flow During Cardiopulmonary Bypass

Pulsatile perfusion may offer microcirculatory advantages over conventional nonpulsatile perfusion during cardiopulmonary bypass (CPB). Here, we present direct visual evidence of microvascular perfusion and vasoreactivity between perfusion modalities. A prospective, randomized cohort study of 20 high-risk cardiac surgical patients undergoing pulsatile (n= 10) or nonpulsatile (n= 10) flow during CPB was conducted. Changes in sublingual mucosal microcirculation were assessed with orthogonal polarization spectral imaging along with near-infrared spectroscopic indices of thenar muscle tissue oxygen saturation (StO2) and its recovery during a vascular occlusion test at the following time points: baseline (T0), 30 minutes on CPB (T1), 90 minutes on CPB (T2), 1 hour after CPB (T3), and 24 hours after CPB (T4). On the basis of our scoring scale, a shift in microcirculatory blood flow occurred over time. The pulsatile group maintained normal perfusion characteristics, whereas the nonpulsatile group exhibited deterioration in perfusion during CPB (T2: 74.0% ± 5.6% versus 57.6% ± 5.0%) and after CPB (T3: 76.2% ± 2.7% versus 58.9% ± 5.2%, T4: 85.7% ± 2.6% versus 69.8% ± 5.9%). Concurrently, no important differences were found between groups in baseline StO2 and consumption slope at all time points. Reperfusion slope was substantially different between groups 24 hours after CPB (T4: 6.1% ± 0.6% versus 3.7% ± 0.5%), indicating improved microvascular responsiveness in the pulsatile group versus the nonpulsatile group. Pulsatility generated by the roller pump during CPB improves microcirculatory blood flow and tissue oxygen saturation compared with nonpulsatile flow in high-risk cardiac surgical patients, which may reflect attenuation of the systemic inflammatory response and ischemia-reperfusion injury.

Isolated kidney perfusion: the influence of pulsatile flow

Within the scope of transplantation research, ex vivo kidney perfusion has been proven an attractive model to study ischemia-reperfusion and preservation injury. Renal perfusion techniques also occupy scientists with the aim to optimize organ reconditioning and preparation prior to transplantation. This study investigated the influence of a pulsatile perfusion pattern that brings flow conditions closer to physiological situations, on renal perfusion characteristic and kidney function in the isolated perfused kidney. Kidneys were perfused via a roller pump at constant pressure set to 90 mmHg, or with addition of pulsatile pressure peaks (90/70 mmHg; 60/min) using an adjustable positive displacement pump. It was found that pulsatile pressure significantly enhanced renal flow rates as compared to non-pulsatile perfusion mode, especially after preceding preservation of the kidney by static cold storage. The improved vascular conductivity went along with a notable improvement of clearance of creatinine, sodium reabsorption and reduced tubular cell injury (Loss of fatty acid binding protein). The better vascular conductance upon pulsatile perfusion could be attributed to improved endothelial release of nitic oxide and reduced secretion of endothelin-1 into the perfusate. It is concluded, that pulsatile perfusion mode should be preferred in isolated kidney perfusion as resulting in better preservation/recovery of renal perfusion and function.

Functional Results of Renal Preservation in Hypothermic Pulsatile Machine Perfusion Versus Cold Preservation: Systematic Review and Meta-Analysis of Clinical Trials

BackgroundHypothermic pulsatile machine perfusion (HPMP) decreases the rate of delayed graft function (DGF) in kidney grafts, compared with cold storage. However, it is not clear its use in the different subgroups of grafts. The objective was to review systematically all studies with better methodologic quality that compare HPMP versus cold storage. MethodsA systematic review was performed. The sources were Pubmed, Pubmed Central, Cochrane Library, Clinical Key, and Ovid. All randomized controlled trials that compared HPMP versus cold storage in renal grafts from human donors were considered. Outcomes analyzed were: percentage of DGF, primary nonfunction (PNF), and graft function in each group and for the different types of grafts, brain-death donors (DBDs), and different subgroups of donors after circulatory death (DCDs). ResultsTwelve clinical trials, out of 9,867 titles, were included. HPMP improved DGF overall, as well as in DBDs and DCDs. The relative risks [RRs] were 0.79 (95% CI, 0.71–0.88), 0.85 (95% CI, 0.74–0.98), and 0.75 (95% CI, 0.61–0.92), respectively. There were no differences in PNF overall and for DBDs or DCDs. The RRs were 0.92 (95% CI, 0.73–1.16), 0.78 (95% CI, 0.22–2.73), and 1.13 (95% CI, 0.73–1.77), respectively. However, analysis with the better quality studies, overall RR for PNF was 0.62 (95% CI, 0.39–0.96). There were no differences between the graft function at 3 months after transplantation. ConclusionsHPMP moderately improved the DGF results in grafts from cadaver donors of all types. HPMP could improve the PNF in grafts from DBDs, although more clinical trials are needed to prove that.