Impact of Pulsatile Perfusion on Clinical Outcomes of Neonates and Infants With Complex Pathologies Undergoing Cardiopulmonary Bypass Procedures

The aim of this clinical trial was to evaluate the pulsatile perfusion mode in pediatric patients who had complex cardiac pathologies according to Jenkins stratifications (category 4) undergoing cardiopulmonary bypass procedures (CPB). Patients with transposition of great arteries (TGA) and ventricular septal defect (VSD) were included in this clinical study. Eighty‐nine consecutive pediatric patients undergoing open heart surgery for repair of TGA‐VSD were prospectively entered into the study and were randomly assigned to either the pulsatile perfusion group (Group P, n = 58) or the nonpulsatile perfusion group (Group NP, n = 31). There were no differences between groups in terms of demographical and intraoperative parameters. The pulsatile group needed significantly less inotropic support (P < 0.05) and had lower lactate levels (P < 0.001), higher urine output (P < 0.01), and higher albumin levels (P < 0.05). In addition, the pulsatile group had less ICU (P < 0.01) and hospital stays (P < 0.001). We conclude that the use of pulsatile flow is a better option and should be considered for repair of the complex congenital heart defects.     

New Technology Mimics Physiologic Pulsatile Flow During Cardiopulmonary Bypass

The Ventri Flo True Pulse Pump (Design Mentor, Inc., Pelham, NH, USA) is the first blood pump designed to mimic human arterial waveforms in a standard oxygenation circuit. Our aim was to demonstrate the feasibility and safety of this pump in preparation for future studies to determine possible clinical advantages. We studied four piglets (41.4–46.2 kg): three with an implanted Ventri Flo pulsatile pump and one with the nonpulsatile ROTAFLOW pump (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) as a control. Hemodynamics was monitored during 6‐h cardiopulmonary bypass (CPB) support and for 2 h after weaning off CPB. The Ventri Flo demonstrated physiologic arterial waveforms with arterial pulse pressure of 24.6 ± 5.7 mm Hg. Pump flows (2.0 ± 0.1 L/min in ROTAFLOW; 1.9 ± 0.1 L/min in Ventri Flo ) and plasma free hemoglobin levels (27.9 ± 12.5 mg/dL in ROTAFLOW; 28.5 ± 14.2 mg/dL in Ventri Flo ) were also comparable, but systemic O₂ extraction (as measured by arterial minus venous O₂ saturation) registered slightly higher with the Ventri Flo (63.2 ± 6.9%) than the ROTAFLOW (55.4 ± 6.5%). Histological findings showed no evidence of ischemic changes or thromboembolism. This pilot study demonstrated that the Ventri Flo system generated pulsatile flow and maintained adequate perfusion of all organs during prolonged CPB.     

Effects of Pulsatile Assistance and Nonpulsatile Flow on Subendocardial Perfusion During Cardiopulmonary Bypass

We compared the effects of pulsatile and nonpulsatile perfusion in 12 dogs on extracorporeal circulation. In beating empty and fibrillating hearts at 37° and 28°, coronary blood flow was measured by flowmeter and microspheres at diastolic pressures ranging between 50 and 130 mm Hg.At fixed systemic flow rates (range, 600 to 2,400 ml/min), pulsatile perfusion produced a transient (3 to 4 second) augmentation of diastolic pressure and then resulted in the following: (1) decreased peripheral vascular resistance (p < 0.05); (2) unchanged peak diastolic pressure (compared with nonpulsatile perfusion); (3) decreased mean aortic pressure (6 to 37%) (p < 0.05); (4) decreased coronary blood flow (10 to 45%) (p < 0.05); and (5) decreased subendocardial blood flow (from 512 to 438 ml/100 gm/min) (p < 0.05). Pulsatile perfusion in beating hearts (37° or 28°) did not reduce subendocardial vascular resistance, but did improve subendocardial perfusion by 27% and 36% in fibrillating hearts at 37° and 28°, respectively.We conclude that with the exception of ventricular fibrillation, pulsatile assistance offers no advantage over nonpulsatile perfusion and has the potential disadvantage of requiring higher pump flow rates to achieve any desired level of coronary and subendocardial flow.     

Gaseous Micro‐Emboli Activity During Cardiopulmonary Bypass in Adults: Pulsatile Flow Versus Nonpulsatile Flow

Cardiopulmonary bypass (CPB) has a risk of cerebral injury, with an important role of gaseous micro‐emboli (GME) coming from the CPB circuit. Pulsatile perfusion is supposed to perform specific conditions for supplementary GME activity. We aimed to determine whether pulsatile CPB augments production and delivery of GME and evaluate the role of different events in GME activity during either type of perfusion. Twenty‐four patients who underwent on‐pump coronary artery bypass grafting surgery at the University of Verona were divided equally into two groups—pulsatile perfusion (PP) group and nonpulsatile perfusion (NP) group. The circuit included a JostraHL‐20 roller pump set in pulsatile or nonpulsatile mode, an open Sorin Synthesis membrane oxygenator with integrated screen‐type arterial filter, and phosphorylcholine‐coated tubes. Hemodynamic flow evaluation was performed in terms of energy equivalent pressure and surplus hemodynamic energy (SHE). GME were counted by means of a GAMPT BCC200 bubble counter (GAMPT, Zappendorf, Germany) with two probes placed at postpump and postarterial filter positions. Results were evaluated in terms of GME number, GME volume, number of over‐ranged GME from both probes, and series of filtering indexes. In PP mode, the pump produced and delivered along the circuit significantly higher amounts of SHE than in NP mode. At the venous postpump site, GME number was significantly higher during PP but no difference was found in terms of GME volume or number of over‐ranged bubbles. No significant difference in GME number, GME volume, or number of over‐ranges was found at the postarterial filter site. Filtering indexes were similar between the two groups. Neither type of perfusion was shown to contribute to excessive GME production during the most important perfusionist manipulation. Pulsatility leads to GME increment by splitting and size diminishing of the existing bubbles but not by additional gas production. PP augmented GME number at the venous postpump site, while mean volume remained comparable with NP. Sorin Synthesis oxygenator showed high efficacy in GME removal during either type of perfusion. Supplementary GME production and delivery during typical perfusionist manipulations did not depend on perfusion type.     

The Renin-Angiotensin-Aldosterone System and Hematologic Changes During Pulsatile and Nonpulsatile Cardiopulmonary Bypass

Abstract: The effects of pulsatile and nonpulsatile cardiopulmonary bypass using a roller pump on levels of vasoactive hormones and hematologic changes were studied in 32 patients subjected to elective primary coronary artery bypass graft surgery. Seventeen patients had nonpulsatile perfusion (nonpulsatile group) and 15 patients had pulsatile perfusion (pulsatile group) during the period of cardiac arrest. Vasoactive hormones (plasma renin, angiotensin II, aldosterone, epinephrine, and norepinephrine) were measured in these patients. In order to clarify hematologic changes, plasma free hemoglobin, number of platelets, platelet factor 4, and β -thromboglobulin were measured. There were no significant differences between the pulsatile and nonpulsatile groups with regard to vasoactive hormones and damage of platelets. In the pulsatile group, however, the rise of plasma free hemoglobin levels was significantly higher than that in the nonpulsatile group during and after cardiopulmonary bypass. We did not see the benefit of pulsatile perfusion using a roller pump on vasoactive hormones. Evidence of increased hemolysis with pulsatile flow was demonstrated in our cases.     

Prevention of Remote Organ Injury in Cardiopulmonary Bypass: The Impact of Flow Generation Technique

Abstract: The purpose of this study was to investigate the effects of 3 different types of flow generation for cardiopulmonary bypass on gastrointestinal permeability and on neutrophil expression of CD11b, a surface marker of neutrophil activation. Fourteen patients undergoing elective coronary revascularization were selected randomly to receive 1 of the 3 flow generation techniques (roller, pulsatile, or centrifugal). Intestinal permeability was assessed by the fraction of an oral dose of ⁵¹chromium-ethylenedi-aminetetraacetate (⁵¹Cr-EDTA) recovered in the urine over 24 h. Neutrophil activation was determined by expression of CD11b markers at 6 time points. Overall, the 14 patients showed significant increases in intestinal permeability. It was not possible to demonstrate statistically significant differences among the flow generation groups: however, when compared to both roller pump groups, the centrifugal pump group showed a 3.2% reduction in intestinal permeability. There was no change in the expression of CD11b receptors throughout the time points, nor was there a relationship of CD11b markers to the flow generation technique.     

Pulse Conductance and Flow‐induced Hemolysis During Pulsatile Cardiopulmonary Bypass

In this study, the hypothesis was tested that a low‐resistant, high‐compliant oxygenator provides better pulse conductance and less hemolysis than a high‐resistant, low‐compliant oxygenator during pulsatile cardiopulmonary bypass. Forty adults undergoing coronary artery bypass surgery were randomly divided into two groups using either an oxygenator with a relatively low hydraulic resistance (Quadrox BE‐HMO 2000, Maquet Cardiopulmonary AG, Hirrlingen, Germany) or with a relatively high hydraulic resistance (Capiox SX18, Terumo Cardiovascular Systems, Tokyo, Japan). The phase shift between the flow signals measured at the inlet and outlet of the oxygenator was used to assess compliance. Pulse conductance in terms of pressure attenuation was calculated by dividing the outlet pulse pressure of the oxygenator by the inlet pulse pressure. A normalized index was used to assess hemolysis. The phase shifts in time of the flow pulses were 36 ± 6 ms in the low‐resistant (high‐compliant) oxygenator, and 14 ± 2 ms in the high‐resistant (low‐compliant) oxygenator group (P < 0.001). The low‐resistant, high‐compliant oxygenator provided 27% better pulse conductance compared with the high‐resistant, low‐compliant oxygenator (0.84 ± 0.02 and 0.66 ± 0.01, respectively, P < 0.001). Inlet pulse pressures were significantly higher (29%) in the high‐resistant, low‐compliant (Capiox) group than in the low‐resistant, high‐compliant (Quadrox) group (838 ± 38 mm Hg and 648 ± 25 mm Hg respectively, P < 0.001), but no significant difference in hemolysis was found. A low‐resistant, high‐compliant oxygenator provides better pulse conduction than a high‐resistant, low‐compliant oxygenator. However, the study data could not confirm the association of high pressures with increased hemolysis.     

Impact of Distinct Oxygenators on Pulsatile Energy Indicators in an Adult Cardiopulmonary Bypass Model

The quantification of pulse energy during cardiopulmonary bypass (CPB) post‐oxygenator is required prior to the evaluation of the possible beneficial effects of pulsatile flow on patient outcome. We therefore, evaluated the impact of three distinctive oxygenators on the energy indicators energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) in an adult CPB model under both pulsatile and laminar flow conditions. The pre‐ and post‐oxygenator pressure and flow were measured at room temperature using a 40% glycerin‐water mixture at flow rates of 1, 2, 3, 4, 5, and 6 L/min. The pulse settings at frequencies of 40, 50, 60, 70, and 80 beats per minute were according to the internal algorithm of the Sorin CP5 centrifugal pump. The EEP is equal to the mean pressure, hence no SHE is present under laminar flow conditions. The Quadrox‐i Adult oxygenator was associated with the highest preservation of pulsatile energy irrespective of flow rates. The low pressure drop–high compliant Quadrox‐i Adult oxygenator shows the best SHE performance at flow rates of 5 and 6 L/min, while the intermediate pressure drop–low compliant Fusion oxygenator and the high pressure drop–low compliant Inspire 8F oxygenator behave optimally at flow rates of 5 L/min and up to 4 L/min, respectively. In conclusion, our findings contributed to studies focusing on SHE values post‐oxygenator as well as post‐cannula in clinical practice. In addition, our findings may give guidance to the clinical perfusionist for oxygenator selection prior to pulsatile CPB based on the calculated flow rate for the individual patient.     

Flow Distribution During Cardiopulmonary Bypass in Dependency on the Outflow Cannula Positioning

Oxygen deficiency in the right brain is a common problem during cardiopulmonary bypass (CPB). This is linked to an insufficient perfusion of the carotid and vertebral artery. The flow to these vessels is strongly influenced by the outflow cannula position, which is traditionally located in the ascending aorta. Another approach however is to return blood via the right subclavian artery. A computational fluid dynamics (CFD) study was performed for both methods and validated by particle image velocimetry (PIV). A 3‐dimensional computer aided design model of the cardiovascular (CV) system was generated from realtime computed tomography and magnetic resonance imaging data. Mesh generation (CFD) and rapid prototyping (PIV) were used for the further model creation. The simulations were performed assuming usual CPB conditions, and the same boundary conditions were applied for the PIV validation. The flow distribution was analyzed for 55 cannula positions inside the aorta and in relation to the distance between the cannula tip and the vertebral artery branch for subclavian cannulation. The study reveals that the Venturi effect due to the cannula jet appears to be the main reason for the loss in cerebral perfusion seen clinically. It provides a PIV‐validated CFD method of analyzing the flow distribution in the CV system and can be transferred to other applications.     

Preservation of Endothelium Nitric Oxide Release by Pulsatile Flow Cardiopulmonary Bypass When Compared With Continuous Flow

The aim of this work is to analyze endothelium nitric oxide (NO) release in patients undergoing continuous or pulsatile flow cardiopulmonary bypass (CPB). Nine patients operated under continuous flow CPB, and nine patients on pulsatile flow CPB were enrolled. Plasma samples were withdrawn for the chemiluminescence detection of nitrite and nitrate. Moreover the cellular component was withdrawn for the detection of nitric oxide synthase (NOS) activity in the erythrocytes, and an estimation of systemic inflammatory response was carried out. Significant reduction in the intraoperative concentration with respect to the preoperative was observed only under continuous flow CPB for both nitrite and NO_x (nitrite + nitrate) concentration (P = 0.010 and P = 0.016, respectively). Significant difference in intraoperative nitrite concentration was also observed between the groups (P = 0.012). Finally, erythrocytes showed a certain endothelial NOS activity, which did not differ between the groups, and no differences in the inflammatory response were pointed out. The significant reduction of NO₂^‐ concentration under continuous perfusion revealed the strong connection among perfusion modality, endothelial NO release, and plasmatic nitrite concentration. The similar erythrocyte eNOS activity between the groups revealed that the differences in blood NO metabolites are mainly ascribable to the endothelium release.     

Comparative Effects of Pulsatile and Nonpulsatile Flow on Plasma Fibrinolytic Balance in Pediatric Patients Undergoing Cardiopulmonary Bypass

In the brain, the components of the fibrinolytic system, tissue plasminogen activator (tPA) and its endogenous inhibitor plasminogen activator inhibitor‐1 (PAI‐1), regulate various neurophysiological and pathological responses. Fibrinolytic balance depends on PAI‐1 and tPA concentrations. The objective of this study is to compare the effects of pulsatile and nonpulsatile perfusion on fibrinolytic balance in children undergoing pediatric cardiopulmonary bypass (CPB). Plasma PAI‐1 antigen and tPA antigen were measured in 40 children (n = 20 pulsatile and n = 20 nonpulsatile group). Plasma samples (1.5 mL) were collected (i) prior to incision, (ii) 1 h after CPB, and (iii) 24 h after CPB. PAI‐1 and tPA levels were measured at each time point. PAI‐1 and tPA levels were significantly increased at 1 h after CPB, followed by a decrease at 24 h. Nonpulsatile but not pulsatile CPB lowered PAI‐1 : tPA ratio significantly at 24 h (median PAI‐1 : tPA ratio 4.63 ± 0.83:1.98 ± 0.48, P = 0.03, for the nonpulsatile group and 4.50 ± 0.92:3.56 ± 1.28, P = 0.2, for the pulsatile group). These results suggest that pulsatile flow maintains endogenous fibrinolytic balance after pediatric cardiopulmonary bypass. Further studies are needed to define the clinical significance of these differences.     

体外循环中搏动和非搏动灌注对皮肤微循环自律运动的影响

关于体外循环期间应用搏动灌注的优点，一直有很大的争议。本实验旨在观察体外循环中搏动灌注和非搏动灌注对皮肤微循环自律运动和氧代谢的影响。观察对象是１５例心脏瓣膜病人。当病人温度平稳时，分别以２．４Ｌ·ｍｉｎ~（－１）／ｍ~２的流量进行搏动灌注和非搏动灌注。搏动灌注的参数为：基线３０％～４０％、脉宽４０％～５０％、脉冲频率６０次／ｍｉｎ。结果表明：搏动灌注和非搏动灌注对皮肤微循环血流量、微循环自律性运动频率、氧代谢的影响不明显。我们对这一现象进行了分析。并认为搏动灌注在临床应用中，由于多种因素的影响，其优越性难以体现。     

Cytokine and Endothelial Damage in Pulsatile and Nonpulsatile Cardiopulmonary Bypass

Recently, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB). However, according to the results of our experimental studies, after cardiogenic shock, pulsatile flow was effective in maintaining the functions and microcirculations of end organs, especially those of the liver and kidney. To estimate the effectiveness of pulsatility during CPB, cytokine and endothelin and other metabolic parameters were measured in clinical pulsatile and nonpulsatile CPB cases. From March to May 1997, CPB was performed in 18 elective cases (14 ischemic and 4 valvular disease). In 9 cases, pulsatile perfusion was achieved by the Jostra HL20, which is a newly developed CPB pump (Group P). A nonpulsatile centrifugal pump was used in 9 patients (Group NP). In both groups, as chemical and metabolic mediators, interleukin-8 (IL-8), endothelin-1 (ET-1), and plasma free hemoglobin were measured before and during CPB, and 0.5, 3, 6, 9, 18 h after weaning from CPB. This pulsatile CPB pump could be very simply and easily controlled and could easily produce pulsatile flow. There were no significant differences in CPB time (CPBT), aortic cross clamp time (ACCT), mean aortic pressure, or pump flow during CPB between the both groups. The ET-1 level of Group P was significantly (p < 0.05) lower than that of Group NP 9 h after CPB weaning. The IL-8 level of Group P also showed a lower value than that of Group NP. As for plasma free hemoglobin, there were no significant differences between the groups. These results suggested that even in conventional CPB, pulsatility was effective to reduce endothelial damage and suppress cytokine activation. It may play a important role in maintaining the functions and microcirculations of end organs during CPB.     

Plasma Vasopressin Levels and Urinary Sodium Excretion during Cardiopulmonary Bypass with and without Pulsatile Flow

The use of pulsatile perfusion during bypass should create a more physiological milieu and thus attenuate the vasopressin stress response. To determine this, 20 patients scheduled for elective coronary artery bypass operation were studied in two groups. Group 1 had standard nonpulsatile perfusion, and in Group 2 a pulsatile pump was used. Measurements were made before and after anesthesia, after surgical incision, and at 15 and 30 minutes during and after cardiopulmonary bypass.In both groups, vasopressin levels were significantly elevated after sternotomy (4.5 ± 1.5 to 37 ± 10 pg/ml in Group 1 and 3.1 ± 1.2 to 33 ± 9 pg/ml in Group 2, p < 0.05) and during bypass (198 ± 19 pg/ml in Group 1 and 113 ± 16 pg/ml in Group 2) but were higher in Group 1 (p < 0.05). With comparable perfusion pressures in both groups, Group 2 required higher flow (4.5 ± 0.2 versus 3.5 ± 0.3 L/min, p < 0.05) and had lower resistance (1,351 ± 182 versus 1,841 ± 229 dynes sec cm^-5, p < 0.05) and higher urine Na⁺ (123 ± 5 versus 101 ± 8 mEq/L, p < 0.05). These data demonstrate that pulsatile flow can significantly attenuate the vasopressin stress response to bypass. Since vasopressin, at these concentrations, is a potent vasoconstrictor and is capable of producing a Na⁺ diuresis, this may partially explain the higher flow requirements and the decrease in Na⁺ excretion.     

Pulsatile Versus Nonpulsatile Flow: No Difference in Cerebral Blood Flow or Metabolism during Normothermic Cardiopulmonary Bypass in Rabbits

Background: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees Celsius.

Methods: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees Celsius for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees Celsius. At 30 and 60 min of CPB, physiologic measurements were made as before.

Results: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 plus/minus 6 vs. 77 plus/minus 9 ml *symbol* 100 g sup -1 *symbol* min1, respectively (median plus/minus quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 plus/minus 0.5 vs. 4.1 plus/minus 0.6 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min1, respectively) and decreased slightly (0.4 plus/minus 0.4 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min1) between measurements.