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Biomedical subjects

Akif Undar

Publications and source records attributed to Akif Undar.

52 records · Page 3Linked to original sources
PubMedDate not supplied

Effect of hypothermic cardiopulmonary bypass on blood viscoelasticity in pediatric cardiac patients.

The objective of this study was to determine the changes in blood viscoelasticity during and after pediatric cardiopulmonary bypass (CPB) procedures. Twelve pediatric cardiac patients, subjected to hypothermic (22-28 degrees C) CPB procedures were enrolled in this study. Viscosity and elasticity were measured at strains of 0.2, 1.0, and 5.0 using a Vilastic-3 Viscoelasticity Analyzer. Arterial blood samples (1 ml each) were taken before CPB, on normothermic CPB, hypothermic CPB, and 1 and 24 hours after CPB. Compared with the pre-CPB levels (0.0464 +/- 0.007 Poise), viscosity at a strain of 1.0 was significantly lower during normothermic CPB (0.0305 +/- 0.006 Poise, p < 0.01), hypothermic CPB (0.03 +/- 0.0007 Poise, p < 0.01), and 1 hour after CPB (0.0334 +/- 0.006 Poise, p < 0.01). Viscosity at a strain of 1.0 24 hours after CPB (0.0525 +/- 0.01 Poise, p = NS) was slightly higher than pre-CPB levels. Elasticity at a strain of 1.0 was significantly altered during normothermic CPB (0.0016 +/- 0.0007 Poise, p < 0.01), hypothermic CPB (0.0015 +/- 0.0007 Poise, p < 0.01), and 1 hour after CPB (0.0017 +/- 0.0005 Poise, p < 0.01) compared to the pre-CPB levels (0.0048 +/- 0.0001 Poise). Elasticity at a strain of 1.0 24 hours after CPB (0.0068 +/- 0.003 Poise, p = 0.06) was significantly higher compared to the pre-CPB level (0.0048 +/- 0.0001 Poise). Viscoelasticity at strains of 0.2 and 5.0 had patterns similar to those seen with a strain of 1.0. Viscosity and elasticity at strains of 0.2, 1.0, and 5.0 were significantly altered during normothermic and hypothermic CPB and 1 hour after CPB. Viscoelasticity of blood was slightly higher 24 hours after CPB at all strains. Further investigation of the effects of hypothermic CPB on blood viscoelasticity and the outcomes of pediatric cardiac patients are warranted.

Analysis of Variance↗
PubMedDate not supplied

Blood plasma separation in microfluidic channels using flow rate control.

Several studies have clearly shown that cardiac surgery induces systemic inflammatory responses, particularly when cardiopulmonary bypass (CPB) is used. CPB induces complex inflammatory responses. Considerable evidence suggests that systemic inflammation causes many postoperative complications. Currently, there is no effective method to prevent this systemic inflammatory response syndrome in patients undergoing CPB. The ability to clinically intervene in inflammation, or even study the inflammatory response to CPB, is limited by the lack of timely measurements of inflammatory responses. In this study, a microfluidic device for continuous, real-time blood plasma separation, which may be integrated with downstream plasma analysis device, is introduced. This device is designed to have a whole blood inlet, a purified plasma outlet, and a concentrated blood cell outlet. The device is designed to separate plasma with up to 45% hematocrit of the inlet blood and is analyzed using computational fluid dynamics simulation. The simulation results show that 27% and 25% of plasma can be collected from the total inlet blood volume for 45% and 39% hematocrit, respectively. The device's functionality was demonstrated using defibrinated sheep blood (hematocrit=39%). During the experiment, all the blood cells traveled through the device toward the concentrated blood outlet while only the plasma flowed towards the plasma outlet without any clogging or lysis of cells. Because of its simple structure and control mechanism, this microdevice is expected to be used for highly efficient, realtime, continuous cell-free plasma separation.

Animals↗
PubMedDate not supplied

Energy equivalent pressure and total hemodynamic energy associated with the pressure-flow waveforms of a pediatric pulsatile ventricular assist device.

A pulsatile pediatric ventricular assist device (VAD) with a dynamic stroke volume of approximately 12 ml was tested to quantify the effect of flowrate and systolic duration on pulsatility as quantified by the energy equivalent pressure (EEP), defined as the hemodynamic energy per unit volume of fluid pumped. The VAD was tested on a mock circulatory loop, adjusted to maintain a systemic arterial pressure of approximately 90/60 mm Hg (systolic/diastolic) and a mean of 75 mm Hg. The EEP was calculated for each beat for 1 minute at both the proximal end of the pump outlet cannula and at the distal end (arterial EEP). Nominal mean flowrates were 0.50, 0.75, 1.00, and 1.25 l/min. Systolic duration was set at either 230 or 400 milliseconds. With a rapid systolic ejection (230 milliseconds), the arterial EEP ranged from 5.58% to 8.41% relative to the mean arterial pressure. The highest EEP occurred at the lowest flowrate. With a slower (400 milliseconds) systolic ejection, the arterial EEP ranged from 2.33% to 4.20%. Hemodynamic energy loss in the outlet cannula was also quantified by the differential EEP and shown to increase markedly as systolic duration was decreased, but was relatively insensitive to mean flowrate.

Blood Flow Velocity↗
PubMedDate not supplied

Viscoelasticity of pediatric blood and its implications for the testing of a pulsatile pediatric blood pump.

Red blood cell hematocrit, aggregation and deformability, and plasma protein concentration influence the viscosity and elasticity of whole blood. These parameters affect the flow properties, especially at low shear rates (< 50 s(-1)). In particular, we have previously shown that the viscoelasticity of fluid affects the inlet filling characteristics and regions of flow separation in small pulsatile blood pumps. Although the viscosity of pediatric blood has been thoroughly studied, its elasticity has not been previously measured. Here we present the viscosity and elasticity of pediatric blood against shear rate for hematocrits from 19-56, measured using an oscillatory rheometer. There is little effect of patient age on blood viscoelasticity. A statistical analysis showed that when compared at constant hematocrit, blood from adult and pediatric patients had similar viscoelastic properties. We present blood analog solutions, as a function of hematocrit, constructed on the basis of the pediatric measurements. Flow field results for viscoelastic analogs of 20, 40 and 60% hematocrit and a Newtonian analog will be compared in the initial, in vitro testing of the Penn State pediatric blood pump, to determine the importance of incorporating a viscoelastic analog into the desigh interaction.

Blood Flow Velocity↗
PubMedDate not supplied

An evaluation of the benefits of pulsatile versus nonpulsatile perfusion during cardiopulmonary bypass procedures in pediatric and adult cardiac patients.

The controversy over the benefits of pulsatile and nonpulsatile flow during cardiopulmonary bypass procedures continues. The objective of this investigation was to review the literature in order to clarify the truths and dispel the myths regarding the mode of perfusion used during open-heart surgery in pediatric and adult patients. The Google and Medline databases were used to search all of the literature on pulsatile vs. nonpulsatile perfusion published between 1952 and 2006. We found 194 articles related to this topic in the literature. Based on our literature search, we determined that pulsatile flow significantly improved blood flow of the vital organs including brain, heart, liver, and pancreas; reduced the systemic inflammatory response syndrome; and decreased the incidence of postoperative deaths in pediatric and adult patients. We also found evidence that pulsatile flow significantly improved vital organ recovery in several types of animal models when compared with nonpulsatile perfusion. Several investigators have also shown that pulsatile flow generates more hemodynamic energy, which maintains better microcirculation compared with nonpulsatile flow. These results clearly suggest that pulsatile flow is superior to nonpulsatile flow during and after open-heart surgery in pediatric and adult patients.

Adult↗
PubMedDate not supplied

Pulsatile ECMO and VAD: a dual use of a new device in pediatric cardiac patients.

The purpose of this investigation was to present the first European clinical experience with the new MEDOS DELTASTREAM DP1 used in pulsatile extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD) options in the pediatric population. Between January 2002 and April 2006, 11 patients required ECMO and 5 patients received a left VAD (LVAD) in the San Vincenzo Hospital. Indications were postcardiotomy heart failure in 15 patients and fulminant myocarditis in one patient. ECMO was established in all patients by cannulation of the right atrium and ascending aorta. LVAD was instituted by cannulation of the left atrium and ascending aorta. The DP1, an extracorporeal rotary blood pump, was used as an ECMO and an LVAD device. The pump features a diagonal-flow impeller and can be used for both continuous and pulsatile modes of perfusion. Priming volume of the pump was approximately 30 ml, with a flow rate of up to 8 l/min. Ten patients were discharged from ECMO and four from VAD. In the ECMO group, one patient died of peritonitis while on ECMO and two patients died on days 3 and 4 after weaning because of persistent pulmonary hypertension and major neurologic complications. In the VAD group, one patient died of low output syndrome 9 days after weaning. A 12-year-old patient was successfully given transplantation on day 8 of ECMO support and discharged on day 30 after heart transplant. All other patients were discharged. Three pumps were changed for pump failure and one pump was electively replaced because of improper anticoagulation management. No other thromboembolic adverse events occurred. Our results suggest that the MEDOS DELTASTREAM DP1 pulsatile pump system can be used as an ECMO or a VAD support. The opportunity to utilize pulsatile flow in postcardiotomy cardiogenic shock significantly improved the outcomes by producing more physiologic hemodynamics and superior end organ function. Easy implantation and simple management of this device represents the major advantage.

Cardiac Output, Low↗
PubMedDate not supplied

Effects of pulsatile and nonpulsatile perfusion on vital organ recovery in pediatric heart surgery: a pilot clinical study.

The use of pulsatile flow during cardiopulmonary bypass (CPB) with regard to improved patient outcomes is controversial. We evaluated pulsatile perfusion in pediatric patients undergoing CPB in a clinical setting. Fifty consecutive pediatric patients undergoing open heart surgery for repair of congenital heart disease were prospectively entered into the study and randomly assigned to either the pulsatile perfusion group (group P, n = 25) or the nonpulsatile perfusion group (group NP, n = 25). Study parameters included intubation time, duration of intensive care unit (ICU) stay and hospital stay, need for inotropic support, preoperative and postoperative enzymes, creatinine, C-reactive protein, blood count, mean urine output, and total drainage. Group P, compared with group NP, had significantly less inotropic support (number of agents, 1.48 +/- 1.05 versus 2.44 +/- 1.03, p = 0.0015; dopamine, 6.48 +/- 3.27 versus 10.3 +/- 4.8 microg/kg per minute, p = 0.0023; dobutamine, 3.12 +/- 6.55 versus 8.03 +/- 9.1 microg/kg per minute, p = 0.034), shorter intubation period (20.36 +/- 17.02 versus 35.44 +/- 30.72 hours, p = 0.038), and shorter duration of ICU stay (2.16 +/- 1.07 versus 4.32 +/- 4.21 days, p = 0.028) and hospital stay (7.64 +/- 2.48 versus 11.84 +/- 6.82 days, p = 0.007). There were no significant differences in creatinine, enzyme levels, or drainage amounts between the two groups. Higher urine output during CPB (553.6 +/- 150.89 versus 465.8 +/- 151.23 ml/d, p = 0.045) and during the ICU period (658.8 +/- 210.99 versus 528,2 +/- 224.71 ml/d, p = 0.039) was observed in group P compared with group NP. We concluded that the use of pulsatile flow resulted in improved patient outcome in preserving cardiac function and maintaining better renal and pulmonic function (shorter intubation period) in the early postbypass period.

Cardiopulmonary Bypass↗
PubMedDate not supplied

DIDECMO: a new polymethylpentene oxygenator for pediatric extracorporeal membrane oxygenation.

We reviewed the performance of a new polymethylpentene oxygenator (DIDECMO, Dideco, Mirandola, Italy) in terms of clinical safety and efficiency in priming, oxygenation, and oxygenator resistance in neonatal and pediatric extracorporeal membrane oxygenation (ECMO) patients. Between March 2005 and January 2006, 14 patients required ECMO in the San Vincenzo Hospital. Of these, 8 (median age, 9 days; range, 3 days to 15 months) received normothermic ECMO for postcardiotomy heart failure after surgery for congenital heart disease. The DIDECMO oxygenator was used in all patients (median weight, 2.4 kg; range, 2 to 7 kg). According to our previous experience, all patients received the same anticoagulation management. DIDECMO is a new phosphorylcholine-coated, polymethylpentene hollow-fiber oxygenator recommended for a maximum blood flow of 2300 ml/min with a membrane surface area of 0.67 m2 and validated to be used up to 5 days. Static priming was 100 ml and mean support time 05 hours (range, 36 to 198 hours). No oxygenators were changed during support. Median pressure drop during overall assistance was 24 mm Hg. Carbon dioxide elimination was obtained with a 1:1 blood flow/air flow ratio. Neither oxygenator-related major nor minor adverse events occurred during support. In our initial experience, the new polymethylpentene DIDECMO oxygenator provided adequate gas exchange and offered technical advantages in terms of low priming volume and acceptable hemodynamic resistance despite pulsatile flow regimen. Also, we used this device for more than 8 days without any technical problems.

Cardiac Output, Low↗
PubMedDate not supplied

Plasma proteomics: a noninvasive window on pathology and pediatric cardiac surgery.

A challenge of pediatric research is the limited ability to obtain tissue samples from small patients. To confront this problem, blood biomarkers can be used as surrogate markers of disease processes and aid in patient monitoring and disease detection. Furthermore, proteomic analysis of plasma samples is one approach for large-scale discovery of disease biomarkers. This study examined the use of plasma for disease process biomarkers in pediatric patients undergoing cardiopulmonary bypass (CPB) surgery. Proteomic studies of plasma are limited by the presence of a few high abundance proteins that mask the presence of lower abundance proteins of interest. Plasma immunoaffinity depletion (removing 6 of the highest abundance proteins of little pathological importance) increases sensitivity of detection for proteins such as those related to inflammation, remodeling, and damage. Using two-dimensional in-gel fluorescence electrophoresis, changes in the expression levels of proteins that occur as a result of CPB can be identified. In the present study, plasma depletion removed 83% of the plasma protein mass, allowing approximately 1400 spots to be observed by two-dimensional in-gel fluorescence electrophoresis. Of the detected spots, 79 (5.7%) were altered by CPB. These data illuminate the strength of plasma proteomics in identification of candidate biomarkers of CPB-associated disease processes.

Biomarkers↗
PubMedDate not supplied

Use of a novel anticoagulation strategy during ECMO in a pediatric population: single-center experience.

We describe a novel anticoagulation strategy with continuous intravenous antithrombin infusion and intermittent heparin infusion in pediatric population during extracorporeal membrane oxygenation (ECMO). From November 2004 through February 2006, 11 patients required ECMO for postcardiotomy cardiorespiratory failure. The mean duration of support time was 112 hours (range 68-192 hours). Since April 2005, we modified our anticoagulation protocol in the last six patients. Continuous antithrombin infusion was started immediately after surgery based on the lab result. The antithrombin level was maintained >100% using the following formula: 100 (target value) - (Antithrombin value on lab test) x weight in 4 hours. Antithrombin value was checked at 4-hour intervals. Heparin infusion was started when the antithrombin value was > 100% and remained stable for more than 12 hours and the amount of bleeding was < 2 ml/kg for more than 3 consecutive hours; then heparin infusion was started at 2 UI/kg/h via the oxygenator (target ACT was not < 150 seconds). Three patients in the first group died. Eight patients were weaned and discharged; the third, fourth, and fifth required surgical revision for bleeding. One experienced minor neurologic sequelae. Neither surgical revision nor thromboembolic complications occurred in the new anticoagulation group. A novel anticoagulation strategy utilizing continuous intravenous antithrombin and intermittent heparin infusion reduced significantly surgical revision for bleeding in the first 48 hours. This has translated into excellent overall outcomes.

Anticoagulants↗
PubMedDate not supplied

Quantification of perfusion modes in terms of surplus hemodynamic energy levels in a simulated pediatric CPB model.

The objective of this investigation was to compare pulsatile versus nonpulsatile perfusion modes in terms of surplus hemodynamic energy (SHE) levels during cardiopulmonary bypass (CPB) in a simulated neonatal model. The extracorporeal circuit consisted of a Jostra HL-20 heart-lung machine (for both pulsatile and nonpulsatile modes of perfusion), a Capiox Baby RX hollow-fiber membrane oxygenator, a Capiox pediatric arterial filter, 5 feet of arterial tubing and 6 feet of venous tubing with a quarter-inch diameter. The circuit was primed with a lactated Ringers solution. The systemic resistance of a pseudo-patient (mean weight, 3 kg) was simulated by placing a clamp at the end of the arterial line. The pseudo-patient was subjected to five pump flow rates in the 400 to 800 ml/min range. During pulsatile perfusion, the pump rate was kept constant at 120 bpm. Pressure waveforms were recorded at the preoxygenator, postoxygenator, and preaortic cannula sites. SHE was calculated by use of the following formula {SHE (ergs/cm) = 1,332 [((integral fpdt) / (integral fdt)) - Mean Arterial Pressure]} (f = pump flow and p = pressure). A total of 60 experiments were performed (n = 6 for nonpulsatile and n = 6 for pulsatile) at each of the five flow rates. A linear mixed-effects model, which accounts for the correlation among repeated measurements, was fit to the data to assess differences in SHE between flows, pumps, and sites. The Tukey multiple comparison procedure was used to adjust p values for post hoc pairwise comparisons. With a pump flow rate of 400 ml/min, pulsatile flow generated significantly higher surplus hemodynamic energy levels at the preoxygenator site (23,421 +/- 2,068 ergs/cm vs. 4,154 +/- 331 ergs/cm, p < 0.0001), the postoxygenator site (18,784 +/- 1,557 ergs/cm vs. 3,383 +/- 317 ergs/cm, p < 0.0001), and the precannula site (6,324 +/- 772 ergs/cm vs. 1,320 +/- 91 ergs/cm, p < 0.0001), compared with the nonpulsatile group. Pulsatile flow produced higher SHE levels at all other pump flow rates. The Jostra HL-20 roller pump generated significantly higher SHE levels in the pulsatile mode when compared with the nonpulsatile mode at all five pump flow rates.

Blood Flow Velocity↗
PubMedDate not supplied

Microfluidic devices for continuous blood plasma separation and analysis during pediatric cardiopulmonary bypass procedures.

As an extension of previous work, a microfluidic device, which can separate blood plasma in a continuous, real-time fashion from a whole blood, is successfully integrated with a mock cardiopulmonary bypass circuit. The functionality of the device is demonstrated with the use of freshly harvested bovine blood. The plasma selectivities were 100% and 99.4% and the plasma separation volume percents were 18.7% and 24.5% for 26% and 37% inlet hematocrit levels, respectively. As an advanced stage of this research, a microfluidic device, which can measure the concentration of clinically relevant blood plasma protein in a continuous fashion, is being developed on the basis of fluid handling circuits coupled to fluorescent cytometric bead assays. The functionality of the device is demonstrated with the use of a biotinylated FITC solution and a streptavidin-coated, 8-mum-diameter bead. The binding event between biotinylated FITC and the streptavidin bead is continuously detected within a detection window at the outlet of the device. For a known concentration (1 microg/ml) of biotinylated FITC solution, the measured fluorescent intensity is fairly constant and shows a stable gaussian distribution of the bead fluorescence intensity. It is expected that the proposed device can be used for continuous measurement of clinically relevant proteins during cardiac surgery with the cardiopulmonary bypass procedure.

Animals↗