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Biomedical subjects

Akif Undar

Publications and source records attributed to Akif Undar.

At least 37 records · Page 2Linked to original sources
PubMed2002

Novel anti-factor D monoclonal antibody inhibits complement and leukocyte activation in a baboon model of cardiopulmonary bypass.

BACKGROUND: Adverse outcomes after cardiopulmonary bypass (CPB) are often related to systemic inflammation triggered by complement and leukocyte activation. To determine how inhibition of the alternative complement pathway affects systemic inflammation and tissue injury, we studied a novel monoclonal antibody (Mab), anti-human factor D murine Mab 166-32, in baboons. METHODS: Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. The treatment group (n = 7) received a single injection of anti-factor D Mab 166-32 (5 mg/kg), and the control group (n = 7) was given saline solution. After initiation of CPB, all animals were subjected to 20 minutes of core cooling (rectal temperature, 27 degrees C), followed by 60 minutes of aortic cross-clamping, 25 minutes of rewarming, and 30 minutes of normothermic CPB. Blood samples were collected before CPB, during CPB, and 1, 2, 3, 6, and 18 hours after CPB. To measure neutrophil and monocyte activation, we performed flow cytometry for CD11b expression, ELISA for complement activation (Bb, C3a, C4d, and sC5b-9) and interleukin-6 (IL-6) production, and tissue injury studies for creatine kinase MB isoenzymes (CK-MB), creatine kinase (CK), and lactic dehydrogenase (LDH) levels. RESULTS: Anti-factor D Mab almost completely inhibited plasma Bb, C3a, and sC5b-9 production during CPB (P < .001). CD11b expression on neutrophils (129 +/- 5% vs. 210 +/- 42%; P = .0006) and on monocytes (139 +/- 14% vs. 245 +/- 43%; P = .0002) was also lower in the treatment group during CPB. The treated animals had a significantly smaller increase in plasma IL-6 concentrations than did the control animals (71 +/- 27 pg/mL vs. 104 +/- 54 pg/mL; P = .0002). CK-MB levels were also lower in the treatment group 6 hours after the end of CPB (204 +/- 30 vs. 335 +/- 59 IU/L; P = .003) and 18 hours after the end of CPB (P < .05). Creatine kinase levels (6 and 18 hours after the end of CPB) and LDH levels (3 and 6 hours after the end of CPB) showed patterns similar to those of CK-MB (P < .05). CONCLUSIONS: The alternative complement pathway plays a major role in systemic inflammation during CPB. Inhibition of complement activation via the alternative pathway by anti-factor D Mab 166-32 significantly reduces leukocyte activation and tissue injury in our baboon model.

Animals↗
PubMed2002

Anomalous origin of left coronary artery from the right pulmonary artery in association with type III aortopulmonary window and interrupted aortic arch.

Anomalous origin of the left coronary artery from the pulmonary artery, also known as Garland-Bland-White syndrome, usually occurs as an isolated condition. We report an infant with caudal regression sequence diagnosed with interrupted aortic arch type B and type III aortopulmonary window, who was found to have anomalous origin of the left coronary artery from the right pulmonary artery at surgical repair. Successful repair of the aortopulmonary window and interruption was performed with reimplantation of the left coronary artery into the ascending aorta. This report highlights the importance of closely assessing the coronary ostia in patients undergoing complex aortopulmonary window repair.

Anastomosis, Surgical↗
PubMed2002

Pediatric physiologic pulsatile pump enhances cerebral and renal blood flow during and after cardiopulmonary bypass.

Controversy over benefits of pulsatile flow after pediatric cardiopulmonary bypass (CPB) continues. Our study objectives were to first, quantify pressure and flow waveforms in terms of hemodynamic energy, using the energy equivalent (EEP) formula, for direct comparisons, and second, investigate effects of pulsatile versus nonpulsatile flow on cerebral and renal blood flow, and cerebral vascular resistance during and after CPB with deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model. Fourteen piglets underwent perfusion with either an hydraulically driven dual-chamber physiologic pulsatile pump (P, n = 7) or a conventional nonpulsatile roller pump (NP, n = 7). The radiolabeled microsphere technique was used to determine the cerebral and renal blood flow. P produced higher hemodynamic energy (from mean arterial pressure to EEP) compared to NP during normothermic CPB (13 +/- 3% versus 1 +/- 1%, p < 0.0001), hypothermic CPB (15 +/- 4% versus 1 +/- 1%, p < 0.0001) and after rewarming (16 +/- 5% versus 1 +/- 1%, p < 0.0001). Global cerebral blood flow was higher for P compared to NP during CPB (104 +/- 12 ml/100g/min versus 70 +/- 8 ml/100g/min, p < 0.05). In the right and left hemispheres, cerebellum, basal ganglia, and brainstem, blood flow resembled the global cerebral blood flow. Cerebral vascular resistance was lower (p < 0.007) and renal blood flow was improved fourfold (p < 0.05) for P versus NP, after CPB. Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.

Age Factors↗
PubMed2002

Effects of mild hypothermic cardiopulmonary bypass on blood viscoelasticity in coronary artery bypass grafting patients.

The purpose of this study was to determine the changes in blood viscoelasticity during and after coronary artery bypass grafting (CABG) and to identify correlations between blood viscoelasticity and patients' age, duration of cardiopulmonary bypass (CPB), and cross-clamp time. After Institutional Review Board approvals, patients (n = 10) who were subjected to mild hypothermic CPB were included in this study. Viscosity and elasticity were measured at strains of 0.2, 1, and 5 using a Vilastic-3 Viscoelasticity Analyzer. Arterial blood samples were collected pre-CPB, on normothermic CPB, hypothermic CPB, after rewarming, and after CPB. Viscosity and elasticity at strains of 0.2 and 1 were altered significantly during and after CPB compared to the pre-CPB (p < 0.01). In particular, elasticity of blood was diminished during normothermic bypass and could not be recovered after CPB (p < 0.01). Although there were strong correlations between blood viscoelasticity, duration of CPB, and cross-clamp time on normothermic CPB, only the patients' age showed a positive correlation between viscosity (r = 0.61, p = 0.05), and elasticity (r = 0.89, p < 0.001) after CPB. These results suggest that mild hypothermic CPB alters the blood viscoelasticity during and after CABG.

Age Factors↗
PubMed2002

Do S100beta protein level increases due to inflammation during cardiopulmonary bypass occur without any neurological deficit?

PURPOSE: S100beta protein level correlates with the duration of cardiopulmonary bypass (CPB) and aortic crossclamp times, but is different during pulsatile and nonpulsatile CPB. In this study, we investigated the time course of the release of S100beta protein during and after pulsatile and nonpulsatile CPB. PATIENTS AND METHODS: This is a prospective study. Twenty patients had open-heart surgery with pulsatile flow and 20 with nonpulsatile flow. We compared complement proteins, interleukins, white blood cells and S100beta protein before the initiation of CPB, immediately prior to aortic crossclamping, following unclamping, and at postoperative 1st and 24th hours. RESULTS: In the pulsatile CPB group following aortic unclamping, S100beta protein (p = 0.028) and C3a (p = 0.011) levels were significantly lower than those of the nonpulsatile group. In the pulsatile CPB group at postoperative first hour, C3a level (p = 0.018) and absolute neutrophil count (p = 0.034) were significantly lower than those of the nonpulsatile group. None of the patients developed a neurological deficit and all of the patients survived after the operation and were discharged from the hospital. CONCLUSION: During CPB, serum S100beta protein level increases and this increase is higher in the nonpulsatile group. High serum level of S100beta protein is associated with increased levels of serum inflammatory mediators and systemic inflammatory response.

Adult↗
PubMed2002

The ABCs of research on pulsatile versus nonpulsatile perfusion during cardiopulmonary bypass.

The literature suggests that pulsatile flow should be routinely used during cardiopulmonary bypass (CPB) in moderate- to high-risk cardiac surgery patients, especially those who must undergo more than 45 minutes of aortic crossclamping. Nevertheless, the use of pulsatile versus nonpulsatile perfusion remains controversial, mainly owing to a lack of precise, complete quantification of pressure-flow waveforms. This editorial briefly summarizes the major factors, or 'basic ABCs, ' that affect the validity of research in this area. A. Because pulsatile flow depends on an energy gradient, investigators must quantify the difference in the hemodynamic energy levels produced by specific pulsatile and nonpulsatile pumps before meaningful direct comparison of these two perfusion modes can be possible. B. The energy equivalent pressure (EEP) formula should be used for this purpose. C. In conducting clinical trials of the perfusion modes, researchers must use appropriate patient-selection criteria, use pulsatile flow continuously during CPB, and choose extracorporeal-circuit components carefully. By following these basic ABCs, researchers will produce more valid and meaningful results that will translate into better outcomes for CPB patients.

Cardiac Surgical Procedures↗
PubMedDate not supplied

Pulsatile perfusion improves regional myocardial blood flow during and after hypothermic cardiopulmonary bypass in a neonatal piglet model.

Pediatric myocardial related morbidity and mortality after cardiopulmonary bypass (CPB) are well documented, but the effects of pulsatile perfusion (PP) versus nonpulsatile perfusion (NPP) on myocardial blood flow during and after hypothermic CPB are unclear. After investigating the effects of PP versus NPP on myocardial flow during and after hypothermic CPB, we quantified PP and NPP pressure and flow waveforms in terms of the energy equivalent pressure (EEP) for direct comparison. Ten piglets underwent PP (n = 5) or NPP (n = 5). After initiation of CPB, all animals underwent 15 minutes of core cooling (25 degrees C), 60 minutes of hypothermic CPB with aortic cross-clamping, 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, the mean arterial pressure (MAP) and pump flow rates were 40 mm Hg and 150 ml/kg per min, respectively. Regional flows were measured with radiolabeled microspheres. During normothermic CPB, left ventricular flow was higher in the PP than the NPP group (202+/-25 vs. 122+/-20 ml/l 00 g per min). During hypothermic CPB, no significant intragroup differences were observed. After 60 minutes of ischemia and after rewarming (276+/-48 vs. 140+/-12 ml/100 g per min; p < 0.05) and after CPB (271+/-10 vs. 130+/-14 ml/100 g per min; p < 0.05), left ventricular flow was higher in the PP group. Right ventricular flow resembled left ventricular flow. The pressure increase (from MAP to EEP) was 10+/-2% with PP and 1% with NPP (p < 0.0001). The increase in extracorporeal circuit pressure (ECCP) (from ECCP to EEP) was 33+/-10% with PP and 3% with NPP (p < 0.0001). Pulsatile flow generates significantly higher energy, enhancing myocardial flow during and after hypothermic CPB and after 60 minutes of ischemia in this model.

Animals↗
PubMedDate not supplied

Precise quantification of pressure flow waveforms of a pulsatile ventricular assist device.

Unreliable quantification of flow pulsatility has hampered many efforts to assess the importance of pulsatile perfusion. Generation of pulsatile flow depends upon an energy gradient. It is necessary to quantify pressure flow waveforms in terms of hemodynamic energy levels to make a valid comparison between perfusion modes during chronic support. The objective of this study was to quantify pressure flow waveforms in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) levels in an adult mock loop using a pulsatile ventricle assist system (VAD). A 70 cc Pierce-Donachy pneumatic pulsatile VAD was used with a Penn State adult mock loop. The pump flow rate was kept constant at 5 L/min with pump rates of 70 and 80 bpm and mean aortic pressures (MAP) of 80, 90, and 100 mm Hg, respectively. Pump flows were adjusted by varying the systolic pressure, systolic duration, and the diastolic vacuum of the pneumatic drive unit. The aortic pressure was adjusted by varying the systemic resistance of the mock loop EEP (mm Hg) = (integral of fpdf)/(integral of fdt) SHE (ergs/cm3) = 1,332 [((integral of fpdt)/(integral of fdt))--MAP] were calculated at each experimental stage. The difference between the EEP and the MAP is the extra energy generated by this device. This difference is approximately 10% in a normal human heart. The EEP levels were 88.3 +/- 0.9 mm Hg, 98.1 +/- 1.3 mm Hg, and 107.4 +/- 1.0 mm Hg with a pump rate of 70 bpm and an aortic pressure of 80 mm Hg, 90 mm Hg, and 100 mm Hg, respectively. Surplus hemodynamic energy in terms of ergs/cm3 was 11,039 +/- 1,236 ergs/cm3, 10,839 +/- 1,659 ergs/cm3, and 9,857 +/- 1,289 ergs/cm3, respectively. The percentage change from the mean aortic pressure to EEP was 10.4 +/- 1.2%, 9.0 +/- 1.4%, and 7.4 +/- 1.0% at the same experimental stages. Similar results were obtained when the pump rate was changed from 70 bpm to 80 bpm. The EEP and SHE formulas are adequate to quantify different levels of pulsatility for direct and meaningful comparisons. This particular pulsatile VAD system produces near physiologic hemodynamic energy levels at each experimental stage.

Adult↗
PubMedDate not supplied

Pulsatile ECMO in neonates and infants: first European clinical experience with a new device.

This study presents the first European clinical experience with the Medos DeltaStream DP1, a new pulsatile flow pump, in neonates and infants. Between January 2002 and December 2004, 420 patients at our institution underwent congenital heart surgery on cardiopulmonary bypass. During this period, 10 patients required extracorporeal membrane oxygenation (ECMO) support for acute postcardiotomy heart failure. Seven patients (median age 7 days, range 1-70 days), were supported by a nonpulsatile Biomedicus centrifugal pump, whereas three patients (aged 1 month, 1 year, and 12 years) were supported by a pulsatile Medos DP1. The DP1 is an extracorporeal rotary blood pump. The pump features a diagonal-flow impeller, and can be used for both continuous and pulsatile output. Special characteristics include a small priming volume of approximately 30 ml and a high pumping capacity. A temperature sensor and speed sensors are integrated in the pump. The pump has a delivery rate of up to 8 l/min and a speed range of 100-10,000 rpm. Overall mortality was 40% (4 of 10 patients), and all four deaths were in the nonpulsatile Biomedicus group. In the nonpulsatile group, the median support duration was 95 hours with a range of 48-140 hours. Two patients assisted with the pulsatile pump system were successfully weaned after 36 and 53 hours, respectively; the 12-year-old patient was successfully transplanted on the eighth postimplant day and discharged from the hospital on the 32nd posttransplant day. Although this preliminary experience doesn't allow for statistical analysis, clinically it was possible to observe a better performance in pulsatile flow recipients with faster lactate recovery, reduced need for inotropic support, reduced assistance duration in bridge-to-recovery settings, and smoother intensive care management. ECMO for postcardiotomy heart failure in neonates and infants still carries high mortality and morbidity rates. Pulsatile flow with the Medos DeltaStream DP1 pump system improves results by producing more physiologic hemodynamics, reducing the duration of support in the case of bridge to recovery, and improving end-organ function.

Body Surface Area↗
PubMedDate not supplied

Precise quantification of pulsatility is a necessity for direct comparisons of six different pediatric heart-lung machines in a neonatal CPB model.

Generation of pulsatile flow depends on an energy gradient. Surplus hemodynamic energy (SHE) is the extra hemodynamic energy generated by a pulsatile device when the adequate pulsatility is achieved. The objective of this study was to precisely quantify and compare pressure-flow waveforms in terms of surplus hemodynamic energy levels of six different pediatric heart-lung machines in a neonatal piglet model during cardiopulmonary bypass (CPB) procedures with deep hypothermic circulatory arrest (DHCA). Thirty-nine piglets (average weight, 3 kg) were subjected to CPB with a hydraulically driven physiologic pulsatile pump (PPP; n=7), Jostra-HL 20 pulsatile roller pump (Jostra-PR; n=6), Stockert Sill pulsatile roller pump (SIII-PR; n=6), Stockert Sill mast-mounted pulsatile roller pump with a miniature roller head (Mast-PR; n=7), Stockert Sill mast-mounted nonpulsatile roller pump (Mast-NP; n=7), or Stockert CAPS nonpulsatile roller pump (CAPS-NP, n=7). Once CPB was begun, each animal underwent 20 minutes of hypothermia, 60 minutes of DHCA, 10 minutes of cold reperfusion, and 40 minutes of rewarming. The pump flow rate was maintained at 150 ml x kg(-1) x min(-1) and the mean arterial pressure (MAP) at 45 mm Hg. In the pulsatile experiments, the pump rate was kept at 150 bpm and the stroke volume at 1 ml/kg. The SHE (ergs/cm3) = 1,332 ([(integral fpdt) / (integral fdt)] - MAP) was calculated at each experimental stage. During normothermic CPB (15 minutes on pump), the physiologic pulsatile pump generated the highest surplus hemodynamic energy (8563 +/- 1918 ergs/cm3, p < 0.001) compared with all other pumps. The Jostra HL-20 and Stockert Sill pulsatile roller pumps also produced adequate surplus hemodynamic energy. Nonpulsatile roller pumps and the Stockert Sill mast-mounted pulsatile roller pump did not generate any extra hemodynamic energy. During hypothermic CPB and after DHCA and rewarming, the results were extremely similar to those seen during normothermic CPB. The surplus hemodynamic energy formula is a novel method to precisely quantify different levels of pulsatility and nonpulsatility for direct and meaningful comparisons. The PPP produced the greatest surplus hemodynamic energy. Most of the pediatric pulsatile pumps (except Mast-PR) generated significant surplus hemodynamic energy. None of the nonpulsatile roller pumps generated adequate surplus hemodynamic energy.

Animals↗