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Biomedical subjects

A Undar

Publications and source records attributed to A Undar.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits.

OBJECTIVES: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. METHODS: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 microg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. RESULTS: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. CONCLUSIONS: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.

Antibodies, Monoclonal↗
PubMed2001

Global and regional cerebral blood flow in neonatal piglets undergoing pulsatile cardiopulmonary bypass with continuous perfusion at 25 degrees C and circulatory arrest at 18 degrees C.

To investigate the influence of hypothermic cardiopulmonary bypass (HCPB) at 25 degrees C and circulatory arrest at 18 degrees C on the global and regional cerebral blood flow (CBF) during pulsatile perfusion, we performed the following studies in a neonatal piglet model. Using a pediatric physiologic pulsatile pump, we subjected six piglets to deep hypothermic circulatory arrest (DHCA) and six other piglets to HCPB. The DHCA group underwent hypothermia for 25 min, DHCA for 60min, cold reperfusion for 10 min, and rewarming for 40 min. The HCPB group underwent 15 min of cooling, followed by 60 min of HCPB, 10min of cold reperfusion, and 30 min of rewarming. The following variables remained constant in both groups: pump flow (150 ml/kg/min), pump rate (150 bpm), and stroke volume (1 ml/kg). During the 60-min aortic crossclamp period, the temperature was kept at 18 degrees C for DHCA and at 25 degrees C for HCPB. The global and regional CBF (ml/100g/min) was assessed with radiolabeled microspheres. The CBF was 48% lower during deep hypothermia at 18degrees C (before DHCA) than during hypothermia at 25 degrees C (55.2 +/- 14.3ml/100g/min vs 106.4 +/- 19.7 ml/100 g/min; p < 0.05). After rewarming, the global CBF was 45% lower in the DHCA group than in the HCPB group 48.3 +/- 18.1 ml/100g/min vs (87 +/- 35.9ml/100g/min; p < 0.05). Fifteen minutes after the termination of CPB, the global CBF was only 25% lower in the DHCA group than in the HCPB group (42.2 +/- 20.7 ml/100 g/min vs 56.4 +/- 25.8ml/100g/min; p = NS). In the right and left hemispheres, cerebellum, basal ganglia, and brain stem, blood flow resembled the global CBF. In conclusion, both HCPB and DHCA significantly decrease the regional and global CBF during CPB. Unlike HCPB, DHCA has a continued negative impact on the CBF after rewarming. However, 15 min after the end of CPB, there are no significant intergroup differences in the CBF.

Animals↗
PubMed2000

Impact of membrane oxygenators on pulsatile versus nonpulsatile perfusion in a neonatal model.

We investigated the effects of two new hollow-fiber membrane oxygenators, the Capiox SX10 and the Lilliput 901, on pulsatile versus nonpulsatile perfusion in an in vitro model designed to simulate a 3 kg infant. The experiments were divided into eight groups (six pulsatile and two nonpulsatile), according to the equipment and settings used. Each group included six tests. In all experiments, the pseudo-patient's mean arterial pressure was 40 mmHg, and the pump flow rate was 550 ml/min. During pulsatile cardiopulmonary bypass, the pump's base flow was set at 30%, and the pump rate was set at 80, 100, 120, 140, or 150 beats/min. The PUMP START and PUMP STOP timing points were adjusted to produce different pulse-width settings. We were especially interested in evaluating the pre- and postoxygenator extracorporeal circuit pressure (ECP), the oxygenator pressure drop, and the precannula ECP. When used with a pulsatile roller pump, the Capiox produced a significantly lower preoxygenator ECP than the Lilliput (p < 0.001); moreover, the Capiox yielded a significantly lower oxygenator pressure drop (p < 0.001). During nonpulsatile perfusion, the Capiox again produced a lower preoxygenator ECP than the Lilliput (p < 0.001). These results suggest that the Capiox may be more suitable than the Lilliput when the pulsatile flow is employed, and pulsatile flow does not increase the ECP with either oxygenator.

Equipment Design↗
PubMed2000

The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model.

The purpose of this study is to determine the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on the viscoelasticity (viscosity and elasticity) of blood and global and regional cerebral blood flow (CBF) in a neonatal piglet model. After initiation of CPB, all animals (n = 3) were subjected to core cooling for 20 min to reduce the piglets' nasopharyngeal temperatures to 18 degrees C. This was followed by 60 min of DHCA, then 45 min of rewarming. During cooling and rewarming, the alpha-stat technique was used. Arterial blood samples were taken for viscoelasticity measurements and differently labeled microspheres were injected at pre-CPB, pre- and post-DHCA, 30 and 60 min after CPB for global and regional cerebral blood flow calculations. Viscosity and elasticity were measured at 2 Hz, 22 degrees C and at a strain of 0.2, 1, and 5 using a Vilastic-3 Viscoelasticity Analyzer. Elasticity of blood at a strain = 1 decreased to 32%, 83%, 57%, and 61% (p = 0.01, ANOVA) while the viscosity diminished 8.4%, 38%, 22%, 26% compared to the baseline values (p = 0.01, ANOVA) at pre-DHCA, post-DHCA, 30 and 60 min after CPB, respectively. The viscoelasticity of blood at a strain of 0.2 and 5 also had similar statistically significant drops (p < 0.05). Global and regional cerebral blood flow were also decreased 30%, 66%, 64% and 63% at the same experimental stages (p < 0.05, ANOVA). CPB procedure with 60 min of DHCA significantly alters the blood viscoelasticity, global and regional cerebral blood flow. These large changes in viscoelasticity may have a significant impact on organ blood flow, particularly in the brain.

Animals↗
PubMed1999

Effects of perfusion mode on regional and global organ blood flow in a neonatal piglet model.

BACKGROUND: Organ injury (brain, kidney, and heart) has been reported in up to 30% of pediatric open heart surgery patients after conventional hypothermic non-pulsatile cardiopulmonary bypass (CPB) support with or without deep hypothermic circulatory arrest (DHCA). The effects of pulsatile (with a Food and Drug Administration approved modified roller pump) versus non-pulsatile perfusion on regional and global cerebral, renal, and myocardial blood flow were investigated during and after CPB with 60 minutes of DHCA in a neonatal piglet model. METHODS: Piglets, mean weight 3 kg, were used in both pulsatile (n = 7) and non-pulsatile (n = 7) groups. After initiation of CPB, all animals were subjected to hypothermia for 25 minutes, reducing the rectal temperatures to 18 degrees C, 60 minutes of DHCA followed by 10 minutes of cold reperfusion and 40 minutes of rewarming with a pump flow of 150 mL/kg/min. During cooling and rewarming, alpha-stat acid-base management was used. Differently labeled radioactive microspheres were injected pre-CPB, on normothermic CPB, pre-DHCA, post-DHCA, and after CPB to measure the regional and global cerebral, renal, and myocardial blood flows. RESULTS: Global cerebral blood flow was significantly higher in the pulsatile group compared to the non-pulsatile group at normothermic CPB (100.4 +/- 6.3 mL/100 gm/min versus 70.2 +/- 8.1 mL/100 gm/min, p < 0.05) and pre-DHCA (77.2 +/- 5.2 mL/100 gm/min versus 56.1 +/- 6.7 mL/100 gm/min, p < 0.05). Blood flow in cerebellum, basal ganglia, brain stem, and right and left cerebral hemispheres had an identical pattern with the global cerebral blood flow. Renal blood flow appeared higher in the pulsatile group compared to the non-pulsatile group during CPB, but the results were statistically significant only at post-CPB (94.8 +/- 9 mL/100 gm/min versus 22.5 +/- 22 mL/100 gm/min, p < 0.05). Pulsatile flow better maintained the myocardial blood flow compared to the non-pulsatile flow after CPB (316.6 +/- 45.5 mL/100 gm/min versus 188.2 +/- 19.5 mL/100 gm/min, p < 0.05). CONCLUSIONS: Pulsatile perfusion provides superior vital organ blood flow compared to non-pulsatile perfusion in this model.

Animals↗
PubMed1999

The effects of pulsatile versus nonpulsatile perfusion on blood viscoelasticity before and after deep hypothermic circulatory arrest in a neonatal piglet model.

Blood trauma increases blood viscoelasticity by increasing red cell aggregation and plasma viscosity and by decreasing cell deformability. During extracorporeal circulation, the mode of perfusion (pulsatile or nonpulsatile) may have a significant impact on blood trauma. In this study, a hydraulically driven dual chamber pulsatile pump system was compared to a standard nonpulsatile roller pump in terms of changes in the blood viscosity and elasticity during cardiopulmonary bypass (CPB) and pre and post deep hypothermic circulatory arrest (DHCA). Piglets, with an average weight of 3 kg, were used in the pulsatile (n = 5) or nonpulsatile group (n = 5). All animals were subjected to 25 min of hypothermia, 60 min of DHCA, 10 min of cold reperfusion, and 40 min of rewarming with a pump flow of 150 ml/kg/min. A pump rate of 150 bpm, pump ejection time of 120 ms, and stroke volume of 1 ml/kg were used during pulsatile CPB. Arterial blood samples were taken pre-CPB (36 degrees C), during normothermic CPB (35 degrees C), during hypothermic CPB (25 degrees C), pre-DHCA (18 degrees C), post-DHCA (19 degrees C), post-rewarming (35 degrees C), and post-CPB (36 degrees C). Viscosity and elasticity were measured at 2 Hz and 22 degrees C and at strains of 0.2, 1, and 5 using the Vilastic-3 Viscoelasticity Analyzer. Results suggest that the dual chamber neonate-infant pulsatile pump system produces less blood trauma than the standard nonpulsatile roller pump as indicated by lower values of both viscosity and elasticity during CPB support.

Animals↗
PubMed1999

Defining pulsatile perfusion: quantification in terms of energy equivalent pressure.

Several clinical and animal studies have demonstrated that pulsatile perfusion is more beneficial than nonpulsatile perfusion during short or long durations of extracorporeal circulation. Other investigators, however, have been unable to document these benefits. The issue remains controversial. Central to the debate is the issue of a precise definition of pulsatile flow. To help resolve the conflict, pulsatile flow may be quantified in terms of energy equivalent pressure. This formula contains both the arterial pressure and pump flow rate, which are the 2 most critical parameters for open heart surgery. This definition establishes common criteria for assessment of the effectiveness of extracorporeal support.

Adult↗
PubMed1998

The type of aortic cannula and membrane oxygenator affect the pulsatile waveform morphology produced by a neonate-infant cardiopulmonary bypass system in vivo.

Although the debate still continues over the effectiveness of pulsatile versus nonpulsatile perfusion, it has been clearly proven that there are several significant physiological benefits of pulsatile perfusion during cardiopulmonary bypass (CPB) compared to nonpulsatile perfusion. However, the components of the extracorporeal circuit have not been fully investigated regarding the quality of the pulsatility. In addition, most of these results have been gathered from adult patients, not from neonates and infants. We have designed and tested a neonate-infant pulsatile CPB system using 2 different types of 10 Fr aortic cannulas and membrane oxygenators in 3 kg piglets to evaluate the effects of these components on the pulsatile waveform produced by the system. In terms of the methods, Group 1 (Capiox 308 hollow-fiber membrane oxygenator and DLP aortic cannula with a very short 10 Fr tip [n = 2]) was subjected to a 2 h period of normothermic pulsatile CPB with a pump flow rate of 150 ml/kg/min. Data were obtained at 5, 30, 60, 90, and 120 min of CPB. In Group 2 (Capiox 308 hollow-fiber membrane oxygenator and Elecath aortic cannula with a very long 10 Fr tip [n = 7]) and Group 3 (cobe VPCML Plus flat sheet membrane oxygenator and DLP aortic cannula with a very short 10 Fr tip [n = 7]), the subjects' nasopharyngeal temperatures were reduced to 18 degrees C followed by 1 h of deep hypothermic circulatory arrest (DHCA) and then 40 min rewarming. Data were obtained during normothermic CPB in the pre- and post-DHCA periods. The criteria of pulsatility evaluations were based upon pulse pressure (between 30 and 40 mm Hg), aortic dp/dt (greater than 1000 mm Hg/s), and ejection time (less than 250 ms). The results showed that Group 1 produced flow which was significantly more pulsatile than that of the other 2 groups. Although the same oxygenator was used for Group 2, the quality of the pulsatile flow decreased when using a different aortic cannula. Group 3 did not meet any of the criteria for physiologic pulsatility. In conclusion these data suggest that in addition to a pulsatile pump, the aortic cannula and the membrane oxygenator must be chosen carefully to achieve physiologic pulsatile flow during CPB.

Animals↗