Intra-aortic balloon pump induced pulsatile perfusion reduces endothelial activation and inflammatory response following cardiopulmonary bypass

Objective: Intra-aortic balloon pump (IABP)-induced pulsatile perfusion has demonstrated that it can preserve organ function during cardiopulmonary bypass (CPB). We evaluated the role of IABP pulsatile perfusion on endothelial response. Methods: Forty consecutive isolated CABG undergoing preoperative IABP were randomized to receive IABP pulsatile CPB during aortic cross-clamping (group A, 20 patients) or standard linear CPB (group B, 20 patients) during cross-clamp time. Hemodynamic results were analyzed by Swan-Ganz catheter [mean arterial pressure (MAP), cardiac index (CI), indexed systemic vascular resistances (ISVR), indexed pulmonary vascular resistances (IPVR), wedge pressure (PCWP)]. Inflammatory/endothelial response was analyzed by pro-inflammatory (IL-2, IL-6, IL-8), anti-inflammatory cytokines (IL-10), and endothelial markers [vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1)]. All measurements were recorded preoperatively (T0), before aortic declamping (T1), at the end of surgery (T2), 12 h (T3) and 24 h (T4) postoperatively. ANOVA for repeated measures was used to evaluate the differences of means. Results: Hemodynamic response was comparable except for higher MAP (p = 0.01 at T1) and lower ISVR (p = 0.001 at T1, p = 0.003 at T2) in group A. No differences were found in perioperative leakage of IL-2, IL-6, and IL-8 between the two groups (within-group p = 0.0001 either in group A and group B; between-groups p = NS at 2-ANOVA). Group A showed significantly lower VEGF (between-groups p = 0.001 at 2-ANOVA, p = 0.001 at T1, T2) and MCP-1 (between-groups p = 0.001 at 2-ANOVA, p = 0.001 at T1, T2) with higher IL-10 secretion (between-groups p = 0.001 at 2-ANOVA, p = 0.01 at T1, T2, T3). Conclusions: IABP-induced pulsatile perfusion allows lower endothelial activation during CPB and higher anti-inflammatory cytokines secretion.     

Clinical Evaluation of New Generation Oxygenators With Integrated Arterial Line Filters for Cardiopulmonary Bypass

New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group‐T) or Sorin Synthesis (40 patients, Group‐S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High‐sensitivity C‐reactive protein (hs‐CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between‐groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group‐P and group*time‐P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group‐T showed higher hs‐CRP (group‐P = 0.034), aPTT (group‐P = 0.0001), and INR (group‐P = 0.05), with lower serum albumin (group‐P = 0.014), total proteins (group‐P = 0.0001), fibrinogen (group‐P = 0.041), and PLTs (group‐P = 0.021). Group‐T also showed higher postoperative bleeding (group‐P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post‐CPB inflammatory response.     

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.     

Pulsatile flow improves cerebral blood flow in pediatric cardiopulmonary bypass

The objective of this study was to evaluate the effect of pulsatile flow on cerebral blood flow (CBF) in infants with the use of a mild hypothermic cardiopulmonary bypass (CPB). Thirty infants scheduled for open heart surgery were randomized to the pulsatile group (Group P, n = 15) and nonpulsatile group (Group NP, n = 15). In Group P, pulsatile perfusion was applied during the aortic cross‐clamping period, whereas nonpulsatile perfusion was used in Group NP. The systolic peak velocity (Vs), the end of diastolic velocity (Vd), the mean velocity (Vm), and the pulsatility index (PI) and the resistance index (RI) of the middle cerebral artery were measured by a transcranial Doppler (TCD) ultrasound after anesthesia (T1; baseline), at the beginning of CPB (T2), 10 min after aortic cross‐clamping (T3), 3 min after declamping (T4), at the cessation of CPB (T5), and at the end of the operation (T6). During T3 and T4, the Vs in Group P was significantly higher than in Group NP. However, there were no statistically significant differences between Vd and Vm. The PI and RI in Group P were also higher than those in Group NP (both P < 0.05). During T5, Vd and Vm were higher in Group P (P < 0.05), whereas there was no difference in Vs. Additionally, PI and RI in Group P were significantly lower than those in Group NP (P < 0.05). However, there was no difference during T6. Pulsatile perfusion may increase CBF and decrease cerebral vascular resistance in the early period after mild hypothermic CPB.     

Coagulation and fibrinolysis system in pediatric cardiopulmonary bypass

Coagulation and fibrinolysis system was evaluated during and after pediatric cardiopulmonary bypass (CPB. Twenty-two atrial septal defect (ASD) patients were surgically repaired under CPB and aortic cross-clamp through right thoracotomy. Drainage was established by gravity, CPB flow was kept 2.4 l/min/m2 and ACT was controlled over 400 seconds. HCT, PLT, fibrinogen, AT-III, D-dimer, thrombin-antithrombin complex (TAT), alpha2 plasmin inhibitor-plasmin complex (PIC), and plasminogen activator inhibitor (PAI-1) were measured at 6 points [after induction of anesthesia, 10 minutes after initiating CPB, end of CPB, on the entrance of intensive care unit (ICU), postoperative day (POD) 1, and at outpatient division]. Both fibrinogen and AT-III showed low values during CPB (121.9 +/- 22.0 mg/dl, 57.6 +/- 10.6%). D-dimer increased at 1 week postoperatively in all patients (5.57 +/- 3.45 microg/ml). There were significantly positive correlations between CPB duration and TAT value at the end of CPB (r = 0.88, p < 0.01), on the entrance of ICU (r = 0.71, p < 0.01). There was also a positive correlation between CPB duration and PIC value on the entrance of ICU (r = 0.53, p < 0.01). Five patients showed high PAI-1 value on the entrance of ICU, which remained high in 2 of them on POD 1. The outcomes from the current study suggest that there is a potential of coagulation-dominant disseminated intravascular coagulation (DIC) during pediatric CPB even in ASD patients who do not need long CPB. Longer CPB and severe hemodilution might become risk factors.     

Comparison of parameters for detection of splanchnic hypoxia in children undergoing cardiopulmonary bypass with pulsatile versus nonpulsatile normothermia or hypothermia during congenital heart surgeries

The aim of this study is to evaluate gastric mucosal oxygenation together with whole-body oxygen changes in infants undergoing congenital heart surgery with cardiopulmonary bypass (CPB) procedure and the use of either pulsatile or nonpulsatile mode of perfusion with normothermia and pulsatile or nonpulsatile moderate hypothermia. Sixty infants undergoing congenital cardiac surgery were randomized into four groups as: nonpulsatile normothermia CPB (NNCPB, n = 15), pulsatile normothermia CPB (PNCPB, n = 15), nonpulsatile moderate hypothermia CPB (NHCPB, n = 15), and pulsatile moderate hypothermia CPB (PHCPB, n = 15) groups. In NNCPB and PNCPB groups, mild hypothermia was used (35°C), whereas in NHCPB and PHCPB groups, moderate hypothermia (28°C) was used. Gastric intramucosal pH (pHi), whole-body oxygen delivery (DO(2)) and consumption (VO(2)), and whole-body oxygen extraction fraction were measured at sequential time points intraoperatively and up to 2 h postoperatively. The measurement of continuous tonometry data was collected at desired intervals. The values of DO(2), VO(2), and whole-body oxygen extraction fraction were not different between groups before CPB and during CPB, whereas the PNCPB group showed higher values of DO(2), VO(2), and whole-body oxygen extraction fraction compared to the other groups at the measurement levels of 20 and 60 min after aortic cross clamp, end of CPB, and 2 h after CPB (P < 0.0001). Between groups, no difference was observed for pHi, lactate, and cardiac index values (P > 0.05). This study shows that the use of normothermic pulsatile perfusion (35°C) provides better gastric mucosal oxygenation as compared to other perfusion strategies in neonates and infants undergoing congenital heart surgery with CPB procedures.     

Safety and indication of open heart surgery without blood transfusion for congenital cardiac defects in infants

Between January 1994 and June 1997, 16 cases of ventricular septal defect (VSD) and endocardial cushion defect (ECD) with pulmonary hypertension (PH), each weighing from 5 to 9 kg, underwent definitive surgery at Matsudo Municipal Hospital. We classified them into 2 groups; Group N: 8 cases without blood transfusion, Group H: 8 cases with blood transfusion. Cardiopulmonary bypass (CPB) system was a closed circuit and priming volume was 370 to 500 ml. There was no difference between the 2 groups in operative age, body weight, preoperative state, operation time, CPB time, aortic cross clamp time, bleeding and postoperative state. In Group N, CPB blood was returned to the patient as soon as possible after CPB was weaned, and postoperative hemodynamics were stable in both groups. In Group N, hematocrit (Ht) values were consistently lower than in Group H, from initiation of CPB to leaving the hospital. To accomplish safe CPB, we measured systemic venous oxygen saturation (SvO₂). In 6 cases of Group N, SvO₂ during rewarming was 48.1 ± 16.0% and Ht value was 13.2 ± 1.5%. It is thought that the safe CPB could be conducted in Group N. In addition, in Group N, respiratory index showed better values than in Group H during the postoperative period. It is thought that CPB without blood transfusion may be favorable to prevent lung injury after CPB. Retrospectively, it is thought that, to accomplish safe CPB without blood transfusion, preoperative Ht values of over 30% are desirable in patients weighing 6 kg and those of over 35% are desirable in patients weighing 5 kg.     

Zero‐Balance Ultrafiltration of Priming Blood Attenuates Procalcitonin and Improves the Respiratory Function in Infants After Cardiopulmonary Bypass: A Randomized Controlled Trial

Blood priming is needed for cardiopulmonary bypass (CPB) in neonates and infants to avoid exceeding hemodilution; however, transfusion‐related inflammation affects post‐CPB outcomes in infant open‐heart surgery. Procalcitonin, a newly detected inflammatory moderator and a sensitive parameter for predicting pulmonary dysfunction secondary to CPB, rises after CPB. We hypothesized that the hemofiltration of priming blood before CPB might decrease inflammatory mediators in the blood and post‐CPB inflammatory replications, thereby improving the respiratory function after CPB in infants. Sixty infants with a weight below 10 kg were divided randomly into two equal groups of CPB with the zero‐balance ultrafiltration (Z‐BUF) of priming blood and CPB without it. The procalcitonin level was measured before anesthesia, after admission to the intensive care unit (ICU), and 24 h afterward. The respiratory index and pulmonary compliance were measured after anesthesia, at the end of CPB, and 2 h after admission to the ICU. Additionally, time to extubation was recorded. The Z‐BUF of priming blood maintained electrolytes within a physiologic level, and procalcitonin had a slighter rise in the Z‐BUF Group at 24 h after admission to the ICU (P = 0.05). The respiratory index was decreased in the Z‐BUF Group, but the difference with the control group did not reach statistical significance (P > 0.05). The change in pulmonary compliance was significantly increased in the cyanotic patients in the intervention group, but there was no significant difference between the two groups. The time to extubation and the ICU stay were shorter in the Z‐BUF Group (P < 0.05). A positive correlation was found between the peak procalcitonin concentration and the time to extubation directly and pulmonary compliance reversely. These results suggest that the Z‐BUF of priming blood may have some beneficial clinical effects such as improved respiratory function and attenuated procalcitonin.     

Evaluation of biocompatible cardiopulmonary bypass circuit use during pediatric open heart surgery

The contact of blood with nonbiological surfaces during cardiopulmonary bypass (CPB) induces a whole body inflammatory response and increases postoperative morbidity directly related to bleeding complications and end organ dysfunction. Methods to reduce these effects have included modification of extracorporeal circuits through biocompatible coating of disposables and the application of various pharmacological agents. Biocompatible coated surfaces are designed to mimic physiologic surfaces. This study was designed to ascertain the effects of using coated circuits during pediatric CPB. After Institutional Review Board approval and parent/guardian consent, patients undergoing CPB, weighing less than 15 kg, with target CPB temperatures more than 28 degrees C, were enrolled into the Coated Circuit Group using an entirely biocompatible CPB circuit with poly(2-methoxyethylacrylate) (PMEA) and a biocompatible coated oxygenator (n = 16). Those patients were retrospectively matched to control patients having the same congenital repair with respect to patient size, surgeon, anesthesiologist, bypass time, cross-clamp time, bypass temperature, and noncoated bypass disposables; (n = 16). CPB data collected included on-bypass platelet count, hematocrit (HCT), and CPB blood product use. Postprotamine data collected in the operating room included blood product use, time from initial protamine administration to chest closure, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR). Postoperative intensive care unit (ICU) data included blood product use, HCT, chest tube output, platelet count, PT, aPTT, INR, blood gases, lactate, and ventilator settings at 1, 2, 4, 6, 12, and 24 hours. Other data collected included intubation time, length of time to chest tube removal, and length of ICU stay. Statistical significance (p < .05) was seen in units of platelets transfused postprotamine, ventilator peak inflation pressure (PIP) on admission to the ICU, postoperative day 0 packed red blood cells (PRBC) and fresh frozen plasma (FFP) transfused, and lactate at 1, 2, 4, 6, and 12 hours postoperative. Several parameters approached statistical significance, including PRBC transfused postprotamine, time from protamine administration to chest closure, postoperative day 0 platelets transfused, and ICU stay. The data suggest that PMEA biocompatible CPB circuits can be used safely during pediatric heart surgery, resulting in a decrease in postoperative blood product use, improved postoperative lung function, and a reduction in the time spent in the ICU.     

Safety and indication of open heart surgery without blood transfusion for congenital cardiac defects in infants]

Between January 1994 and June 1997, 16 cases of ventricular septal defect (VSD) and endocardial cushion defect (ECD) with pulmonary hypertension (PH), each weighing from 5 to 9 kg, underwent definitive surgery at Matsudo Municipal Hospital. We classified them into 2 groups; Group N: 8 cases without blood transfusion, Group H: 8 cases with blood transfusion. Cardiopulmonary bypass (CPB) system was a closed circuit and priming volume was 370 to 500 ml. There was no difference between the 2 groups in operative age, body weight, preoperative state, operation time, CPB time, aortic cross clamp time, bleeding and postoperative state. In Group N, CPB blood was returned to the patient as soon as possible after CPB was weaned, and postoperative hemodynamics were stable in both groups. In Group N, hematocrit (Ht) values were consistently lower than in Group H, from initiation of CPB to leaving the hospital. To accomplish safe CPB, we measured systemic venous oxygen saturation (SvO2). In 6 cases of Group N, SvO2 during rewarming was 48.1 +/- 16.0% and Ht value was 13.2 +/- 1.5%. It is thought that the safe CPB could be conducted in Group N. In addition, in Group N, respiratory index showed better values than in Group H during the postoperative period. It is thought that CPB without blood transfusion may be favorable to prevent lung injury after CPB. Retrospectively, it is thought that, to accomplish safe CPB without blood transfusion, preoperative Ht values of over 30% are desirable in patients weighing 6 kg and those of over 35% are desirable in patients weighing 5 kg.     

Comparative Assessment of Coagulation Changes Induced by Two Different Types of Heart–Lung Machine

The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect on hemostasis. The aim of our study was to assess by means of standard laboratory and point-of-care methods changes induced by CPB in coagulation parameters, particularly in platelet function, and to determine whether these changes differ depending on the type of heart–lung machine (HLM) used: minimal extracorporeal circulation system (MECC) and standard HLM. The study enrolled 88 patients scheduled for coronary artery bypass surgery performed on pump. Forty-four interventions were performed with MECC and 44 with standard HLM. Blood was sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h postoperatively. Coagulation and platelet function were assessed using multiple electrode aggregometry (MEA), rotation thromboelastometry, as well as standard laboratory tests. Rotation thromboelastometry and standard laboratory reflected significantly impaired hemostasis after weaning from CPB but no significant differences between the two groups at different time points. Aggregation decreased significantly in both groups as early as 30 min after the institution of CPB ( P  < 0.05, Mann–Whitney U -test) and recovered within the first 24 h postoperatively, without reaching the preoperative level. Intraoperatively, aggregometry values reflected a significantly more severe reduction of platelet function in standard HLM group than in the MECC group ( P  < 0.01, ProcMixed test). Our findings suggest that MEA and thromboelastometry reflect impairment of coagulation in cardiac surgery performed on different types of HLM and that platelet function is less affected by MECC than by standard HLM.     

Large-dose propofol during cardiopulmonary bypass decreases biochemical markers of myocardial injury in coronary surgery patients: a comparison with isoflurane

We investigated if increasing propofol's dosage to augment its antioxidant capacity during cardiopulmonary bypass (CPB) could confer cardiac protection. Fifty-four coronary artery bypass graft surgery patients were randomly assigned to small-dose propofol (Group P; n = 18), large-dose propofol (Group HiP; n = 18), or isoflurane Group (Group I; n = 18). After the induction, anesthesia was maintained with an inspired concentration of isoflurane 1%-3.5% (Group I) or a continuous infusion of propofol 60 microg x kg(-1) x min(-1) (Group P) throughout the surgery. In Group HiP, this dose of propofol was increased to 120 microg x kg(-1) x min(-1) for 10 min before the onset of CPB until 15 min after aortic unclamping and then decreased to 60 microg x kg(-1) x min(-1) until the end of surgery. The duration of aortic cross-clamping was 83 +/- 24, 88 +/- 22, and 81 +/- 20 min in Group P, Group HiP, and Group I, respectively (P > 0.1). Plasma malondialdehyde, a marker of oxidative stress, was significantly lower at 8 h after CPB, and Troponin I was lower at 24 h after CPB in Group HiP compared with Group P and Group I (P < 0.05). There was a significant reduction in inotropic requirements for separation from CPB in Group HiP compared with Group I. Postoperative systemic vascular resistance was significantly reduced in Group HiP as compared with Group I. Mean cardiac index was significantly higher at 24 h after CPB in Group HiP compared with Group P and Group I (P < 0.05) (Group I, 2.2 +/- 0.1; Group P, 2.3 +/- 0.2; and Group HiP, 2.8 +/- 0.3 L x min(-1) x m(-2), respectively). The duration of intensive care unit stay was significantly shorter in Group Hi-P compared with Group I. We conclude that administration of a large dose of propofol during CPB attenuates postoperative myocardial cellular damage as compared with isoflurane or small-dose propofol anesthesia.     

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°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.     

Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass

BACKGROUND AND OBJECTIVE: The aim was to determine whether the administration of aprotinin can cause deleterious effects on renal function in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Sixty consecutive patients with normal preoperative renal function undergoing elective coronary artery bypass surgery with CPB using the same anaesthetic; CPB and surgical protocols were randomized into three groups. Patients received placebo (Group 1), low-dose aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG) excretion. Measurements were performed before surgery, during CPB and 24 and 72 h, and 7 and 40 days postoperatively. RESULTS: In the three groups, alpha1-microglobulin and beta-NAG excretions significantly increased during CPB, at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to preoperative levels at postoperative day 40. Plasma creatinine levels were within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin excretion during CPB was significantly higher than in Group 1 (P < 0.001), and 24h after surgery it still remained significantly higher in Group 3 compared to Groups 1 and 2 (P < 0.05). CONCLUSIONS: Aprotinin caused a significant increase in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB, which may be interpreted as a greater renal tubular overload without tubular damage. This effect persisted for 24 h after surgery when high-dose aprotinin doses had been administered. Creatinine plasma levels were not sensitive to detect these prolonged renal effects in our study.     

The Impact of Intraaortic Balloon Counterpulsation on Bypass Graft Flow in Patients with Peripheral ECMO

Abstract   Objective: Numerous reports have been performed to investigate the hemodynamic effects of intraaortic balloon pumping (IABP) and nonpulsatile circulatory extracorporeal membrane oxygenation (ECMO), but studies on its impact on coronary artery bypass graft flow during concomitant use of IABP and ECMO are lacking. The aim of this study was to assess the impact of additional IABP support on the degree of blood flow increase in bypass grafts in high-risk patients with nonpulsatile femoral venoarterial ECMO. Methods: In six emergency coronary artery bypass graft patients (mean age = 66.3 ± 2.1 years, gender = five males and one female, ejection fraction = 25.0 ± 3.0%) requiring mechanical circulatory support with ECMO hemodynamic parameters and bypass graft flows were measured with and without IABP counterpulsation. A transit time flowmeter was used for intraoperative graft flow and pulsatility index (PI) measurements. Patients provided their control values. Results: The average value of the mean arterial pressure recorded prior to IABP was 63.6 + 2.9 mmHg and during IABP support 67.8 + 2.9 mmHg (p < 0.0001). IABP augmented the mean bypass graft flow from 46.8 ± 9.6 mL/min to 56.4 ± 12.1 mL/min (p < 0.005), resulting in a 17% increase. The difference in the PI was not statistically significant (2.6 ± 0.2 with IABP, 2.6 ± 0.3 without IABP). Conclusions: We conclude that IABP-induced pulsatility significantly improves coronary bypass graft flows during nonpulsatile peripheral ECMO.     

Apolipoprotein E Levels in Pediatric Patients Undergoing Cardiopulmonary Bypass

Apolipoprotein E (apoE) may play a critical role in modulating the response to neurological injury after cardiopulmonary bypass (CPB) in children. Plasma samples were collected from 38 pediatric patients. Half of the patients received nonpulsatile flow and the other half underwent pulsatile flow during CPB. Plasma samples were collected at three time points: at baseline prior to incision (T1), 1 h after CPB (T2), and 24 h after CPB (T3). The study included 38 pediatric patients undergoing heart surgery (mean age 2.5 ± 2.1 years). Baseline apoE levels were low (<30 μg/mL) in 21 patients (55%). ApoE levels were significantly decreased at 1 h after CPB compared with baseline (22 ± 14 vs. 34 ± 18 μg/mL, P = 0.001). At 24 h after CPB, apoE levels were significantly increased compared with baseline (47 ± 25 vs. 34 ± 18 μg/mL, P = 0.002). Pulsatile mode was associated with lower apoE levels at 24 h after CPB compared with nonpulsatile mode (38 ± 14 vs. 57 ± 29 μg/mL, P = 0.018). ApoE levels correlated negatively with pump time (r = ?0.525, P = 0.021) and cross‐clamp time (r = ?0.464, P = 0.045) at 24 h following CPB for the nonpulsatile group but not for the pulsatile group. In this cohort of young children with congenital heart disease, baseline apoE levels were low in the majority of patients prior to surgery. ApoE levels decreased further at 1 h after CPB, and then significantly increased by 24 h. The mode of perfusion and the duration of pump time and clamp time influence the apoE levels after CPB. An improved understanding of these mechanisms may translate into the development of new techniques to improve the clinical outcomes after pediatric CPB.     

体外循环期间纤溶系统的变化规律及其机制的探讨

目的　探讨体外循环 (CPB)心脏直视手术期间纤溶系统的动态变化规律 ,探讨纤溶系统激活的机制。方法　 2 0例心脏直视手术患者 ,分别于麻醉诱导后切皮前、体外循环开始后 8、3 0min、鱼精蛋白中和肝素后 10min、术后 2h采集血标本 ,检测组织型纤溶酶原激活物 (t PA)、纤溶酶原激活物抑制剂 (PAI)、纤溶酶活性 (PLm)、D 二聚体 (D dimer)的动态变化。结果　术中t PA活性与术前相比显著升高 ,术后 2h恢复正常。PAI活性术中术后与术前相比差异无显著性。体外循环期间t PA/PAI比值显著升高 ,术后 2h恢复正常。手术期间D 二聚体含量显著升高 ,术后 2h仍维持较高水平。PLm活性在体外循环期间及中和后显著升高。结论　体外循环期间纤溶系统被明显激活 ,其主要机制是t PA分泌增加 ,t PA、PAI间的平衡失调和纤溶酶原的激活。     

D-Dimer formation during cardiac and noncardiac thoracic surgery.

The ability to make therapeutic decisions regarding excessive fibrinolysis in the perioperative period is limited by the lack of availability of a near site monitor of fibrinolysis. We investigated the use of a latex agglutination D-dimer assay to detect perioperative fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. We studied 27 patients who underwent thoracic surgery requiring cardiopulmonary bypass (CPB; coronary artery bypass grafting, n = 12; valvular surgery, n = 15) and a cohort of 20 patients who underwent noncardiac thoracic surgical procedures not requiring CPB. The purpose of this investigation was to determine the relationship among alterations in the latex agglutination D-dimer assay, use of extracorporeal circulation, type of cardiac surgical procedure, and mediastinal and/or chest tube drainage (cardiac surgery only) in patients undergoing thoracic surgery. Perioperative D-dimer levels, measured by latex agglutination, had significant (P < or = 0.05) intragroup changes among patients undergoing cardiac surgery (requiring CPB) and the cohort of patients who underwent noncardiac thoracic surgery without CPB. Although intraoperative D-dimer levels were not increased in patients undergoing noncardiac thoracic surgery, postoperative levels were significantly (P < 0.05) increased (compared with preinduction). In cardiac surgery patients requiring CPB, intraoperative D-dimer formation was significantly (P < or = 0.05) increased but did not demonstrate any intragroup (coronary artery bypass grafting versus valvular surgery) differences. Finally, D-dimer levels were not associated with postoperative mediastinal and/or chest tube accumulative drainage measured at intervals up to 48 h postoperatively in patients undergoing cardiac surgery requiring CPB. Our study indicates that the latex agglutination D-dimer assay can detect excessive fibrinolysis perioperatively, and that extracorporeal circulation can significantly influence the pattern of D-dimer formation in patients undergoing thoracic surgery. IMPLICATIONS: We assessed the ability of a readily available D-dimer assay to detect excessive fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. The findings demonstrate that the assay used in this investigation reflected variable amounts of fibrinolysis in patients undergoing both types of thoracic surgery.     

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckberg's blood cardioplegia during coronary artery bypass grafting (CABG). METHODS: Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS: There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.     

Evaluation of perfusion modes on vital organ recovery and thyroid hormone homeostasis in pediatric patients undergoing cardiopulmonary bypass

The objectives of this study were: (i) to evaluate the effects of perfusion modes (pulsatile vs. nonpulsatile) on vital organs recovery and (ii) to investigate the influences of two different perfusion modes on the homeostasis of thyroid hormones in pediatric patients undergoing cardiopulmonary bypass (CPB) procedures. Two hundred and eighty‐nine consecutive pediatric patients undergoing open heart surgery for repair of congenital heart disease were prospectively entered into the study and were randomly assigned to two groups: the pulsatile perfusion group (Group P, n = 208) and the nonpulsatile perfusion group (Group NP, n = 81). All patients received identical surgical, perfusional, and postoperative care. Study parameters included total drainage, mean urine output in the intensive care unit (ICU), intubation time, duration of ICU and hospital stay, the need for inotropic support, pre‐ and postoperative enzyme levels (ALT [alanine aminotransaminase] and AST [aspartate aminotransaminase]), c‐reactive protein, lactate, albumin, blood count (leukocytes, hematocrit, platelets), creatinine levels, and thyroid hormones (thyroid stimulating hormone [TSH], FT₃[free triiodothyronine], FT₄[free thyroxine]). All patients survived the perioperative and postoperative periods. There were no statistically significant differences in either preoperative or operative parameters between the two groups. Group P, compared to Group NP, required significantly less inotropic support, had a shorter intubation period, higher urine output in ICU, and shorter duration of ICU and hospital stay. Lower lactate levels and higher albumin levels were observed in Group P and there were no significant differences in creatinine, enzyme levels, blood counts, or drainage amounts between two groups. TSH, Total T₃, Total T₄, and FT₃, FT₄ levels were markedly reduced versus their preoperative values in both groups. FT₃ and FT₄ levels were reduced significantly further in the nonpulsatile group both during CPB and at 72 h postoperation. The results of this study confirm our opinion that pulsatile perfusion leads to better vital organ recovery and clinical outcomes in the early postoperative period as compared to nonpulsatile perfusion in pediatric patients undergoing CPB cardiac surgery. The plasma concentrations of thyroid hormones are dramatically reduced during and after CPB, but pulsatile perfusion seems to have a protective effect of thyroid hormone homeostasis compared to nonpulsatile perfusion.