Normothermic Bypass Research Articles

Effect of hypothermic versus normothermic cardiac bypass in patients undergoing coronary artery bypass grafting surgery on coagulation: a randomized controlled trial

Objectives To assess and compare early postoperative (PO) hematological and coagulation profile of patients undergoing on-pump coronary artery bypass grafting surgery with hypothermic (HT) versus normothermic (NT) cardiopulmonary bypass. Patients and methods A total of 86 patients were divided into two equal groups: NT group included patients who received warm bypass and HT group included patients who received cold bypass. PO monitoring included changes in 2-h PO hematological and coagulation profile in relation to preoperative profile and amount of PO daily blood loss and number of transfused blood units and its relation to change in coagulation profile. Results Mean activated clotting time estimated before wound closure was significantly longer in patients of HT group. At 2-h PO, hemoglobin concentration and platelet count (PC) were significantly lower, ADP-induced platelet aggregation (IPA) was significantly decreased, whereas activated partial thromboplastin time (aPTT) and international normalized ratio (INR) were significantly increased in HT patients. Estimated activated clotting time, IPA, INR, aPTT, and PC showed a negative significant correlation with the use of HT. The amount of PO daily bleeding and number of transfused units showed a positive significant correlation with the use of HT, 2-h PO aPTT, and INR, whereas showed a negative significant correlation with 2-h PO estimated IPA and hemoglobin concentration Regression analysis and receiver operating characteristic curve analysis defined the use of HT and prolonged aPTT as significant predictors for development of PO bleeding. Conclusion On-pump coronary artery bypass grafting surgery deleteriously affects hematological and coagulation profiles of patients, and this effect was accentuated by the use of HT. Two-hour PO altered PC and function and prolonged clotting times correlated with amount of PO daily bleeding and number of transfused blood units, but prolonged aPTT is the best predictor for these events.

Recent achievements and future developments in neonatal cardiopulmonary bypass.

A primary goal of improving neonatal cardiopulmonary bypass has been making the circuit smaller and reduce the blood contacting surfaces. As bypass circuit size has decreased, bloodless surgery has become possible even in neonates. Since transfusion guidelines are difficult to construct based on existing literature, these technical advances should be taken advantage of in conjunction with an individualized transfusion scheme, based on monitoring of oxygen availability to the tissues. For the majority of neonatal heart operations, several centers have shifted toward normothermic bypass even for complex neonatal surgeries, in order to avoid the adverse effects of hypothermia. Deep hypothermic circulatory arrest is no longer a necessity but an option, and selective antegrade cerebral perfusion has become common practice; however, technical uncertainties with regard to this technique have to be addressed, based on reliable neurologic monitoring. Maintenance of patient-specific heparin concentrations during bypass is another key goal, since neonates have lower baseline antithrombin concentrations and, therefore, a higher risk for inadequate thrombin inhibition and postoperative bleeding. Due to the immaturity of their hemostatic system, the standard coagulation tests alone are inappropriate to guide hemostatic therapy in neonates. The use of indirect heparin concentration assays and global viscoelastic assays in the operating room is likely to represent the optimal strategy, and requires validation in neonates. Monitoring of global and regional indexes of oxygen availability and consumption on bypass have become possible; however, their use in neonates still has outstanding technical issues which should be addressed and hence needs further validation. Due to the immaturity of the neonatal myocardium, single-shot cold cardioplegia solutions are thought to confer the best myocardial protection; their superiority when compared to more conventional modalities, however, remains to be demonstrated.

Effects of Cardiopulmonary Bypass Temperature and Time on Inflammatory Response

Background: To investigate the effect of cardiopulmonary bypass temperature and duration on inflammatory response in patients undergoing open heart surgery. Methods: The study group consisted of 43 patients and the patients were divided into two groups. Group 1 (n: 17) was operated using hypothermic bypass and group 2 (n: 26) was operated using normothermic bypass. Blood samples were taken for CRP, IL-6, IL-10 and TNF-α levels in the preoperative and postoperative period. Results: The demographic and preoperative characteristics of the patients were similar. The CRP level was significantly higher in the normothermic group than in the hypothermic group (Group 1: 92.2 ± 36.36, Group2: 120.58 ± 47.55) (p <0.05). In both groups, TNF-α, IL-6 and IL- No statistically significant difference was found in 10 values. (p> 0.05) When we evaluated the effect of CPB duration on inflammatory response, one unit change in aortic cross clamp duration increased IL-10 by 0.175 fold (p = 0.042 <0.05). The operation time was 10% significant. It was observed that 1 unit increase in the duration of operation increased the IL-6 level by 0.203 fold. (P <0.05) Conclusion: According to these results, it was seen that there was no significant difference in normothermic and hypothermic CPB patients, but prolonged operation time and aortic cross clamp duration increased inflammatory response. Key words : Cardiopulmonary bypass, hypothermia, inflammatory response, cytokine, open heart surgery DOI : 10.7176/JSTR/5-2-35

Comparison between normothermic and mild hypothermic cardiopulmonary bypass in myocardial revascularization of patients with left ventricular dysfunction

The aim of this study was to investigate whether normothermic bypass is superior to mild hypothermia in patients with poor left ventricular function. This was achieved by studying defibrillation rates, postoperative requirements of cardiac pacing or other morbidity issues and mortality in patients with left ventricular dysfunction operated upon for elective coronary revascularization. Data were collected retrospectively from 252 consecutive patients with left ventricular dysfunction (ejection fraction ≤35%) undergoing coronary revascularization between January 2005 and January 2011. Patients operated upon under mild hypothermia (32 ºC) were placed in Group 1 and under normothermia (≥35 ºC) were placed in Group 2. Comorbidities and postoperative complications were recorded. There were 128 patients in Group 1 and 124 patients in Group 2. Plasma concentrations of CK-MB and troponin T peaked at 6 hours postoperatively, with no significant difference between the groups. Despite longer aortic cross-clamp time and total bypass time in Group 2, significantly less defibrillation requirement rates after aortic declamping was observed. Hospital mortality occured in 16 patients; 8 patients in each group. Normothermia enables less requirement for defibrillation after aortic declamping and postoperative cardiac pacing in patients with left ventricular dysfunction, which may be interpreted as better myocardial protection under normothermic bypass. However, maintaining normothermia had no effect on postoperative stroke, postoperative atrial fibrillation, renal failure development and mortality.

Clinical and ultramicroscopic myocardial randomized study of beating versus arrested heart for mitral surgery

Beating heart surgery on normothermic bypass simulates physiologic cardiac status. This study compared clinical and transmission electron microscopic aspects of myocardial protection during mitral valve replacement using warm retrograde perfusion in empty beating versus arrested heart with cold blood anterograde cardioplegia. Randomized study to evaluate myocardial cellular ischemia-reperfusion of both techniques to replace the mitral valve. Thirty-four patients were randomly assigned into group A (beating heart) and group B (arrested heart). The following parameters were assessed: echocardiography, blood chemistry, hemoglobin, lactate. During the surgical procedure a total of 102 myocardial biopsies were performed for ultrastructural analysis from anterior left ventricular wall: before cardiopulmonary bypass, before aortic desclamping and 10 minutes after reperfusion. Elevation of lactate at 3 hours during the procedure was higher in group A, but similar at the end of surgery (P=0.06). Cardioversion was necessary in 5/17 (A) vs. 13/17 (B) P=0.07. Median intraoperative systemic temperature was significantly lower in the group B compared to A (32° C vs. 36° C), P<0.001. There was no significant difference of the ultramicroscopic aspects of the heart biopsies before, during and after surgery in both groups. Cellular and mitochondrial transient abnormalities such as mitochondrial swelling, glycogen loss and cytosol swelling were detected independently of the moment of the biopsies. Myocardial protection and ultrastructural abnormalities were similar for both types of mitral valve replacement beating or arrested heart techniques.

Can pregnant women be safely placed on cardiopulmonary bypass?

A best evidence topic was written according to a structured protocol. The question addressed was whether cardiopulmonary bypass can be used safely with satisfactory maternal and foetal outcomes in pregnant patients undergoing cardiac surgery. A total of 679 papers were found using the reported searches of which 14 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were maternal and foetal mortality and complications, mode of delivery, cardiopulmonary bypass and aortic cross-clamp times, perfusate flow rate and temperature and maternal NYHA functional class. The most recent of the best evidence studies, a retrospective observational study of 21 pregnant patients reported early and late maternal mortalities of 4.8 and 14.3%, respectively, and a foetal mortality of 14.3%. Median cardiopulmonary bypass and aortic cross-clamp times were 53 and 35 min, respectively, and the median bypass temperature was 37°C. Three larger retrospective reviews of the literature reported maternal mortality rates of 2.9-5.1% and foetal mortality rates of 19-29%. Mean cardiopulmonary bypass times ranged from 50.5 to 77.8min. Another retrospective observational study reported maternal mortality of 13.3% and foetal mortality of 38.5%. Mean cardiopulmonary bypass and aortic cross-clamp times were 89.1 and 62.8min, respectively, with a mean bypass temperature of 31.8°C. A retrospective case series reported no maternal mortality and one case of foetal mortality. Median cardiopulmonary bypass and aortic cross-clamp times were 101 and 88min, respectively. Eight case reports described 10 patients undergoing cardiopulmonary bypass. There were no reports of maternal mortality and one report of foetal mortality. Mean cardiopulmonary bypass and aortic cross-clamp times were 105 and 50min, respectively. We conclude that while the use of cardiopulmonary bypass during pregnancy poses a high risk for both the mother and the foetus, the use of high-flow, high-pressure, pulsatile, normothermic bypass and continuous foetal and uterine monitoring can allow cardiac surgery with the use of cardiopulmonary bypass to be performed with the greatest control of risk in the pregnant patient.

“Closed-Vein” Technique for Primary Sutureless Repair of Anomalous Pulmonary Venous Connection

Deep hypothermic circulatory arrest or low-flow bypass are commonly used in primary repair of total anomalous pulmonary venous connection, or individual veins may be dissected to allow clamp or snare application, in order to provide a bloodless field for anastomosis by the direct or sutureless marsupialization technique. In the described technical modification, the marsupialization of the opened atrium to the posterior pericardium is completed before opening the pulmonary venous confluence, allowing bloodless exposure during full-flow normothermic bypass. In addition, vein branch dissection is avoided.

Effectiveness of an Underbody Forced Warm-Air Blanket during Coronary Artery Bypass Surgery in the Prevention of Postoperative Hypothermia: A Prospective Controlled Randomized Clinical Trial

Introduction: Perioperative hypothermia in cardiac surgery is associated with adverse outcome. The aim of this investigation was to study whether an underbody forced-air warming blanket during coronary artery bypass graft surgery with normothermic cardiopulmonary bypass can prevent postoperative hypothermia. Methods: After Medical Ethics Committee approval, 60 low-risk cardiac surgery patients at random were assigned into a group that received standard thermal care management (control group n = 30) and a group that received the underbody forced-air warming system plus the standard thermal care (intervention group n = 30). Results: The temperature after-drop from the end of cardiopulmonary bypass to arrival in the ICU was less in the intervention group versus control group (0.4°C ± 0.3°C vs 0.6°C ± 0.4°C; P = 0.027). Out of the intervention group, 27 patients arrived in the ICU with a bladder temperature ? 36°C (90%) as compared to 14 patients (46.7%) from the control group (P < 0.001). The peripheral temperature was significantly higher in the intervention group as compared to the control group (P < 0.001). Conclusions: A full underbody forced-air warming blanket prevents postoperative hypothermia in normothermic coronary artery bypass graft surgery patients.

Invited Commentary

Among the voluminous advice and instruction given to graduating medical students, perhaps none is more familiar than the phrase, primum non nocere, which is translated as “first, do no harm.” This injunction, which is often attributed to Hippocrates, is violated daily by pediatric cardiac surgeons. Proof of this is encountered in the postoperative intensive care unit, where our patients virtually all “require” continuous infusions of inotropic drugs that they did not need before the operation. In severe cases, patients may emerge from the operating room with open sternotomy incisions, and some may even require temporary mechanical cardiac support. Happily for most patients, these deleterious effects of the operation are temporary and are reversed within a few days, when the benefit of the intervention finally begins to overwhelm its physiologic cost. Nonetheless, an enormous amount of effort has been devoted to minimization of iatrogenic harm during pediatric cardiac operations, with the emergence of such concepts as myocardial “protection” and improved whole-body homeostasis during cardiopulmonary bypass. To this end, several French centers have recently advocated the avoidance of hypothermia during bypass and cardioplegia and have reported excellent results with such an approach [1Durandy Y. Hulin S. Intermittent warm blood cardioplegia in the surgical treatment of congenital heart disease: clinical experience with 1400 cases.J Thorac Cardiovasc Surg. 2007; 133: 241-246Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 2Pouard P. Mauriat P. Ek F. et al.Normothermic cardiopulmonary bypass and myocardial cardioplegic protection for neonatal arterial switch operation.Eur J Cardiothorac Surg. 2006; 30: 695-699Crossref PubMed Scopus (62) Google Scholar]. The study by Belli and colleagues [3Belli E. Roussin R. Ly M. et al.Anomalous origin of the left coronary artery from the pulmonary artery associated with severe left ventricular dysfunction: results in normothermia.Ann Thorac Surg. 2010; 90: 856-861Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar] adds to this body of literature by describing outcomes for 21 patients with anomalous origin of the left coronary artery from the pulmonary artery and severely impaired ventricular function (shortening fraction <0.15), who underwent reimplantation of the anomalous left coronary into the aorta. This was accomplished with normothermic cardiopulmonary bypass and intermittent warm antegrade sanguineous cardioplegia. Early survival in the group was excellent (20 of 21), and there have been no late deaths. No patient required mechanical support after the operation, although 16 patients were managed with delayed sternal closure. One patient required transcatheter stent placement in the reimplanted left coronary artery for early stenosis and has undergone additional percutaneous angioplasty of the left main coronary artery. There were no operations on the mitral valve concomitant with or subsequent to the original coronary operation. Ventricular function and mitral valve function have both either improved or normalized in nearly all patients. The authors conclude that repair of anomalous origin of the left coronary artery from the pulmonary artery performed with normothermic bypass and cardioplegia is safe and effective in this particularly vulnerable population, even in the setting of severe left ventricular dysfunction. The authors are to be congratulated for truly superb results, but unfortunately, their study was not designed to answer the question of whether their approach is superior to the more commonly used hypothermic conduct of bypass and myocardial protection. The outcomes in the present study were achieved in patients with severe left ventricular dysfunction, and thus the approach the authors have taken seems to have neutralized such dysfunction as a risk factor in patients with anomalous origin of the left coronary artery from the pulmonary artery. However, the absence of a control group does not allow for such a conclusion to be regarded as definitive. The authors have, nonetheless, certainly answered whether or not a normothermic approach is safe in these sickest of patients. It is, and we must thank them for providing our community with the equipoise mandatory to allow a definitive randomized trial between normothermic and hypothermic approaches. Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Associated With Severe Left Ventricular Dysfunction: Results in NormothermiaThe Annals of Thoracic SurgeryVol. 90Issue 3PreviewRepair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) carries a high risk of operation, particularly in those with poor left ventricular function. In this study, we assessed the outcomes of patients who presented with severe preoperative left ventricular dysfunction (shortening fraction <15%) who underwent the repair under normothermic bypass. Full-Text PDF

A Comparison of Temporal Artery and Oral Electronic With Core Temperature in Normothermic Postoperative Coronary Artery Bypass Graft (CABG) Patients

A Comparison of Temporal Artery and Oral Electronic With Core Temperature in Normothermic Postoperative Coronary Artery Bypass Graft (CABG) Patients

Mixed venous versus central venous oxygen saturation in patients undergoing on pump beating coronary artery bypass grafting.

Objective:To examine the validity of central venous oxygen saturation (ScvO2) as a numerical substitution of mixed venous oxygen saturation (SvO2) in adult patients undergoing normothermic on pump beating coronary artery bypass grafting (CABG).Materials and Methods:Prospective clinical observational study was done at King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. Thirty four adult patients scheduled for coronary artery surgery were included. Patients were monitored by a pulmonary artery catheter (PAC) as a part of our routine intraoperative monitoring. SvO2 and ScvO2 were simultaneously measured 15 minutes (T1) and 30 minutes (T2) after induction of anesthesia, 15 and 30 minutes after initiation of cardiopulmonary bypass (T3 and T4), and 15 and 30 minutes after admission to intensive care unit (T5 and T6).Results:ScvO2 showed higher reading than SvO2 all through our study. Our results showed perfect positive statistically significant correlation between SvO2 and ScvO2 at all data points. Individual mean of difference (MOD) between both the readings at study time showed MOD of 1.34 and 1.44 at T1 and T2 simultaneously. This MOD was statistically insignificant, but after on pump beating normothermic bypass was initiated; MOD was 5.2 and 4.4 at T3 and T4 with high statistical significance. In ICU, MOD continues to have high statistical significance, MOD was 6.3 at T5 and at T6 it was 4.6.Conclusions:In on pump beating CABG patients; ScvO2 and SvO2 are not interchangeable numerically. ScvO2 is useful in the meaning of trend; our data suggest that ScvO2 is equivalent to SvO2 , only in the course of clinical decisions as long as absolute values are not required.

On-Pump Beating Heart Versus Hypothermic Arrested Heart Valve Replacement Surgery

Comparison of neurological parameters in patients undergoing prosthetic heart valve replacement with two operating techniques-either cardioplegic arrest of the heart under hypothermic cardiopulmonary bypass (CPB) or the heart beating on normothermic bypass, with or without cross-clamping the aorta, without cardioplegic arrest. methods: Fifty valvular surgery patients were randomly assigned into three groups. Sixteen patients underwent beating heart valve replacement with normothermic bypass without cross-clamping the aorta, 17 patients underwent the same procedure with cross-clamping the aorta and retrograde coronary sinus perfusion, and the remaining 17 patients had conventional surgery with hypothermic bypass and cardioplegic arrest. Two-channel electroencephalography (EEG) was recorded to assess changes in cerebral cortical synaptic activity and 95% spectral edge frequency values were recorded continuously. Bispectral monitoring was used to measure the depth of anesthesia. Blood flow rates in middle cerebral artery (MCA) were measured by transcranial Doppler (TCD). Reduction in spectral edge frequency (>50%) or bispectral index (BIS) (<20) or transcranial Doppler flow velocity (>50%) was detected in four patients in Group 1, five patients in Group 2, and three patients in Group 3. BIS or EEG values never reached zero, which indicates isoelectric silence during surgery. Gross neurological examinations were normal in all patients postoperatively. There is no difference regarding neurological monitoring results between on-pump beating heart and hypothermic arrested heart valve replacement surgery. Also no significant difference was encountered among the groups regarding the clinical outcomes.

Mitral and Tricuspid Valve Surgery in Homozygous Sickle Cell Disease: Perioperative Considerations for a Successful Outcome

Homozygous sickle cell disease (SCD) presents a multitude of challenges in patients undergoing cardiac surgery with cardiopulmonary bypass. Special consideration must be made in such patients and routine practice modified to prevent hypoxia, hypothermia, acidaemia and low-flow states which may potentially trigger a fatal sickling crisis perioperatively. We discuss several perioperative management strategies including a preoperative exchange transfusion, high flow normothermic bypass and warm blood cardioplegia that was utilized in a woman with homozygous SCD who underwent a successful double valve procedure.

The Response of the Vascular Beds to Sodium Bicarbonate in Patients During Normothermic Bypass

Cardiopulmonary bypass (CPB) provides a unique circumstance to study the effects of drugs on the systemic vasculature. Thus, this study was designed to evaluate the effects of sodium bicarbonate on the systemic circulation during CPB in humans. Randomized, double-blind study. Tertiary care university hospital. Patients presenting for coronary artery bypass graft surgery with CPB. In this double-blind study, 22 consecutive adult patients of both sexes undergoing cardiac surgery were randomized into 2 groups. After establishing CPB and cardioplegia, patients in group 1 (n = 11) received saline (0.9%) (1.2 mL/kg), and group 2 received sodium bicarbonate (SB) (7%) (1.2 mL/kg). The blood level in the cardiotomy reservoir, pump flow, and mean arterial pressure were measured for 25 minutes. The SB-treated patients (group 2) showed significantly greater (p < 0.05) decreases in cardiotomy reservoir blood volume (336 +/- 186 mL) than the saline-treated (140 +/- 97 mL) patients. The mean arterial pressure in group 2 patients significantly (p < 0.05) increased (from 49 +/- 11.9 to 65 +/- 5.3 mmHg) more than in the saline group (from 50 +/- 6.8 to 57 +/- 9.2 mmHg) after 20 minutes. The decrease in reservoir volume significantly (p < 0.05) and inversely correlated (r = -0.61) with the acidotic state of the patients before SB. This study found a biphasic response to SB on the systemic circulation during CPB. Early dilation of venous capacitance vessels occurred followed by arteriolar constriction over the 20-minute study interval.

Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation

High flow rates during cardiopulmonary bypass are assumed to increase fluid accumulation. This study aimed to determine whether two different flow rates during cardiopulmonary bypass alter the intraoperative fluid balance and extravasation rate. Sixteen pigs underwent 60 minutes of normothermic bypass, followed by 90 minutes of hypothermic bypass. A high-flow group (HF group, n = 8) had a cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) and a low-flow group (LF group, n = 8) had a rate of 80 mL x kg(-1) x min(-1). Blood chemistry, hemodynamic parameters, plasma and interstitial colloid osmotic pressure, net fluid balance, plasma volume, fluid extravasation rate, and total tissue water content were measured or calculated. Results are presented as mean (standard deviation). The average net fluid balance during cardiopulmonary bypass was 1.02 (0.25) and 0.73 (0.23) mL x kg(-1) x min(-1) in the HF group and LF group, respectively (P < .05). The average fluid extravasation rate was 0.98 (0.22) and 0.77 (0.22) mL x kg(-1) x min(-1) in the HF group and the LF group (P = .07). Total water content was higher in the kidneys (P < .05) and tended to be higher in the lungs (P = .05), liver (P = .07), and brain (P = .07) of the HF group than in those of the LF group. The between-group differences in net fluid balance and fluid extravasation rate were present during the first 30 minutes of normothermic cardiopulmonary bypass. Thereafter, the values stabilized and remained similar in the two groups. Plasma volume and systemic vascular resistance differed between the groups. Cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) was associated with higher positive net fluid balance and fluid extravasation rate than 80 mL x kg(-1) x min(-1). The effect was mainly observed in the initial phase of cardiopulmonary bypass.

Increased cerebral and renal endothelial nitric oxide synthase gene expression after cardiopulmonary bypass in the rat

Hemodilution and endothelial nitric oxide synthase genetic polymorphism may contribute to cerebral and renal injury after cardiopulmonary bypass. This study tested the hypothesis that cardiopulmonary bypass and anemia stimulate an increase in cerebral and renal endothelial nitric oxide synthase gene expression in an experimental model of cardiopulmonary bypass. Anesthetized rats underwent a sham procedure without cardiopulmonary bypass (sham, n = 5), normothermic bypass for 1 hour (CPB, n = 7), or bypass plus hemodilutional anemia (CPB anemia, n = 9). After 24 hours of recovery, RNA was extracted from the cerebral cortex, renal cortex, and renal medulla. Quantitative reverse transcriptase polymerase chain reaction was used to assess endothelial nitric oxide synthase messenger RNA levels in brain and kidney tissues. The hemoglobin concentration of anemic CPB rats was significantly lower than that of nonanemic rats on bypass (64 +/- 5 vs 99 +/- 8 g x L(-1), P < .001). Cerebral cortical endothelial nitric oxide synthase messenger RNA levels were increased after cardiopulmonary bypass relative to those of the sham group (11.2 +/- 4.2 vs 6.3 +/- 1.5 fg, P = .031), without a further increase in anemic rats. Renal medullary endothelial nitric oxide synthase messenger RNA levels were significantly higher in the CPB anemia group than in the sham and CPB groups (7.1 +/- 4.4 fg vs 1.8 +/- 0.4 fg vs 3.0 +/- 0.6 fg, P < .001). Renal cortical endothelial nitric oxide synthase messenger RNA levels did not change significantly. Normothermic cardiopulmonary bypass was associated with higher endothelial nitric oxide synthase messenger RNA levels in kidney and brain than was the sham procedure 24 hours after cardiopulmonary bypass. Anemia accentuated the increase in renal medullary, but not cerebral cortical, endothelial nitric oxide synthase expression. These data provide an approach for exploring potential mechanisms by which endothelial nitric oxide synthase may contribute to renal and cerebral dysfunction after cardiopulmonary bypass and anemia.

Comparison of hollow-fiber membrane oxygenators with different perfusion modes during normothermic and hypothermic CPB in a simulated neonatal model

The objectives of this investigation were (1) to compare two hollow-fiber membrane oxygenators (Capiox Baby RX versus Lilliput 1-D901) in terms of pressure drops and surplus hemodynamic energy (SHE) during normothermic and hypothermic cardiopulmonary bypass (CPB) in a simulated neonatal model; and (2) to evaluate pulsatile and non-pulsatile perfusion modes for each oxygenator in terms of SHE levels. In a simulated patient, CPB was initiated at a constant pump flow rate of 500 mL/min. The circuit was primed with fresh bovine blood. After 5 min of normothermic CPB, the pseudo-patient was cooled down to 25 degrees C for 10 min followed by 30 min of hypothermic CPB. The pseudo-patient then underwent 10 min of rewarming and 5 min of normothermic CPB. At each experimental site (pre- and post-oxygenator and pre-aortic cannula), SHE was calculated using the following formula {SHE (ergs/cm3) = 1332 [((integralfpdt)/(integralfdt)) - mean arterial pressure]} (f = pump flow and p = pressure). A linear mixed-effects model that accounts for the correlation among repeated measurements was fit to the data to assess differences in SHE between oxygenators, pumps, and sites. Tukey's multiple comparison procedure was used to adjust p-values for post-hoc pairwise comparisons. The pressure drops in the Capiox group compared to the Lilliput group were significantly lower during hypothermic non-pulsatile (21.3 +/- 0.5 versus 50.7 +/- 0.9 mmHg, p < 0.001) and pulsatile (22 +/- 0.0 versus 53.3 +/- 0.5 mmHg, p < 0.001) perfusion, respectively. Surplus hemodynamic energy levels were significantly higher in the pulsatile group compared to the non-pulsatile group, with Capiox (1655 +/- 92 versus 10008 +/- 1370 ergs/cm3, p < 0.001) or Lilliput (1506 +/- 112 versus 7531 +/- 483 ergs/cm3, p < 0.001) oxygenators. During normothermic CPB, both oxygenators had patterns similar to those observed under hypothermic conditions. The Capiox oxygenator had a significantly lower pressure drop in both pulsatile and non-pulsatile perfusion modes. For each oxygenator, the SHE levels were significantly higher in the pulsatile mode.

Normothermic bypass in pediatric surgery: technical aspect and clinical experience with 1400 cases.

We analyzed our experience with warm perfusion and blood cardioplegia in pediatric surgery. Warm surgery was performed in 1400 patients. Prime and perfusate are kept at 37 degrees C before and during bypass and intermittent warm blood cardioplegia is used for myocardial protection. Analyzed parameters were: perioperative blood gas, hydric balance of cardioplegia, spontaneous resumption of rhythm after aortic unclamping, troponin I level, postoperative neurologic and renal function, duration of mechanical ventilation (five diagnostic groups), and duration of intensive care unit (ICU) stay. Satisfactory gas exchange is the rule, and fluid addition is negligible during warm cardioplegia. Spontaneous resumption of sinus rhythm occurred in 99% of patients, Troponin I elevation was < 10 ng/ml in 46% of cases. Prevalence of neurologic complications (0.3%) and of renal insufficiency treated by peritoneal dialysis (0.35%) favorably compares with data reported in the literature. Average mechanical ventilation time was < 48 hours in each diagnostic group. Duration of ICU stay was < 48 hours in 86% of the 1400 patients. In our experience, normothermic surgery is an excellent alternative to hypothermia.

GP IIb‐IIIa Receptor Blockers Minimize Vascular and Perivascular Damage in the Hippocampus after Cardiopulmonary Bypass Management

Brain injury remains a significant and potentially devastating outcome of cardiopulmonary bypass (CPB) under circulatory arrest. These outcomes caused by a microvasculature embolization are associated with increased mortality, longer hospital stays and increased use of intermediate or long term care facilities. The administration of heparin in heart surgery during deep hypothermic cardiopulmonary bypass is the basic prophylactic strategy for reducing or even preventing, microvasculature embolization. Unfortunately, an incidence of neuropsychological impairments (NPI) is found in as many as 25 % of the survivors. As it is suspected that these impairments are correlated with morphological alterations, in our study we use the GP IIb‐IIIa receptor blocker Eptifibatide for the inhibition of platelet aggregation, in order to look for a reduction of tissue damage compared to the standard treatment. Two groups of 11 piglets (mean body weight of 15±5 kg) underwent 10‐minute normothermic bypass, 40‐minute cooling on cardiopulmonary bypass, 60‐minutes deep hypothermic circulatory arrest (DHCA) at 15°C, and 40‐minute rewarming to 37°C. Group 1 was treated only with unfractionated heparin (UFH), whereas Group 2 was medicated with Eptifibatide, in addition to the UFH‐treatment group 1. After rewarming, all animals underwent bilateral carotid perfusion with 4% paraformaldehyde. Histological investigations of semi thin sections reveal a marked decrease of hippocampal alterations by using the GP IIb‐IIIa receptor blocker in addition to standard UFH treatment. We detect a reduction of degenerative areas in perivascular (vessels with 10–30 μm in diameter) tissue. These semi‐quantitative data are confirmed by ultrastructural findings.

Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: An intravital fluorescence microscopy study in pigs

Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.