Strategies to Improve Survival from Surgery for Heart Valve Implantation in Sheep.

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

The influence of gaseous microemboli on various biomarkers after minimized cardiopulmonary bypass.

INTRODUCTION: Gaseous microemboli that originate from the cardiopulmonary bypass circuit may contribute to adverse outcome after cardiac surgery. We prospectively evaluated the influence of gaseous microemboli on the release of various biomarkers after use of a minimally invasive extracorporeal technology system. METHODS: In 70 patients undergoing coronary artery bypass grafting with minimized cardiopulmonary bypass, gaseous microemboli were measured intraoperatively with a bubble counter. Intra- and postoperative biomarker levels for inflammatory response (interleukin-6, C5b-9), endothelial damage (von Willebrand factor, soluble vascular cell adhesion molecule-1), oxidative stress (malondialdehyde, 8-isoprostane, neuroketal), and neurological injury (neuron-specific enolase, brain-type fatty acid-binding protein) were analyzed using immune assay techniques. The relationship between gaseous microemboli number or volume and the incremental area under the curve (iAUC24h) or peak change for the biomarkers was calculated. RESULTS: All biomarkers except for malondialdehyde increased at least temporarily after coronary artery bypass grafting with a minimally invasive extracorporeal technology system. The median total gaseous microemboli number was 6,174 (interquartile range: 3,507-10,531) and the median total gaseous microemboli volume was 4.31 µL (interquartile range: 2.71-8.50). There were no significant correlations between total gaseous microemboli number or volume and iAUC24h or peak change for any of the biomarkers. After controlling for the variance of possible other predictor variables, multiple linear regression analysis showed no association between gaseous microemboli parameters and release of biomarkers. CONCLUSION: This study showed no evidence that gaseous microemboli contribute to increased biomarker levels after coronary artery bypass grafting with cardiopulmonary bypass. A reason for the absence of damage by gaseous microemboli may be the relative and considerably small amount of gaseous microemboli entering the patients in this study.

Air removal capacity of two different minimal invasive ECC systems: an in vitro comparison.

Minimally invasive extracorporeal circulation systems are developed to decrease the deleterious effects of cardiopulmonary bypass. For instance, prime volume and foreign surface area are decreased in these systems. However, because of the lack of a venous reservoir in minimized systems, air handling properties of these minimally invasive extracorporeal circulation systems may be decreased as compared to conventional cardiopulmonary bypass systems. The aim of this in vitro study is to compare the air handling properties of two complete minimized cardiopulmonary bypass systems of two manufacturers, of which one system is provided with the air purge control. In an in vitro study, two minimally invasive extracorporeal circulation systems, Inspire Min.I manufactured by Sorin Group Italia, Mirandola, Italy (LivaNova, London, United Kingdom) and minimized extracorporeal circulation manufactured by Maquet, Rastatt, Germany (Getinge, Germany), were challenged with two types of air challenges; a bolus air challenge and a gaseous microemboli challenge. The air removal characteristics of the venous bubble traps and of the complete minimally invasive extracorporeal circulation systems were assessed by measuring the gaseous microemboli volume and number downstream of the venous bubble traps in the arterial line with a bubble counter. No significant differences were observed in air reduction between the venous bubble traps of Getinge (venous bubble traps) and LivaNova (Inspire venous bubble traps 8 in conjunction with the air purge control). Similarly, no significant differences were observed in volume and number of gaseous microemboli in the arterial line of both complete minimally invasive extracorporeal circulation systems. However, the gaseous microemboli load of the Inspire Min.I system was marginally lower after both the bolus air and the gaseous microemboli challenges. Both minimally invasive extracorporeal circulation systems assessed in this study, the LivaNova Inspire Min.I and the Getinge minimized extracorporeal circulation, showed comparable air removal properties, after both bolus and gaseous microemboli air challenges. Besides, air purge control automatic air removal system provided with the LivaNova Inspire Min.I. system may enhance patient's safety with the use of a minimally invasive extracorporeal circulation system. We consider both systems equally safe for clinical use.

Carbon Dioxide Flush of an Integrated Minimized Perfusion Circuit Prior to Priming Prevents Spontaneous Air Release Into the Arterial Line During Clinical Use.

Recently, an oxygenator with an integrated centrifugal blood pump (IP) was designed to minimize priming volume and to reduce blood foreign surface contact even further. The use of this oxygenator with or without integrated arterial filter was compared with a conventional oxygenator and nonintegrated centrifugal pump. To compare the air removal characteristics 60 patients undergoing coronary artery bypass grafting were alternately assigned into one of three groups to be perfused with a minimized extracorporeal circuit either with the conventional oxygenator, the oxygenator with IP, or the oxygenator with IP plus integrated arterial filter (IAF). Air entering and leaving the three devices was measured accurately with a bubble counter during cardiopulmonary bypass. No significant differences between all groups were detected, considering air entering the devices. Our major finding was that in both integrated devices groups incidental spontaneous release of air into the arterial line in approximately 40% of the patients was observed. Here, detectable bolus air (>500 µm) was shown in the arterial line, whereas in the minimal extracorporeal circulation circuit (MECC) group this phenomenon was not present. We decided to conduct an amendment of the initial design with METC-approval. Ten patients were assigned to be perfused with an oxygenator with IP and IAF. Importantly, the integrated perfusion systems used in these patients were flushed with carbon dioxide (CO2 ) prior to priming of the systems. In the group with CO2 flush no spontaneous air release was observed in all cases and this was significantly different from the initial study with the group with the integrated device and IAF. This suggests that air spilling may be caused by residual air in the integrated device. In conclusion, integration of a blood pump may cause spontaneous release of large air bubbles (>500 µm) into the arterial line, despite the presence of an integrated arterial filter. CO2 flushing of an integrated cardiopulmonary bypass system prior to priming may prevent spontaneous air release and is strongly recommended to secure patient safety.

Clinical evaluation of the air-handling properties of contemporary oxygenators with integrated arterial filter.

Gaseous microemboli (GME) may originate from the extracorporeal circuit and enter the arterial circulation of the patient. GME are thought to contribute to cerebral deficit and to adverse outcome after cardiac surgery. The arterial filter is a specially designed component for removing both gaseous and solid microemboli. Integration of an arterial filter with an oxygenator is a contemporary concept, reducing both prime volume and foreign surface area. This study aims to determine the air-handling properties of four contemporary oxygenator devices with an integrated arterial filter. Two oxygenator devices, the Capiox FX25 and the Fusion, showed significant increased volume of GME reduction rates (95.03 ± 3.13% and 95.74 ± 2.69%, respectively) compared with both the Quadrox-IF (85.23 ± 5.84%) and the Inspire 6F M (84.41 ± 12.93%). Notably, both the Quadrox-IF and the Inspire 6F M as well as the Capiox FX 25 and the Fusion showed very similar characteristics in volume and number reduction rates and in detailed distribution properties. The Capiox FX25 and the Fusion devices showed significantly increased number and volume reduction rates compared with the Quadrox-IF and the Inspire 6F M devices. Despite the large differences in design of all four devices, our study results suggest that the oxygenator devices can be subdivided into two groups based on their fibre design, which results in screen filter (Quadrox-IF and Inspire 6F M) and depth filter (Capiox FX25 and Fusion) properties. Depth filter properties, as present in the Capiox FX25 and Fusion devices, reduced fractionation of air and may ameliorate GME removal.

Effect of Oxygenator Size on Air Removal Characteristics: A Clinical Evaluation.

During cardiopulmonary bypass (CPB), gaseous microemboli (GME) are released into the patients' arterial bloodstream. Gaseous microemboli may contribute to the adverse outcome after cardiac surgery. Recently, two oxygenator models with or without integrated arterial filter (IAF) were designed and only differ in size, leading to a change of 20% in surface area of the hollow fibers and 25% in blood velocities. The aim of this study was to assess the air removal characteristics of the inspire oxygenators with or without IAF. Sixty-eight patients were randomly assigned to four different groups: optimized adult and full adult and an additional IAF. Gaseous microemboli reduction rates were measured with a bubble counter. The number of GME reduction rates showed no differences. However, both models reduced significantly less volume of GME (optimized adult: 40.6% and full adult: 50.3%) compared with both models with IAF (88.7% and 88.5%, respectively). No significant differences of reduction rates were found between both devices without IAF and also not between both models with IAF. In conclusion, the larger inspire oxygenator tends to remove more GME. No effect from size of oxygenator device with integrated screen filter on GME reduction was observed. The inspire oxygenators with IAF may be considered as an adequate GME filter.

Comparison of Warm Blood Cardioplegia Delivery With or Without the Use of a Roller Pump.

Various techniques for administration of blood cardioplegia are used worldwide. In this study, the effect of warm blood cardioplegia administration with or without the use of a roller pump on perioperative myocardial injury was studied in patients undergoing coronary artery bypass grafting using minimal extra-corporeal circuits (MECCs). Sixty-eight patients undergoing elective coronary bypass surgery with an MECC system were consecutively enrolled and randomized into a pumpless group (PL group: blood cardioplegia administration without roller pump) or roller pump group (RP group: blood cardioplegia administration with roller pump). No statistically significant differences were found between the PL group and RP group regarding release of cardiac biomarkers. Maximum postoperative biomarker values reached at T1 (after arrival intensive care unit) for heart-type fatty acid binding protein (2.7 [1.5; 6.0] ng/mL PL group vs. 3.2 [1.6; 6.3] ng/mL RP group, p = .63) and at T3 (first postoperative day) for troponin T high-sensitive (22.0 [14.5; 29.3] ng/L PL group vs. 21.1 [15.3; 31.6] ng/L RP group, p = .91), N-terminal pro-brain natriuretic peptide (2.1 [1.7; 2.9] ng/mL PL group vs. 2.6 [1.6; 3.6] ng/mL RP group, p = .48), and C-reactive protein (138 [106; 175] µg/mL PL group vs. 129 [105; 161] µg/mL RP group, p = .65). Besides this, blood cardioplegia flow, blood cardioplegia line pressure, and aortic root pressure during blood cardioplegia administration were similar between the two groups. Administration of warm blood cardioplegia with or without the use of a roller pump results in similar clinically acceptable myocardial protection.

In vitro air removal characteristics of two neonatal cardiopulmonary bypass systems: filtration may lead to fractionation of bubbles.

Introduction of gaseous microemboli (GME) into the arterial line of a pediatric cardiopulmonary bypass (CPB) circuit may lead to cognitive decline and adverse outcomes of the pediatric patient.Arterial filters are incorporated into CPB circuits as a safeguard for gross air and to reduce GME. Recently, arterial filters were integrated in two neonatal oxygenators to reduce volume and foreign surface area. In this study a clinical CPB scenario was simulated. The oxygenators, the corresponding venous reservoirs and the complete CPB circuits were compared regarding air removal and bubble size distribution after the introduction of an air bolus or GME. During a GME challenge, the Capiox FX05 oxygenator removed a significantly higher volume of GME than the QUADROX-i Neonatal oxygenator (97% vs. 86%). Detailed air removal characteristics showed that more GME in the range of 20-50 µm were leaving the devices than were entering. This phenomenon seems to be more present in the Capiox FX05. The circuits were also challenged with an air bolus. Each individual component tested removed 99.9%, which resulted in an air volume reduction of 99.99% by either complete CBP circuit. Overall, we conclude that both CPB systems were very adequate in removing GME and gross air. The air removal properties of both systems are considered safe and reliable. Detailed GME distribution data show that the Capiox FX05 showed more small GME (<50 µm) due to fractionation of larger GME when compared to the QUADROX-i Neonatal. We may conclude that filtration may lead to fractionation.

Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P < 0.01]. Cell salvage resulted in the lowest hemolysis levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

Clinical evaluation of the air removal characteristics of an oxygenator with integrated arterial filter in a minimized extracorporeal circuit.

The use of minimized extracorporeal circuits (MECC) in cardiac surgery is an important measure to increase the biocompatibility of cardiopulmonary bypass during coronary artery bypass grafting (CABG). These circuits eliminate volume storage reservoirs and bubble traps to minimize the circuit. However, the reduction in volume may increase the risk of gaseous microemboli (GME). The MECC system as used by our group consists of a venous bubble trap, centrifugal pump, and an oxygenator. To further reduce the risk of introducing GME, an oxygenator with an integrated arterial filter was developed based on the concept of minimal volume and foreign surface. We studied the air removal characteristics of this oxygenator with and without integrated arterial filter. The quantity and volume of GME were measured with precision at both the inlet and outlet of the devices. Our results showed that integration of an arterial filter into this oxygenator increased GME reducing capacity from 69.2% to 92%. Moreover, we were able to obtain data on the impact of an arterial filter on the exact size-distribution of GME entering the arterial line. The present study demonstrates that an MECC system and oxygenator with integrated arterial filter significantly reduces the volume and size of GME. The use of an integrated arterial filter in an MECC system may protect the patient from the deleterious effects of CPB and may further improve patient safety.

Air removal efficiency of a venous bubble trap in a minimal extracorporeal circuit during coronary artery bypass grafting.

The use of minimized extracorporeal circuits (MECC) in cardiac surgery is expanding. These circuits eliminate volume storage and bubble trap reservoirs to minimize the circuit. However, this may increase the risk of gaseous micro emboli (GME). To reduce this risk, a venous bubble trap was designed. This study was performed to evaluate if incorporation of a venous bubble trap in a MECC system as compared to our standard minimized extracorporeal circuit without venous bubble trap reduces gaseous micro emboli during cardiopulmonary bypass (CPB). Forty patients were randomly assigned to be perfused either with or without an integrated venous bubble trap. After preliminary evaluation of the data of 23 patients, the study was terminated prior to study completion. The quantity and volume of GME were significantly lower in patients perfused with a venous bubble trap compared to patients perfused without a venous bubble trap. The present study demonstrates that a MECC system with a venous bubble trap significantly reduces the volume of GME and strongly reduces the quantity of large GME (>500 µm). Therefore, the use of a venous bubble trap in a MECC system is warranted.

The association of hemodilution and transfusion of red blood cells with biochemical markers of splanchnic and renal injury during cardiopulmonary bypass.

BACKGROUND: Hemodilution is the main cause of a low hematocrit concentration during cardiopulmonary bypass. This low hematocrit may be insufficient for optimal tissue oxygen delivery and often results in packed cell transfusion. Our objective in this study was to find a relationship between intraoperative hematocrit and allogeneic blood transfusion on release of postoperative injury markers from the kidneys and the splanchnic area. METHODS: Fifty consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were included. Systemic tissue hypoxia was assessed by lactate concentrations. Kidney and splanchnic ischemia were assessed by the measurement of N-acetyl-beta-D-glucosaminidase (NAG) and intestinal fatty acid binding protein (IFABP) in urine. Patients were retrospectively placed into groups according to their lowest hematocrit concentration on bypass (<24% or >or=24%). RESULTS: The intraoperative lactate and the postoperative NAG and IFABP concentrations were higher in the low hematocrit group (<24%) than in the high hematocrit group (>or=24%; P < 0.05). Low hematocrit correlated with higher lactate concentrations (R(2) = 0.150, P < 0.01) and with higher NAG concentrations (R(2) = 0.138, P < 0.01) and IFABP concentrations (R(2) = 0.107, P < 0.01) postoperatively. Transfusion of packed cells during cardiopulmonary bypass correlated with higher lactate (R(2) = 0.089, P < 0.05), NAG (R(2) = 0.431, P < 0.01), and IFABP concentrations (R(2) = 0.189, P < 0.01). CONCLUSIONS: The results support the concept that hemodilution below an intraoperative hematocrit of 24% and consequently transfusion of red blood cells is related to release of injury markers of the kidneys and splanchnic area.

A new system for right atrial cooling.

PURPOSE: Controlled hypothermia of the right atrium has been shown to reduce postoperative atrial fibrillation after on-pump coronary artery bypass grafting. A device has been developed that couples right atrial and nodal cooling with modified dual-stage venous drainage by circulating cold sterile saline through an intracavity, shape-memory balloon. DESCRIPTION: The atrial cooling device was used in 41 patients undergoing elective coronary artery bypass grafting. Systemic temperatures were held at 36 degrees C, and temperatures of atrial structures were reduced to about 19 degrees to 20 degrees C at 30 minutes. EVALUATION: Electrical activity was effectively suppressed during cross-clamp by controlled cooling of the right atrium. Hemodilution was reduced by right atrial isolation and collection of crystalloid cardioplegia. Cardiac electrical activity returned without sustained arrhythmias in all patients. Postoperative atrial fibrillation developed in only 3 of the 38 patients. CONCLUSIONS: The results indicate that local atrial cooling may contribute to protection of the right atrium, subsequently reducing the incidence of transient postoperative atrial fibrillation.

Attenuated renal and intestinal injury after use of a mini-cardiopulmonary bypass system.

BACKGROUND: Transient, subclinical myocardial, renal, intestinal, and hepatic tissue injury and impaired homeostasis is detectable even in low-risk patients undergoing conventional cardiopulmonary bypass (CPB). Small extracorporeal closed circuits with low priming volumes and optimized perfusion have been developed to reduce deleterious effects of CPB. METHODS: A prospective, randomized trial was conducted in 49 patients undergoing elective coronary artery bypass graft surgery either with the use of a standard or mini-CPB system (Synergy). We determined early postoperative inflammatory response (leukocytosis, C-reactive protein, urine interleukin-6), platelet consumption and activation (urine thromboxane B2), proximal renal tubular injury (urine N-acetyl-glucosaminidase), and intestinal injury (intestinal fatty acid binding protein). RESULTS: In patients undergoing coronary artery bypass grafting with a mini-CPB system, we observed decreased priming volumes with subsequent attenuation of on-pump hemodilution, improved hemostatic status with reduced platelet consumption and platelet activation, decreased postoperative bleeding and minimized transfusion requirements. We also found reduced leukocytosis and decreased urinary interleukin-6. Levels of urine N-acetyl-glucosaminidase were on average threefold lower, and urinary intestinal fatty acid binding protein was 40% decreased in the patients on the mini-CPB system, as compared with standard CPB. CONCLUSIONS: The use of the mini-CPB system during myocardial revascularization represents a viable nonpharmacologic strategy that can attenuate the alterations in the hemostatic system, reduce bleeding and transfusion requirements, decrease systemic inflammatory response, and reduce immediate postoperative renal and intestinal tissue injury.

First clinical experience with the air purge control and electrical remote-controlled tubing clamp in mini bypass.

Most mini bypass systems do not contain a venous and cardiotomy reservoir in the cardiopulmonary bypass (CPB) circuit and lack the capability to remove venous air. In conjunction with the manufacturer the air purge control system, a system which automatically removes air that is captured in a venous bubble trap, has been developed. This system is combined with an electrical remote clamp, which automatically clamps the arterial line in case air leaves the bubble trap. Twenty consecutive patients undergoing surgery with CPB were included in this clinical validation. Venous air was removed by the air purge control during bypass. The electrical remote clamp was never activated by the system, confirming that the air purge control adequately removed venous air during these cases. The air purge control, in conjunction with the electrical remote clamp, is a valuable safety feature in mini bypass, enhancing patient safety and user friendliness while providing a level of safety equivalent to those of conventional bypass systems.

The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass.

This study was performed to investigate if heparin-coated extracorporeal circuits can reduce the systemic inflammatory reaction with the subsequent release of vasoactive substances during and after cardiopulmonary bypass. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin-coated or an uncoated circuit. During bypass the mean arterial pressure was maintained as near as possible to 60 mm Hg. Mediators for inflammation, hemodynamic, and oxygen parameters were determined during and after bypass. To reach the target mean arterial pressure in the first hour of bypass the pump flow in the uncoated group had to be increased (P<0.05), consequently the systemic vascular resistance index decreased (P<0.05). After bypass more inotropic support was necessary in this group to reach this pressure. In the coated group less bradykinin, complement activation, and elastase was generated during bypass (P<0.05). The results of this study suggest that heparin coating not only improves biocompatibility, but also ameliorates the hemodynamic instability during and after bypass.

The impact of heparin coated circuits upon metabolism in vital organs: effect upon cerebral and renal function during and after cardiopulmonary bypass.

During cardiopulmonary bypass (CPB), the brain and the kidneys may be damaged because of microemboli, ischemia, and inflammation. The latter has been reduced by the use of heparin coated circuits. We questioned whether heparin coated circuits could also reduce cerebral and renal damage and whether inflammatory markers correlate with damage to the brain and the kidneys. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin coated or an uncoated circuit. To compare the effect of a heparin coated circuit with an uncoated circuit upon cerebral and renal function in relation to inflammation, we assessed markers of cerebral (S100beta) and renal (N-acetyl-beta-D-glucosaminidase [NAG], creatinine, and urea) function, inflammation, and oxygen metabolism. S100beta levels and NAG levels increased during CPB in both groups as compared with baseline levels (p < 0.01), without differences between the groups. After 15 minutes on CPB, C4b/c levels were significantly higher in the coated group compared with the uncoated group (p < 0.02). C4b/c correlated with S100beta (p < 0.01). Total body oxygen delivery (DO2) and consumption (VO2) decreased significantly in both groups during CPB (p < 0.01), but recovery was better in the coated group. After protamine infusion, total body oxygen delivery and consumption correlated negatively with S100beta levels (both p < 0.05) and with NAG levels (both p < 0.01). This study suggests that, if adequate tissue perfusion is not maintained, the use of a heparin coated circuit gives no additional benefit beyond that of the uncoated circuit. The inverse relationship of both cerebral and renal markers with DO2 and VO2 suggests that increased levels of S100beta and NAG during CPB may primarily be caused by an oxygen deficit and secondary to the inflammatory response.