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A minimized perfusion circuit (MPC) has proven to be superior to the conventional circulatory perfusion bypass (CCPB) as it reduces the blood-material interaction and hemodilution. Until now not much is known about impact these different perfusion systems have on the brain. The objective of this study is to determine carnosinase and brain-type fatty binding protein (BFABP) activity as novel specific biomarkers for ischemic brain tissue damage and how their activity differs during and after MPC and CCPB as well as to compare the inflammatory response of both perfusion systems. In a prospective pilot study, 28 patients undergoing coronary artery bypass grafting were randomly divided into an MPC group (n = 14) and a CCPB group (n = 14). Blood samples were taken before, during, and after operation until the fifth postoperative day. The brain biomarker carnosinase was determined by measuring the rate of histidine production from the substrate homocarnosine, whereas BFABP and interleukin-6 were determined by enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) and endothelin-1 were determined by enzyme immunoassay. The mean serum carnosinase activity was significantly higher in MPC (0.57 ± 0.34 nM histidine/mL/min) as compared with the CCPB group (0.36 ± 0.13 nM histidine/mL/min) at the end of operation (P = 0.02). The BFABP did not show any difference between the two groups in the immediate postoperative period until the second postoperative day. From that time point onward, it showed a steep increase in the CCPB group (581.3 ± 157.11 pg/mL) as compared with the concentrations in the MPC group (384.6 ± 39 pg/mL) (P = 0.04). The inflammation markers interleukin-6 and CRP showed a similar pattern in both groups without significant difference. In contrast, the leukocyte count on operation day and endothelin-1 on the first postoperative day were significantly higher in the CCPB group (P = 0.01, P = 0.03, respectively). MPC showed a significant higher and stable serum carnosinase activity during extracorporeal circulation as compared with the CCPB due to less hemodilution and a better preserved oxygen capacity. As a consequence, the antioxidant stress during MPC is limited as compared with CCPB, which means less brain tissue damage reflected by a lower BFABP release. Except endothelin-1 and leukocyte count, the inflammatory response of the MPC and CCPB was equal., (© 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Although the centrifugal pump has been widely used as a nonpulsatile pump for cardiopulmonary bypass (CPB), little is known about its performance as a pulsatile pump for CPB, especially on its efficacy in producing hemodynamic energy and its clinical effectiveness. We performed a study to evaluate whether the Rotaflow centrifugal pump produces effective pulsatile flow during CPB and whether the pulsatile flow in this setting is clinically effective in adult patients undergoing cardiac surgery. Thirty-two patients undergoing CPB for elective coronary artery bypass grafting were randomly allocated to a pulsatile perfusion group (n = 16) or a nonpulsatile perfusion group (n = 16). All patients were perfused with the Rotaflow centrifugal pump. In the pulsatile group, the centrifugal pump was adjusted to the pulsatile mode (60 cycles/min) during aortic cross-clamping, whereas in the nonpulsatile group, the pump was kept in its nonpulsatile mode during the same period of time. Compared with the nonpulsatile group, the pulsatile group had a higher pulse pressure (P < 0.01) and a fraction higher energy equivalent pressure (EEP, P = 0.058). The net gain of pulsatile flow, represented by the surplus hemodynamic energy (SHE), was found much higher in the CPB circuit than in patients (P < 0.01). Clinically, there was no difference between the pulsatile and nonpulsatile groups with regard to postoperative acute kidney injury, endothelial activation, or inflammatory response. Postoperative organ function and the duration of hospital stay were similar in the two patient groups. In conclusion, pulsatile CPB with the Rotaflow centrifugal pump is associated with a small gain of EEP and SHE, which does not seem to be clinically effective in adult cardiac surgical patients., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 +/- 0.12 vs. 0.345 +/- 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts.

Heparin treatment of decellularized xenografts has been reported to reduce graft thrombogenicity. However, little is known about the in vivo comparison of heparin-treated with non-heparin-treated xenografts, especially for small-caliber vascular implants. We implanted either a heparin-treated or a non-heparin-treated canine carotid artery as bilateral carotid xenograft in rabbits (n = 24). Small-caliber xenografts (3 approximately 4 mm) were decellularized by enzymatic and detergent extraction and were further covalently linked with heparin. During implantation, thrombosis rate was 4% in the heparin-treated xenografts and 25% in the non-heparin-treated xenografts after 3 weeks (P < 0.05). After 6 months, it was 8 versus 58%, respectively (P < 0.01). Both heparin-treated and non-heparin-treated xenografts harvested at the end of 3 and 6 months showed a satisfactory cellular reconstruction of either smooth muscle cells or endothelial cells. These results indicate that heparin treatment of the small-caliber decellularized xenograft reduces the in vivo thrombogenicity. Both heparin-treated and non-heparin-treated xenografts seem to undergo a similar cellular remodeling process up to 6 months.

Hemodynamic instability, mostly due to vertical lifting of the heart, is usually observed during beating-heart surgical procedures. However, some hemodynamic parameters, such as coronary blood flow, are not routinely measured. A digital computer model of the circulation able to simulate and analyze the effects of heart lifting and the Trendelenburg maneuver, and thus supply detailed hemodynamic information to the clinicians would provide a useful analytical tool. A lumped parameters model of the circulation was applied to both beta-blocked and not beta-blocked pigs. The results confirmed a drop of cardiac output and coronary flow during heart lifting and a rise of both variables after the Trendelenburg maneuver for beta-blocked animals. In not beta-blocked pigs, the analysis was more complex but the model reproduced experimental data and permitted coronary flow to be estimated. These results showed the feasibility of numerical simulation for specific circulatory conditions encountered during beating-heart surgery.

This study was aimed to mimic clinical heart failure (HF) conditions and to assess the effect of pulsatile catheter (PUCA) pump support on hemodynamics and tissue perfusion in a sheep model of acute HF. In 14 sheep, HF was induced by partial occluding the middle left circumflex coronary artery combined with pacemaker-induced tachycardia. PUCA pump was then activated to support the HF for 3 h. Hemodynamic parameters were recorded at baseline, HF, and then every 30 min during experiments. Blood samples were taken in carotid artery (CA), pulmonary artery (PA), and coronary sinus (CS) for the determination of oxygen saturation (SO2) and lactate concentration as markers of tissue perfusion. Results showed that HF model was induced successfully in 10 sheep and failed in four sheep due to refractory ventricular fibrillation. PUCA pump support was successful in seven out of 10 sheep for 3 h. Three cases failed due to technical problems. After HF (n = 10), cardiac output (CO) was decreased from 3.7 +/- 0.5 to 2.0 +/- 0.5 L/min (P < 0.001). Mean arterial pressure (MAP) was lowered from 116.1 +/- 14.2 to 68.1 +/- 14.7 mm Hg (P < 0.001). In seven sheep supported with PUCA pump, MAP rose from 68.9 +/- 15.2 to 94.7 +/- 14.7 mm Hg (P = 0.005), systolic blood pressure increased from 86.6 +/- 17.0 to 112.6 +/- 17.1 mm Hg (P = 0.009), and diastolic blood pressure increased from 57.7 +/- 12.6 to 79.9 +/- 13.9 mm Hg (P = 0.011). CO remained at about 2.0 L/min. SO2 in CA, PA, and CS decreased significantly after HF (P < 0.001), with an increase after support (compared with HF, P < 0.001, 0.066 and 0.114, respectively). Lactate concentrations increased gradually in CA, PA, and CS toward the end of experiments without difference among different sampling sites. This HF model in sheep is simple, easy to manipulate, reproducible and reflecting clinical HF conditions. PUCA pump can maintain the hemodynamic status for 3 h in this acute HF model.

Cardiopulmonary bypass (CPB) is known to impair the integrity of the gastrointestinal tract. However, little is known about the movement behavior of the gastrointestinal tract during CPB. This study was aimed to assess the gastrointestinal motility with sonomicrometry, a distance measurement using ultrasound, in a porcine model of CPB. Twelve pigs weighing 70-112 kg were having a standard hypothermic CPB for 120 min either with the nonpulsatile flow (n = 6) or the pulsatile flow (n = 6). Before CPB, piezoelectric echo crystals were placed either along the longitudinal or the circular axis of the pylorus. Patterns of gut movement and the total sonomicrometric activity (TSA) were recorded at several time intervals during experiments as qualitative and quantitative parameters of gut motility. Results showed that the intact regular rhythmic pattern of gut movement was detected before CPB. This pattern changed little when CPB started, but it disappeared at 60 min when the body temperature lowered down to 32 degrees Celsius. During the same period, the TSA reduced significantly along the longitudinal as well as the circular directions of the pylorus. There was no significant difference between the nonpulsatile and pulsatile groups. Gut blood flow reduced significantly in both groups, but it was not associated with the reduced sonomicrometric activity. In conclusion, gastrointestinal motility during CPB can be measured qualitatively and quantitatively by sonomicrometry in a large animal model. Suppression of gut motility during CPB does not seem to be associated with the mode of perfusion but with the reduced body temperature during the hypothermic phase of CPB.

Activated leukocytes and fat particles are associated with organ injury after a cardiac surgery. Filters are currently used to remove either leukocytes or fat particles. A novel approach with a filter that combines leukocyte and fat removal might be clinically useful. As it is not known which type of filter has a good and safe performance in both leukocyte and fat removal, we measured in this study the leukocyte and fat removal properties and the biocompatibility of three different filters. We used six Pall RS1 (Pall, Portsmouth, England) leukocyte removal filters, six Pall LipiGuard fat removal filters, and six Fresenius Biofil 02 (Fresenius, Emmer-Compascuum, The Netherlands) leukocyte removal filters and measured the passage times of 500 and 1000 mL of residual heart-lung machine blood. We determined the circulating leukocyte and platelet counts, and total hemoglobin, triglyceride, and free fatty acid concentration after the filters. In addition, we measured free hemoglobin, plasma elastase (Merck, Darmstadt, Germany), and complement C5-9 (Quidel, San Diego, CA, U.S.A.) to assess the biocompatibility of the filters. The circulating fat particles were calculated with an automated hematology analyzer. The passage time for the blood was shortest for the Biofil filter (P = 0.02, analysis of variance). The total leukocyte counts (P = 0.04) and fat particles (P = 0.02) were higher after the LipiGuard filter. This filter also had a higher increase in free hemoglobin concentration (P = 0.03). We conclude that the leukocyte removal filters were superior to the fat removal filter both in leukocyte and fat removal.

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.

To evaluate the biocompatibility and the efficacy of leukocyte removal filters, we performed a prospective study by using the cardiopulmonary bypass perfusate taken from the heart-lung machine for 20 patients who underwent cardiac surgery and were randomly divided into four groups according to the filters used. A leukocyte removal filter was installed in the transfusion line while the perfusate was transfused to the patients. No increases of C3a, C5a, elastase, and thromboxane were found during leukocyte filtration by polyester filters (Optima, Sepacell R500, and Pall RC100). Activation of the complement cascade was observed during filtration by the cellulose acetate filter (Cellselect) although the efficacy of the Cellselect filter was evidently higher than that of the polyester filter. These results imply that polyester leukocyte filters are superior to cellulose acetate filters in terms of biocompatibility but have a reduced efficacy. An optimal leukocyte filter providing both high efficacy and biocompatibility has yet to be developed.