Perfusion

Computer- and sensor-aided control of the heart-lung machine is considered a major goal for perfusion sciences for the next few years. At present, control of perfusion is achieved by surgeons, anaesthesiologists and perfusionists making short-term decisions, which leads to variations of the perfusion regimens between different centres and even between different teams in the operating theatre. As the basis for an integrated control of extracorporeal circulation (ECC), we proposed a mathematical model for simulating haemodynamics during pulsatile perfusion. This model was then modified to allow it to simulate the effects of different perfusion regimens on arterial haemodynamics and whole body oxygen consumption.

The model was constructed on a PC using MATLAB/SIMULINK. The human arterial tree was divided into a multibranch structure consisting of 128 segments characterized by their particular physical properties. Peripheral branches were terminated by a resistance term representing smaller vessels like arterioles and capillaries. Flow and pressure were expressed by the intensity of current and voltage in an electrotechnical analogon; inductivity, resistance and capacitance were implemented according to the physical properties of the arterial tree and the rheology of blood. The effects of different perfusion regimens (pulsatility, flow amount, acid-base regulation) were studied.

After introducing an input signal to the model, flow and pressure waves established themselves throughout the simulated arterial tree. During the simulation experiments, marked differences among different perfusion regimens were displayed by the model. Variations in acid-base management mainly influenced the distribution of perfusion: during simulation of low-flow perfusion (1.2 l/min/m²), cerebral blood flow was 6.2 ml/s using an alpha-stat regimen, while it was increased to 9.4 ml/s during pH-stat, caused by an implementation of reduced cerebral resistance. Whole body oxygen consumption was predominantly regulated by the perfusion rate. While central venous oxygen saturation was calculated to be 84.7% during simulation of high-flow perfusion (2.4 l/min/m²), it dropped to 70% during simulation of low-flow perfusion regimens.

The model proved to be useful for a realistic simulation of different perfusion regimens. Therefore it can be considered a continuing step for the derivation of a ‘state’ observer leading to the realization of an automatically controlled heart-lung machine.

We have evaluated the effect of nitric oxide (NO) on the pressure drop across a membrane oxygenator in one in vitro model and two in vivo models (using four dogs and five pigs). In all the experiments sodium nitroprusside (SNP) was used as a NO source, whereas gaseous NO was only used in the in vitro model. The drugs were given when the pressure drop or resistance across the device increased to at least twice the baseline values.

In the in vitro model, both SNP and gaseous NO decreased the pressure drop to 75% of its peak value after 10 min and to 67% after 20 min. In the dog model, resistance decreased from 390 to 153 mmHg/l/min after 5 min and to 85 mmHg/l/min after 20 min for a baseline value of 75 mmHg/l/min.

The initial resistance across the membrane oxygenator in the pig model increased from 6.6 ± 1.3 to 74 ± 38 mmHg/l/min. An infusion of 10 μg/kg/min SNP reduced the resistance to 16 ± 5 mmHg/l/min.

Electroencephalographic (EEG) changes have been reported with cardiopulmonary bypass (CPB). We tested whether the type of priming solution (blood versus nonblood) affected the EEG. Twenty-six anesthetized pigs (29.5 ± 1.6 kg) were cannulated for CPB primed with 1 liter plasmalyte and 500 ml 6% hetastarch (nonblood prime). EEG signals were recorded during the initiation of normothermic CPB. Three minutes later, animals were weaned from CPB and allowed to stabilize. CPB was reinstituted using the animals’ hemodiluted blood as prime. We found that with nonblood prime, abrupt and marked EEG suppression lasting 12.6 ± 0.7 s was found in all animals, followed by gradual resumption of baseline EEG activity. In contrast, CPB with blood prime caused no detectable EEG changes. We conclude that severe reductions in EEG activity occur after initiating CPB with nonblood prime; these reductions are not seen when using blood prime. The cause of EEG suppression is unknown, but may represent transient impairment of oxygen delivery to the brain caused by nonblood perfusion.

The flow of fluids in extracorporeal circuits does not conform to conventional Poiseuille mechanics which confounds calculating cardioplegia (CP) flow distribution. The purpose of this study was to quantify CP flow dynamics in a model simulating coronary atherosclerosis across varying sized restrictions.

An in vitro preparation was designed to assess hydraulic fluid movement across paired restrictions of 51, 81 and 98% lumen reductions. Volume data were obtained at variable flow, temperature, viscosity and pressure conditions.

CP delivered through 14- and 18-gauge (GA) conduits at 8°C and 100 mmHg infusion pressure revealed that both four to one and crystalloid CP solutions had significantly less total percentage flow through the 14-GA conduit, p < 0.0001 and p < 0.001, respectively. Overall, 4:1 CP exhibited the most favorable fluid dynamics at 8°C in that it delivered the highest percentages of total CP flow through the smaller lumen conduit. At both 8°C and 37°C delivery, blood CP resulted in the least homogeneous fluid distribution at all delivery parameters. The results in relation to blood viscosity indicate that, although the 8°C blood CP had a significantly greater viscosity than 37°C blood CP, it did not produce an effect in fluid distribution.

These data show that increasing the cardioplegic solution hematocrit causes an inhomogeneous fluid distribution regardless of delivery temperature or infusion pressure.

Reduction of priming volumes of the cardiopulmonary bypass (CPB) circuit in neonatal cardiac surgery to decrease haemodilution and blood transfusion requirements can be achieved with the use of neonatal low prime oxygenators and smaller diameter tubing. We have further reduced our prime volume with the use of a custom-designed arm allowing for remote positioning of a double-headed roller pump. This arm enables the double pump to be placed alongside the main heart-lung machine close to the operating table, and to position the pump inlet and outlet tubing immediately at the reservoir outlet and oxygenator inlet, respectively, therefore reducing tubing lengths. Priming volumes of four cases using this configuration were compared to four cases using our standard neonatal bypass setup. Results showed a 29% decrease in priming volume and a 58% reduction in blood utilization during CPB. This reduction in priming volume is clinically significant as it lowers the ratio of priming volume to patient blood volume and reduces homologous blood requirements.

Thirty patients scheduled for elective myocardial revascularization and having undergone preoperative heparin treatment have been admitted to this prospective, randomized study. The aim of the study was to test two different strategies for preserving circulating antithrombin III (AT-III) during cardiopulmonary bypass. Patients in the control group (group C, n = 10) were treated with a standard heparinization (300 IU/kg). Patients in group A (n = 10) received the same management plus two doses of purified antithrombin III (1000 IU each). Patients in group GA received 200 IU/kg heparin and a continuous infusion of heparin (100 IU/kg/h) and gabexate mesilate (2 mg/kg/h) plus the same dose of antithrombin III as group A. Both group A and group GA demonstrated a preservation of circulating AT-III when compared to group C; this effect was more pronounced in group GA. The total heparin dosage was less in group GA than in groups A and C. Purified AT-III administration is recommended in heparin pretreated patients; the addition of gabexate mesilate to this protocol decreases the heparin requirement and increases the AT-III preservation.

For many years it has been known that roller pumps interfere regularly with the electrocardiogram (ECG) signal. This electrical activity is also considered responsible for the electrostatic charge build-up in some oxygenators with a plastic heat exchanger. During use of such an oxygenator, an electrical shock can be felt when touching the device. In the absence of a provoked discharge, a spontaneous discharge may occur. The construction of the heat exchanger and the use of nonconductive materials enable some devices to function as a capacitor. If the voltage difference across the fibre wall is too high, an electrostatic discharge may occur. In 1997, four blood-to-water leaks in Maxima Forté oxygenators were reported on a worldwide basis. After thorough research by Medtronic Cardiac Surgery (Cardiopulmonary Division), the cause of the leaks was found to be an electrothermal event across the fibre wall of one single fibre. No patient injuries were reported in any of the events. Medtronic patented a number of US Food and Drug Administration-approved and patient-safe solutions to prevent this electrostatic charge build-up.

We studied the electrostatic phenomenon in order to clarify the clinical aspects. The in vitro part of the study is related to the behaviour of the Medtronic Biopump and the Stockert Shiley roller pump - in combination with the use of a PVC or silicone pumpheader. Subsequently, we have investigated the influence of the rotation or flow of both types of blood pumps and occlusion settings on the roller pump. Furthermore, we tried to capture the electrical charge generated by the roller pumps in a capacitor and in some oxygenators with different types of heat exchanger. Finally, we tested the external CEL™ (Charge Equalization Line) and the internal ‘Gold Wire’ charge equalization systems, both patented by Medtronic.

In the in vivo part of the study, 15 patients were divided into three groups of five patients each. In the first group a roller pump with a PVC pumpheader was evaluated and, in the second group, a roller pump with a silicone pumpheader. The third group consisted of the Medtronic Biopump. In all the groups, a Maxima Forté oxygenator with the external CEL protection was used. Owing to the fact that, at the time, the Maxima Forté ‘Gold Wire’ oxygenator was not available for clinical use, only the external CEL could be evaluated.

This study investigated the effects of leucocyte-depleted cardioplegia on postreperfusion oxidative stress and myocardial injury in elective hypothermic coronary artery bypass surgery. Forty patients were randomized to receive either cardioplegia with leucocytes depleted by an in-line Pall BC1B filter, or blood cardioplegia without leucocyte depletion. Transmyocardial oxidative stress was assessed by oxidized glutathione measurements in samples taken simultaneously from the coronary sinus and aortic root, and myocardial injury by postoperative CKMB and troponin-T measurements. The BC1B filters reduced numbers of cardioplegia leucocytes by a mean of 90.7%. Both patient groups demonstrated significant increases (p < 0.001) in transcardiac oxidized glutathione gradients after crossclamp release. No significant differences were found between the groups for postreperfusion oxidized glutathione gradients, postoperative levels of CKMB or troponin-T, or in the frequency of perioperative and postoperative complications. These results suggest that leucocyte-depleted cardioplegia does not significantly improve myocardial protection in patients undergoing elective coronary artery bypass surgery.

Femoral venous cannulae (17-28 French) were tested to compare flows obtained by their placement in a simulated inferior vena cava (IVC) or right atrium (RA) and by varying drainage pressures using gravity siphon drainage or a centrifugal pump in the venous line. The circuit consisted of conventional tubing and equipment including a segment of thin-walled latex tubing to simulate the IVC connected to a flexible reservoir to simulate the RA. The test fluid was a 40% glycerin solution. Flow was measured at height differentials of 30-60 cm (cannula-to-inlet of hard-shell venous reservoir) and with a -10 to -80 mmHg negative pressure created by the centrifugal pump. A roller pump returned the test fluid to a flexible bag to maintain a filling pressure of 0-1 mmHg. Flow increased modestly with an increasing height differential. When negative pressure was applied with the centrifugal pump, flow increased 10% and 18% (IVC and RA positions, respectively) compared to gravity siphon drainage conditions. There also was a tendency for flow to plateau or cease when the centrifugal pump was used at higher levels of negative pressure or when larger cannulae were used. We conclude: (1) position of smaller cannulae in the RA yield better flows than when the cannulae are larger and placed in the IVC; (2) smaller-sized cannulae are capable of achieving higher flows when the centrifugal pump is used; (3) cannulae must be properly positioned to achieve maximum flow; (4) the centrifugal pump will augment flow, but should be regulated to avoid extreme negative pressures; and (5) cannula design has no demonstrable effect on flow.

Conventional cardiopulmonary bypass (CPB) in neonates results in increased transfusion requirements and hemodilution. There has been little advancement in CPB for the neonatal population. There is evidence that increased priming volumes and blood product transfusion enhances inflammatory response to CPB and increases myocardial and pulmonary dysfunction. We have devised a miniaturized CPB circuit that utilizes vacuum-assisted venous drainage (VAVD) in an effort to decrease priming volume and avoid transfusion requirements. The purpose of this study was to evaluate the safety and efficacy of this miniaturized CPB system and determine the feasibility of an asanguineous prime. Ten 1-week-old piglets were randomized to five mini- and five conventional CPB pump circuits. Subjects were supported with CPB at 100 ml/kg/min, cooled to 28°C, exposed to 10 min aortic crossclamp with cardioplegic arrest, rewarmed to 37°C, weaned from bypass, and subjected to modified-ultrafiltration (MUF) for approximately 10 min. This method was chosen to simulate a situation with all the elements of clinical CPB. Blood transfusion trigger was a hematocrit <15 on CPB. Serum samples were obtained pre-CPB, at 15 min of CPB onset, immediately post-CPB completion, and immediately post-MUF. Indices of hemolysis (SGOT, LDH), production of inflammatory mediators (interleukin (IL)-8, tumor necrosis factor-alpha (TNFα)), and physiologic parameters of inflammation were measured. The overall blood requirement was significantly less in the mini-circuit compared to conventional CPB (47.0 ± 5.8 ml vs 314.2 ± 31.6 ml; p < 0.0001). The only significant blood requirement in the mini-circuit was to replace the volume removed for samples. During the study, mean arterial pressure (MAP) (p = 0.004), static pulmonary compliance (p = 0.04), platelets (p = 0.0003), and white blood cells (p = 0.003) significantly decreased across the groups. Lung water content (p = 0.02), TNFα levels (p = 0.05), and SGOT (p = 0.009) increased significantly during the study, across the groups. Among all parameters tested, except for blood requirement and hematocrit post-CPB, there were no significant differences between the two circuits. VAVD makes asanguineous prime in neonates feasible. When used in this study to miniaturize a conventional-CPB circuit, VAVD with a reconfigured neonatal CPB console and circuit resulted in no detrimental effects, and allowed for markedly decreased priming volumes and blood transfusion requirements.

Cardiopulmonary bypass (CPB) was used during the replacement of the aortic and mitral valves in a 43-year-old female patient. The case was complicated by the presence of a rare hypercoagulable condition called anticardiolipin (antiphospholipid) antibody syndrome. The course of bypass was uneventful and the patient was released from the intensive care unit on the first postoperative day. CPB in the presence of anticardiolipin antibodies is an unusual situation that requires diligent hematological monitoring. Since 1989 there have been only 14 reported cases of these antibodies and cardiopulmonary bypass. Eight of these have involved valve replacements.