Left ventricular assist device mode: Co-pulse left ventricular unloading in a working mode of ex vivo heart perfusion.

BACKGROUND: For normothermic ex vivo heart perfusion (EVHP), a resting mode and working mode have been proposed. We newly developed a left ventricular assist device (LVAD) mode that supports heart contraction by co-pulse synchronized LVAD. METHODS: Following resting mode during time 0 to 1 hour, pig hearts (n = 18) were perfused in either resting, working, or LVAD mode during time 1 to 5 hour, and then myocardial function was evaluated in working mode at 6 hour. The preservation ratio was defined as the myocardial mechanical function at 330 minute divided by the function at 75 minute. In LVAD mode, LVAD unloaded the pressure and the volume in the left ventricle in the systolic phase. RESULTS: The LVAD group was significantly associated with higher preservation ratios in cardiac output (resting, 33 ± 3; working, 35 ± 5; LVAD, 76% ± 5%; p < 0.001), stroke work, dP/dt maximum, and dP/dt minimum compared with the other groups. Glucose consumption was significantly reduced in the resting group. The LVAD group was significantly associated with higher myocardial oxygen consumption (resting, 2.2 ± 0.3; working; 4.6 ± 0.5; LVAD, 6.1 ± 0.5 mL O2/min/100 g, p < 0.001) and higher adenosine triphosphate (ATP) levels (resting, 1.1 ± 0.1; working, 0.7 ± 0.1; LVAD, 1.6 ± 0.2 µmol/g, p = 0.001) compared with the others. CONCLUSION: These data suggest that myocardial mechanical function was better preserved in LVAD mode than in resting and working modes. Although our data suggested similar glycolysis activity in the LVAD and working groups, the higher final ATP in the LVAD group might be explained by reduced external work in LVAD.

Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.

BACKGROUND: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. METHODS: This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). RESULTS: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. CONCLUSIONS: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.

Novel application of indocyanine green fluorescence imaging for real-time detection of thrombus in a membrane oxygenator.

Extracorporeal membrane oxygenation (ECMO) plays an important role in the coronavirus disease 2019 (COVID-19) pandemic. Management of thrombi in ECMO is generally an important issue; especially in ECMO for COVID-19 patients who are prone to thrombus formation, the thrombus formation in oxygenators is an unresolved issue, and it is very difficult to deal with. To prevent thromboembolic complications, it is necessary to develop a method for early thrombus detection. We developed a novel method for detailed real-time observation of thrombi formed in oxygenators using indocyanine green (ICG) fluorescence imaging. The purpose of this study was to verify the efficacy of this novel method through animal experiments. The experiments were performed three times using three pigs equipped with veno-arterial ECMO comprising a centrifugal pump (CAPIOX SL) and an oxygenator (QUADROX). To create thrombogenic conditions, the pump flow rate was set at 1 L/min without anticoagulation. The diluted ICG (0.025 mg/mL) was intravenously administered at a dose of 10 mL once an hour. A single dose of ICG was 0.25mg. The oxygenator was observed with both an optical detector (PDE-neo) and the naked eye every hour after measurement initiation for a total of 8 hours. With this dose of ICG, we could observe it by fluorescence imaging for about 15 minutes. Under ICG imaging, the inside of the oxygenator was observed as a white area. A black dot suspected to be the thrombus appeared 6-8 hours after measurement initiation. The thrombus and the black dot on ICG imaging were finely matched in terms of morphology. Thus, we succeeded in real-time thrombus detection in an oxygenator using ICG imaging. The combined use of ICG imaging and conventional routine screening tests could compensate for each other's weaknesses and significantly improve the safety of ECMO.

Evaluation of real-time thrombus detection method in a magnetically levitated centrifugal blood pump using a porcine left ventricular assist circulation model.

Pump thrombosis induces significant complications and requires timely detection. We proposed real-time monitoring of pump thrombus in a magnetically levitated centrifugal blood pump (mag-lev pump) without using additional sensors, by focusing on the changes in the displacement of the pump impeller. The phase difference between the current and displacement of the impeller increases with pump thrombus. This thrombus detection method was previously evaluated through simulated circuit experiments using porcine blood. Evaluation of real-time thrombus detection in a mag-lev blood pump was performed using a porcine left ventricular assist circulation model in this study. Acute animal experiments were performed five times using five Japanese domestic pigs. To create thrombogenic conditions, fibrinogen coating that induces thrombus formation in a short time was applied to the inner surfaces of the pump. An inflow and an outflow cannula were inserted into the apex of the left ventricle and the carotid artery, respectively, by a minimally invasive surgical procedure that allowed minimal bleeding and hypothermia. Pump flow was maintained at 1 L/min without anticoagulation. The vibrational frequency of the impeller (70 Hz) and its vibrational amplitude (30 µm) were kept constant. The thrombus was detected based on the fact that the phase difference between the impeller displacement and input current to the magnetic bearing increases when a thrombus is formed inside a pump. The experiment was terminated when the phase difference increased by over 1° from the lowest value or when the phase difference was at the lowest value 12 hours after commencing measurements. The phase difference increased by over 1° in three cases. The pump was stopped after 12 hours in two cases. Pump thrombi were found in the pump in three cases in which the phase difference increased by over 1°. No pump thrombus was found in the other two cases in which the phase difference did not increase. We succeeded in real-time thrombus monitoring of a mag-lev pump in acute animal experiments.

Optical Dynamic Analysis of Thrombus Inside a Centrifugal Blood Pump During Extracorporeal Mechanical Circulatory Support in a Porcine Model.

Complications due to pump thrombus remain the weak point of mechanical circulatory support (MCS), such as the use of a left ventricular assist device (LVAD) or extracorporeal membrane oxygenation, leading to poor outcomes. Hyperspectral imaging (HSI) is an effective imaging method using a hyperspectral (HS) camera, which comprises a spectrophotometer and a charge-coupled device camera to discriminate thrombus from whole blood. Animal experiments were conducted to analyze dynamic imaging of thrombus inside a prototype of a hydrodynamically levitated centrifugal blood pump using an HSI system. Six pigs were divided into a venous circulation group (n = 3) and an arterial circulation group (n = 3). Inflow and outflow cannulae were inserted into the jugular veins in the venous circulation group. The latter simulated an LVAD application. To create thrombogenic conditions, pump flow was maintained at 1 L/min without anticoagulation. An image of the bottom surface of the pump was captured by the HS camera every 4 nm over the wavelength range of 608-752 nm. Real-time dynamic images of the inside of the pump were displayed on the monitor. Appearance of an area displaying thrombus was detected within 24 h after the start of the circulation in every experiment. This imaging system also succeeded in determining the origins of pump thrombus: from inside the pump in two cases, and from outside in four cases. Two main possible sources of pump thrombus originating outside the pump were identified on autopsy: wedge thrombus around the inflow cannula; and string-like thrombus at the junction between the pump inlet and circuit tube. The results of this study from close observation of the changing appearance of pump thrombus may contribute to improvements in the safety of extracorporeal MCS.