Editorial: Recent advances in the design and preclinical evaluation of ventricular assist devices.

Platelet adhesion emulation: A novel method for estimating the device thrombosis potential of a ventricular assist device.

Device thrombosis inside ventricular assist devices remains a limitation to their long-term clinical use. Thrombosis potential exists in almost all ventricular assist devices because the device-induced high shear stress and vortices can activate platelets, which then aggregate and adhere to the surfaces inside the ventricular assist device. To decrease the device thrombosis potential of long-term use of ventricular assist devices, a methodology entitled platelet adhesion emulation for predicting the thrombosis potential and thrombosis position inside the ventricular assist devices is developed. The platelet adhesion emulation methodology combines numerical simulations with in vitro experiments by correlating the structure of the flow passage components within the ventricular assist device with the platelet adhesion to estimate the thrombosis potential and location, with the goal of developing ventricular assist devices with optimized antithrombotic performance. Platelet adhesion emulation is aimed at decreasing the device thrombus potential of ventricular assist devices. The platelet adhesion emulation effectiveness is validated by simulating and testing an axial left ventricular assist device. The blood velocity relative to the surfaces of the flow passage components is calculated to estimate the platelet adhesion potential, indicating the probability of thrombus formation on the surfaces. Platelet adhesion emulation experiments conducted in a mock circulation loop with pump prototypes show the distribution of platelet adhesion on the surfaces. This methodology of emulating the device thrombosis distribution indicates the potential for improving the component structure and reducing the device thrombosis of ventricular assist devices.

Platelet deposition estimation: A novel method for emulating the pump thrombosis potential of blood pumps.

Pump thrombosis potential exists in most blood pumps and limits their clinical use. To improve the pump thrombosis performance of blood pumps, a method for emulating the platelet deposition on the flow passage component surfaces inside blood pumps was presented and tested. The method emulates the blood platelet deposition, employing laser-induced fluorescence tracing technology. The blood pump was rotated in a mock circulation loop with deionized water filled with fluorescent particles. The component surfaces were then explored via laser. The fluorescent particles were induced by laser and imaged in a charge-coupled device (CCD) camera to show the distribution of fluorescent particles gathering on the blood pump component surfaces. The activated platelet deposition was emulated by fluorescent particle gathering. The experiment showed obvious particle gathering on the interface surfaces and cross-sectional surface (perpendicular to the flow). This platelet deposition estimation (PDE) method can be easily incorporated in the in vitro testing phase to analyze and decrease a pump's thrombosis potential before animal experimentation, thereby reducing the cost of blood pump development. This methodology of emulating blood platelet deposition indicates its potential for improving flow passage component structure and reducing device thrombosis of blood pumps.

Numerical investigation of the influence of a bearing/shaft structure in an axial blood pump on the potential for device thrombosis.

Adverse events caused by flow-induced thrombus formation around the bearing/shaft of an axial blood pump remain a serious problem for axial blood pumps. Moreover, excessive anticoagulation with thrombosis around the bearing potentially increases the risk of postoperative gastrointestinal bleeding. The purpose of this study is to analyze the influence of the bearing structure on the thrombosis potential of an axial blood pump. The bearing/shaft structure was embedded into an axial blood pump numerical model. The numerical simulation and analysis are focused on the low wall shear stresses, recirculation, and residence time close to the bearing region to evaluate the potential for thrombosis around the bearing. Then, the flow field near the blood pump bearing was tested via in vitro particle image velocimetry experiments to verify the numerical results. The simulation results showed that after embedding the bearing/shaft structure a recirculation zone appeared in the outlet guide vane bearing/shaft region, the residence time increased 11-fold in comparison to the pump without the bearing/shaft structure, the scalar shear stress in the shaft surface was less than 7.8 Pa, and the stress accumulation was less than 0.10 Pa s. The numerical results showed that platelets that flow through the bearing region are exposed to significantly lower wall shear stress and a longer residence time, leading to activated platelet adhesion. The reduced stress accumulation and increased time in the bearing region lead to increased platelet activation.

Numerical Investigation of the Influence of Blade Radial Gap Flow on Axial Blood Pump Performance.

The gaps between the blades and the shroud (or hub) of an axial blood pump affect the hydraulics, efficiency, and hemolytic performance. These gaps are critical parameters when a blood pump is manufactured. To evaluate the influence of blade gaps on axial blood pump performance, the flow characteristics inside an axial blood pump with different radial blade gaps were numerically simulated and analyzed with special attention paid to the hydraulic characteristics, gap flow, hydraulic efficiency, and hemolysis index (HI). In vitro hydraulic testing and particle image velocimetry testing were conducted to verify the numerical results. The simulation results showed that the efficiency and pressure rise decreased when the gap increased. The efficiency of the axial blood pump at design point decreased from 37.1% to 27.1% and the pressure rise decreased from 127.4 to 71.2 mm Hg when the gap increased from 0.1 to 0.3 mm. Return and vortex flows were present in the outlet guide vane channels when the gap was larger than 0.2 mm. The HI of the blood pump with a 0.1 mm gap was 1.5-fold greater than that with a 0.3 mm gap. The results illustrated poor hydraulic characteristics when the gap was larger than 0.15 mm and rapidly deteriorated hemolysis when the gap was larger than 0.1 mm. The numerical and experimental results demonstrated that the pressure rise, pump efficiency, and scalar shear stress decreased when the gap increased. The HI did not strictly decrease with gap increases. The preliminary results encourage the improvement of axial blood pump designs.

[Design of an axial blood pump of diffuser with splitter blades and cantilevered main blades].

An implantable axial blood pump was designed according to the circulation assist requirement of severe heart failure patients of China. The design point was chosen at 3 L/min flow rate with 100 mm Hg pressure rise when the blood pump can provide flow rates of 2-7 L/min. The blood pump with good hemolytic and anti-thrombogenic property at widely operating range was designed by developing a structure that including the spindly rotor impeller structure and the diffuser with splitter blades and cantilevered main blades. Numerical simulation and particle image velocimetry (PIV) experiment were conducted to analyze the hydraulic, flow fields and hemolytic performance of the blood pump. The results showed that the blood pump could provide flow rates of 2-7 L/min with pressure rise of 60.0-151.3 mm Hg when the blood pump rotating from 7 000 to 11 000 r/min. After adding the splitter blades, the separation flow at the suction surface of the diffuser has been reduced efficiently. The cantilever structure changed the blade gap from shroud to hub that reduced the tangential velocity from 6.2 m/s to 4.3-1.1 m/s in blade gap. Moreover, the maximum scalar shear stress of the blood pump was 897.3 Pa, and the averaged scalar shear stress was 37.7 Pa. The hemolysis index of the blood pump was 0.168% calculated with Heuser's hemolysis model. The PIV and simulated results showed the overall agreement of flow field distribution in diffuser region. The blood damage caused by higher shear stress would be reduced by adopting the spindle rotor impeller and diffuser with splitter blades and cantilevered main blades. The blood could flow smoothly through the axial blood pump with satisfactory hydraulics performance and without separation flow.

Design and numerical evaluation of an axial partial-assist blood pump for Chinese and other heart failure patients.

A fully implantable axial left ventricular assist device LAP31 was developed for Chinese or other heart failure patients who need partial support. Based on the 5-Lpm total cardiac blood output of Chinese without heart failure disease, the design point of LAP31 was set to a flow rate of 3 Lpm with 100-mmHg pressure head. To achieve the required pressure head and good hemolytic performance, a structure that includes a spindly rotor hub and a diffuser with splitter and cantilevered main blades was developed. Computational fluid dynamics (CFD) was used to analyze the hydraulic and hemodynamic performance of LAP31. Then in vitro hydraulics experiments were conducted. The numerical simulation results show that LAP31 could generate a 1 to 8 Lpm flow rate with a 60.9 to 182.7 mmHg pressure head when the pump was rotating between 9,000 and 12,000 rpm. The average scalar shear stress of the blood pump was 21.7 Pa, and the average exposure time was 71.0 milliseconds. The mean hemolysis index of LAP31 obtained using Heuser's hemolysis model and Giersiepen's model was 0.220% and 3.89 × 10-5% respectively. After adding the splitter blades, the flow separation at the suction surface of the diffuser was reduced. The cantilever structure reduced the tangential velocity from 6.1 to 4.7-1.4 m/s within the blade gap by changing the blade gap from shroud to hub. Subsequently, the blood damage caused by shear stress was reduced. In conclusion, the hydraulic and hemolytic characteristics of the LAP31 are acceptable for partial support.

Effects of Cone-Shaped Bend Inlet Cannulas of an Axial Blood Pump on Thrombus Formation: An Experiment and Simulation Study.

BACKGROUND Cannula shape and connection style influence the risk of thrombus formation in the blood pump by varying the blood flow characteristics inside the pump. Inlet cannulas should be designed based on the need for anatomical fit and reducing the risk of thrombus generation in the blood pump. The effects on thrombus formation of the cone-shaped bend inlet cannulas of axial blood pumps should be studied. MATERIAL AND METHODS The cannulas were designed as cone-shaped, with 1 bent section connecting 2 straight sections. Both the silicone tube and novel cone-shaped cannula were simulated for comparison. The flow fields of a blood pump with inlet cannula were simulated by computational fluid dynamics (CFD) at flows of 2.0, 2.5, and 3.0 liters per minute (lpm), with pump rotational speeds of 7500, 8000, and 8500 rpm, respectively. Then, 6 two-dimensional (2D) particle image velocimetry (PIV) tests were conducted and the velocity distributions were analyzed. RESULTS A low-velocity region was located inside the pump entrance when a soft silicone tube was used. At 8500 rpm and 3.0 lpm working condition, the minimum velocity inside the pump with cone-shaped cannulas was 2.5×10^-1 m/s. The cone-shaped cannulas eliminated the low-velocity region inside the pump. Both CFD and PIV results showed that the low-velocity region did not spread to the entrance of the blood pump within the flow range from 2.0 lpm to 7.0 lpm. CONCLUSIONS The designed cone-shaped bent cannulas can eliminate the low-velocity region inside the blood pump and reduce the risk of thrombus formation in the blood pump.

Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats.

The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1-LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery.

The miRNA Expression Profile in Acute Myocardial Infarct Using Sheep Model with Left Ventricular Assist Device Unloading.

This study attempted to establish miRNA expression profiles in acute myocardial infarct (AMI) sheep model with left ventricular assist device (LVAD) unloading. AMI was established in sheep model and FW-II type axial flow pump was implanted to maintain continuous unloading for 3 days. The cardiomyocyte survival, inflammatory cell infiltration, and myocardial fibrosis were detected by tissue staining, and cardiomyocyte apoptosis was detected by TUNEL assay. High throughput sequencing technique was used to detect miRNA expression in cardiomyocytes and to establish miRNA expression profile. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were established. miRNA sequencing results identified 152 known mature miRNAs and 1582 new mature miRNAs. The unloading and control groups differentially expressed genes, of which RT-PCR verified oar-miR-19b and oar-miR-26a. The GO and KEGG pathway annotation and enrichment established that the regulating functions and signaling pathways of these miRNAs were closely related to cardiovascular diseases (CVD). In this study, LVAD effectively reduced the cell death degree of cardiomyocyte in MI. The established miRNA expression profiles of AMI and LVAD intervention in this study suggest that the expression profile could be used to explore the unknown miRNA and the regulatory mechanisms involved in AMI.

Editorial: Recent advances in the design and preclinical evaluation of ventricular assist devices.

Platelet adhesion emulation: A novel method for estimating the device thrombosis potential of a ventricular assist device.

Device thrombosis inside ventricular assist devices remains a limitation to their long-term clinical use. Thrombosis potential exists in almost all ventricular assist devices because the device-induced high shear stress and vortices can activate platelets, which then aggregate and adhere to the surfaces inside the ventricular assist device. To decrease the device thrombosis potential of long-term use of ventricular assist devices, a methodology entitled platelet adhesion emulation for predicting the thrombosis potential and thrombosis position inside the ventricular assist devices is developed. The platelet adhesion emulation methodology combines numerical simulations with in vitro experiments by correlating the structure of the flow passage components within the ventricular assist device with the platelet adhesion to estimate the thrombosis potential and location, with the goal of developing ventricular assist devices with optimized antithrombotic performance. Platelet adhesion emulation is aimed at decreasing the device thrombus potential of ventricular assist devices. The platelet adhesion emulation effectiveness is validated by simulating and testing an axial left ventricular assist device. The blood velocity relative to the surfaces of the flow passage components is calculated to estimate the platelet adhesion potential, indicating the probability of thrombus formation on the surfaces. Platelet adhesion emulation experiments conducted in a mock circulation loop with pump prototypes show the distribution of platelet adhesion on the surfaces. This methodology of emulating the device thrombosis distribution indicates the potential for improving the component structure and reducing the device thrombosis of ventricular assist devices.

Platelet deposition estimation: A novel method for emulating the pump thrombosis potential of blood pumps.

Pump thrombosis potential exists in most blood pumps and limits their clinical use. To improve the pump thrombosis performance of blood pumps, a method for emulating the platelet deposition on the flow passage component surfaces inside blood pumps was presented and tested. The method emulates the blood platelet deposition, employing laser-induced fluorescence tracing technology. The blood pump was rotated in a mock circulation loop with deionized water filled with fluorescent particles. The component surfaces were then explored via laser. The fluorescent particles were induced by laser and imaged in a charge-coupled device (CCD) camera to show the distribution of fluorescent particles gathering on the blood pump component surfaces. The activated platelet deposition was emulated by fluorescent particle gathering. The experiment showed obvious particle gathering on the interface surfaces and cross-sectional surface (perpendicular to the flow). This platelet deposition estimation (PDE) method can be easily incorporated in the in vitro testing phase to analyze and decrease a pump's thrombosis potential before animal experimentation, thereby reducing the cost of blood pump development. This methodology of emulating blood platelet deposition indicates its potential for improving flow passage component structure and reducing device thrombosis of blood pumps.

Numerical investigation of the influence of a bearing/shaft structure in an axial blood pump on the potential for device thrombosis.

Adverse events caused by flow-induced thrombus formation around the bearing/shaft of an axial blood pump remain a serious problem for axial blood pumps. Moreover, excessive anticoagulation with thrombosis around the bearing potentially increases the risk of postoperative gastrointestinal bleeding. The purpose of this study is to analyze the influence of the bearing structure on the thrombosis potential of an axial blood pump. The bearing/shaft structure was embedded into an axial blood pump numerical model. The numerical simulation and analysis are focused on the low wall shear stresses, recirculation, and residence time close to the bearing region to evaluate the potential for thrombosis around the bearing. Then, the flow field near the blood pump bearing was tested via in vitro particle image velocimetry experiments to verify the numerical results. The simulation results showed that after embedding the bearing/shaft structure a recirculation zone appeared in the outlet guide vane bearing/shaft region, the residence time increased 11-fold in comparison to the pump without the bearing/shaft structure, the scalar shear stress in the shaft surface was less than 7.8 Pa, and the stress accumulation was less than 0.10 Pa s. The numerical results showed that platelets that flow through the bearing region are exposed to significantly lower wall shear stress and a longer residence time, leading to activated platelet adhesion. The reduced stress accumulation and increased time in the bearing region lead to increased platelet activation.

Numerical Investigation of the Influence of Blade Radial Gap Flow on Axial Blood Pump Performance.

The gaps between the blades and the shroud (or hub) of an axial blood pump affect the hydraulics, efficiency, and hemolytic performance. These gaps are critical parameters when a blood pump is manufactured. To evaluate the influence of blade gaps on axial blood pump performance, the flow characteristics inside an axial blood pump with different radial blade gaps were numerically simulated and analyzed with special attention paid to the hydraulic characteristics, gap flow, hydraulic efficiency, and hemolysis index (HI). In vitro hydraulic testing and particle image velocimetry testing were conducted to verify the numerical results. The simulation results showed that the efficiency and pressure rise decreased when the gap increased. The efficiency of the axial blood pump at design point decreased from 37.1% to 27.1% and the pressure rise decreased from 127.4 to 71.2 mm Hg when the gap increased from 0.1 to 0.3 mm. Return and vortex flows were present in the outlet guide vane channels when the gap was larger than 0.2 mm. The HI of the blood pump with a 0.1 mm gap was 1.5-fold greater than that with a 0.3 mm gap. The results illustrated poor hydraulic characteristics when the gap was larger than 0.15 mm and rapidly deteriorated hemolysis when the gap was larger than 0.1 mm. The numerical and experimental results demonstrated that the pressure rise, pump efficiency, and scalar shear stress decreased when the gap increased. The HI did not strictly decrease with gap increases. The preliminary results encourage the improvement of axial blood pump designs.

[Design of an axial blood pump of diffuser with splitter blades and cantilevered main blades].

An implantable axial blood pump was designed according to the circulation assist requirement of severe heart failure patients of China. The design point was chosen at 3 L/min flow rate with 100 mm Hg pressure rise when the blood pump can provide flow rates of 2-7 L/min. The blood pump with good hemolytic and anti-thrombogenic property at widely operating range was designed by developing a structure that including the spindly rotor impeller structure and the diffuser with splitter blades and cantilevered main blades. Numerical simulation and particle image velocimetry (PIV) experiment were conducted to analyze the hydraulic, flow fields and hemolytic performance of the blood pump. The results showed that the blood pump could provide flow rates of 2-7 L/min with pressure rise of 60.0-151.3 mm Hg when the blood pump rotating from 7 000 to 11 000 r/min. After adding the splitter blades, the separation flow at the suction surface of the diffuser has been reduced efficiently. The cantilever structure changed the blade gap from shroud to hub that reduced the tangential velocity from 6.2 m/s to 4.3-1.1 m/s in blade gap. Moreover, the maximum scalar shear stress of the blood pump was 897.3 Pa, and the averaged scalar shear stress was 37.7 Pa. The hemolysis index of the blood pump was 0.168% calculated with Heuser's hemolysis model. The PIV and simulated results showed the overall agreement of flow field distribution in diffuser region. The blood damage caused by higher shear stress would be reduced by adopting the spindle rotor impeller and diffuser with splitter blades and cantilevered main blades. The blood could flow smoothly through the axial blood pump with satisfactory hydraulics performance and without separation flow.

Design and numerical evaluation of an axial partial-assist blood pump for Chinese and other heart failure patients.

A fully implantable axial left ventricular assist device LAP31 was developed for Chinese or other heart failure patients who need partial support. Based on the 5-Lpm total cardiac blood output of Chinese without heart failure disease, the design point of LAP31 was set to a flow rate of 3 Lpm with 100-mmHg pressure head. To achieve the required pressure head and good hemolytic performance, a structure that includes a spindly rotor hub and a diffuser with splitter and cantilevered main blades was developed. Computational fluid dynamics (CFD) was used to analyze the hydraulic and hemodynamic performance of LAP31. Then in vitro hydraulics experiments were conducted. The numerical simulation results show that LAP31 could generate a 1 to 8 Lpm flow rate with a 60.9 to 182.7 mmHg pressure head when the pump was rotating between 9,000 and 12,000 rpm. The average scalar shear stress of the blood pump was 21.7 Pa, and the average exposure time was 71.0 milliseconds. The mean hemolysis index of LAP31 obtained using Heuser's hemolysis model and Giersiepen's model was 0.220% and 3.89 × 10-5% respectively. After adding the splitter blades, the flow separation at the suction surface of the diffuser was reduced. The cantilever structure reduced the tangential velocity from 6.1 to 4.7-1.4 m/s within the blade gap by changing the blade gap from shroud to hub. Subsequently, the blood damage caused by shear stress was reduced. In conclusion, the hydraulic and hemolytic characteristics of the LAP31 are acceptable for partial support.

Effects of Cone-Shaped Bend Inlet Cannulas of an Axial Blood Pump on Thrombus Formation: An Experiment and Simulation Study.

BACKGROUND Cannula shape and connection style influence the risk of thrombus formation in the blood pump by varying the blood flow characteristics inside the pump. Inlet cannulas should be designed based on the need for anatomical fit and reducing the risk of thrombus generation in the blood pump. The effects on thrombus formation of the cone-shaped bend inlet cannulas of axial blood pumps should be studied. MATERIAL AND METHODS The cannulas were designed as cone-shaped, with 1 bent section connecting 2 straight sections. Both the silicone tube and novel cone-shaped cannula were simulated for comparison. The flow fields of a blood pump with inlet cannula were simulated by computational fluid dynamics (CFD) at flows of 2.0, 2.5, and 3.0 liters per minute (lpm), with pump rotational speeds of 7500, 8000, and 8500 rpm, respectively. Then, 6 two-dimensional (2D) particle image velocimetry (PIV) tests were conducted and the velocity distributions were analyzed. RESULTS A low-velocity region was located inside the pump entrance when a soft silicone tube was used. At 8500 rpm and 3.0 lpm working condition, the minimum velocity inside the pump with cone-shaped cannulas was 2.5×10^-1 m/s. The cone-shaped cannulas eliminated the low-velocity region inside the pump. Both CFD and PIV results showed that the low-velocity region did not spread to the entrance of the blood pump within the flow range from 2.0 lpm to 7.0 lpm. CONCLUSIONS The designed cone-shaped bent cannulas can eliminate the low-velocity region inside the blood pump and reduce the risk of thrombus formation in the blood pump.

Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats.

The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1-LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery.

The miRNA Expression Profile in Acute Myocardial Infarct Using Sheep Model with Left Ventricular Assist Device Unloading.

This study attempted to establish miRNA expression profiles in acute myocardial infarct (AMI) sheep model with left ventricular assist device (LVAD) unloading. AMI was established in sheep model and FW-II type axial flow pump was implanted to maintain continuous unloading for 3 days. The cardiomyocyte survival, inflammatory cell infiltration, and myocardial fibrosis were detected by tissue staining, and cardiomyocyte apoptosis was detected by TUNEL assay. High throughput sequencing technique was used to detect miRNA expression in cardiomyocytes and to establish miRNA expression profile. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were established. miRNA sequencing results identified 152 known mature miRNAs and 1582 new mature miRNAs. The unloading and control groups differentially expressed genes, of which RT-PCR verified oar-miR-19b and oar-miR-26a. The GO and KEGG pathway annotation and enrichment established that the regulating functions and signaling pathways of these miRNAs were closely related to cardiovascular diseases (CVD). In this study, LVAD effectively reduced the cell death degree of cardiomyocyte in MI. The established miRNA expression profiles of AMI and LVAD intervention in this study suggest that the expression profile could be used to explore the unknown miRNA and the regulatory mechanisms involved in AMI.