Eisuke Tatsumi - Academia.edu (original) (raw)

Papers by Eisuke Tatsumi

Journal of the Visualization Society of Japan, 1999

We have developed a novel image measurement technique called paint erosion method (PEM) to estima... more We have developed a novel image measurement technique called paint erosion method (PEM) to estimate wall shear stress (WSS). In the PEM, the WSS is estimated from the paint erosion rate obtained by the instantaneous change of light transmission power on the image. In this study, we attempted to depict WSS distribution of the diaphragm-type pulsatile blood pump in our total artificial heart by the PEM, and further compared the obtained WSS distribution with in vivo thrombus deposition area. The average WSS contour map inside the blood pumps were successfully obtained by using the PEM, and in vivo thrombus deposition area coincided with the low WSS of less than 2.7 Pa. We concluded that WSS mapping based on the PEM provides useful information for predicting the preference area of in vivo thrombus formation in a pulsatile blood pump and facilitates improving its antithrombogenicity from the viewpoint of flow dynamics.

SICE 2004 Annual Conference, 2004

We have been developing an electrohydraulic total artificial heart (EHTAH) system. The system con... more We have been developing an electrohydraulic total artificial heart (EHTAH) system. The system consists of diaphragm-type blood pumps, an electrohydraulic energy converter, an internal control unit, a transcutaneous energy transfer (TET) system, a transcutaneous optical telemetry (TOT) system, and an internal battery. The energy converter reciprocates and delivers hydraulic silicone oil to the alternate blood pumps. The displacement volume and the weight of the system are 872 ml and 2492 g, respectively. The maximum flow rate was 12 L/min and the maximum efficiency was 15.4%. The system performance was examined in a series of in vivo experiments. The system was successfully implanted in 16 calves in the range of 60 kg or more. Four of the 16 calves survived for more than 1 month approximately. One of them lived for 70 days. The system was basically driven by the TET system, and was driven by the internal battery for 40 minutes everyday. The internal battery was fully charged within 3...

Acta medica Okayama, 2008

Percutaneous cardiopulmonary support (PCPS) has been applied for cardiopulmonary arrest (CPA). We... more Percutaneous cardiopulmonary support (PCPS) has been applied for cardiopulmonary arrest (CPA). We have developed a novel method of cardiopulmonary resuscitation using PCPS combined with liposome-encapsulated hemoglobin (TRM645) to improve oxygen delivery to vital organs. Ventricular fibrillation was electrically induced to an adult goat for 10 min. Next, PCPS (30 ml/kg/min, V/Q: 1) was performed for 20 min. Then, external defibrillation was attempted and observed for 120 min. The TRM group (n5) was filled with 300 mL of TRM645 for the PCPS circuit. The control group (n5) was filled with the same volume of saline. The delivery of oxygen (DO2) and oxygen consumption (VO2) decreased markedly by PCPS after CPA, compared to the preoperative values. DO2 was kept at a constant level during PCPS in both groups, but VO2 slowly decreased at 5, 10, and 15 min of PCPS in the control groups, demonstrating that systemic oxygen metabolism decreased with time. In contrast, the decreases in VO2 were...

The International Journal of Artificial Organs

Despite its wide clinical application, patient recovery from cardiopulmonary support (CPS) is not... more Despite its wide clinical application, patient recovery from cardiopulmonary support (CPS) is not necessarily satisfactory. To clarify what influence CPS has on organ perfusion, we investigated the oxygen metabolism under various bypass flow (BF) conditions in a series of chronic animal CPS experiments. The CPS system, which consists of a pulsatile ventricular assist device and a compact artificial lung was installed without anesthesia in 6 adult goats weighing 49-51 kg. BF was adjusted stepwise from 0% to 50%, 75%, 90%, and 100% of total systemic blood flow (TSF) by balancing the pulmonary arterial flow. The animals' TSF and oxygen delivery (DO2) were sufficiently maintained throughout the experiments. The oxygen consumption (VO2) and the oxygen extraction rate (ExO2) increased from 178+/-14 to 342+/-19 ml/min, and from 28+/-2% to 64+/-1%, respectively, in proportion to the increase of CPBF dependency from 0% to 100%. The blood lactate level did not change appreciably even at 90% BF from 5.7+/-0.3 to 11.2+/-1.2 mg/dl, but drastically elevated to 23.5+/-4.6 mg/dl at the total bypass. This indicates that CPS leads to a relative lack of oxygen and can induce organ dysfunction due to increasing VO2 and ExO2 in proportion to the increase of BF dependence even if TSF and DO2 are sufficiently maintained.

The Journal of Thoracic and Cardiovascular Surgery

Actuators

Research interests of compact magnetically levitated motors have been strongly increased in devel... more Research interests of compact magnetically levitated motors have been strongly increased in development of durable and biocompatible mechanical circulatory support (MCS) devices for pediatric heart disease patients. In this study, an ultra-compact axial gap type self-bearing motor with 5-degrees of freedom (DOF) active control for use in pediatric MCS devices has been developed. The motor consists of two identical motor stators and a centrifugal levitated rotor. This paper investigated a design improvement of the magnetic circuit for the self-bearing motor undergoing development in order to diminish energy input by enhancing magnetic suspension and rotation performances. Geometries of the motor were refined based on numerical calculation and three-dimensional (3D) magnetic field analysis. The modified motor can achieve higher suspension force and torque characteristics than that of a previously developed prototype motor. Oscillation of the levitated rotor was significantly suppresse...

The International Journal of Artificial Organs

We investigated possible functional changes in the vascular system accompanying the morphological... more We investigated possible functional changes in the vascular system accompanying the morphological change in prolonged nonpulsatile left heart bypass (LHB). Three adult goats underwent pulsatile LHB. Two weeks postoperatively, the pulsatile ventricular assist device was replaced with a centrifugal pump and nonpulsatile LHB was subsequently conducted for 4 weeks. The mean aortic pulse pressure was 39 and 16 mmHg during the pulsatile and nonpulsatile LHB, respectively Systemic vascular resistance (SVR) and plasma norepinephrine levels were measured at the end of pulsatile LHB (PUL), and at the end of 1st, 2nd, 3rd, and 4th week of nonpulsatile LHB (NP1w, NP2w, NP3w, NP4w, respectively). At each point, 50 microg/kg nitroglycerin and 1 microg/kg norepinephrine were injected and the minimal and maximal values of SVR after injection were calculated as parameters reflecting the vascular tonus and contractility. The SVR and plasma nor epinephrine level did not significantly change during the entire course (SVR: 1106, 895, 982, 920, and 938 dyne x sec x cm(-5); norepinephrine level: 0.3, 0.2, 0.1, 0.2, and 0.1 ng/ml; at PUL, NP1w, NP2w, NP3w, and NP4w, respectively). The minimal value of SVR after nitroglycerin injection remained unchanged, indicating that vascular tonus was stable during the entire course (618, 687, 623, 560, 653 dyne x sec x cm(-5), respectively). In contrast, the maximal value of SVR after norepinephrine injection at NP3w and NP4w (1695 and 1759 dyne x sec x cm(-5)) became significantly reduced compared to that at PUL (2346 dyne x sec x cm(-5)). These results indicated that prolonged nonpulsatile left heart bypass did not affect the vascular tonus, but significantly diminished the vascular contractility.

American Journal of Physiology-Heart and Circulatory Physiology

To investigate the effects of pulsatile and nonpulsatile systemic circulation on the sympathetic ... more To investigate the effects of pulsatile and nonpulsatile systemic circulation on the sympathetic nerve activity, using a left heart bypass technique, we converted systemic circulation between the pulsatile and the nonpulsatile mode in anesthetized goats and analyzed differences in periodicity and quantity of renal nerve activity (RNA). After pulsatile systemic circulation was converted to the nonpulsatile mode, the mean RNA was significantly increased from 10.7 +/- 3.6 to 13.1 +/- 3.4 microV and periodic discharges of RNA, which corresponded to pulse-related rhythm during pulsatile circulation, became obscure, whereas an 8-12 cycle/s rhythm, which was distinguished and accounted for 30 +/- 9% of total intervals during pulsatile circulation, became dominant (48 +/- 11%). These results clarified a significant increase in mean RNA after depulsation of the systemic circulation and indicated that the cardiac-related rhythm in RNA could be produced by periodic inputs from arterial barocep...

Cardiovascular drugs and therapy, Jan 8, 2018

The management of heart failure patients presenting in a moribund state remains challenging, desp... more The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A ...

Frontiers in physiology, 2018

Cardiopulmonary bypass (CPB) induced systemic inflammation significantly contributes to the devel... more Cardiopulmonary bypass (CPB) induced systemic inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately can lead to failure of multiple organs. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. Herein, we investigated the protective effects of ghrelin against CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male Sprague Dawley rats randomly received vehicle (= 5) or a bolus of ghrelin (150 μg/kg, sc,= 5) and were subjected to CPB for 4 h (protocol 1). In separate rats, ghrelin pre-treatment (protocol 2) was compared to two doses of ghrelin (protocol 3) before and after CPB for 2 h followed by recovery for 2 h. Blood samples were taken prior to CPB, and following CPB at 2 h and 4 h. Organ nitrosative stress (3-nitrotyrosine) was measured by Western blottin...

Biochemical pharmacology, Nov 5, 2017

Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. ... more Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3 mg/kg/d oral gavage) from the age of 8 to 16 weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF) -α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obe...

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, Jan 19, 2016

Continuous-flow left ventricular assist devices (LVADs) have improved the prognosis of end-stage ... more Continuous-flow left ventricular assist devices (LVADs) have improved the prognosis of end-stage heart failure. However, continuous-flow LVADs diminish pulsatility, which possibly result in bleeding, aortic insufficiency, and other adverse effects. We previously developed a novel control system for a continuous-flow LVAD (EVAHEART(®); Sun Medical), and demonstrated that we could create sufficient pulsatility by increasing its rotational speed (RS) in the systolic phase (Pulsatile Mode) in the normal heart model. Here, we aimed to evaluate differences between systolic assist with advanced and delayed loads by shifting the timing of increased RS. We implanted EVAHEART in six goats (55.3 ± 4.3 kg) with normal hearts. We reduced their heart rates to <60 bpm using propranolol and controlled the heart rates at 80 and 120 bpm using ventricular pacing. We shifted the timing of increasing RS from -60 to +60 ms in the systolic phase. We found significant increases in all the following para...

The International journal of artificial organs, Jan 15, 2016

In vitro antithrombogenic testing with mock circulation is a useful type of pre-evaluation in ex ... more In vitro antithrombogenic testing with mock circulation is a useful type of pre-evaluation in ex vivo testing of mechanical assist devices. For effective in vitro testing, we have been developing a clear quantitative thrombogenesis model based on shear stress and blood coagulability. Bovine blood was used as the test medium. The activating clotting time (ACT) was adjusted with trisodium citrate and calcium chloride from 200 to 1,000 seconds. The blood was then applied to a rheometer and subjected to shear at 50 to 2,880 s-1. Blood coagulation time and degree of thrombogenesis were measured by the torque sensor of the rheometer. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the test blood were also measured after the application of shear. Blood coagulation time increased, and the degree of thrombogenesis decreased, with increases in shear rate to between 50 and 2,880 s-1. for test bloods with ACTs of 200 to 250 seconds. An ACT of 200 to 250 seconds is thus...

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, Jan 4, 2016

A long-term durability test was conducted on a newly developed axial-flow ventricular assist devi... more A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average f...

Circulation, Nov 20, 2012

Introduction; Heart rate variability (HRV) is conceived to have a close relationship with prognos... more Introduction; Heart rate variability (HRV) is conceived to have a close relationship with prognosis of heart failure (HF). However, there is few study on HRV during diagnostic and treating process of HF in clinical settings. By investigating this process, HRV may become a more useful approach for non-invasive estimation of cardiac function. In this study, we examined the change of HRV and its correlation with cardiac function throughout the entire course of progressing HF in newly developed large animal chronic heart failure (CHF) models created by combination of micro-embolization and rapid pacing. Methods; CHF was introduced in 12 adult goats (60.9±4.1 kg) by coronary microsphere embolization (50μm, 0.201±0.014 million) to the left anterior descending artery and subsequent rapid ventricular pacing (HR[[Unable to Display Character: ≒]]200) for 5 weeks. Electrocardiogram was recorded continuously for 24 hours under pacing off per week. HRV was analyzed by Memcalc/CHIRAM (Suwa Trust, GMS Inc.), which calculated time-domain index (SDNN etc.) and frequency domain index (LF, HF etc.), evaluated correlation with left ventricle ejection fraction (EF) and cardiac output (CO). Results; Ten goats survived and developed CHF successfully, showing decreased EF (from 90.4±4.1% to 48.3±5.6%) and CO (from 5.6±0.5L/min to 4.0±0.6 L/min). All indexes of HRV were decreased along with progress of HF (SDNN decreased from 166.1±39.1msec to 51.9±33.3msec). LF/HF which is the index of sympathetic nerve activity increased from 1.4±0.9 to 10.7±8.3. A strong correlation was observed between SDNN and cardiac function (Fig). Two cases of sudden death in course showed significant decrease of HRV as compared with the surviving cases. Conclusions; HRV was decreased along with progress of HF, strongly indicating aggravation of sympathetic nerve activity. These findings suggest that HRV analysis has a potential to become a useful and reliable approach for non-invasive estimation of cardiac function and severity of HF.

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, Jan 14, 2016

We have previously developed a native heart load control system for a continuous-flow left ventri... more We have previously developed a native heart load control system for a continuous-flow left ventricular assist device (LVAD) ((EVAHEART(®); Sun Medical) and demonstrated that the rotational speed (RS) in synchronization with the cardiac cycle can alter pulsatility and left ventricular (LV) load under general anesthesia. In this study, we assessed the effects of different levels of increase in RS on pulsatility and LV load in the chronic awake phase. We implanted the EVAHEART via left thoracotomy in 7 normal goats (59.3 ± 4.6 kg). Two weeks after implantation, we examined the effects of co-pulse mode (increased RS in the systolic phase) and counter-pulse mode (increased RS in the diastolic phase), as well as shifting the change in RS from 250 to 500 rpm, and 750 rpm in both modes on pulsatility and LV load. Pulsatility was assessed using pulse pressure and mean dP/dt max of aortic pressure. LV load was assessed using stroke work and left ventricle end-diastolic volume determined from ...

Artificial organs, Jan 19, 2016

Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by ca... more Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by causing a leftward shift of the interventricular septum in patients with mitral regurgitation (MR) receiving left ventricular assist device (LVAD) support. Optimal settings for the LVAD should be chosen to appropriately control the MR without causing RV dysfunction. In this study, we assessed the utility of our electrocardiogram-synchronized rotational speed (RS) modulation system along with a continuous-flow LVAD in a goat model of MR. We implanted EVAHEART devices after left thoracotomy in six adult goats weighing 66.4 ± 10.7 kg. Severe MR was induced through inflation of a temporary inferior vena cava filter placed within the mitral valve. We evaluated total flow (TF; the sum of aortic flow and pump flow [PF]), RV fractional area change (RVFAC) calculated by echocardiography, left atrial pressure (LAP), LV end-diastolic pressure (LVEDP), LV end-diastolic volume (LVEDV), and LV stroke wo...

Journal of the Visualization Society of Japan, 1999

We have developed a novel image measurement technique called paint erosion method (PEM) to estima... more We have developed a novel image measurement technique called paint erosion method (PEM) to estimate wall shear stress (WSS). In the PEM, the WSS is estimated from the paint erosion rate obtained by the instantaneous change of light transmission power on the image. In this study, we attempted to depict WSS distribution of the diaphragm-type pulsatile blood pump in our total artificial heart by the PEM, and further compared the obtained WSS distribution with in vivo thrombus deposition area. The average WSS contour map inside the blood pumps were successfully obtained by using the PEM, and in vivo thrombus deposition area coincided with the low WSS of less than 2.7 Pa. We concluded that WSS mapping based on the PEM provides useful information for predicting the preference area of in vivo thrombus formation in a pulsatile blood pump and facilitates improving its antithrombogenicity from the viewpoint of flow dynamics.

SICE 2004 Annual Conference, 2004

We have been developing an electrohydraulic total artificial heart (EHTAH) system. The system con... more We have been developing an electrohydraulic total artificial heart (EHTAH) system. The system consists of diaphragm-type blood pumps, an electrohydraulic energy converter, an internal control unit, a transcutaneous energy transfer (TET) system, a transcutaneous optical telemetry (TOT) system, and an internal battery. The energy converter reciprocates and delivers hydraulic silicone oil to the alternate blood pumps. The displacement volume and the weight of the system are 872 ml and 2492 g, respectively. The maximum flow rate was 12 L/min and the maximum efficiency was 15.4%. The system performance was examined in a series of in vivo experiments. The system was successfully implanted in 16 calves in the range of 60 kg or more. Four of the 16 calves survived for more than 1 month approximately. One of them lived for 70 days. The system was basically driven by the TET system, and was driven by the internal battery for 40 minutes everyday. The internal battery was fully charged within 3...

Acta medica Okayama, 2008

Percutaneous cardiopulmonary support (PCPS) has been applied for cardiopulmonary arrest (CPA). We... more Percutaneous cardiopulmonary support (PCPS) has been applied for cardiopulmonary arrest (CPA). We have developed a novel method of cardiopulmonary resuscitation using PCPS combined with liposome-encapsulated hemoglobin (TRM645) to improve oxygen delivery to vital organs. Ventricular fibrillation was electrically induced to an adult goat for 10 min. Next, PCPS (30 ml/kg/min, V/Q: 1) was performed for 20 min. Then, external defibrillation was attempted and observed for 120 min. The TRM group (n5) was filled with 300 mL of TRM645 for the PCPS circuit. The control group (n5) was filled with the same volume of saline. The delivery of oxygen (DO2) and oxygen consumption (VO2) decreased markedly by PCPS after CPA, compared to the preoperative values. DO2 was kept at a constant level during PCPS in both groups, but VO2 slowly decreased at 5, 10, and 15 min of PCPS in the control groups, demonstrating that systemic oxygen metabolism decreased with time. In contrast, the decreases in VO2 were...

The International Journal of Artificial Organs

Despite its wide clinical application, patient recovery from cardiopulmonary support (CPS) is not... more Despite its wide clinical application, patient recovery from cardiopulmonary support (CPS) is not necessarily satisfactory. To clarify what influence CPS has on organ perfusion, we investigated the oxygen metabolism under various bypass flow (BF) conditions in a series of chronic animal CPS experiments. The CPS system, which consists of a pulsatile ventricular assist device and a compact artificial lung was installed without anesthesia in 6 adult goats weighing 49-51 kg. BF was adjusted stepwise from 0% to 50%, 75%, 90%, and 100% of total systemic blood flow (TSF) by balancing the pulmonary arterial flow. The animals&#39; TSF and oxygen delivery (DO2) were sufficiently maintained throughout the experiments. The oxygen consumption (VO2) and the oxygen extraction rate (ExO2) increased from 178+/-14 to 342+/-19 ml/min, and from 28+/-2% to 64+/-1%, respectively, in proportion to the increase of CPBF dependency from 0% to 100%. The blood lactate level did not change appreciably even at 90% BF from 5.7+/-0.3 to 11.2+/-1.2 mg/dl, but drastically elevated to 23.5+/-4.6 mg/dl at the total bypass. This indicates that CPS leads to a relative lack of oxygen and can induce organ dysfunction due to increasing VO2 and ExO2 in proportion to the increase of BF dependence even if TSF and DO2 are sufficiently maintained.

The Journal of Thoracic and Cardiovascular Surgery

Actuators

Research interests of compact magnetically levitated motors have been strongly increased in devel... more Research interests of compact magnetically levitated motors have been strongly increased in development of durable and biocompatible mechanical circulatory support (MCS) devices for pediatric heart disease patients. In this study, an ultra-compact axial gap type self-bearing motor with 5-degrees of freedom (DOF) active control for use in pediatric MCS devices has been developed. The motor consists of two identical motor stators and a centrifugal levitated rotor. This paper investigated a design improvement of the magnetic circuit for the self-bearing motor undergoing development in order to diminish energy input by enhancing magnetic suspension and rotation performances. Geometries of the motor were refined based on numerical calculation and three-dimensional (3D) magnetic field analysis. The modified motor can achieve higher suspension force and torque characteristics than that of a previously developed prototype motor. Oscillation of the levitated rotor was significantly suppresse...

The International Journal of Artificial Organs

We investigated possible functional changes in the vascular system accompanying the morphological... more We investigated possible functional changes in the vascular system accompanying the morphological change in prolonged nonpulsatile left heart bypass (LHB). Three adult goats underwent pulsatile LHB. Two weeks postoperatively, the pulsatile ventricular assist device was replaced with a centrifugal pump and nonpulsatile LHB was subsequently conducted for 4 weeks. The mean aortic pulse pressure was 39 and 16 mmHg during the pulsatile and nonpulsatile LHB, respectively Systemic vascular resistance (SVR) and plasma norepinephrine levels were measured at the end of pulsatile LHB (PUL), and at the end of 1st, 2nd, 3rd, and 4th week of nonpulsatile LHB (NP1w, NP2w, NP3w, NP4w, respectively). At each point, 50 microg/kg nitroglycerin and 1 microg/kg norepinephrine were injected and the minimal and maximal values of SVR after injection were calculated as parameters reflecting the vascular tonus and contractility. The SVR and plasma nor epinephrine level did not significantly change during the entire course (SVR: 1106, 895, 982, 920, and 938 dyne x sec x cm(-5); norepinephrine level: 0.3, 0.2, 0.1, 0.2, and 0.1 ng/ml; at PUL, NP1w, NP2w, NP3w, and NP4w, respectively). The minimal value of SVR after nitroglycerin injection remained unchanged, indicating that vascular tonus was stable during the entire course (618, 687, 623, 560, 653 dyne x sec x cm(-5), respectively). In contrast, the maximal value of SVR after norepinephrine injection at NP3w and NP4w (1695 and 1759 dyne x sec x cm(-5)) became significantly reduced compared to that at PUL (2346 dyne x sec x cm(-5)). These results indicated that prolonged nonpulsatile left heart bypass did not affect the vascular tonus, but significantly diminished the vascular contractility.

American Journal of Physiology-Heart and Circulatory Physiology

To investigate the effects of pulsatile and nonpulsatile systemic circulation on the sympathetic ... more To investigate the effects of pulsatile and nonpulsatile systemic circulation on the sympathetic nerve activity, using a left heart bypass technique, we converted systemic circulation between the pulsatile and the nonpulsatile mode in anesthetized goats and analyzed differences in periodicity and quantity of renal nerve activity (RNA). After pulsatile systemic circulation was converted to the nonpulsatile mode, the mean RNA was significantly increased from 10.7 +/- 3.6 to 13.1 +/- 3.4 microV and periodic discharges of RNA, which corresponded to pulse-related rhythm during pulsatile circulation, became obscure, whereas an 8-12 cycle/s rhythm, which was distinguished and accounted for 30 +/- 9% of total intervals during pulsatile circulation, became dominant (48 +/- 11%). These results clarified a significant increase in mean RNA after depulsation of the systemic circulation and indicated that the cardiac-related rhythm in RNA could be produced by periodic inputs from arterial barocep...

Cardiovascular drugs and therapy, Jan 8, 2018

The management of heart failure patients presenting in a moribund state remains challenging, desp... more The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A ...

Frontiers in physiology, 2018

Cardiopulmonary bypass (CPB) induced systemic inflammation significantly contributes to the devel... more Cardiopulmonary bypass (CPB) induced systemic inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately can lead to failure of multiple organs. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. Herein, we investigated the protective effects of ghrelin against CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male Sprague Dawley rats randomly received vehicle (= 5) or a bolus of ghrelin (150 μg/kg, sc,= 5) and were subjected to CPB for 4 h (protocol 1). In separate rats, ghrelin pre-treatment (protocol 2) was compared to two doses of ghrelin (protocol 3) before and after CPB for 2 h followed by recovery for 2 h. Blood samples were taken prior to CPB, and following CPB at 2 h and 4 h. Organ nitrosative stress (3-nitrotyrosine) was measured by Western blottin...

Biochemical pharmacology, Nov 5, 2017

Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. ... more Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3 mg/kg/d oral gavage) from the age of 8 to 16 weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF) -α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obe...

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, Jan 19, 2016

Continuous-flow left ventricular assist devices (LVADs) have improved the prognosis of end-stage ... more Continuous-flow left ventricular assist devices (LVADs) have improved the prognosis of end-stage heart failure. However, continuous-flow LVADs diminish pulsatility, which possibly result in bleeding, aortic insufficiency, and other adverse effects. We previously developed a novel control system for a continuous-flow LVAD (EVAHEART(®); Sun Medical), and demonstrated that we could create sufficient pulsatility by increasing its rotational speed (RS) in the systolic phase (Pulsatile Mode) in the normal heart model. Here, we aimed to evaluate differences between systolic assist with advanced and delayed loads by shifting the timing of increased RS. We implanted EVAHEART in six goats (55.3 ± 4.3 kg) with normal hearts. We reduced their heart rates to <60 bpm using propranolol and controlled the heart rates at 80 and 120 bpm using ventricular pacing. We shifted the timing of increasing RS from -60 to +60 ms in the systolic phase. We found significant increases in all the following para...

The International journal of artificial organs, Jan 15, 2016

In vitro antithrombogenic testing with mock circulation is a useful type of pre-evaluation in ex ... more In vitro antithrombogenic testing with mock circulation is a useful type of pre-evaluation in ex vivo testing of mechanical assist devices. For effective in vitro testing, we have been developing a clear quantitative thrombogenesis model based on shear stress and blood coagulability. Bovine blood was used as the test medium. The activating clotting time (ACT) was adjusted with trisodium citrate and calcium chloride from 200 to 1,000 seconds. The blood was then applied to a rheometer and subjected to shear at 50 to 2,880 s-1. Blood coagulation time and degree of thrombogenesis were measured by the torque sensor of the rheometer. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the test blood were also measured after the application of shear. Blood coagulation time increased, and the degree of thrombogenesis decreased, with increases in shear rate to between 50 and 2,880 s-1. for test bloods with ACTs of 200 to 250 seconds. An ACT of 200 to 250 seconds is thus...

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, Jan 4, 2016

A long-term durability test was conducted on a newly developed axial-flow ventricular assist devi... more A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average f...

Circulation, Nov 20, 2012

Introduction; Heart rate variability (HRV) is conceived to have a close relationship with prognos... more Introduction; Heart rate variability (HRV) is conceived to have a close relationship with prognosis of heart failure (HF). However, there is few study on HRV during diagnostic and treating process of HF in clinical settings. By investigating this process, HRV may become a more useful approach for non-invasive estimation of cardiac function. In this study, we examined the change of HRV and its correlation with cardiac function throughout the entire course of progressing HF in newly developed large animal chronic heart failure (CHF) models created by combination of micro-embolization and rapid pacing. Methods; CHF was introduced in 12 adult goats (60.9±4.1 kg) by coronary microsphere embolization (50μm, 0.201±0.014 million) to the left anterior descending artery and subsequent rapid ventricular pacing (HR[[Unable to Display Character: ≒]]200) for 5 weeks. Electrocardiogram was recorded continuously for 24 hours under pacing off per week. HRV was analyzed by Memcalc/CHIRAM (Suwa Trust, GMS Inc.), which calculated time-domain index (SDNN etc.) and frequency domain index (LF, HF etc.), evaluated correlation with left ventricle ejection fraction (EF) and cardiac output (CO). Results; Ten goats survived and developed CHF successfully, showing decreased EF (from 90.4±4.1% to 48.3±5.6%) and CO (from 5.6±0.5L/min to 4.0±0.6 L/min). All indexes of HRV were decreased along with progress of HF (SDNN decreased from 166.1±39.1msec to 51.9±33.3msec). LF/HF which is the index of sympathetic nerve activity increased from 1.4±0.9 to 10.7±8.3. A strong correlation was observed between SDNN and cardiac function (Fig). Two cases of sudden death in course showed significant decrease of HRV as compared with the surviving cases. Conclusions; HRV was decreased along with progress of HF, strongly indicating aggravation of sympathetic nerve activity. These findings suggest that HRV analysis has a potential to become a useful and reliable approach for non-invasive estimation of cardiac function and severity of HF.

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, Jan 14, 2016

We have previously developed a native heart load control system for a continuous-flow left ventri... more We have previously developed a native heart load control system for a continuous-flow left ventricular assist device (LVAD) ((EVAHEART(®); Sun Medical) and demonstrated that the rotational speed (RS) in synchronization with the cardiac cycle can alter pulsatility and left ventricular (LV) load under general anesthesia. In this study, we assessed the effects of different levels of increase in RS on pulsatility and LV load in the chronic awake phase. We implanted the EVAHEART via left thoracotomy in 7 normal goats (59.3 ± 4.6 kg). Two weeks after implantation, we examined the effects of co-pulse mode (increased RS in the systolic phase) and counter-pulse mode (increased RS in the diastolic phase), as well as shifting the change in RS from 250 to 500 rpm, and 750 rpm in both modes on pulsatility and LV load. Pulsatility was assessed using pulse pressure and mean dP/dt max of aortic pressure. LV load was assessed using stroke work and left ventricle end-diastolic volume determined from ...

Artificial organs, Jan 19, 2016

Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by ca... more Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by causing a leftward shift of the interventricular septum in patients with mitral regurgitation (MR) receiving left ventricular assist device (LVAD) support. Optimal settings for the LVAD should be chosen to appropriately control the MR without causing RV dysfunction. In this study, we assessed the utility of our electrocardiogram-synchronized rotational speed (RS) modulation system along with a continuous-flow LVAD in a goat model of MR. We implanted EVAHEART devices after left thoracotomy in six adult goats weighing 66.4 ± 10.7 kg. Severe MR was induced through inflation of a temporary inferior vena cava filter placed within the mitral valve. We evaluated total flow (TF; the sum of aortic flow and pump flow [PF]), RV fractional area change (RVFAC) calculated by echocardiography, left atrial pressure (LAP), LV end-diastolic pressure (LVEDP), LV end-diastolic volume (LVEDV), and LV stroke wo...