Ho Sung Son

Regeneration of ischemic heart using hyaluronic acid-based injectable hydrogel.

An injectable hydrogel was applied to regenerate a myocardial infarction and functional recovery of the heart. A myocardial infarction was induced in rat by circumflex artery ligation. A hyaluronic acid-based hydrogel was injected into the epicardium of the infarcted area. Then, cardiac functions and regeneration of the myocardium in sham-operated (SHAM), myocardial infarction (MI), and gel-injected group (GEL) (n = 6) were evaluated 4 weeks after the injection. Measurements of the thickness of the wall showed that the thickness in the GEL group increased by up to 200% compared with that in the MI group (p < 0.001). The infarcted area of the left ventricular in the GEL group decreased by 53% compared with the MI group (p < 0.001). The number of arterioles and capillaries in the border zone of the GEL group increased by 152% and 148%, whereas the apoptotic index decreased by 42% (p < 0.05). Measurement of the heart functions, such as ejection fraction, arterial elastance (Ea), dP/dt max, and dP/dt min, indicated that the injection of a hydrogel significantly facilitated the functional recovery compared with the MI group. Because of its simplicity, easy applicability, and a great regenerating potential, this injectable hydrogel promises as a treatment for myocardial infarction.

The effects of pulsatile flow upon renal tissue perfusion during cardiopulmonary bypass: A comparative study of pulsatile and nonpulsatile flow

This study was conducted to directly compare the effects of pulsatile and nonpulsatile blood flow in the extracorporeal circulation upon renal tissue perfusion by using a tissue perfusion measurement system. A total cardiopulmonary bypass circuit was constructed to accommodate twelve Yorkshire swine, weighing 20∼30 kg. Animals were randomly assigned to group 1 (n = 6, nonpulsatile centrifugal pump) or group 2 (n = 6, pulsatile T-PLS pump). A tissue perfusion measurement probe (Q-Flow 500) was inserted into the renal parenchymal tissue, and the extracorporeal circulation was maintained for an hour at a pump flow rate of 2 L/min after aortic cross-clamping. Tissue perfusion flow in the kidney was measured before bypass and every 10 minutes after bypass. Renal tissue perfusion flow was substantially higher in the pulsatile group throughout bypass (ranging 48.5-64.1 ml/min/100 g in group 1 vs. 51.0-88.1 ml/min/100 g in group 2). The intergroup difference was significant at 30 minutes (47.5 ± 18.3 ml/min/100 g in group 1 vs. 83.4 ± 28.5 ml/min/100 g in group 2; p = 0.026). Pulsatile flow achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation. A further study is required to observe the effects of pulsatile flow upon other vital organs and its long-term significance.

In vitro evaluation of the performance of Korean pulsatile ECLS (T-PLS) using precise quantification of pressure-flow waveforms

The Twin-Pulse Life Support System (T-PLS) is a novel pulsatile extracorporeal life support system developed in Korea. It has been reported that the T-PLS achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation and provides more blood flow to coronary artery than nonpulsatile blood pumps. However, these results lack pulsatility quantifications and thus make it hard to analyze the effects of pulsatility upon hemodynamic performance. We have adopted the concepts of hemodynamic energy, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) to evaluate pulsatility performance in the different circuit configurations of the T-PLS and a membrane oxygenator (MO) in vitro. In a mock system, three different circuits were constructed depending on the location of an MO: pump-MO-pump (serial), MO-pumps (parallel A), and pumps-MO (parallel B). In parallel A, a low-resistance MO was used to preserve the pulsatility from the pump. All circuits showed good pulsatility in terms of EEP (serial: 13.2% ± 3.2%, parallel A: 10.0% ± 1.6%, parallel B: 7.00% ± 1.1%; change from aortic pressure to EEP; p < 0.003). The SHE levels were 17,404 ± 3,750 ergs/cm3, 13,170 ± 1,486 ergs/cm3, and 9,192 ± 1,122 ergs/cm3 in each circuit setup (p < 0.001). Although EEP levels were somewhat lower, both parallel types provided higher pump output compared with the serial type (serial: 1.87 ± 0.29 l/min, parallel A: 3.09 ± 0.74 l/min, parallel B: 3.06 ± 0.56 l/min; p < 0.003 except parallel A vs. parallel B, p = 0.90). Conclusively, the precise quantifications of pressure flow waveforms, EEP, and SHE are valuable tools for evaluating pulsatility of the mechanical circulatory devices, and are expected to be used as additional performance indexes of a blood pump. The pulsatility performances are different according to circuit setups. However, the parallel A circuit could achieve higher pump output and generate adequate pulsatility level. Thus, the parallel A circuit is suggested as the optimal configuration in T-PLS applications.

Hemodynamic energy generated by a combined centrifugal pump with an intra-aortic balloon pump.

We examined the pulsatility generated by an intra-aortic balloon pump/centrifugal pump (IABP/CP) combination in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). In five cardiac-arrested pigs, the outflow cannula of the CP was inserted into the ascending aorta, the inflow cannula in the right atrium. A 30-ml IABP was subsequently placed in the descending aorta. Extracorporeal circulation was maintained for 30 minutes using a pump flow of 75 ml/kg per minute by CP alone or by IABP/CP with pressure and flow measured in the right internal carotid artery. The IABP/CP combination converted the flow to pulsatile and increased pulse pressure significantly from 9.1 ± 1.3 mm Hg to 54.9 ± 6.1 mm Hg (p = 0.012). It also significantly increased the percent change from mean arterial pressure to EEP from 0.2 ± 0.3% to 23.3 ± 6.1% (p = 0.012) and SHE from 133.2 ± 234.5 erg/cm3 to 20,219.8 ± 5842.7 erg/cm3 (p = 0.012). However, no statistical difference was observed between CP and IABP/CP in terms of mean carotid artery pressure (p = NS). In a cardiac-arrested animal model, pulsatility generated by a IABP/CP combination may be effective in terms of energy equivalent pressure and surplus hemodynamic energy.

Management of Descending Necrotizing Mediastinitis Using Minimally Invasive Video-assisted Thoracoscopic Surgery

Early diagnosis and aggressive surgical drainage are very important for successful treatment of descending necrotizing mediastinitis (DNM). However, the surgical techniques used for DNM treatment remain controversial. The purpose of this study was to evaluate the effectiveness of video-assisted thoracoscopic surgery (VATS) and cervical drainage for the management of DNM. Nine patients diagnosed with DNM were treated from May 2001 to April 2004. The mean age of the patients was 51.1±15.0 years. VATS and cervical drainage, including debridement and drainage of the mediastinum and pleura, were performed simultaneously. The mean postoperative hospital stay was 20.6±6.6 days. One patient (11%) died of sepsis and renal failure on the 15th postoperative day. Minimal mastication difficulty developed in 2 patients (22%). The mean postoperative follow-up period was 28.7±14.7(5 to 52) months. All the survivors are in good health with no recurrences. VATS was safe, effective, and a less invasive surgical option for the management of DNM and should be considered as a good alternative therapeutic modality.

The effects of pulsatile versus non-pulsatile extracorporeal circulation on the pattern of coronary artery blood flow during cardiac arrest.

Background In sudden cardiac arrest, the effective maintenance of coronary artery blood flow is of paramount importance for myocardial preservation as well as cardiac recovery and patient survival. The purpose of this study was to directly compare the effects of pulsatile versus non-pulsatile circulation to coronary artery flow and myocardial preservation in a cardiac arrest condition. Methods A cardiopulmonary bypass circuit was constructed in a ventricular fibrillation model using fourteen Yorkshire swine weighing 25–35 kg each. The animals were randomly assigned to group I (n=7, non-pulsatile centrifugal pump) or group II (n=7, pulsatile T-PLS pump). Extracorporeal circulation was maintained for two hours at a pump flow of 2 L/min. The left anterior descending coronary artery flow was measured with an ultrasonic coronary artery flow measurement system at baseline (before bypass) and at every 20 minutes after bypass. Serologic parameters were collected simultaneously at baseline, 1 hour, and 2 hours after bypass in the systemic arterial and coronary sinus venous blood. The Mann-Whitney U test of STATISTICA 6.0 was used to determine intergroup significances using a p value of < 0.05. Results The resistance index of the coronary artery was lower in group II and the difference was significant at 40 min, 80 min, 100 min and 120 min (p < 0.05). The mean velocity of the coronary artery was higher in group II throughout the study, and the difference was significant from 20 min after starting the pump (p < 0.05). The coronary artery blood flow was higher in group II throughout the study, and the difference was significant from 40 min to 120 min (p < 0.05) except at 80min. Serologic parameters showed no differences between the groups at 1 hour and 2 hours after bypass in the systemic and coronary sinus blood (p=NS). Conclusion In the cardiac arrest condition, pulsatile extracorporeal circulation provides more blood flow, higher flow velocity and less resistance to coronary artery than non-pulsatile circulation.

Experimental Investigation of Pulsatility Effect on the Deformability and Hemolysis of Blood Cells

In this study, we investigated the differences between pulsatile cardiopulmonary bypass (CPB) procedure and nonpulsatile CPB procedure in terms of their effects on hemolysis and deformability of red blood cells (RBCs) under various shear stress conditions. In order to research the effects on hemolysis and deformability, four parameters--free hemoglobin (fHb) concentration, normalized index of hemolysis (NIH), deformability index (DI) of RBCs, and elongation index of RBCs--have been deeply investigated. For these investigations, two randomly assigned adult mongrel dog groups-nonpulsatile group (NP, n = 6) and pulsatile group (P, n = 6)--were examined. According to our results, both types of perfusion did not show any statistical differences in terms of the concentrations of fHb as well as NIH. In addition, there were no significant differences in RBC deformability between perfusion types within an operation time of 3 h. Therefore, our studies suggest that pulsatile perfusion has no significant difference from nonpulsatile perfusion in terms of hemolysis and deformability of RBCs.

Optimization of the circuit configuration of a pulsatile ECLS: An in vivo experimental study

An extracorporeal life support system (ECLS) with a conventional membrane oxygenator requires a driving force for the blood to pass through hollow fiber membranes. We hypothesized that if a gravity-flow hollow fiber membrane oxygenator is installed in the circuit, the twin blood sacs of a pulsatile ECLS (the Twin-Pulse Life Support, T-PLS) can be placed downstream of the membrane oxygenator. This would increase pump output by doubling pulse rate at a given pump-setting rate while maintaining effective pulsatility. The purpose of this study was to determine the optimal circuit configuration for T-PLS with respect to energy and pump output. Animals were randomly assigned to 2 groups in a total cardiopulmonary bypass model. In the serial group, a conventional membrane oxygenator was located between the twin blood sacs of the T-PLS. In the parallel group, the twin blood sacs were placed downstream of the gravity-flow membrane oxygenator. Energy equivalent pressure (EEP), surplus hemodynamic energy (SHE) and pump output were collected at the different pump-setting rates of 30, 40, and 50 beats per minute (BPM). At a given pump-setting rate the pulse rate doubled in the parallel group. Percent changes of mean arterial pressure to EEP were 13.0 ± 1.7, 12.0 ± 1.9, and 7.6 ± 0.9% in the parallel group, while 22.5 ± 2.4, 23.2 ± 1.9, and 21.8 ± 1.4 in the serial group at 30, 40, and 50 BPM of pump-setting rates. SHE at each pump setting rate was 20,131 ± 1,408, 21,739 ± 2,470, and 15,048 ± 2,108 erg/cm3 in the parallel group, while 33,968 ± 3,001, 38,232 ± 3,281, 37,964 ± 2,693 erg/cm3 in the serial group. Pump output was higher in the parallel circuit at 40, and 50 BPM pump-setting rates (3.1 ± 0.2, 3.7 ± 0.2 L/min vs. 2.2 ± 0.1 and 2.5 ± 0.1 L/min, respectively, p =0.01). Either parallel or serial circuit configuration of T-PLS generates effective pulsatility. As for the pump out, the parallel circuit configuration provides higher flow than the serial circuit configuration by doubling the pulse rate at a given pump-setting rate.

Comparison of myocardial loading between asynchronous pulsatile and nonpulsatile percutaneous extracorporeal life support.

We hypothesized that myocardial loading can be increased when extracorporeal pulse flow occurs during systole, and that this may adversely affect myocardial working conditions in heart failure patients supported by extracorporeal life support (ECLS). This study was designed to compare myocardial loading and myocardial oxygen consumption/supply balance between nonpulsatile ECLS and asynchronized pulsatile ECLS in a myocardial stunning model. Thirteen, 23–42 kg dogs were allotted to a nonpulsatile group and an asynchronous pulsatile group. Coronary sinus lactate level, mixed venous oxygen consumption (MvO2), and left anterior descending coronary artery flow were measured. The real-time pressure of the left ventricle and the ascending aorta was monitored, and the lowest left ventricular pressure and tension time index were calculated. Our results showed that the lactate level and the lowest left ventricular pressure were lower in the pulsatile group than in the nonpulsatile group at 30 minutes after ECLS was applicated (p < 0.05, respectively). Tension time index in the pulsatile ECLS group was substantially lower than in the nonpulsatile group. Left anterior descending coronary flow did not show significant difference between the two groups. In conclusion, asynchronous pulsatile ECLS may also be superior to nonpulsatile ECLS in myocardial volume unloading and oxygen consumption/supply balance.

Comparison of coronary artery blood flow and hemodynamic energy in a pulsatile pump versus a combined nonpulsatile pump and an intra-aortic balloon pump.

We compared the coronary artery blood flow and hemodynamic energy between pulsatile extracorporeal life support (ECLS) and a centrifugal pump (CP)/intra-aortic balloon pump (IABP) combination in cardiac arrest. A total cardiopulmonary bypass circuit was constructed for six Yorkshire swine weighing 30 to 40 kg. The outflow cannula of the CP or a pulsatile ECLS (T-PLS) was inserted into the ascending aorta, and the inflow cannula of the CP or T-PLS was placed into the right atrium. A 30-ml IABP was subsequently placed in the descending aorta. Extracorporeal circulation was maintained for 30 minutes with a pump flow of 75 ml/kg per minute by a CP with an IABP or T-PLS. Pressure and flow were measured in the right internal carotid artery. The energy equivalent pressure (EEP) and surplus plus hemodynamic energy (SHE) were recorded. The left anterior descending coronary artery flow was measured with an ultrasonic coronary artery flow measurement system. The percent change of the mean arterial pressure to EEP was effective in both groups (23.3 ± 6.1 in CP plus IABP vs. 19.8 ± 6.2% in T-PLS, p = NS). The SHE was high enough in the CP/IABP and the T-PLS (20,219.8 ± 5824.7 vs. 13,160.2 ± 4028.2 erg/cm3, respectively, p = NS). The difference in the coronary artery flow was not statistically significant at 30 minutes after bypass was initiated (28.2 ± 9.79 ml/min in CP plus IABP vs. 27.7 ± 9.35 ml/min in T-PLS, p = NS).