Choon Hak Lim

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.

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.

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).

Ventricular assist device implantation using a right thoracotomy

Most patients needing implantation of a ventricular assist device (VAD) require repeated sternotomy; some after cardiac surgery, and others later for heart transplantation. The purpose of this study was to establish the right thoracotomy technique as an alternative for VAD implantation to reduce repeated sternotomy-related morbidity and mortality. We performed a right thoracotomy in animals, preclinical cadaver fitting tests, and a clinical case. A total of 20 various animals underwent right thoracotomy for implantation of bi-VAD (BVAD, n = 17) and left VAD (LVAD, n = 3). The right chest cavity was entered through the fourth intercostal space with partial resection of the fifth rib. There was no procedure-related morbidity or mortality, except for one calf with right anterior leg paralysis. Preclinical fitting tests were performed on 7 human cadavers to observe the anatomical feasibility of BVAD cannulation from the right side of the heart. In humans, the ascending aorta, interatrial groove, right atrium, and main pulmonary artery were identified as optimal cannula insertion sites for BVAD implantation. A patient with cardiogenic shock underwent a right thoracotomy for implantation of an external LVAD. Cardiac function recovered after 3 weeks, and the device was successfully explanted through a repeat right thoracotomy. In conclusion, a right thoracotomy can be an alternative method to the standard median sternotomy for patients who need repeated sternotomy because of previous cardiac surgery, transplantation at a later date, or those with mediastinal infections.

Inter-species hemorheologic differences in arterial and venous blood

BACKGROUND Hemorheologic factors such as red blood cell (RBC) aggregation and deformability differ according to species. In many comparative hemorheologic studies, only venous blood samples have been used for measurements. There is little published information comparing arterial and venous blood differences between species. We compared hemorheologic factors in arterial and venous blood in rats, dogs and humans. METHODS Nineteen dogs and 12 rats were used. Human blood was obtained from 12 healthy volunteers. Blood gas analysis, hematocrit and elongation index which represents RBC deformability were measured in arterial and venous blood samples. The critical shear stress and aggregation index, both of which represent RBC aggregation, were also measured in arterial and venous blood. RESULTS There were no arterial or venous differences in hematocrit, critical shear stress, or elongation index in dogs. In rats, RBC aggregation was not measurable. The hematocrit and elongation index of arterial blood were significantly lower than those of venous blood in rats. There were no arterial or venous differences in hematocrit, aggregation index, or elongation index in humans. CONCLUSION Arterial and venous hemorheologic factors differed depending on the species. Further standardization is necessary for the measurement of hemorheologic variables.

Pulsatile versus nonpulsatile flow to maintain the equivalent coronary blood flow in the fibrillating heart.

How much flow is required by a nonpulsatile pump to match the coronary blood flow equivalent to that of pulsatile pump? A cardiopulmonary bypass circuit from the right atrium to the ascending aorta was constructed in a ventricular fibrillation model using 13 Yorkshire swine. The animals were randomly divided into two groups: CONTROL (pulsatile T-PLS, n = 7) or EXPERIMENTAL (nonpulsatile Biopump, n = 6). The hemodynamic data at mid-LAD level was measured with a flow meter at baseline and every 20 minutes after pump flow initiation. The pump flow was started from 2 L/min in both groups (67 ± 8 in CONTROL and 70 ± 9 ml/kg/min in EXPERIMENTAL; p = NS), and the pump flow of the EXPERIMENTAL group was increased to match the coronary flow of the CONTROL group. To maintain mean velocity and flow in the LAD, the EXPERIMENTAL group required significantly higher pump flow at 20, 40, and 60 minutes (84 ± 17 vs. 67 ± 8, 87 ± 24 vs. 67 ± 8, 85 ± 18 vs. 67 ± 8 ml/kg/min, respectively, p < 0.05). The LAD diameter was substantially smaller in the CONTROL group and the resistance index was significantly lower in the CONTROL group at 80 minutes and 120 minutes after bypass (0.56 ± 0.26 vs. 0.87 ± 0.20 and 0.61 ± 0.23 vs. 0.90 ± 0.06; p < 0.05). In conclusion, we found that the nonpulsatile pump may require 25%–28% higher pump flow than the pulsatile pump to maintain equivalent coronary blood flow.