Kenji Nonaka

Blood trauma induced by clinically accepted oxygenators.

Hemolysis remains one of the most serious problems during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and percutaneous cardiopulmonary support (PCPS). However, the hemolytic characteristics associated with oxygenators are not well defined. A specialized hemolysis test protocol for oxygenators was developed. A comparative study was performed following this protocol to determine the hemolytic characteristics of the clinically available oxygenators during CPB; pressure drop measurements in the blood chamber were also performed. Four oxygenators (Medtronic Affinity, Cobe Optima, Terumo Capiox SX25, and Bard Quantum) were evaluated. Fresh blood from healthy Dexter calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 5 L/min, similar to that used in CPB. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials (ASTM) standards. The NIH value, which was obtained from the circuit without an oxygenator, was subtracted from the primary NIH value, obtained from the circuit with an oxygenator to eliminate the effects of a centrifugal pump or other artifacts. The NIHO value was the lowest in the Affinity (0.0116 ± 0.0017) and increased from Affinity < Optima (0.0270 ± 0.0038) < Capiox (0.0335 ± 0.0028) < Quantum (0.0416 ± 0.0015 g/100 L). The Optima and Capiox did not demonstrate a significant difference. In addition, this NIHO value has a close relationship to the pressure drop. In conclusion, this new evaluation method is suitable to compare the biocompatibility performance of different types of clinically available oxygenators for CPB usage.

Non-blood contacting biventricular support for severe heart failure

BACKGROUND Direct mechanical ventricular actuation (DMVA) is a non-blood contacting method of biventricular support. DMVA employs a vacuum attached, pneumatically regulated, flexible membrane to transfer both systolic and diastolic forces to the ventricular myocardium. The purpose of this study was to determine if DMVA effectively restores pump performance when applied to the severely failing heart. METHODS Bovines (n = 10) underwent thoracotomy and were instrumented for continuous hemodynamic monitoring. Cardiac failure was induced by beta1-blockade to achieve a cardiac index of < 1.5 l/min/m2 for 1 hour. Heart rate was maintained at 100 bpm by atrioventricular sequential pacing. Synchronous DMVA support was then applied for 3 hours. RESULTS Eight animals achieved significant reductions in cardiac index and mean arterial pressures (35%* and 43%* control, respectively; *p < 0.05). DMVA restored cardiac index to baseline and significantly increased arterial pressures (p < 0.05; DMVA versus cardiac failure). Pulmonary flow and mean pulmonary artery pressures were similar to baseline during DMVA (p = NS). Pathologic exam did not demonstrate evidence of significant device trauma. CONCLUSIONS DMVA support can effectively restore pump performance of the acutely failing heart. Synchronization may be inherent to the stimulus of cardiac compression. These data further substantiate DMVAs potential as an adjunct to the field of circulatory support.

Hemolytic characteristics of oxygenators during clinical extracorporeal membrane oxygenation.

A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass. We examined this association during extracorporeal membrane oxygenation (ECMO) conditions. Three oxygenators for ECMO or pediatric cardiopulmonary bypass (Menox EL4000, Dideco Module 4000, and Mera HPO-15H) were evaluated. Fresh blood from healthy Dexter strain calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min, similar to that in ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials standards, as was previously reported. The NIHO value was the lowest in the Menox (0.0070 ± 0.0009) and increased from Menox to Dideco (0.0113 ± 0.0099) to Mera (0.0164 ± 0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. In conclusion, this evaluation method is also applicable to comparison of the biocompatibility performance of different types of clinically available oxygenators for ECMO.

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application.

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 ± 0.56 ml/m2/L/min and 38.72 ± 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 ± 0.5 ml/m2/L/min and 24.7 ± 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.

Operating point control system for a continuous flow artificial heart: In vitro study

We proposed and developed a practical and effective servo control system for rotary blood pumps. A rotary blood pump for assisting the failing natural heart should be operated only in physiologically acceptable conditions. The operation of a rotary blood pump is based on the rotational speed of the impeller and pressure head. If the pump flow and the pressure head are set within an acceptable range, the driving condition is deemed normal condition, and this control system maintains the preset operating point by applying proportional and detective control (PD control). If the pump flow or pressure head is outside the acceptable range, the driving condition is determined to be abnormal condition, and this system operates the pump in a recovery fashion. If the driving condition is kept under abnormal conditions of sudden decrease of the flow, the condition is termed a suction condition. The controller releases the pump from the suction condition and later returns it to the normal condition. In this study, we evaluated these servo control modes of the centrifugal pump and confirmed whether the performance of this proposed operating point control system was practical.

Direct detection of red blood cell fragments: a new flow cytometric method to evaluate hemolysis in blood pumps.

Pump induced hemolysis is presently evaluated by measuring plasma free hemoglobin (fHb). However, this method has disadvantages because quantification of fHb depends on hematocrit (HCT) and hemoglobin (Hb) levels. The aim of this work was to devise a hemoglobin independent method, capable of quantifying cell trauma directly by measuring the number of red blood cell (RBC) fragments. Whole blood flow cytometry was used to quantify circulating RBC fragments derived from a roller pump (Sarns, Inc. Model 2 M 6,002) and a centrifugal pump (Gyro C1E3, Kyocera Corp.). The pumps were tested in a mock circuit for 2 hr (5 L/min flow against 100 mm Hg pressure head). Red blood cell fragments were quantified by a phycoerythrin (PE) labeled glycophorin A antibody specific for erythrocytes. Red blood cell fragments were smaller than the intact RBC population and overlapped in size with the platelet population (based on forward- and side-light scattering measurements). For the roller pump, the values for RBC fragments increased from 1,090 ± 260/&mgr;l at 0 min to 14,880 ± 5,900/&mgr;l after 120 min. In contrast, using the centrifugal pump, there was little increase in RBC fragments (from 730 ± 270/&mgr;l at 0 min to 1,400 ± 840/&mgr;l after 120 min). Flow cytometry can be used for the rapid, sensitive, hemoglobin independent evaluation of pump induced RBC trauma.