The objective of this study was to compare the effects of pulsatile and nonpulsatile extracorporeal membrane oxygenation (ECMO) on hemodynamic energy and systemic microcirculation in an acute cardiac failure model in piglets. Fourteen piglets with a mean body weight of 6.08 ± 0.86 kg were divided into pulsatile (N = 7) and nonpulsatile (N = 7) ECMO groups. The experimental ECMO circuit consisted of a centrifugal pump, a membrane oxygenator, and a pneumatic pulsatile flow generator system developed in‐house. Nonpulsatile ECMO was initiated at a flow rate of 140 mL/kg/min for the first 30 min with normal heart beating, with rectal temperature maintained at 36°C. Ventricular fibrillation was then induced with a 3.5‐V alternating current to generate a cardiac dysfunction model. Using this model, we collected the data on pulsatile and nonpulsatile groups. The piglets were weaned off ECMO at the end of the experiment (180 min after ECMO was initiated). The animals did not receive blood transfusions, inotropic drugs, or vasoactive drugs. Blood samples were collected to measure hemoglobin, methemoglobin, blood gases, electrolytes, and lactic acid levels. Hemodynamic energy was calculated using the Shepard's energy equivalent pressure. Near‐infrared spectroscopy was used to monitor brain and kidney perfusion. The pulsatile ECMO group had a higher atrial pressure (systolic and mean), and significantly higher regional saturation at the brain level, than the nonpulsatile group (for both, P < 0.05). Additionally, the pulsatile ECMO group had higher methemoglobin levels within the normal range than the nonpulsatile group. Our study demonstrated that pulsatile ECMO produces significantly higher hemodynamic energy and improves systemic microcirculation, compared with nonpulsatile ECMO in acute cardiac failure.

Systemic inflammatory responses in patients receiving cardiac surgery with the use of the cardiopulmonary bypass (CPB) significantly contribute to CPB-associated morbidity and mortality. We hypothesized that insufflated hydrogen gas (H₂) would provide systemic anti-inflammatory and anti-apoptotic effects during CPB, therefore reducing proinflammatory cytokine levels. In this study, we examined the protective effect of H₂ on a rat CPB model. Rats were divided into three groups: the sham operation (SHAM) group, received sternotomy only; the CPB group, which was initiated and maintained for 60 min; and the CPB + H₂ group in which H₂ was given via an oxygenator during CPB for 60 min. We collected blood samples before, 20 min, and 60 min after the initiation of CPB. We measured the serum cytokine levels of (tumor necrosis factor-α, interleukin-6, and interleukin-10) and biochemical markers (lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase). We also measured the wet-to-dry weight (W/D) ratio of the left lung 60 min after the initiation of CPB. In the CPB group, the cytokine and biochemical marker levels significantly increased 20 min after the CPB initiation and further increased 60 min after the CPB initiation as compared with the SHAM group. In the CPB + H₂ group, however, such increases were significantly suppressed at 60 min after the CPB initiation. Although the W/D ratio in the CPB group significantly increased as compared with that in the SHAM group, such an increase was also suppressed significantly in the CPB + H₂ group. We suggest that H₂ insufflation is a possible new potential therapy for counteracting CPB-induced systemic inflammation.

These results suggest that rolipram prevents acute lung injury via the inhibition of neutrophil activation during and after CPB in this setting of a rat model.

Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECCcauses damage to blood components and is non-physiologic, its pathophysiology has not been fully elucidated. This is because difficulty in clinical research and animal experiments keeps the knowledge insufficient. Therefore, it is desirable to have a miniature ECC model for small animals, which enables repetitive experiments, to study the mechanism of pathophysiological changes during ECC. We developed a miniature ECC system and applied it to the rat. We measured changes in hemodynamics, blood gases and hemoglobin (Hb) concentration, serum cytokines (TNF-α, IL-6, IL-10), biochemical markers (LDH, AST, ALT), and the wet-to-dry weight (W/D) ratio of the lung for assessing whether the rat ECC model is comparable to the human ECC. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride), and roller pump. Priming volume of this system is only 8 ml. Rats (400-450 g) were divided into the SHAM group (n = 7) and the ECC group (n = 7). Blood samples were collected before, 60 and 120 min after initiation of ECC. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10 g/dL, respectively. The levels of the inflammatory and biochemical markers and the W/D ratio were significantly elevated in the ECC group, indicating some organ damages and systemic inflammatory responses during ECC. We successfully established the ECC for the rat. This miniature ECC model could be a useful approach for studying the mechanism of pathophysiology during ECC and basic assessment of the ECC devices.

Currently, nonpulsatile selective cerebral perfusion for cerebroprotection against thoracic aortic aneurysm is used in clinical settings. We performed synchrotron radiation microangiography to determine the effects on selective cerebral perfusion modulation by pulsatile flow. We established cerebral perfusion at normothermia and severe hypothermia in anesthetized rats, during which cerebral angiography was performed. NG-nitro-L-arginine-methyl ester hydrochloride (L-NAME) was administered to determine the effect of pulsatile flow with nitric oxide synthesis. In comparison with nonpulsatile flow, the relative diameters of small internal carotid artery were 132.11 ± 5.49% and 114.96 ± 4.60% during pulsatile flow at normothermia and severe hypothermia (p < 0.05). The angiographic scores, an indicator of vessel count, for nonpulsatile and pulsatile flow at normothermia were 0.198 ± 0.013 vs. 0.258 ± 0.010 (p < 0.001) and those at severe hypothermia were 0.158 ± 0.017 vs. 0.214 ± 0.015 (p < 0.01), respectively. In comparison with nonpulsatile flow, the relative internal carotid artery diameters during pulsatile flow with and without L-NAME were 98.50 ± 1.7% vs. 114.96 ± 4.6%, respectively, during severe hypothermia. These results show that pulsatile flow is effective in increasing blood vessel diameter, number of vessels, and perfusion distribution range in the rat model and that it was more effective at normothermia during nitric oxide production.

Quick setup is mandatory for cardiopulmonary resuscitation using an extracorporeal membrane oxygenation (ECMO) assist device. Our conventional ECMO circuit for pediatric patients consists of a centrifugal pump (CX-HP) and membrane oxygenator (CX10H). Because of the large priming volume (260 ml), the circuit had to be primed with donor blood and required 30 minutes for setup. We started to use a low-prime ECMO with small centrifugal pump (HPM-15) and membrane oxygenator (MENOX Alpha Cube) for induction of ECMO beginning in 2000. The priming volume of this low-prime circuit is only 99 ml. The circuit can be primed without donor blood, even in the small patient, and requires only 10 minutes to set up. We review our experiences with cardiopulmonary resuscitation for sudden cardiopulmonary collapse in pediatric patients, including postcardiotomy patients. From 1997 to 2000, 23 patients underwent ECMO support with a conventional circuit (group A). From 2000 to 2004, we used low-prime circuit for induction of ECMO in 12 patients (group B). After the induction of ECMO with low-prime circuit, ECMO was converted to conventional heparin-bonded circuit for the longer support. The results suggested that the quick induction of ECMO with low-prime circuit has significant advantages in cardiopulmonary support in pediatric patients.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) preserves the life of heart failure patients by providing an adequate oxygen supply and blood flow to vital organs. For patients with severe cardiogenic shock secondary to acute myocardial infarction or acute myocarditis, V-A ECMO is commonly used as the first choice among cardiac circulatory support devices. While V-A ECMO generates circulatory flow using a centrifugal pump, the provision of pulsatile flow is difficult. We previously reported our development of a new circulatory flow assist device (K-beat) for cardiac management with pulsatile flow. To obtain more efficient pulsatile assist flow (diastolic augmentation), an electrocardiogram (ECG)-analyzing device that can detect R waves and T waves increases the assist flow selectively in the diastole phase by controlling (opening and closing) the magnetic valve of the tamper. Here, we describe the first use of the K-beat on a large animal in combination with a clinical device. In addition, the diastolic augmentation effect of the K-beat as a circulatory flow assist device was examined in a pig V-A ECMO model. The K-beat was stopped every 60 min for a period of a few minutes, and blood pressure waveforms in the pulsatile and non-pulsatile phases were checked. This experiment showed that stable V-A ECMO could be achieved and that hemodynamics were managed in all animals. The pulsatile flow was provided in synchrony with the ECG in all cases. A diastolic augmentation waveform of femoral arterial pressure was confirmed in the pulsatile phase. K-beat could be useful in patients with severe heart failure.

We developed a new circulation-assist device that can generate pulsatile assist flow synchronized with the patient's diastolic phase. The device is composed of a drainage tube, a centrifugal pump, an oxygenator, and a sending tube. A portable magnetic valve device composed of a pulse generator and a tamper, which produces intermittent mechanical compression, is attached to the pillow of the sending tube. Preliminary animal experiments were conducted. No changes in the animals' hemodynamics or any device problems were observed during a preliminary 48-h test run. Significant diastolic augmentation was confirmed. This new device may be useful in treating patients with severe heart failure and could be more useful than using percutaneous cardiopulmonary support (PCPS) alone.