In vivo evaluation of the pulsatile ECLS system.

Extracorporeal life support (ECLS) systems have been increasingly applied to groups of patients with cardiorespiratory failure, including pediatric and adult patients with respiratory failure. Current pulsatile ECLS systems use a single pulsatile blood pump that generates a high inlet pressure in the membrane oxygenator. To minimize this high inlet pressure, we have developed a new and improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute heart failure model was constructed by using a pulmonary artery banding technique. Fourteen pigs (22-31 kg) were used, with cardiac outputs of 2.0 l/min and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator and four polymer valves 30 mm in diameter were used in the T-PLS system. In the single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin (fHb) was measured while the systems were in use. The results show that fHb levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system. There is a possibility that T-PLS could be used as an ECLS system for emergency situations.     

In vivo evaluation of the pulsatile ECLS sysem

 Extracorporeal life support (ECLS) systems have been increasingly applied to groups of patients with cardiorespiratory failure, including pediatric and adult patients with respiratory failure. Current pulsatile ECLS systems use a single pulsatile blood pump that generates a high inlet pressure in the membrane oxygenator. To minimize this high inlet pressure, we have developed a new and improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute heart failure model was constructed by using a pulmonary artery banding technique. Fourteen pigs (22–31 kg) were used, with cardiac outputs of 2.0 l/min and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator and four polymer valves 30 mm in diameter were used in the T-PLS system. In the single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin (fHb) was measured while the systems were in use. The results show that fHb levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system. There is a possibility that T-PLS could be used as an ECLS system for emergency situations. Received: June 7, 2002 / Accepted: December 10, 2002 Present address: Department of Artificial Organs, Research Institute, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita 565-8565, Japan Tel. +81-6-6833-5012; Fax +81-6-6835-5406 e-mail: hslee@ri.ncvc.go.jp Correspondence to:H.S. Lee     

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).     

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 pumpsetting 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 +/- 1408, 21,739 +/- 2470, and 15,048 +/- 2108 erg/ cm3 in the parallel group, while 33,968 +/- 3001, 38,232 +/- 3281, 37,964 +/- 2693 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.     

Precise quantification of pulsatility is a necessity for direct comparisons of six different pediatric heart-lung machines in a neonatal CPB model

Generation of pulsatile flow depends on an energy gradient. Surplus hemodynamic energy (SHE) is the extra hemodynamic energy generated by a pulsatile device when the adequate pulsatility is achieved. The objective of this study was to precisely quantify and compare pressure-flow waveforms in terms of surplus hemodynamic energy levels of six different pediatric heart-lung machines in a neonatal piglet model during cardiopulmonary bypass (CPB) procedures with deep hypothermic circulatory arrest (DHCA). Thirty-nine piglets (average weight, 3 kg) were subjected to CPB with a hydraulically driven physiologic pulsatile pump (PPP; n=7), Jostra-HL 20 pulsatile roller pump (Jostra-PR; n=6), Stockert Sill pulsatile roller pump (SIII-PR; n=6), Stockert Sill mast-mounted pulsatile roller pump with a miniature roller head (Mast-PR; n=7), Stockert Sill mast-mounted nonpulsatile roller pump (Mast-NP; n=7), or Stockert CAPS nonpulsatile roller pump (CAPS-NP, n=7). Once CPB was begun, each animal underwent 20 minutes of hypothermia, 60 minutes of DHCA, 10 minutes of cold reperfusion, and 40 minutes of rewarming. The pump flow rate was maintained at 150 ml x kg(-1) x min(-1) and the mean arterial pressure (MAP) at 45 mm Hg. In the pulsatile experiments, the pump rate was kept at 150 bpm and the stroke volume at 1 ml/kg. The SHE (ergs/cm3) = 1,332 ([(integral fpdt) / (integral fdt)] - MAP) was calculated at each experimental stage. During normothermic CPB (15 minutes on pump), the physiologic pulsatile pump generated the highest surplus hemodynamic energy (8563 +/- 1918 ergs/cm3, p < 0.001) compared with all other pumps. The Jostra HL-20 and Stockert Sill pulsatile roller pumps also produced adequate surplus hemodynamic energy. Nonpulsatile roller pumps and the Stockert Sill mast-mounted pulsatile roller pump did not generate any extra hemodynamic energy. During hypothermic CPB and after DHCA and rewarming, the results were extremely similar to those seen during normothermic CPB. The surplus hemodynamic energy formula is a novel method to precisely quantify different levels of pulsatility and nonpulsatility for direct and meaningful comparisons. The PPP produced the greatest surplus hemodynamic energy. Most of the pediatric pulsatile pumps (except Mast-PR) generated significant surplus hemodynamic energy. None of the nonpulsatile roller pumps generated adequate surplus hemodynamic energy.     

Postoperative extracorporeal life support in pediatric cardiac surgery: recent results

We retrospectively reviewed the files of 19 extracorporeal life support (ECLS) applications performed after cardiac surgery in 15 patients from January 2002 to December 2004. We placed 16 arteriovenous ECLS applications with oxygenator, 2 venovenous ECLS applications with oxygenator, and 1 biventricular ECLS application without oxygenator (graft dysfunction after heart transplant). Mean age was 4.9 +/- 7 years (median 5.9 months, range 11 days to 21 years). All patients underwent surgery for congenital heart disease, except for one patient who had a heart transplant. Indications were hemodynamic failure in 12 cases, respiratory failure in 5 cases, and mixed failure in 2 cases. Four patients were undergoing cardiopulmonary resuscitation during ECLS placement (no deaths). Mean delay between surgery and ECLS placement was 3.2 +/- 3.4 days (median 2 days). Mean ECLS duration was 3.4 +/- 5.8 days (mean 6 days, range 3-16 days). Three patients had further surgery for residual lesions. Thirteen patients (86.7%) survived to ECLS weaning; 12 patients survived to hospital discharge (80%). No survivor presented obvious neurologic damage. Specific morbidity included reentry for bleeding, multiple transfusions, and mediastinitis. These results support early placement of ECLS in children whenever a severe postoperative hemodynamic or respiratory failure, refractory to medical treatment, is present.     

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.     

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 +/- 3750 ergs/cm3, 13,170 +/- 1486 ergs/cm3, and 9192 +/- 1122 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.     

Augmentation of abdominal organ perfusion during cardiopulmonary bypass with a novel intra-aortic pulsatile catheter pump

BACKGROUND: Current pulsatile pumps for cardiopulmonary bypass (CPB) are far from satisfactory because of the poor pulsatility. This study was undertaken to examine the efficiency of a novel pulsatile catheter pump on pulsatility and its effect on abdominal organ perfusion during CPB. METHODS: Twelve pigs weighing 89+/-11 kg were randomly divided into a pulsatile group (n=6) and a non-pulsatile group (n=6). All animals had a CPB for 120 min, aorta clamped for 60 min, temperature down to 32 degrees C, and a perfusion flow of 60 ml/kg/min. In the pulsatile group, a 21 Fr intra-aortic pulsatile catheter, which was connected to a 40 mL membrane pump, was placed in the descending aorta and activated by a balloon pump driver during the first 90 minutes of CPB until aortic declamping. Hemodynamics, organ blood flow, body metabolism, and blood trauma were studied during experiments. RESULTS: Compared with the non-pulsatile group during CPB, the pulsatile group had a higher systolic blood pressure (p<0.01), higher mean arterial pressure (p<0.05), and higher blood flow to the superior mesenteric artery (p<0.05). The hemodynamic energy, indicated by the energy equivalent pressure (EEP) was higher in the gastrointestinal tract and kidney in the pulsatile group (p<0.01, p<0.01). Abdominal organ perfusion status, as indicated by SvO 2 in the inferior vena cava, was higher in the pulsatile group (p<0.05) 30 min after cessation of CPB. Hemolysis indicated by release of free hemoglobin during CPB was similar in the two groups. CONCLUSION: Applying the pulsatile catheter pump in the descending aorta is effective in supplying the pulsatile flow to the abdominal organs and results in improved abdominal organ perfusion during the ischemic phase of CPB.     

Quantification of perfusion modes in terms of surplus hemodynamic energy levels in a simulated pediatric CPB model

The objective of this investigation was to compare pulsatile versus nonpulsatile perfusion modes in terms of surplus hemodynamic energy (SHE) levels during cardiopulmonary bypass (CPB) in a simulated neonatal model. The extracorporeal circuit consisted of a Jostra HL-20 heart-lung machine (for both pulsatile and nonpulsatile modes of perfusion), a Capiox Baby RX hollow-fiber membrane oxygenator, a Capiox pediatric arterial filter, 5 feet of arterial tubing and 6 feet of venous tubing with a quarter-inch diameter. The circuit was primed with a lactated Ringers solution. The systemic resistance of a pseudo-patient (mean weight, 3 kg) was simulated by placing a clamp at the end of the arterial line. The pseudo-patient was subjected to five pump flow rates in the 400 to 800 ml/min range. During pulsatile perfusion, the pump rate was kept constant at 120 bpm. Pressure waveforms were recorded at the preoxygenator, postoxygenator, and preaortic cannula sites. SHE was calculated by use of the following formula {SHE (ergs/cm) = 1,332 [((integral fpdt) / (integral fdt)) - Mean Arterial Pressure]} (f = pump flow and p = pressure). A total of 60 experiments were performed (n = 6 for nonpulsatile and n = 6 for pulsatile) at each of the five flow rates. A linear mixed-effects model, which accounts for the correlation among repeated measurements, was fit to the data to assess differences in SHE between flows, pumps, and sites. The Tukey multiple comparison procedure was used to adjust p values for post hoc pairwise comparisons. With a pump flow rate of 400 ml/min, pulsatile flow generated significantly higher surplus hemodynamic energy levels at the preoxygenator site (23,421 +/- 2,068 ergs/cm vs. 4,154 +/- 331 ergs/cm, p < 0.0001), the postoxygenator site (18,784 +/- 1,557 ergs/cm vs. 3,383 +/- 317 ergs/cm, p < 0.0001), and the precannula site (6,324 +/- 772 ergs/cm vs. 1,320 +/- 91 ergs/cm, p < 0.0001), compared with the nonpulsatile group. Pulsatile flow produced higher SHE levels at all other pump flow rates. The Jostra HL-20 roller pump generated significantly higher SHE levels in the pulsatile mode when compared with the nonpulsatile mode at all five pump flow rates.     

PMEA coating of pump circuit and oxygenator may attenuate the early systemic inflammatory response in cardiopulmonary bypass surgery

We investigated the effects of coating a cardiopulmonary bypass (CPB) circuit and oxygenator with poly-2-methoxy-ethyl acrylate (PMEA) on the systemic inflammatory response during and after CPB. Thirty patients undergoing elective cardiac surgery were randomized into three groups (each group n = 10): noncoated (group N), heparin coated (group H), and PMEA coated circuit and oxygenator (group X). Bradykinin (BK), complement 3 activation (C3a) and interleukin-6 (IL-6) levels were measured as early phase indicators of inflammatory response, as were maximum C reactive proteins (CRP) and white blood cell (WBC) levels. The alveolar-arterial oxygen gradient (A-a DO2) was measured as a parameter of respiratory function. IL-6 levels after CPB were significantly higher in group N than in groups H and X (p < 0.05). Serum BK and C3a levels showed similar patterns in all groups. A-a DO2 was lower at the end of and 3 hours after CPB in groups H and X than in group N (p < 0.05). Maximum CRP levels were lower in group X than in groups N (p < 0.05). This prospective study suggests that PMEA coated CPB may improve respiratory function and decrease systemic inflammatory response after cardiac surgery, possibly because this circuit is as biocompatible as heparin coated CPB circuit.     

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 80 min. 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.     

Early experience with a polymethyl pentene oxygenator for adult extracorporeal life support

Silicone oxygenators are the standard devices used for Extracorporeal Life Support (ECLS), but they have some limitations. Microporous polypropylene hollow fiber oxygenators overcome many of these problems but, unfortunately, develop plasma leak. Polymethyl-pentene (PMP) is a novel oxygenator material. We report our initial experience with the Medos Hilite 7000LT, a PMP hollow fiber oxygenator, in six adult respiratory ECLS patients with these characteristics: age, mean 32.2 (+/-13) years; weight, mean 81.2 (+/-17) kg; PaO2/FIO2, mean 62.8 [+/-33] mm Hg; Murray Score, mean 3.4 [+/-0.3]; and sepsis related organ failure assessment score, mean 9.6 [+/-2.3]. One patient was cannulated within 10 hours of multiple trauma and 1 hour after thoracolaparotomy; another patient was cannulated 12 hours after a thoracotomy. All six patients survived. Heparin was infused (7.8-32.5 u/kg/hr) to maintain activated clotting time at 162 to 238 seconds; international normalized ratio was 0.9 to 3.4. Two of the six patients required transfusions of fresh frozen plasma, receiving one and five units, respectively. Fibrinogen was 1.4 to 6 g/dl; no cryoprecipitate was needed. Platelet counts were between 65 and 306, and very little platelet transfusion (mean 2.33; +/-3.03 units per patient) was required to maintain these levels. Two patients did not require any platelet transfusion. Maximum blood flow was 5.3 L/min, sweep was 3 to 10 L/min, and resistance was 11 to 43 Paul Wood Units. There were no oxygenator failures. Mean duration of ECLS was 151.7 hours (+/-75.6). Our initial experience with PMP oxygenators in adults was satisfactory, and platelet consumption and resistance to blood flow seem to be greatly reduced with PMP.     

Non-contact determination of arterial blood pressure alterations induced by blood loss using laser irradiation on the common carotid artery

In order to avoid the secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we have reported a method for non-contact monitoring of heart and respiratory rates, using microwave radar or laser irradiation. In large-scale disasters, it is important to be able to diagnose shock without touching patients. We evaluated a non-contact method of monitoring arterial blood pressure alterations of New Zealand rabbits induced by blood loss, using He-Ne laser reflection on the common carotid artery. PVR was significantly correlated with systolic blood pressure (r = 0.95, p < 0.01), where PV = peak voltage of reflected laser amplitude, and PVR = PV(present moment state)/PV(normal state). The following formula was derived using the least-squares linear fitting: SBP = 69.6 PVR + 8.2, in which SBP is the systolic blood pressure. Before blood withdrawal, the mean blood pressure, heart rate and haematocrit were 68 +/- 3 mmHg, 154 +/- 10 bpm and 40 +/- 2%, respectively. After intervention, the mean blood pressure, heart rate and haematocrit were 38 +/- 5 mmHg, 197 +/- 25 bpm and 30 +/- 2%, respectively. The proposed non-contact method appears promising for future clinical application in determining arterial blood pressure alterations. It is likely to be useful in reducing the risk of secondary exposure to toxic chemicals or infectious organisms in the case of large-scale disasters.     

Nitric oxide added to the sweep gas infusion reduces local clotting formation in adult blood oxygenators

Nitric oxide (NO) is an inhibitor of platelet aggregation. We analyzed the effect of direct infusion of NO into adult blood oxygenators on local clot formation. Nonheparinized calves in a control group (n = 3) and NO group (n = 4) were connected to a jugulocarotid cardiopulmonary bypass (CPB; centrifugal pump) for 6 hours. The venous line and pumphead were heparin coated, whereas the oxygenator, the heat exchanger, and the arterial line were not. A total of 80 ppm of NO was mixed with the sweep gas infusion in the NO group. The pressure gradient through the oxygenator (deltaP.Ox.) was monitored, and its evolution was compared between groups. Oxygenators membranes were analyzed and photographed, allowing for calculation of the percentage of surface area covered with clots by using a computer image analysis program. The deltaP.Ox. reached a plateau of 193 +/- 26% of the basal value in the NO group after 120 minutes, whereas a similar plateau of 202 +/- 22% was reached after only 20 minutes in the control group (p < 0.05). The surface area of the oxygenator covered with clots was significantly reduced in the NO group (0.54 +/- 0.41%) compared with the control group (5.78 +/- 3.80%, p < 0.05). However, general coagulation parameters were not modified by local NO administration. The activated coagulation time remained stable between 110 and 150 seconds in both groups (p = not significant [ns]), and there were no differences in hematocrit, thrombin time, partial thromboplastin time, or fibrinogen between groups during the 6 hours of CPB. Thus, the mixed infusion of a continuous low dose of NO into adult oxygenators during prolonged CPB prevented local clot formation, whereas the general coagulation pattern remained unchanged.     

Effects of pulsatile and nonpulsatile perfusion on vital organ recovery in pediatric heart surgery: a pilot clinical study

The use of pulsatile flow during cardiopulmonary bypass (CPB) with regard to improved patient outcomes is controversial. We evaluated pulsatile perfusion in pediatric patients undergoing CPB in a clinical setting. Fifty consecutive pediatric patients undergoing open heart surgery for repair of congenital heart disease were prospectively entered into the study and randomly assigned to either the pulsatile perfusion group (group P, n = 25) or the nonpulsatile perfusion group (group NP, n = 25). Study parameters included intubation time, duration of intensive care unit (ICU) stay and hospital stay, need for inotropic support, preoperative and postoperative enzymes, creatinine, C-reactive protein, blood count, mean urine output, and total drainage. Group P, compared with group NP, had significantly less inotropic support (number of agents, 1.48 +/- 1.05 versus 2.44 +/- 1.03, p = 0.0015; dopamine, 6.48 +/- 3.27 versus 10.3 +/- 4.8 microg/kg per minute, p = 0.0023; dobutamine, 3.12 +/- 6.55 versus 8.03 +/- 9.1 microg/kg per minute, p = 0.034), shorter intubation period (20.36 +/- 17.02 versus 35.44 +/- 30.72 hours, p = 0.038), and shorter duration of ICU stay (2.16 +/- 1.07 versus 4.32 +/- 4.21 days, p = 0.028) and hospital stay (7.64 +/- 2.48 versus 11.84 +/- 6.82 days, p = 0.007). There were no significant differences in creatinine, enzyme levels, or drainage amounts between the two groups. Higher urine output during CPB (553.6 +/- 150.89 versus 465.8 +/- 151.23 ml/d, p = 0.045) and during the ICU period (658.8 +/- 210.99 versus 528,2 +/- 224.71 ml/d, p = 0.039) was observed in group P compared with group NP. We concluded that the use of pulsatile flow resulted in improved patient outcome in preserving cardiac function and maintaining better renal and pulmonic function (shorter intubation period) in the early postbypass period.     

Autonomic modulation of arterial pressure and heart rate variability in hypertensive diabetic rats

OBJECTIVE: The aim of the present study was to evaluate the autonomic modulation of the cardiovascular system in streptozotocin (STZ)-induced diabetic spontaneously hypertensive rats (SHR), evaluating baroreflex sensitivity and arterial pressure and heart rate variability. METHODS: Male SHR were divided in control (SHR) and diabetic (SHR+DM, 5 days after STZ) groups. Arterial pressure (AP) and baroreflex sensitivity (evaluated by tachycardic and bradycardic responses to changes in AP) were monitored. Autoregressive spectral estimation was performed for systolic AP (SAP) and pulse interval (PI) with oscillatory components quantified as low (LF:0.2-0.6Hz) and high (HF:0.6-3.0Hz) frequency ranges. RESULTS: Mean AP and heart rate in SHR+DM (131+/-3 mmHg and 276+/-6 bpm) were lower than in SHR (160+/-7 mmHg and 330+/-8 bpm). Baroreflex bradycardia was lower in SHR+DM as compared to SHR (0.55+/-0.1 vs. 0.97+/-0.1 bpm/mmHg). Overall SAP variability in the time domain (standard deviation of beat-by-beat time series of SAP) was lower in SHR+DM (3.1+/-0.2 mmHg) than in SHR (5.7+/-0.6 mmHg). The standard deviation of the PI was similar between groups. Diabetes reduced the LF of SAP (3.3+/-0.8 vs. 28.7+/-7.6 mmHg2 in SHR), while HF of SAP were unchanged. The power of oscillatory components of PI did not differ between groups. CONCLUSIONS: These results show that the association of hypertension and diabetes causes an impairment of the peripheral cardiovascular sympathetic modulation that could be, at least in part, responsible for the reduction in AP levels. Moreover, this study demonstrates that diabetes might actually impair the reduced buffer function of the baroreceptors while reducing blood pressure.     

Pulsatile and nonpulsatile flows can be quantified in terms of energy equivalent pressure during cardiopulmonary bypass for direct comparisons

The purpose of this study was to quantify and compare pulsatile and nonpulsatile pressure and flow waveforms in terms of energy equivalent pressure (EEP) during cardiopulmonary bypass in a neonatal piglet model. EEP is the ratio of the area under the hemodynamic power curve and the flow curve. Piglets, mean weight of 3 kg, were used in physiologic pulsatile pump (n = 7), pulsatile roller pump (n = 6), and nonpulsatile roller pump (n = 7) groups. Data (waveforms of the femoral artery pressure, pump flow, and preaortic cannula extracorporeal circuit pressure) were collected during normothermic cardiopulmonary bypass at 35 degrees C (15 minutes on-pump), before deep hypothermic circulatory arrest (pre-DHCA) at 18 degrees C, and after cold reperfusion and rewarming (post-DHCA) at 36 degrees C. The pump flow rate was 150 ml/kg/min in all three groups. During pulsatile perfusion, the pump rate was 150 bpm in both pulsatile groups. Although there was no difference in mean pressures in all groups, EEP and the percentage increase of pressure (from mean pressure to EEP) of mean arterial pressure and preaortic cannula extracorporeal circuit pressure were higher with pulsatile perfusion compared with nonpulsatile perfusion (p < 0.001). In particular, the physiologic pulsatile pump group produced significantly higher hemodynamic energy compared with the other groups (p < 0.001). These results suggest that pulsatile and nonpulsatile flows can be quantified in terms of EEP for direct comparisons, and pulsatile flow generates higher energy, which may be beneficial for vital organ perfusion during cardiopulmonary bypass.     

Bloodless testing for microporous membrane oxygenator failure: a preliminary study

The use of a bloodless solution and high pressure to accelerate microporous membrane oxygenator (MMO) failure was investigated. It was hypothesized that albumin acts as a wetting agent, contributing to plasma leakage through the membrane, and that high MMO outlet pressure accelerates the process. Three MMO, B-Bentley BCM-40 (n = 7), M-Medtronic Maxima (n = 4), and S-Sarns 16310 (n = 7) were tested at 37 +/- 2 degrees C using three identical closed recirculating circuits and four conditions: 1) Lactated Ringer solution (LR) with MMO outlet pressure (Pmo) 750 mmHg; 2) LR + albumin (4 g/100 ml), Pmo 150 mmHg; 3) LR + albumin, Pmo 300 mmHg; and 4) LR + albumin, Pmo 750 mmHg. "Blood" flow and gas flow were maintained at 2 l/min. Failure was indicated when Na+ was detected in the effluent of the MMO exhaust gas. There were no failures without albumin in the solution. B and M showed no signs of failure under any of the test conditions at 78 hours. S failed at (mean +/- SEM) 4.9 +/- 1.0, 12.1 +/- 0.2, and 19 hours for conditions 4, 3, and 2 respectively. Preceding failure, inlet gas pressure increased more than eightfold (27 +/- 1 to 224 +/- 34 mmH2O). These preliminary results are similar to previous findings with blood and suggest that high MMO outlet pressure and the presence of albumin may promote plasma breakthrough for S. The combination may provide a basis for an accelerated bloodless test for MMO compatibility with long-term respiratory support.     

Pulsatile support using a rotary left ventricular assist device with an electrocardiography-synchronized rotational speed control mode for tracking heart rate variability

We previously developed a novel control system for a continuous-flow left ventricular assist device (LVAD), the EVAHEART, and demonstrated that sufficient pulsatility can be created by increasing its rotational speed in the systolic phase (pulsatile mode) in a normal heart animal model. In the present study, we assessed this system in its reliability and ability to follow heart rate variability. We implanted an EVAHEART via left thoracotomy into five goats for the Study for Fixed Heart Rate with ventricular pacing at 80, 100, 120 and 140 beats/min and six goats for the Study for native heart rhythm. We tested three modes: the circuit clamp, the continuous mode and the pulsatile mode. In the pulsatile mode, rotational speed was increased during the initial 35 % of the RR interval by automatic control based on the electrocardiogram. Pulsatility was evaluated by pulse pressure and dP/dt max of aortic pressure. As a result, comparing the pulsatile mode with the continuous mode, the pulse pressure was 28.5 ± 5.7 vs. 20.3 ± 7.9 mmHg, mean dP/dt max was 775.0 ± 230.5 vs 442.4 ± 184.7 mmHg/s at 80 bpm in the study for fixed heart rate, respectively (P < 0.05). The system successfully determined the heart rate to be 94.6 % in native heart rhythm. Furthermore, pulse pressure was 41.5 ± 7.9 vs. 27.8 ± 5.6 mmHg, mean dP/dt max was 716.2 ± 133.9 vs 405.2 ± 86.0 mmHg/s, respectively (P < 0.01). In conclusion, our newly developed the pulsatile mode for continuous-flow LVADs reliably provided physiological pulsatility with following heart rate variability.