Development of an ambulatory artificial lung in an ovine survival model.

We are developing an artificial lung (AL) as an eventual bridge to lung transplant or recovery. The device is rigidly housed, noncompliant, and has a very low resistance to blood flow. In eight sheep, arterial cannulae were anastomosed end-to-side to the proximal and distal main pulmonary artery, and attached to the AL. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the AL. Eight of eight sheep survived the preparation. Mean pressure gradient across the AL was 8 mm Hg (3 Wood units; 8 mm Hg/2.8 L/min). Four of eight sheep tolerated immediate full diversion of blood flow and died at 24 and 40 hours (exsanguination) or 168 and 168 hours (elective sacrifice). Four of eight sheep were intolerant of full flow: two died of right heart failure at <8 hours with full flow through the device (full snare); the other two survived with partial device flow (partial snare), but the device clotted. These two then underwent successful closed-chest cannula thrombectomy and device change-out at 53 and 75 hours, and subsequently tolerated full flow. Long-term (up to 7 day) survival with complete diversion of pulmonary blood flow through a non-compliant, low-resistance AL is possible. Initial right heart failure in this model was 50% (4 of 8).

Improved right heart function with a compliant inflow artificial lung in series with the pulmonary circulation.

BACKGROUND: We previously reported a 50% incidence of immediate right heart failure using a rigidly housed, noncompliant inflow artificial lung in series with the pulmonary circulation in a healthy ovine survival model. Three device modifications resulted: (1) an inflow cannula compliance chamber, (2) an inlet blood flow separator, and (3) modification of the artificial lung outlet geometry, all to reduce resistance and mimic the compliance of the pulmonary vascular bed. METHODS: In 7 sheep, arterial grafts were anastomosed end-to-side to the proximal and distal main pulmonary artery, with the paracorporeal artificial lung interposed. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the artificial lung for up to 72 hours. RESULTS: Six of 7 sheep exhibited good cardiac function throughout the test period: mean central venous pressure was 6.8 mm Hg (range, 4 to 11 mm Hg), mean cardiac output, 4.17 +/- 0.12 L/min (range, 2.4 to 6.3 L/min); before and after device mean pulmonary arterial pressure, 21.8 and 18.5 mm Hg, and left atrial pressure, 10.8 mm Hg. CONCLUSIONS: This modified artificial lung prototype with an inflow compliance chamber, blood flow separator, and modified outlet geometry has greatly improved cardiac function and initial survival in our healthy ovine model.

Total extracorporeal arteriovenous carbon dioxide removal in acute respiratory failure: a phase I clinical study.

OBJECTIVE: To evaluate the safety and efficacy of pumpless extracorporeal arteriovenous carbon dioxide removal (AVCO2R) in subjects with acute respiratory failure and hypercapnia. DESIGN: A phase I within-group time series trial in which subjects underwent up to 72 h of support with AVCO2R in intensive care units of two university hospitals. PATIENTS: Eight patients with acute hypercapnic respiratory failure or hypoxemic respiratory failure managed with permissive hypercapnia. INTERVENTIONS: Extracorporeal CO2 removal was achieved through percutaneous cannulation of the femoral artery and vein, and a simple extracorporeal circuit using a commercially available membrane gas exchange device for carbon dioxide exchange. MEASUREMENTS AND RESULTS: Measurements of hemodynamics, blood gases, ventilatory settings, and laboratory values were made before initiation of AVCO2R, and at subsequent intervals for 72 h. PaCO2 decreased significantly from 90.8+/-7.5 mmHg to 52.3+/-4.3 and 51.8+/-3.1 mmHg at 1 and 2 h, respectively. This decrease occurred despite a decrease in minute ventilation from a baseline of 6.92+/-1.64 l/min to 4.22+/-.46 and 3.00+/-.53 l/min at 1 and 2 h. There was a normalization of pH, with an increase from 7.19+/-.06 to 7.35+/-.07 and 7.37+/-.05 at 1 and 2 h. These improvements persisted during the full period of support with AVCO2R. Four subjects underwent apnea trials in which AVCO2R provided total carbon dioxide removal during apneic oxygenation, resulting in steady-state PaCO2 values from 57 to 85 mmHg. Hemodynamics were not significantly altered with the institution of AVCO2R. There were no major complications attributed to the procedure. CONCLUSION: Pumpless extracorporeal AVCO2R is capable of providing complete extracorporeal removal of carbon dioxide during acute respiratory failure, while maintaining mild to moderate hypercapnia. Applied in conjunction with mechanical ventilation and permissive hypercapnia, AVCO2R resulted in normalization of arterial PCO2 and pH and permitted significant reductions in the level of mechanical ventilation.

Percutaneous venovenous perfusion-induced systemic hyperthermia for advanced non-small cell lung cancer: initial clinical experience.

BACKGROUND: Venovenous perfusion-induced systemic hyperthermia raises core body temperature by extracorporeal heating of the blood. Five patients with advanced non-small cell lung carcinoma stage IV (4.4+/-1 months after initial diagnosis) received venovenous perfusion-induced systemic hyperthermia to 42.5 degrees C (core temperature) to assess technical and patient risks. METHODS: After general anesthesia and systemic heparinization (activated clotting time > 300 seconds), percutaneous cannulation of the right internal jugular vein (15F) for drainage and common femoral vein (15F) for reinfusion allowed extracorporeal flow rates up to 1,500 mL/min (20 mL x kg(-1) x min(-1)) with the ThermoChem System. This device uses charcoal-based sorbent for electrolyte homeostasis. Six monitored sites (rectal, bladder, tympanic x2, nasopharyngeal, and esophageal) determined average core temperature. RESULTS: All patients achieved a core target temperature of 42.5 degrees C for 2 hours. Electrolyte balance was maintained throughout hyperthermia (mean) in mmol/L: Na+, 136.2+/-2.2 mmol/L; K+, 4.0+/-0.3 mmol/L; Ca2+, 4.1+/-0.2 mg/dL; Mg2+, 1.9+/-0.1 mg/dL; PO4-, 4.5+/-0.9 mg/dL). Plasma cytokine concentration revealed significant heat-induced activation of proinflammatory and antiinflammatory cascades. All patients exhibited systemic vasodilation requiring norepinephrine infusion, 4 of 5 patients required vigorous diuresis, and 3 of 5 required intubation for 24 to 36 hours because of pulmonary edema or somnolence, with full recovery. Average length of hospital stay was 5.4 days. Serial tumor measurements (1 patient withdrew) revealed a decrease (64.5%+/-18%) in tumor size in 2 patients, no change in 1, and enlargement in 1, with no 30-day mortality. Median survival after hyperthermia treatment was 172 days (range, 40 to 271 days). CONCLUSIONS: Venovenous perfusion-induced systemic hyperthermia is feasible and provides the following potential advantages for better tumoricidal effect: (1) homogeneous heating, and (2) a higher sustained temperature.

Hemodynamic stability during arteriovenous carbon dioxide removal for adult respiratory distress syndrome: a prospective randomized outcomes study in adult sheep.

To evaluate the ability of arteriovenous carbon dioxide removal (AVCO2R) to maintain hemodynamic stability during treatment of adult respiratory distress syndrome (ARDS), we used our smoke/burn, LD40 sheep model of ARDS. With onset of ARDS (PaO2/FiO2 < 200) animals were randomized to AVCO2R (n = 20) or SHAM (n = 8). With AVCO2R, the carotid artery (10-14 F) and jugular vein (14-16 F) were cannulated; SHAM received identical management, sparing the vessels. AVCO2R maintained stable hemodynamics compared to SHAM at 48 hours; heart rate (114.8+/-6.1 vs. 110.1+/-11.0 beats/min.), mean arterial pressure (112+/-5.1 vs. 107.0+/-8.5 mm Hg), cardiac output (7.4+/-0.5 vs. 7.5+/-0.9 L/min.), pulmonary arterial pressure (26+/-2.4 vs. 21+/-1.3 mm Hg), pulmonary arterial wedge pressure (14.1+/-1.8 vs. 14.0+/-1.2 mm Hg), and central venous pressure (7+/-1.6 vs. 8+/-0.9 mm Hg). At 48 hours, AVCO2R allowed significant reductions (p<0.05) in minute ventilation (13.6+/-2.5 to 7.6+/-0.8 L/min); tidal volume (TV) (389.4+/-24.1 to 295.0+/-10.1 ml); peak inspiratory pressure (PIP) (25.4+/-9.2 to 18.8+/-2.5 cm H2O); RR (27.5+/-0.7 to 21.6+/-1.8 breaths/min); and FiO2 (0.96+/-0.00 to 0.48+/-0.2) while normocapnia was maintained. AVCO2R is an effective method of CO2 removal during severe respiratory failure that is hemodynamically well tolerated.

Percutaneous extracorporeal arteriovenous carbon dioxide removal improves survival in respiratory distress syndrome: a prospective randomized outcomes study in adult sheep.

OBJECTIVE: Arteriovenous carbon dioxide removal (AVCO(2)R) uses a simple arteriovenous shunt for CO(2) removal to minimize barotrauma/volutrauma from mechanical ventilation. We performed a prospective randomized outcomes study of AVCO(2)R in our new, clinically relevant model of respiratory distress syndrome. METHODS: Adult sheep (n = 18) received an LD(50) severe smoke inhalation and 40% third-degree burn. When respiratory distress syndrome developed (PaO (2)/FIO (2) < 200 at 40 to 48 hours), animals were randomized to the AVCO(2)R (n = 9) or sham group (n = 9) for 7 days. Ventilator management protocols mandated reductions in minute ventilation, first tidal volume to peak inspiratory pressure less than 30 cm H(2)O, then respiratory rate when PaCO (2) was less than 40 mm Hg. PaO (2) was kept above 60 mm Hg by adjusting FIO (2). When FIO (2) was 0.21, animals were weaned. RESULTS: The study required 2946 animal-hours of critical care with 696 AVCO(2)R hours. One died in each group during model development. AVCO(2)R flow from 820 mL/min to 970 mL/min (11% to 14% cardiac output) removed CO(2) at a rate of 92 to 116 mL/min (mean 103 mL/min; 93%-97% of CO(2) production). Heart rate, mean arterial pressure, cardiac output, and pulmonary arterial wedge pressure remained relatively constant. Within 48 hours, AVCO(2)R allowed significant ventilator reductions versus baseline in the following measurements: tidal volume (420 to 270 mL), peak inspiratory pressure (25 to 14 cm H(2)O), minute ventilation (13 to 5 L/min), respiratory rate (26 to 16 breaths/min), and FIO (2) (0.88 to 0.35). Ventilator-free days with AVCO(2)R were 3.9 versus 0.2 (P <.01) for sham animals, and ventilator-dependent days with AVCO(2)R were 2.4 versus 6.2 (P <.01) for the 3 sham survivors. All 8 AVCO(2)R animals and 3 of 8 sham animals survived 7 days after randomization. CONCLUSIONS: Percutaneous AVCO(2)R achieved significant reduction in airway pressures, increased ventilator-free days, decreased ventilator-dependent days, and improved survival in a sheep model of respiratory distress syndrome.

Anatomic study of the pulmonary artery as a conduit for an artificial lung.

Our group is developing an artificial lung as a bridge to transplant. We evaluated the sheep pulmonary artery (PA) for the presence or absence of a septum, which may increase PA resistance and affect artificial lung flow. We also measured the PA size to determine whether it is a suitable conduit for artificial lung implantation using a PA-PA shunt. Adult Suffolk ewes in two groups were studied. Group 1 consisted of animals (n = 12, 30-43 kg) prepared for thoracotomy. Group 2 (n = 21, 30-43 kg) consisted of postmortem dissections. In both groups, the length and girth of the PA was measured. The heart and lungs were removed on all postmortem animals (group 2), the ductus arteriosum was crosscut, and the common PA was incised. The average length of the PA in live animals was 5.5 cm and the average diameter was 2.2 cm. The average length of the PA in postmortem animals was 4.8 cm and the average diameter was 2.0 cm. All pulmonary arteries were aseptate, and the ligamentum arteriosum in each PA was not patent. We conclude that the PA is not a source of increased resistance and is a suitable conduit for artificial lung implantation in the PA-PA configuration.

Safety and efficacy of a heparin removal device: a prospective randomized preclinical outcomes study.

BACKGROUND: Systemic protamine sulfate for heparin reversal after cardiopulmonary bypass (CPB) is associated with uncommon, but life-threatening adverse reactions. METHODS: In a prospective randomized 3-day outcomes study, a heparin removal device (HRD) group (n = 12; 60-, 80-, 100-kg subgroups) was compared with a matched systemic Protamine group (Protamine; n = 6) for safety and efficacy using an adult swine model of CPB (60 minutes, 28 degrees C). RESULTS: HRD run time was 25 to 38 minutes depending on weight without complications. After HRD, heparin concentration decreased from 4.77 +/- 0.17 to 0.45 +/- 0.06 U/mL (activated clotting time [ACT] 776 +/- 83 to 180 +/- 12 seconds), and in Protamine, 3.94 +/- 0.63 to 0.13 +/- 0.02 U/mL (ACT 694 +/- 132 to 101 +/- 5 seconds) (p = 0.01 between groups, but no significant differences 60 minutes later). No significant difference between HRD and Protamine to 72 hours was seen in plasma-free hemoglobin C3a, heparin concentration, thromboelastogram index, platelet count, activated partial thromboplastin time, anti-thrombin III, fibrinogen, ACT, and tissue histology. CONCLUSIONS: In a prospective randomized outcomes study, HRD achieved predictable reversal of systemic heparinization after CPB with no difference in safety or outcomes compared with protamine.

Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal.

The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep (n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300s, n = 6) and LD heparin (ACT < 200s, n =7) and placed on AVCO2R for approximately 72 h using an oxygenator with the Trillium Bio-Passive Surface. Mean ACTs were significantly different, as expected (HD: 446 +/- 26s, LD: 213 +/- 12s, p < 0.05). AVCO2R shunt flow averaged approximately 13% of cardiac output with mean CO2 removal similar in HD and LD, p = NS. The hematocrit, platelet count, and fibrin degradation products for the two groups were not different. No differences in thrombosis or bleeding were noted. In conclusion, LD systemic heparin (ACT < 200s) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep.

Chromosome aberrations as a predictor of clinical outcome for smoking associated lung cancer.

The ability to identify individuals at greatest risk of developing lung cancer can significantly enhance the efficacy of intervention modalities. One strategy for identifying these individuals is through biomarkers that reflect the severity of their cancer. In the present study, we evaluated 22 lung cancer patients and 35 controls to determine whether the frequency of chromosome aberrations was significantly associated with specific clinical variables such as the histological type, grade and stage of the tumors. Chromosome aberrations (expressed as total breaks) were investigated on chromosome 1 in interphase nuclei obtained from blood lymphocytes of the study participants using the fluorescence in situ hybridization (FISH) chromosome aberration assay. Our results indicate a significant linear increase (P=0.01) in the level of breaks with respect to the grade of the carcinoma. The poorly differentiated tumors had a significantly higher level of chromosome breaks mean+/-SD (1.7+/-0.46) as compared to the well differentiated tumors (0.98+/-0.23, P<0.05). These results indicate that chromosome aberrations, as determined by the FISH assay, can be used as a biomarker for identifying individuals with aggressive types of lung cancer and potentially, as a predictor for prognostic outcome of the disease.

New clinically relevant sheep model of severe respiratory failure secondary to combined smoke inhalation/cutaneous flame burn injury.

OBJECTIVES: To develop a predictable, dose-dependent, clinically relevant model of severe respiratory failure associated with a 40% total body surface area, full-thickness (third-degree) cutaneous flame burn and smoke inhalation injury in adult sheep. DESIGN: Model development. SETTING: Research laboratory. SUBJECTS: Adult female sheep (n = 22). INTERVENTIONS: Animals were divided into three groups, determined by the number of smoke breaths administered (24, 36, 48) for a graded inhalation injury. The smoke was insufflated into a tracheostomy with a modified bee smoker at airway temperatures <40 degrees C. All animals concurrently received a 40% total body surface area (third-degree) cutaneous flame burn to the body (flanks). After injury, the animals were placed on volume-controlled ventilation to achieve PaO2 >60 mm Hg and PaCO2 <40 mm Hg. Arterial blood gases and ventilator settings were monitored every 6 hrs postinjury for up to 7 days. MEASUREMENTS AND MAIN RESULTS: All animals survived the induction of injury. In the 24 smoke breath/40% total body surface area burn (24/40) group, PaO2/F(IO2) never decreased below 300, and peak inspiratory pressure was consistently <14 cm H2O with normal arterial blood gases throughout the observation period. With 36 smoke breaths/40% total body surface area burn (36/40) (n = 7), all animals had PaO2/F(IO2) of <200 and peak inspiratory pressure of 26 cm H2O within 40-48 hrs, as 30% died during the study period. With 48 smoke breaths/40% total body surface area burn (48/40) (n = 12), all animals developed respiratory distress syndrome (RDS) in 24-30 hrs, but none survived the experimental period. CONCLUSIONS: Development of RDS by smoke and cutaneous flame bum injury depends on smoke inhalation dose. A combination of 36 breaths of smoke and a 40% total body surface area (third-degree) cutaneous flame burn injury can induce severe RDS (PaO2/F(IO2) <200) within 40-48 hrs to allow evaluation of various treatment modalities of RDS.

Pathogenesis and management of respiratory insufficiency following pulmonary resection.

The underlying principle of the surgical treatment of non-small-cell lung cancer (NSCLC) is complete removal of the local/regional disease within the thorax. Pulmonary resection should be as conservative as possible without compromising the adequacy of tumor removal. A multitude of factors influence the incidence and severity of complications following pulmonary resection including the pre-operative physical and psychological status of the patient, the pathologic process requiring resection, the physiologic impact of the procedure, and the addition of pre-operative or postoperative adjuvant therapy. The insidious onset of interstitial changes on chest X-ray (CXR) 1 to 2 days after pulmonary resection forewarns of respiratory distress; however, the pathophysiology of adult respiratory distress syndrome (ARDS) with progression to respiratory failure requiring mechanical ventilation and advanced critical care often unfolds. Management of patients with severe respiratory failure remains primarily supportive. "Good critical care" is the mainstay of therapy: this includes gentle mechanical ventilation to avoid ventilator-induced barotrauma and over-extension of remaining functional alveoli, diuresis, infection identification and management, and nutritional support. New therapeutic strategies that may impact on outcomes in the adult population include pressure-limited ventilation (permissive hypercapnia), inverse ratio ventilation, high-frequency jet ventilation, high-frequency oscillatory ventilation, intratracheal pulmonary ventilation, and prone position ventilation. In addition, alternative therapies such as partial liquid ventilation, inhaled nitric oxide, and extracorporeal techniques including extracorporeal membrane oxygenation (ECMO), extracorporeal carbon dioxide removal (ECCO(2)R), intravascular oxygenation (IVOX), and arteriovenous carbon dioxide removal (AVCO(2)R), provide additional modalities. A component of some or all of these strategies is finding a role in clinical practice.

Reduced ventilator pressure and improved P/F ratio during percutaneous arteriovenous carbon dioxide removal for severe respiratory failure.

OBJECTIVE: To evaluate the effect of percutaneous arteriovenous carbon dioxide removal (AVCO2R) on ventilator pressures and P/F ratio in a clinically relevant large-animal model of severe respiratory failure. SUMMARY BACKGROUND DATA: AVCO2R was developed as a simple arteriovenous shunt with a commercially available low-resistance gas exchange device of sufficient surface area for near-total CO2 removal. With an AV shunt 10% to 15% of cardiac output, AVCO2R allows a reduction in ventilator airway pressures without hypercapnia or the complex circuitry and monitoring required for conventional ECMO. METHODS: AVCO2R was applied to a new, clinically relevant large-animal model of severe respiratory failure created by smoke inhalation and cutaneous flame bum injury. Adult sheep (n = 9, 38+/-6 kg) received a 40% total body surface area, third-deinsufflation. After injury, all animals were placed on volume-controlled mechanical ventilation to achieve PaO2 > 60 mmHg and PacO2 < 40 mmHg. Animals were placed on AVCO2R within 40 to 48 hours of injury when the PaO2/FiO2 was <200. Animals underwent cannulation of the carotid artery and jugular vein with percutaneous 10F arterial and 14F venous cannulas. Shunt flow was continuously monitored using an ultrasonic flow probe and calculated as a percentage of cardiac output. RESULTS: AVCO2R flows of 800 to 900 ml/min (11% to 13% cardiac output) achieved 77 to 104 ml/min of CO2 removal (95% to 97% total CO2 production) while maintaining normocapnia. Significant reductions in ventilator settings were tidal volume, 421.3+/-39.8 to 270.0+/-6.3 ml; peak inspiratory pressure, 24.8+/-2.4 to 13.7+/-0.7 cm H2O; minute ventilation, 12.7+/-1.4 to 6.2+/-0.8 L/min; respiratory rate, 25.4+/-1.3 to 18.4+/-1.8 breaths/min; and FiO2, 0.88+/-0.1 to 0.39+/-0.1. The P/F ratio increased from 151.5+/-40.0 at baseline to 320.0+/-17.8 after 72 hours. CONCLUSIONS: Percutaneous AVCO2R allows near-total CO2 removal and significant reductions in ventilator pressures with improvement in the P/F ratio.

Early complications. Respiratory failure.

Pulmonary complications following thoracic surgery are common and associated with significant morbidity and mortality. Respiratory failure after pneumonectomy occurs in approximately 5% to 15% of cases and significantly increases patient mortality. Strategies for ventilator support are based on the nature of the underlying complication and the pathophysiology of respiratory failure. This article describes the cause and pathophysiology of respiratory failure and pulmonary embolus postpneumonectomy. Diagnosis, management, and innovative therapies are also reviewed.

Percutaneous extracorporeal arteriovenous CO2 removal for severe respiratory failure.

BACKGROUND: In previous animal studies, arteriovenous CO2 removal (AVCO2R) achieved significant reduction in ventilator pressures and improvement in the Pao2 to fraction of inspired oxygen ratio during severe respiratory failure. For our initial clinical experience, 5 patients were approved for treatment of severe respiratory failure and CO2 retention to evaluate the feasibility and safety of percutaneous AVCO2R. METHODS: Patients were anticoagulated with heparin (activated clotting time, 260 to 300 seconds), underwent percutaneous femoral cannulation (10F to 12F arterial and 12F to 15F venous catheters), and then were connected to a low-resistance, 2.5-m2 hollow-fiber oxygenator for 72 hours. RESULTS: Mean AVCO2R flow at 24, 48, and 72 hours was 837.4+/-73.9, 873+/-83.6, and 750+/-104.5 mL/min, respectively, with no vascular complications and no significant change in heart rate or mean arterial pressure. Removal of CO2 plateaued at an AVCO2R flow of 1086 mL/min with 208 mL/min CO2 removed. Average CO2 transfer at 24 and 48 hours was 142+/-17 and 129+/-16 mL/min. Use of AVCO2R allowed a significant decrease in minute ventilation from 7.2+/-2.3 L/min at baseline to 3.4+/-0.8 L/min at 24 hours. CONCLUSIONS: All patients survived the experimental period without adverse sequelae. Percutaneous AVCO2R can achieve approximately 70% CO2 removal in adults with severe respiratory failure and CO2 retention without hemodynamic compromise or instability.

Significant reduction in circuit pressure with modified plasma separation chamber for a heparin removal device.

The heparin removal device (HRD), using plasma separation and poly-L-lysine (PLL) affinity adsorption, has been shown to be an effective alternative to protamine after cardiopulmonary bypass (CPB). Previous designs of the HRD used standard Luer-Lok ((phi = 2.3 mm) port connections between the extracorporeal tubing and the plasma separation chambers, which resulted in excessively high circuit pressures (> 750 mm Hg) at an HRD flow of 1,400 ml/min. To reduce circuit pressures, we enlarged the connection ports to phi = 4.2 mm, keeping other circuit components and sorbent amounts unchanged. The modified circuit HRD was divided into the SMALL PORT group (phi = 2.3 mm, A = 4.15 mm2) and the LARGE PORT group (phi = 4.2 mm, A = 13.85 mm2) in adult swine (70+/-5 kg) given 300 U/kg heparin. A dual lumen cannula was inserted into the right atrium and connected to the HRD. Inlet pressure ranged from 749+/-42 to 795+/-57 mm Hg in the SMALL PORT group during the HRD run at 1,400 ml/min, whereas it ranged from 345+/-5 to 372+/-34 mm Hg in the LARGE PORT group (p < 0.01 between groups). Likewise, the chamber pressure ranged from 447+/-21 to 452+/-27 mm Hg in the SMALL PORT group and from 190+/-14 to 204+/-19 mm Hg in the LARGE PORT group (p < 0.01 between groups). There were no significant differences in ACT between groups. We conclude that enlarged chamber ports significantly lower circuit pressures for the HRD without changing heparin removal capability.