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We performed long-term closed-chest cardiopulmonary bypass in an animal model of total heart failure (induced ventricular fibrillation). The extracorporeal system included a venous reservoir, a roller pump, a membrane lung, and a blood pulsator system. We cannulated the right external jugular vein for venous drainage and the right subclavian artery for arterial return. To decompress the left heart we passed by percutaneous cannulation a special helical spring mounted on a Swan-Ganz catheter (Baxter Edwards Divisions, Irvine, Calif.) and positioned it to rest within the pulmonary artery and tricuspid valves, which rendered them partly incompetent. After induced ventricular fibrillation, blood flow was raised to keep the central venous pressure at baseline values. The lungs were ventilated with 5 % carbon dioxide in room air. During bypass, mean pulmonary artery pressure was 10.0 ± 1.7 mm Hg, mean wedge pressure 11.9 ± 1.8 mm Hg, and mean blood pressure 95.2 ± 5.6 mm Hg. After 2 days (four animals) and 3 days (two animals) the hearts were defibrillated. There was immediate ejection from both sides of the heart. All sheep were weaned from bypass within 29 ± 11 minutes and their lungs were ventilated with room air within 42 ± 34 minutes. At autopsy hearts and lungs grossly appeared normal. We conclude that the percutaneous helical spring resting within right heart valves provided excellent decompression throughout the study, with full recovery of heart and lung function on defibrillation.

A novel technique to produce a monolithic integrally formed system for countercurrent chromatography is introduced here. Through a molding technique, complex repetitive flow channels were formed into sheets of polypropylene. Two of these sheets were fused to form a closed separation chamber with a complete set of locules and integral transfer tubes. This system, called monolithic integrated flow circuit (MIFC), was produced in various configurations and tested while rotated, gyrated, or oscillated so as to promote mixing of the two solvent phases. Performance of each scheme was examined by separations of DNP-alanine and DNP-glutamic acid with a two-phase solvent system composed of chloroform: acetic acid: 0.1 N HCl (2:2:1). Under optimal conditions, the efficiencies of the schemes using gyration and oscillation were 94% and 74%, respectively. Simply rotational mixing was considerably less efficient.This compact MIFC system was found to be a simple yet ideal way of producing flow channels of great complexity for conventional droplet CCC and locular CCC. The performance of the tested configurations was outstanding.

We provided total cardiopulmonary support for 1-18 hours in unanesthetized tethered lambs by peripheral vascular cannulation, using a roller pump and the spiral membrane lung. Respirations were allowed to remain spontaneous and unaided. A Swan-Ganz catheter was placed for retrograde pulmonary artery blood flow sampling. Within a few minutes following induced ventricular fibrillation the PCO2of sampled blood flowing retrograde through the lungs fell below 10 mm Hg, the PO2rose to near 150 mm Hg, the pH rose to above 7.8, and the glucose level fell to less than 20 mg %. All of these values later gradually shifted, approaching mixed venous blood values within minutes. After 1-18 hrs of perfusion the animals went into shock and were sacrificed. At autopsy, the lungs of animals breathing room air were beefy and hemorrhagic.In lambs that were «breathing» CO2enriched air the retrograde pulmonary artery blood pH and PCO2was usually maintained close to the mixed venous blood values. The observed pulmonary changes were considerably less abnormal, and the microscopic abnormalities were at times nonexistent.We believe the integrity of pulmonary blood flow is vital to the survival of the lungs as a functioning organ. Cessation of total forward pulmonary blood flow (unlike partial cardiopulmonary bypass), combined with spontaneous pulmonary ventilation, rapidly leads to massive, pulmonary infactions, shock, and death.

The pulmonary effects of hyperventilation following infusion of sodium salicylate into the cisterna magna was studied in 16 spontaneously breathing adult sheep. We found a fall in PaO2, a decrease in the static compliance of the respiratory system, abnormal chest roentgenographic films, and grossly abnormal lungs following 3.5 to 13 h of hyperventilation. A control group of 15 sheep (10 sheep similarly injected with sodium salicylate, but then sedated and paralyzed and ventilated at normal tidal volume and respiratory rate on a mechanical ventilator, and 5 sheep infused with saline alone and breathing spontaneously) showed no pulmonary or arterial blood gas abnormalities. We conclude that prolonged hyperventilation under the conditions of this experiment precipitated events that resulted in acute lung injury.

A total of 44 preterm fetal lambs at great risk of developing respiratory failure were delivered by Cesarean section, and were then managed on conventional mechanical pulmonary ventilation. Fifteen animals initially fared well, and 14 of these were long term survivors. Twenty-nine other lambs showed a progressive deterioration in arterial blood gases within 30 minutes of delivery, of which 10 lambs were continued on mechanical pulmonary ventilation (20% survival), while the remaining 19 lambs were placed on an extracorporeal membrane lung respiratory assist (79% survival). Extracorporeal membrane lung bypass rapidly corrected arterial blood gas values, and permitted the use of high levels of CPAP instead of the continuation of mechanical pulmonary ventilation at high peak airway pressures. Improvement in lung function was gradual, and predictable.Early institution of extracorporeal respiratory assist using a membrane artificial lung rapidly corrected arterial blood gas values and significantly improved on neonate survival.

A group of 36 patients with severe adult respiratory distress syndrome (ARDS) meeting previously established blood gas criteria (mortality rate 90%) became candidates for possible extracorporeal respiratory support [low frequency positive pressure ventilation with extracorporeal CO2removal (LFPPV-ECCO2R)]. Before connecting the patients to bypass we first switched the patients from conventional mechanical ventilation with positive end expiratory pressure (PEEP) to pressure controlled inverted ratio ventilation (PC-IRV), and then when feasible, to spontaneous breathing with continuous positive airways pressure (CPAP). Forty eight hours after the patients had entered the treatment protocol, only 19 out of the 36 patients in fact required LFPPV-ECCO2R, while 5 were still on PC-IRV, and 12 were on CPAP. The overall mortality rate of the entire population was 23%. The only predictive value of success or failure of a particular treatment mode was total static lung compliance (TSLC). No patients with a TSLC lower than 25 ml (cm H2O)-1tolerated either PC-IRV or CPAP, while all patients with a TSLC higher than 30 ml (cm H2O)-1were successfully treated with CPAP. Borderline patients (TSLC between 25 and 30 ml (cm H2O)-1) had to be treated with PC-IRV for more than 48 h, or were then placed on LFPPV-ECCO2R if Paco2rose prohibitively. We conclude that TSLC is a most useful measurement in deciding on the best management of patients with severe ARDS, unresponsive to conventional treatment.

Hyaline membrane disease is found only in lungs where pulmonary ventilation has been established, i.e. after birth. We delivered eleven fetal lambs of a gestational age of 128–130 days but instead kept their lungs in total apnea and inflated to constant pressure, while removing all metabolically produced carbon dioxide with an extracorporeal membrane lung. Oxygen was provided by the membrane lung, and by apneic oxygenation through the natural lungs. Hence, arterial blood gases remained always normal, without any pulmonary ventilation. After 6–66 h the lungs had sufficiently cleared to allow normal mechanical pulmonary ventilation in 10 out of 11 lambs so treated. In a control group treated with mechanical ventilation alone, five of seven lambs died within the first 24 h of severe hyaline membrane disease.

A new tissue culture system has been developed to sup-port high density cell growth using the sheep as the host. Cellular nutrition is provided by plasma solutes as they diffuse from arterial blood across microporous polycarbonate membranes into a device attached to an arteriovenous shunt. Culture chambers are constructed with transparent polycarbonate to allow photomicroscopy of the tissue in situ. System performance is demonstrated by the high density growth of fetal sheep thymus allografts and rat soft tissue sarcoma xenografts.

Five lambs were anaesthetized, paralysed, mechanically ventilated and connected to a membrane “lung” to permit removal of carbon dioxide. When part of the carbon dioxide was removed in this manner, the tidal volume was decreased to keep PaCO2, constant. For example, when 70% of carbon dioxide was removed by the membrane lung, total ventilation was reduced by 50%, peak inspiratory pressure was decreased by 45%, and PaO2 was kept constant by increasing the inspired oxygen fraction from 0.21 to 0.27%. The removal of carbon dioxide by a membrane during positive pressure breathing could decrease barotrauma, particularly in poorly compliant lungs. Technically, the extracorporeal removal of carbon dioxide is a relatively simple procedure.