New Approaches to Respiratory Assist: Bioengineering an Ambulatory, Miniaturized Bioartificial Lung.

Although state-of-the-art treatments of respiratory failure clearly have made some progress in terms of survival in patients suffering from severe respiratory system disorders, such as acute respiratory distress syndrome (ARDS), they failed to significantly improve the quality of life in patients with acute or chronic lung failure, including severe acute exacerbations of chronic obstructive pulmonary disease or ARDS as well. Limitations of standard treatment modalities, which largely rely on conventional mechanical ventilation, emphasize the urgent, unmet clinical need for developing novel (bio)artificial respiratory assist devices that provide extracorporeal gas exchange with a focus on direct extracorporeal CO2 removal from the blood. In this review, we discuss some of the novel concepts and critical prerequisites for such respiratory lung assist devices that can be used with an adequate safety profile, in the intensive care setting, as well as for long-term domiciliary therapy in patients with chronic ventilatory failure. Specifically, we describe some of the pivotal steps, such as device miniaturization, passivation of the blood-contacting surfaces by chemical surface modifications, or endothelial cell seeding, all of which are required for converting current lung assist devices into ambulatory lung assist device for long-term use in critically ill patients. Finally, we also discuss some of the risks and challenges for the long-term use of ambulatory miniaturized bioartificial lungs.

In Vivo Testing of Extracorporeal Membrane Ventilators: iLA-Activve Versus Prototype I-Lung.

A side-by-side comparison of the decarboxylation efficacy of two pump-driven venovenous extracorporeal lung assist devices, i.e., a first prototype of the new miniaturized ambulatory extracorporeal membrane ventilator, I-lung versus the commercial system iLA-activve for more than a period of 72 hours in a large animal model. Fifteen German Landrace pigs were anesthetized and underwent mechanical hypoventilation to induce severe hypercapnia. Decarboxylation was accomplished by either the I-lung or the iLA-activve via a double lumen catheter in the jugular vein. Sham-operated pigs were not connected to extracorporeal devices. Cardiovascular, respiratory, and metabolic parameters were continuously monitored, combined with periodic arterial blood sampling for subsequent clinical blood diagnostics, such as gas exchange, hemolysis, coagulation parameters, and cytokine profiles. At the termination of the studies, lung tissue was harvested and examined histologically for pulmonary morphology and leukocyte tissue infiltration. Both extracorporeal devices showed high and comparable efficacy with respect to carbon dioxide elimination for more than 72 hours and were not associated with either bleeding events or clotting disorders. Pigs of both groups showed cardiovascular and hemodynamic stability without marked differences to sham-operated animals. Groups also did not differ in terms of inflammatory and metabolic parameters. We established a preclinical in vivo porcine model for comparative long-term testing of I-lung and iLA-activve. The I-lung prototype proved to be safe and feasible, providing adequate decarboxylation without any adverse events. Once translated into the clinical treatment, the new miniaturized and transportable I-lung device might represent a promising tool for treating awake and mobilized patients with decompensated pulmonary disorders.

Pulsatile venoarterial perfusion using a novel synchronized cardiac assist device augments coronary artery blood flow during ventricular fibrillation.

Patients with cardiogenic shock have a very high mortality. Here we report the first use of a percutaneous pulsatile cardiac assist device, based on a diagonal pump synchronized with the heart cycle by means of an electrocardiographic signal in adult pigs. Eight domestic pigs underwent mandatory ventilation. During sinus rhythm, there were no differences between pulsatile and nonpulsatile perfusion with regard to pulmonary artery pressure, pulmonary wedge pressure, central venous pressure, mean arterial pressure (MAP), mean pulse pressure, and mean coronary artery flow (CAF). After 2 min of complete cardiac arrest (ventricular fibrillation), circulatory support with the i-cor in venoarterial nonpulsatile extracorporeal membrane oxygenation (ECMO) mode (3 L/min) restored systemic circulation, with an increase of MAP to 78.3 mm Hg and CAF to 5.27 mL/min. After changing from ECMO settings to pulsatile mode (3 L/min, 75 bpm, pulse amplitude range 3500 rpm), MAP did not change significantly (75.6 mm Hg); however, CAF increased to 8.45 mL/min. After changing back to nonpulsatile mode, MAP remained stable (83.6 mm Hg), but CAF decreased to 4.85 mL/min. Thereafter, pulsatile cardiac assist was established with a reduced blood flow of 2.5 L/min, and the pulse amplitude range was extended to 4500 rpm. Under these conditions, MAP remained stable (71.0 mm Hg), but CAF significantly increased to 15.2 mL/min (P < 0.05). Percutaneous cardiac support using a venoarterial cardiac assist device equipped with a novel diagonal pump is able to restore and increase systemic and coronary circulation during ventricular fibrillation. Electrocardiographically triggered synchronized cardiac assist provides an additional increase of coronary artery flow. These promising results are to be confirmed in humans.

The influence of controlled limb reperfusion with PGE1 on reperfusion injury after prolonged ischemia.

BACKGROUND: Controlled reperfusion of ischemic limbs has been found to be protective in limiting ischemia-reperfusion injury. We aimed to analyze local hemodynamic effects of prostaglandin E1 (PGE1) administrated during controlled reperfusion in an in vivo setting. MATERIAL AND METHODS: Twenty-four pigs underwent exposure of the infrarenal aorta and iliac vessels. Pigs were observed for 7.5 h without limb ischemia (group I). In the others, limb ischemia was produced by clamping the aorta for 6 h. Reperfusion was conducted in uncontrolled (group II), controlled (group III), and controlled fashion with addition of PGE1 (group IV) for the initial 30 min. We evaluated regional blood flow in the left common iliac artery, cardiac output, systemic vascular resistance, oxygen and glucose consumption, muscle adenosine triphosphate (ATP), and potassium levels in iliac vein. RESULTS: Benefits after reperfusion were observed in group IV compared with group III regarding regional blood flow at 60 min (P < 0.01) and 90 min (P < 0.01), glucose consumption at 30 min, (P < 0.05) and potassium regulation at 30 (P < 0.05) and 90 min (P < 0.05). CONCLUSION: The addition of PGE1 to controlled reperfusion further reduces local hemodynamic effects of ischemia-reperfusion injury compared with standard controlled and uncontrolled reperfusion in an animal model.

New technologies for respiratory assist.

"The artificial lung especially has lingered behind progress with artificial hearts and ventricular assist devices, not because the need for lungs has not been recognized, but because we have not had a full understanding of the engineering problems and the unique material requirements until recent years." Brack Hattler, MD PhD. The development from the first clinical use of haemodialysis over five decades ago to widespread chronic treatment took more than two decades. The histories of other artificial organ technologies, such as artificial hearts, follow similar long development paths. For five decades, due to a lack of technology, artificial lungs have been limited to use with a heart-lung machine for cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO). The advent of pumpless biocompatible artificial lungs will open new treatment options for patients with acute or chronic lung failure.

Myocardial rewarming mirrors intraoperative mammary artery graft function.

BACKGROUND: The internal mammary artery (IMA) bypass graft provides a satisfactorily long-lasting blood supply to the myocardium. However, its initial flow capacity can be insufficient with subsequent regional myocardial ischemia. We evaluated a method to assess the IMA graft function intraoperatively. METHODS: Twenty-five patients with three-vessel coronary artery disease underwent coronary artery bypass grafting on cardiopulmonary bypass. The in situ IMA was grafted to the left anterior descending coronary artery (LAD) in combination with two saphenous vein grafts to the left circumflex and right coronary artery. Distal anastomoses were performed during cold intermittent blood cardioplegia. After unclamping of the aorta and of the grafted IMA, the temperature at the cardiac anterior and posterior side was measured during the first 5 minutes of warm reperfusion. RESULTS: A sufficient IMA graft function was expressed by a typical rise in temperature: the cardiac anterior and posterior sides showed a parabolic and exponential course, respectively. The rewarming velocity expressed as the first derivative of temperature over time led to a sharp and early peak for the anterior side, and a smaller and delayed peak for the posterior side. Insufficient IMA graft function could be recognized by an atypical temperature course. CONCLUSIONS: Temperature measurement of the heart during warm reperfusion after hypothermic cardioplegia can help to assess the effectiveness of the IMA-LAD graft function.

Graded reoxygenation limits lipid peroxidation during surgical reperfusion.

BACKGROUND: Most cardiac operations with cardiopulmonary bypass (CPB) are conducted with high oxygen partial pressure. The hyperoxic reoxygenation of the ischemic heart induced by aortic declamping may be an important component of cardiac reperfusion injury. The present clinical study assessed the preventive effect of graded reoxygenation on lipid peroxidation. Malondialdehyde (MDA) levels reflect lipid peroxidation, and therefore can be used to quantify reoxygenation damage. MATERIAL/METHODS: 19 patients with coronary artery disease were enrolled consecutively and divided into two groups. In Group I, graded reoxygenation was initiated 1 min before, and continued for 9 min after aortic declamping (paO2: 50-70 mmHg, n=10). Patients undergoing conventional hyperoxic reoxygenation (paO2: >250 mmHg) on CPB (Group II, n=9) served as controls. Blood was collected before commencement of CPB, 2 min before release of the aortic crossclamp, 1 min and 10 min after release of the aortic crossclamp, and 3 hours after CPB. RESULTS: MDA levels [KM/l] did not differ between groups before CPB, but 1 min after aortic declamping MDA increased significantly more in group II (11.02 +/- 1.05; p=0.04) as compared to group I (8.16 +/- 0.74). There was no difference between groups late after reperfusion. CONCLUSIONS: Hyperoxic reoxygenation by release of the aortic crossclamp is associated with increased MDA levels immediately after aortic declamping. Graded normoxic reoxygenation therefore limits lipid peroxidation in the early reperfusion period.

Occupational exposure to inhalational anesthetics during cardiac surgery on cardiopulmonary bypass.

BACKGROUND: Eventual hazards from occupational exposure of operating room personnel to inhalational anesthetic agents cannot yet be definitively excluded. We determined if occupational exposure of operating room personnel to waste anesthetic gases during cardiopulmonary bypass (CPB) complies with the established governmental limits. METHODS: Ten adults underwent inhalational anesthesia for coronary artery bypass grafting with nitrous oxide and either sevoflurane (n = 5) or desflurane (n = 5). The administration of inhalational anesthetic agents was stopped before initiation of CPB. Gas samples were obtained before and during CPB every 90 seconds from the breathing zones of anesthesiologist (A), surgeon (S), and perfusionist (P). Time-weighted averages (TWA) over the time of exposure were calculated. RESULTS: The surgeon's exposure to nitrous oxide was 9.3 +/- 1.9 parts per million (ppm) before and 3.0 +/- 1.4 ppm during CPB (A: 6.7 +/- 1.1 ppm and 0.5 +/- 0.1 ppm; P: 3.7 +/- 1.4 ppm during CPB). Occupational exposure to desflurane was 0.21 +/- 0.10 ppm before and 0.62 +/- 0.28 ppm during CPB for the surgeon (A: 0.02 +/- 0.01 ppm and 0.02 +/- 0.003 ppm; P: 0.82 +/- 0.26 ppm during CPB), thereby exceeding the given limit of 0.5 ppm. Exposure levels of sevoflurane were below the 0.5 ppm limit at all times, as were nitrous oxide levels (threshold limit: 25 ppm). CONCLUSIONS: Although occupational exposure to inhalational anesthetic agents was low at most times during the study and none of the operating room staff complained about subjective or objective impairment or discomfort, all measures must be taken to further minimize occupational exposure, including sufficient air conditioning and routine use of waste gas scavenging systems on CPB equipment.

Cariporide (HOE642) limits S-100B release during cardiac surgery.

Cardiac surgery with cardiopulmonary bypass (CPB) results in transient cerebral swelling in most patients. Cognitive decline occurs in 24-57% of patients and 2-5% experience stroke. Serum levels of S-100B, a potential marker of increased blood-brain barrier permeability, increase during and early after surgery. The authors studied the effects of the novel Na /H exchange inhibitor cariporide (HOE642) on postoperative serum levels of S-100B and neuron-specific enolase (NSE) in 53 patients at high risk undergoing coronary artery bypass grafting. Patients were randomly assigned to one of four groups: I, placebo; II, 20 mg cariporide; III, 80 mg cariporide; IV, 120 mg cariporide). In addition, the leukocyte activation marker myeloperoxidase (MPO) and malondialdehyde (MDA), a marker for lipid peroxidation, were evaluated by enzyme-linked immunoassay. Postoperatively, five patients experienced transient ischemic attack or stroke. S-100B levels increased from 0.43 microg/l +/- 0.33 before operation to 2.27 microg/l +/- 0.69 1 hour after surgery in the placebo group. Preoperative S-100B levels in the HOE642 groups did not differ from the placebo group whereas, 1 hour after surgery, levels were significantly lower in groups II, III, and IV (1.63 microg/l +/- 0.2, 1.27 microg/l +/- 0.27, and 0.90 microg/l +/- 0.21, respectively). NSE, MPO, and MDA serum levels did not differ among groups. These findings may stimulate larger clinical studies to examine the effects of HOE642 on cerebral swelling and neurologic/cognitive outcome of cardiac surgery with CPB.

Coronary artery bypass grafting through complete sternotomy in conscious patients.

BACKGROUND: Complete sternotomy is the standard approach in cardiac surgery, and coronary artery bypass grafting (CABG) is the most common revascularization procedure to use this approach. A new technique has been developed that permits complete surgical revascularization with arterial grafts in awake patients. This technique, which we refer to as awake coronary artery bypass grafting, avoids general anesthesia, mechanical ventilation, and extracorporeal circulation, thereby creating the least invasive method for heart operations yet described. METHODS: A thoracic epidural catheter was placed at T2-T3 level one day before surgery. In 12 patients, single (n = 6), double (n = 5), or triple (n = 1) vessel coronary artery bypass grafting was performed without general anesthesia. In six patients, this procedure was performed after complete median sternotomy. RESULTS: Ten patients remained awake throughout the whole procedure. Two patients required secondary intubation due to incomplete analgesia in one case and pneumothorax in the other. Procedural time was 98.2 +/- 19.8 minutes. Intermediate care stay was 4.9 +/- 0.6 hours. There were no perioperative complications, and early angiographic results before discharge were excellent in all patients. CONCLUSIONS: The data presented show the feasibility and safety of complete surgical revascularization via median sternotomy using arterial grafts without general anesthesia. This approach shortens recovery time and increases patient comfort, suggesting that outpatient cardiac surgery may eventually be possible.

Distribuiçäo da soluçäo Euro-Collins em pulmöes de porcos ministrada por diferentes vias de perfusäo rápida: estudo comparativo / Distribution of the Euro-Collins solution in swine lungs, given through different rapid perfusion routes: a comparative study

No transplante pulmonar as complicaçöes brônquicas säo causas importantes de morbidade e mortalidade, contribuindo para tal a qualidade de proteçäo das vias aéreas, durante armazenamento e implantaçäo do enxerto. omo a "flush perfusion" (perfusäo rápida-PR) via artéria pulmonar (AP), com diferentes soluçöes de preservaçäo, seguida de armazenamento hipotérmico do enxerto, é a técnica mais utilizada nos centros de TP, foi nosso objetivo comparar o fluxo de Euro-Collins (EUC) em pulmöes de porcos, enfatizando o efeito sobre as vias aéreas, por diferentes técnicas de PR. Os animais foram divididos em grupos sem PR: controle (n=6) e com PR pelas seguintes vias: AP (n=6); artérias pulmonar e brônquicas, simultaneamente...