Progress toward an ambulatory pump-lung

ObjectivesCurrently available therapies for acute and chronic lung diseases have not been effective and have various problems associated with the technologies used. We present a novel active mixing pump-lung with the goal of providing total respiratory support to ambulatory patients.MethodsThe pump-lung is based on the concept of active mixing oxygenation within a constrained vortex. The rotation of hollow-fiber membranes disrupts the concentration boundary layer, increasing gas exchange efficiency, and simultaneously pumps the blood. Consequently, the amount of membranes required to achieve gas transfer sufficient for total respiratory support is considerably small. A series of studies, including computational design, experimental bench testing, and in vivo animal experiments, have been performed to implement this concept into a viable artificial pump-lung device.ResultsA series of pump-lung prototypes with a membrane surface area of 0.17 to 0.5 m2 were designed and characterized in vitro with bovine blood, demonstrating extremely high gas exchange efficiency. The prototype with a gas exchange surface area of 0.5 m2 was evaluated in calves. The device provided oxygen transfer of approximately 115 mL/min for respiratory support of an animal for up to 5 days.ConclusionsProgress to date suggests a high likelihood of success for an extracorporeal shorter-term lung that can be switched in and out like dialysis devices. Our device is unique in that it incorporates an integrated pumping and active mixing principle for excellent gas transfer and eliminates the need of the native right ventricle’s ability to power blood through the artificial and natural lungs

Extracorporeal Membrane Oxygenation (ECMO) for Long-Term Support: Recent Advances

Considerable progress has been made in component technology, circuitry, and clinical practice related to extracorporeal membrane oxygenation (ECMO). These advances allow prolonged support with fewer complications when compared to the past eras. Long-term support cases were frequently reported with indications including respiratory failure, cardiac failure, bridge to transplantation, extracorporeal cardiopulmonary resuscitation (ECPR), and even ambulatory extracorporeal membrane oxygenation (ECMO) support. The common complications associated with ECMO, including thrombosis, hemorrhage, nosocomial infection, neurological injury, vessel injury, multiple organ failure and mechanical failure, and the disease process of patients remain limiting factors. In spite of the complications, ECMO remains the only possible option in treatments for patients requiring long-term respiratory or cardiopulmonary support. In this chapter, the recent advances in long-term ECMO support are reviewed. Clinical etiology of patients placed on long-term ECMO support, the various circuit configurations, clinical and technical issues, management aspects, and clinical outcomes are discussed

Parameters for successful nonoperative management of traumatic aortic injury

ObjectiveBlunt traumatic aortic injury is associated with significant mortality, and increased computed tomography use identifies injuries not previously detected. This study sought to define parameters identifying patients who can benefit from medical management.MethodsWe reviewed 4.5 years of blunt traumatic aortic injuries. Injury was classified as grade I (intimal flap or intramural hematoma), II (small pseudoaneurysm <50% circumference), III (large pseudoaneurysm >50% circumference), and IV (rupture/transection). Secondary signs of injury included pseudocoarctation, extensive mediastinal hematoma, and large left hemothorax. Follow-up, including computed tomography, was reviewed.ResultsWe identified 97 patients: 31 grade I, 35 grade II, 24 grade III, and 7 grade IV; 67(69%) male; mean age 47 ± 18.8 years, mean Injury Severity Score 38.8 ± 14.6; overall survival 76 (78.4%). Secondary signs of injury were found in 30 patients. Overall, 52 (53.6%) underwent repair, 45 undergoing thoracic endovascular aortic repair, with 2 (2.22%) procedure-related deaths, and 7 undergoing open repair. Five patients undergoing thoracic endovascular aortic repair required 7 additional procedures. In 45 medically managed patients, there were 14 deaths (31%), all secondary to associated injuries. Injury Severity Scores of survivors and nonsurvivors were 33 ± 10.8 and 48.6 ± 12.8, respectively (P < .001). Follow-up showed resolution or no change in 21 (91%) and a small increase in 2 grade I injuries.ConclusionsAll blunt traumatic aortic injury does not necessitate repair. Stratification by injury grade and secondary signs of injury identifies patients appropriate for medical management. Grade IV injury necessitates emergency procedures and carries high mortality. Grade III injury with secondary signs of injury should be urgently repaired; patients without secondary signs of injury may undergo delayed repair. Grade I and II injuries are amenable to medical management

Clinical trial of FK 506 immunosuppression in adult cardiac transplantation

The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient. © 1992

Hemodynamic effects of partial ventricular support in chronic heart failure: Results of simulation validated with in vivo data

ObjectiveCurrent left ventricular assist devices are designed to provide full hemodynamic support for patients with end-stage failing hearts, but their use has been limited by operative risks, low reliability, and device-related morbidity. Such concerns have resulted in minimum use of left ventricular assist devices for destination therapy. We hypothesize that partial circulatory support, which could be achieved with small pumps implanted with less-invasive procedures, might expand the role of circulatory support devices for treatment of heart failure.MethodsWe examine the hemodynamic effects of partial left ventricular support using a previously described computational model of the cardiovascular system. Results from simulations were validated by comparison with an in vivo hemodynamic study.ResultsSimulations demonstrated that partial support (2-3 L/min) increased total cardiac output (left ventricular assist device output plus native heart output) by more than 1 L/min and decreased left ventricular end-diastolic pressure by 7 to 10 mm Hg with moderate-to-severe heart failure. Analyses showed that the hemodynamic benefits of increased cardiac output and decreased left ventricular end-diastolic pressure are greater in less-dilated and less-dysfunctional hearts. Both the relationships between ventricular assist device flow and cardiac output and ventricular assist device flow and left atrial pressure predicted by the model closely approximated the same relationships obtained during hemodynamic study in a bovine heart failure model.ConclusionsResults suggest that a pump with a flow rate of 2 to 3 L/min could meaningfully affect cardiac output and blood pressure in patients with advanced compensated heart failure. The development of small devices capable of high reliability and minimal complications that can be implanted with less-invasive techniques is supported by these findings

A decade (1982 to 1992) of pediatric cardiac transplantation and the impact of FK 506 immunosuppression

The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14 %) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67 %. In children with congenital heart disease (>6 months of age) the perioperative (30 day) mortality was 66 % before mid-1988 (n = 10) and 0 % since mid-1988 (n = 11). The late mortality (>30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66 % (n = 14) and 7 % since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82 % in children with congenital heart disease and 90 % in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82 % at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60 % at 3 and 6 months after transplantation versus 20 % and 12 %, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p < 0.001, Mantel-Cox and Breslow). Twenty of 24 children (83 %) in the FK 506 group are receiving no steroids. The prevalence of posttransplantation hypertension was 4 % in the FK 506 group versus 70 % in the cyclosporine group (p < 0.001, Fisher). Renal toxicity in children treated with FK 506 has been mild. Additionally, eight children have been switched to FK 506 because of refractory rejection and drug toxicity. FK 506 has not produced hirsutism, gingival hyperplasia, or abnormal facial bone growth. The absence of these debilitating side effects, together with the observed immune advantage and steroid-sparing effects of FK 506, hold tremendous promise for the young patient facing cardiac transplantation and a future wedded to immunosuppression

Regional remodeling strain and its association with myocardial apoptosis after myocardial infarction in an ovine model

ObjectiveProgressive left ventricular remodeling after myocardial infarction has been viewed as an important contributor to progressive heart failure. The objective of this study was to investigate the relationship between myocardial apoptosis and strain during progressive cardiac remodeling.MethodsBefore creation of an anterolateral left ventricular infarction by ligation of diagonal arteries, 16 sonomicrometry transducers were placed in the left ventricular free wall of 8 sheep to assess regional deformation in the infarct, adjacent, and normally perfused remote myocardial regions over 8 weeks' duration. Hemodynamic, echocardiographic and sonomicrometric data were collected before infarction and then 30 minutes and 2, 6, and 8 weeks after infarction. At the end of the study, regional myocardial tissues were collected for apoptotic signaling proteins.ResultsAt terminal study, an increase in left ventricular end-diastolic pressure of 8.1 ± 0.1 mm Hg, a decrease in ejection fraction from 54.19% ± 5.68% to 30.55% ± 2.72%, and an end-diastolic volume increase of 46.08 ± 5.02 mL as compared with the preinfarct values were observed. The fractional contraction at terminal study correlated with the relative abundance of apoptotic protein expressions: cytochrome c (r2 = 0.02, P < .05), mitochondrial Bax (r2 = 0.27, P < .05), caspase-3 (r2 = 0.31, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r2 = 0.30, P < .05). These myocardial apoptotic activities also correlated with remodeling strain: cytochrome c (r2 = 0.02, P < .05), mitochondrial Bax (r2 = 0.28, P < .05), caspase-3 (r2 = 0.43, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r2 = 0.37, P < .05).ConclusionIncrease in regional remodeling strain led to an increase in myocardial apoptosis and regional contractile dysfunction in heart failure