Regeneration of severely damaged lungs using an interventional cross-circulation platform.

The number of available donor organs limits lung transplantation, the only lifesaving therapy for the increasing population of patients with end-stage lung disease. A prevalent etiology of injury that renders lungs unacceptable for transplantation is gastric aspiration, a deleterious insult to the pulmonary epithelium. Currently, severely damaged donor lungs cannot be salvaged with existing devices or methods. Here we report the regeneration of severely damaged lungs repaired to meet transplantation criteria by utilizing an interventional cross-circulation platform in a clinically relevant swine model of gastric aspiration injury. Enabled by cross-circulation with a living swine, prolonged extracorporeal support of damaged lungs results in significant improvements in lung function, cellular regeneration, and the development of diagnostic tools for non-invasive organ evaluation and repair. We therefore propose that the use of an interventional cross-circulation platform could enable recovery of otherwise unsalvageable lungs and thus expand the donor organ pool.

Methods for the Preparation of an Excised, Cross-Circulated Rat Heart.

The Emax-Pressure-Volume Area (PVA)-VO2 framework proposed by Dr. Suga for canine hearts has dramatically advanced the field of cardiac mechanical work and energetics, i.e., mechanoenergetics. He and his collaborators investigated mechanoenergetics in the left ventricle (LV) of excised, cross-circulated canine heart preparations. We instituted the excised cross-circulated rat whole heart preparations and found a curvilinear end-systolic pressure-volume relation (ESPVR) in the rat LV, in contrast to the linear ESPVR in canine, rabbit, and human LVs. Although Emax, the slope of the linear ESPVR, could be used as an index of LV contractility, it was not applicable for evaluating LV contractility in the rat LV. Thus, we proposed a new index of contractility, equivalent Emax (eEmax) in the rat LV. We also found a linear VO2-PVA relationship in the rat LV. Here, we introduce the methods for the preparation of excised, cross-circulated rat whole hearts and the eEmax-PVA-VO2 framework in the rat LV. Using this method, we can obtain accurate LV volume and myocardial O2 consumption in real time for estimating cardiac mechanoenergetics, which is very challenging in in vivo experiments.

Efficacy of double-filtration plasmapheretic cross-circulation with a high-permeability membrane using canine harvested liver in porcine fulminant hepatic failure model.

INTRODUCTION: The use of bioartificial liver devices requires. A sufficient liver cell mass to provide adequate metabolic support, reduction of xenogeneic immune reactions, and avoidance of viral transmission. We have developed a plasmapheresis system using a semipermeable membrane combined with canine whole liver perfusion (PMCWLP). In this study, we investigated the efficacy of our system in a porcine fulminant hepatic failure (FHF) model. METHODS: The porcine FHF model was established by intraportal administration of alpha-amanitin (0.1 mg/kg) and lipopolysaccharide (1 microg/kg). Nine hours after drug injection, xenogenic perfusion treatment was performed twice within 6 hours (n = 5). As the plasmapheresis device, we used a hollow-fiber module with cellulose diacetate porous fibers (pore size, 0.05 microm, surface area, 2 m2). The canine whole liver was perfused with modified Krebs solution, which is commonly used in many laboratories, containing albumin (2 g/dL) and glucose (300 mg/dL). Control pigs (n = 10), had the circuit not connected to the whole canine liver. RESULTS: The survival of FHF pigs was significantly increased by the treatment (58.9 +/- 21.8 hour) compared with the controls (22.3 +/- 8.1 hour). Mean blood ammonia levels and intracranial pressure during treatment were significantly lower compared with control groups. CONCLUSION: Treatment of FHF pigs with the system significantly increased survival time, suggesting that this method may have applications as a clinical liver assist device.

Efficacy of double filtration plasmapheretic cross-circulation using a high permeability membrane between totally hepatectomized dogs and donor pigs.

BACKGROUND: Major obstacles to develop a bioartificial liver are xenogeneic immune reactions and viral infection from donor pigs. To solve these problems, we studied the effect of xenogeneic double filtration plasmapheretic cross-circulation (DFPCC) using a high performance semipermeable membrane on totally hepatectomized dogs. METHODS: Mongrel dogs, weighing 12-15 kg, underwent total hepatectomy in one stage (n=18). One hr after total hepatectomy, the femoral vein and the jugular vein were cannulated in both dogs and pigs by using the blood access catheter tubes that were connected to the DFPCC system. In the DFPCC circuit, filtrated dog plasma and pig plasma counterflowed in a hollow fiber cartilage at a rate of 25 ml/min for 6 hr and met through a semipermeable membrane with 100 kd nominal molecular weight cut-off (n=5). In control dogs, the circuit was not connected to the pig (n=13). RESULTS: In vitro mass transfer study suggested that very little immunoglobulins crossed the semipermeable membrane. During and after 6 hr of DFPCC, anhepatic dogs had significantly lower blood ammonia and aromatic amino acid levels than did controls. DFPCC-treated dogs demonstrated decreased intracranial pressure and survived significantly longer than control dogs (20.75+/-3.80 hr vs. 14.75+/-1.30 hr, P<0.05). Histology showed no xenogeneic rejection in both dogs and pigs. CONCLUSIONS: Our DFPCC systems with a high permeability membrane demonstrated detoxification-function and contributed to intracranial decompression and longer animal survivals without adverse immune reaction and the possibility of zoonosis.

[Extracorporeal xenospleen perfusion in vial-bacterial pneumonia in children]. / Ekstrakorporal'naia perfuziia ksenoselezenki pri virusno-bakterial'noi pnevmonii u detei.

Extracorporeal perfusion of xenospleen was used in the management of 11 critically ill children with acute multisegmental pneumonia. The first 24 h were characterized by progressive mounting in blood O2 saturation, optimization of hemodynamics and immune status, decrease of toxemia. On days 4-7 after perfusion stabilization of clinical, laboratory and functional indexes was observed. Radiological findings of pulmonary infiltration disappeared 10-14 days after sorption and all the patients were transferred to a somatic unit.

Pressure-volume relation around zero transmural pressure in excised cross-circulated dog left ventricle.

Left ventricular (LV) pressure-volume (PV) relations of quasi-isobaric contractions around zero transmural pressure were studied with a new volumetric method. Left ventricles of isolated cross-circulated dog hearts were connected to a large air tank through the mitral annulus. The volume of the air space was changed with a volume servo pump to oscillate the transmural pressure (P) around zero. Instantaneous LV volume (V) was computed from P by Boyle's law (P.V = constant) to draw the PV trajectories of the isobaric contractions. The end-systolic PV relation (ESPVR) and end-diastolic PV relation (EDPVR) curves intercepted the volume axis at two different volumes (Vo and Vu, respectively). The slopes of both ESPVR and EDPVR curves as well as Vo and Vu were variably influenced by positive and negative inotropic states, heart rate changes, arrhythmias, ischemia, and rigor. In control before any interventions, LV stroke and suction volume (delta V = Vu - Vo) at zero P was 7.5 +/- 2.5 (SD) ml/100 g left ventricle, which changed with the changes in Vo and Vu. delta V decreased with decreases in P from zero and virtually vanished at a pressure (Pn) of -9.5 +/- 2.0 mm Hg. Directly measured LV dead volume (Vd) at Pn was 4.1 +/- 1.3 ml/100 g. The results seem essential for evaluation of LV filling and suction during diastole.