Reliable long-term non-pulsatile circulatory support without anticoagulation.

OBJECTIVE: The Terumo implantable left ventricular assist system (T-ILVAS) consists of a titanium centrifugal pump with a unique magnetically suspended impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior surface is heparin-coated and there is no purge system. We implanted the device into six sheep to ascertain in-vivo haemodynamic function, mechanical reliability and biocompatibility. METHODS: The T-ILVAS was implanted via left thoracotomy without cardiopulmonary bypass. The inflow cannula was placed in the left ventricular apex and a Dacron outflow graft anastomosed to the descending aorta. All animals recovered well. No anticoagulation (heparin or warfarin) was given after the surgery. Suspension position, motor current, impeller speed and pump flow were continuously monitored and stored by on-line computer. Serial blood samples were collected to determine haematological and biochemical indices of renal function, liver function and haemolysis. All animals were electively euthanized between 3 and 7 months postoperatively. The explanted pumps were examined for mechanical reliability and thrombus formation. Major organs were examined macroscopically and histologically for thromboembolism. RESULTS: All animals appeared completely normal for up to 210 days. At speeds between 1500 and 2000 rev./min the device pumped up to 8 l/min capturing all mitral flow. There were no major complications (pump failure, thromboembolism, haemorrhage, or driveline infection). Indices of haemolysis, liver and renal function remained within normal limits. All pumps were mechanically sound and free from thrombus. One embolus was found in a sectioned kidney. CONCLUSION: The T-ILVAS successfully supported the systemic circulation without anticoagulation for up to 210 days. Mechanical reliability and biocompatibility were demonstrated. Organ function remained within normal limits during continuous non-pulsatile flow.

Effect of hypercarbia on surface proteins of cultured bovine endothelial cells.

Hypercarbia is a common complication of respiratory failure, and the technique of "permissive hypercapnia" is used to ventilate individuals with increased peak airway pressures on mechanical ventilators, resulting in elevated arterial PCO2. We studied the effects of hypercarbia on cultured bovine aortic and main pulmonary artery endothelial cell surface proteins, assessing cell surface iodination using lactoperoxidase bound to latex microspheres. We found that 4 h of exposure to 10% CO2 increased the display of substances of apparent molecular masses of 27, 47, and 52 kDa. This effect was not mimicked by acidotic media. Western blots of detergent extracts of main pulmonary artery endothelial cell monolayers did not show increased expression of carbonic anhydrase IV (molecular mass = 52 kDa) after incubation under hypercarbic conditions. Hypercarbia did not change the pattern of [35S]methionine incorporation into endothelial cell proteins. We conclude that hypercarbia of 4-h duration changes iodinated endothelial cell surface proteins. We speculate that this effect may be related to changes in secretion or display of apical cell membrane-associated proteins.

Movement of human mammary tumour cells in culture: exclusion of fibroblasts by epithelial territories.

Time-lapse cinematography was used to investigate the movement of confronting populations of human mammary epithelium and stromal cells (fibroblasts). Epithelial cell islands from fibroadenomas and from normal lacteal secretions completely excluded the fibroblasts, and individual cell territories were maintained even in dense cultures. Electron microscopy of the boundary between epithelium and fibroblasts showed that the two cell types made contact. In contrast, epithelial islands from two carcinomas did not retain territorial integrity and allowed penetration of mammary fibroblasts. Confronting homologous eptihelial islands from benign tumours merged, but this was shown to be due to interdigitation rather than free mixing of cell. Epithelial cells moved actively but unlike fibroblasts they retained their neighbour relationships.