We studied the cardiopulmonary, hematologic, and inflammatory response to
hemodialysis with seven different membranes in sheep. We also compared
acetate dialysate with
bicarbonate dialysate and evaluated the role of
thromboxane in mediating these responses to dialysis with
Cuprophan membranes (Baxter Healthcare Corp., Renal Division, Deerfield, Ill.) in sheep. The data generated in these studies indicate that dialyzer membranes can be divided into three major categories, defined by propensity to activate
complement. High
complement activators such as
Cuprophan (low surface-area CF-1511 and high surface-area ST-25 dialyzers) produced dramatic
neutropenia and
hypoxemia and significant (p < 0.01) increases in the plasma concentration of
thromboxane and in mean pulmonary artery blood pressure. The magnitude of these effects appeared to be surface area related. The low-flux Fresenius F-6
polysulfone membrane (Fresenius USA Inc., Concord, Calif.) also resulted in the generation of significant levels of C3a. In contrast, low
complement activators such as
polyacrylonitrile (
AN-69; Gambro Hospal, Inc., Lakewood, Colo.) and
cellulose triacetate (CT-110G; Baxter) produced little or no
neutropenia, small transient increases in
thromboxane, and no rise in mean pulmonary artery pressure. Dialyzers with intermediate
complement-activating potential such as
cellulose acetate (CA-110; Baxter) and
Hemophan (HT-100; Baxter) produced small to moderate degrees of
neutropenia and small increases in
thromboxane and mean pulmonary artery pressure. Treatment of sheep with
sodium ibuprofen before dialysis with
Cuprophan CF-1511 membranes prevented the initial increases in mean pulmonary arterial pressure and
thromboxane generation and the decrease in arterial
oxygen tension, but did not affect the degree of complement activation or
neutropenia. In sheep undergoing
Cuprophan dialysis,
bicarbonate dialysate did not prevent the increase in circulating
complement and the associated
neutropenia otherwise seen during the early portions of dialysis with
acetate dialysate.
Bicarbonate dialysate did, however, reduce (not prevent) the initial increases in
thromboxane and mean pulmonary arterial pressure, and the magnitude of the
hypoxemia seen with the use of
acetate dialysate. The results of these experiments therefore indicate that (1) reactions in sheep correlate well with data collected in human beings and the model can be an effective means for comparing novel dialysis membranes and pharmacologic interventions during dialysis and (2) although
complement appears to be the transducer of the hematologic and immunologic response,
thromboxane appears to be the final effector of the cardiovascular responses to
hemodialysis with
Cuprophan membranes.