A reliable cross-circulation model: its use in studying humoral agents.

The purpose of this study was to develop an expeditious and reliable system to examine early alterations in proliferating liver tissue in vivo, uncomplicated by the haemodynamic changes associated with partial hepatectomy. We describe an improved, dependable, massive blood-exchange system, involving aortic blood transposition between two rats, which meets these criteria. The use of heparinized, silicone-rubber tubing and postoperative recirculation obviate the need for supplemental anticoagulants and minimizes haemorrhage. The procedure is rapid, and survival is > 95% for up to 48 h. We cite both the advantages of using this model generally to study humoral agents, and specific advantages associated with studies relating to a humoral hepatic mitogen. As an example in this regard, we present results obtained using this system to examine chromatin protein methylation in the intact liver of rats coupled to partially hepatectomized partners. Labelling with a mixture of 3H-methyl-L-methionine and 2-14C-DL-methionine, we demonstrate an enhancement of methylation in crude chromatin protein fractions obtained from intact liver tissue responding to humoral agents provided by blood exchanged from partially hepatectomized rats. This substituent enhancement appears to correlate with the degree of stimulation of DNA replication in this organ.