Long-Term Hepatic Vascular Access in the Nonhuman Primate for Recurrent Portal Vein Infusion

ABSTRACT

Islet cell transplantation in nonhuman primates is generally performed in the liver, by infusion of the transplant into the portal vein. We introduced a vascular access port with the catheter tip located in the splenic vein to avoid multiple major survival surgeries. This procedure was conducted in 16 cynomolgus and 9 rhesus macaques. A subset underwent islet cell transplantation. A historic control group (n = 17) received the transplant via open midline laparotomy. The groups did not differ in operation time (median about 60 min): however, animals undergoing midline laparotomy required significantly more opioid pain relief postoperatively than animals implanted with a hepatic vascular access port. Animals after port placement and transplantation had significantly higher blood hemoglobin values than those in the control group, but these values were still in the normal range. In addition to transplantation, the port could be used for administration of biologics and for blood sampling. In all cases, the port remained patent for infusion purposes (median follow-up 336 days, range 62–485 days). Patency for blood sampling was maintained in about half of the animals: the 50% survival of patency for sampling was 255 days. This difference between infusion and sampling patency is most likely due to the location of the catheter tip in the splenic vein, with occlusion caused by the small vessel-to-catheter ratio. We conclude that hepatic vascular access enables long-term frequent administration of cells, medication, or other products and also serves to sample blood: hence, this procedure contributes to a higher level of animal's well-being.

Keywords: :

• blood sampling
• catheter
• conservational refinement
• islet transplantation
• intravenous administration
• nonhuman primate
• vascular access port

Acknowledgments

We would like to acknowledge with gratitude the excellent care of the animals by Angela Craig, Theresa DuFour, Aaron Faig, Jessica Kittredge, and James Munson. The Clinical Pathology Laboratory, University of Minnesota Veterinary Medical Center, is acknowledged for performing hematology and chemistry analysis. Our study was supported by the Schulze Family Foundation, the National Institutes of Health, and the Juvenile Diabetes Research Foundation.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.