Effect of semi-invasive cardiovascular monitoring on the perioperative outcome of kidney or lung xenotransplantation in cynomolgus monkeys

>Background:

Cynomolgus monkeys (Macaca fascicularis) are one of the predominant primate models in experimental transplantation. Particularly in xenotransplantation experiments, they can be subjected to profound cardiovascular instability by surgical trauma, volume shifts and inflammatory mediator release. Meticulous perioperative management including deliberate intraoperative monitoring is therefore required.

Methods:

26 porcine kidneys (group A) and 3 single lung lobes (group B), obtained from unmodified pigs or from pigs transgenic for human complement regulators, were transplanted into 29 cynomolgus monkeys. In group A₁ (n = 11) the monkeys were monitored intraoperatively by ECG, non-invasive arterial, and central venous blood pressure (standard cardiovascular monitoring, SCVM). In group A₂ (n = 15) measurements of cardiac output (CO), intrathoracic blood volume and extravascular lung water (extended cardiovascular monitoring, XCVM) were added to the intraoperative monitoring regime. XCVM plus continuous pulse contour CO was used in the 3 monkeys undergoing porcine single lung xenotransplantation. Results: In group A₂ significantly more animals had initial graft function if compared to group A₁. 40% of the monkeys of group A₂ but 73% of group A₁ died within the first postoperative week. Group A₂ displayed a trend towards greater overall survival rates, but this difference did not reach statistical significance (p = 0,07). In group B stable lung xenograft reperfusion was achieved in all 3 recipients despite recurrent phases of severe cardiovascular instability. Two lung recipients could be weaned from the ventilator, and 1 monkey survived more than 24 hours postoperatively.

Conclusions:

The application of XCVM in small primates undergoing kidney xenotransplantation led to significantly better early postoperative results and longer survival times. In single lung xenotransplantation XCVM plus continuous pulse contour CO showed to be indispensable for the therapeutic management of the profound cardiovascular instabilities observed. Our data indicate that comprehensive anaesthesiologic monitoring can contribute substantially to the advancement of experimental organ transplantation in small monkeys.