Application of telemetry system in xenogeneic cardiac transplantation using a heterotopic thoracic model

Xenotransplantation is thought to have the potential to solve the
critical shortage of donor’s hearts with the development of
genetically modified organ-source pigs and improvement of
immunosuppressive strategies. As an appropriate preclinical animal
model, the pig-to-baboon cardiac xenotransplantation model has been
widely adopted. Traditionally, the evaluation of cardiac xenograft
function in a pig-to-baboon model has been accomplished by means of
palpation, ultrasound and biopsy. However, those methods pose
increased risk of complications such as bleeding, infection, and
apnea, leading to increased morbidity and mortality. Telemetric
monitoring systems have been widely applied in the life science
research involving a wide variety of animal models. These systems
enable non-invasive, reliable and continuous measurements of
cardiac xenograft function and provide information valuable for the
improved understanding of transplantation pathophysiology.
Importantly, these systems do not only avoid repeated anesthesia of
the animals but also allow measurements independent from the
effects of anesthetics. In preclinical pig-to-baboon
xenotransplantations, telemetry systems have only been used in the
heterotopic abdominal experiments. The aim of this study was the
evaluation of a telemetry system for the monitoring of cardiac
xenograft function after heterotopic thoracic cardiac
xenotransplantation. Seven baboons underwent heterotopic thoracic
cardiac xenotransplantation, for which double or triple transgenic
pigs were used as donors. Hemodynamic parameters such as left
ventricular peak systolic pressure (LVPSP), left ventricular end
diastolic pressure (LVEDP), heart rate (HR), maximal rate of rise
or decline of left ventricular pressure (±dP/dtmax), deviation of
S-T segment, and the duration and amplitude of QRS complex in
electrocardiogram (QRSA) were continuously monitored, using a
telemetry system (DSI, St. Paul, MN, USA). Postoperatively, the
serum levels of anti-pig antibodies (APA) were analyzed using a
hemolytic assay with pig erythrocytes and the serum level of
troponin was determined by the clinical laboratory on a daily
basis. Based on the changes of troponin levels and APA levels, the
baboons were grouped into elevated and unelevated. All parameters
were compared between groups and between days. During the last two
days of their survival, LVPSP, HR, +dP/dtmax, -dP/dtmax and QRSA
were significantly lower in the baboons with elevated troponin
compared to the group with unelevated troponin. Regarding
specifically the group of baboons with elevation of troponin, the
following observation was made: LVPSP, HR, -dP/dtmax, and QRSA
decreased significantly on the day elevation of troponin was
observed and the next day. In addition, The decrease of the
parameter +dP/dtmax was significant one day after troponin
increased. In contrast, the analysis of the group of baboons with
elevated anti-pig antibodies revealed no significant changes in
hemodynamic or electrocardiographic parameters before and after the
rise of antibodies. In conclusion, this study demonstrates the
ability of the telemetry system to assess changes in xenograft
function in the heterotopic thoracic pig-to-baboon cardiac
xenotransplant model. In particular, the parameters LVPSP, HR,
±dP/dtmax and QRSA are perceived to be reliable indicators of
myocardial damage associated with graft rejection at an early stage
following cardiac xenotransplantation. The use of the telemetry
system might help to guide immunosuppressive therapy and further
improve graft survival in future experiments.