Left ventricular pressure measurement by telemetry is an effective means to evaluate transplanted heart function in experimental heterotopic cardiac xenotransplantation

Abstract

Evaluation of the function of heterotopic cardiac transplants has traditionally been accomplished by either manual palpation or serial biopsies. Both methods have drawbacks. Palpation can be difficult to differentiate a pulse from the graft versus a transmitted pulse from the native aorta. Serial biopsies, though accurate, require multiple laparotomies, leading to increased morbidity and possibly mortality rates. In this study we used an advanced telemetry system, consisting of an intra-abdominal implant, that was capable of continuously monitoring simultaneously several parameters of the transplanted heart and the status of the recipient. In a large animal model of heterotopic cardiac xenotransplantation (pig donor to baboon recipient), we implanted the device in 12 animals: 8 with and 4 without immunosuppression. We monitored and continuously recorded the left ventricular pressure (both peak-systolic and end-diastolic [LVEDP]), heart rate, and the electrocardiogram pattern of the transplanted heart as well as the temperature of the recipient. The left ventricular pressure proved to be the most valuable parameter to assess graft heart function. In the 4 nonimmunosuppressed cases, grafts were rejected acutely. In these cases, the end-diastolic pressure increased sharply and the heart stopped contracting when the difference between the systolic and the diastolic pressure decreased to <10 mm Hg. The earliest reproducible sign of rejection was an increased LVEDP. Among long-term survivors, the increase in diastolic pressure was gradual, indicating progressive thickening of the myocardium and decreased compliance of the ventricle. Six of 8 immunosuppressed animals died of other complications before rejecting the transplanted heart. The telemetry was also helpful to indicate early onset of fever in the recipients, thus allowing us to intervene early and prevent potentially lethal septic complications. Continuous monitoring of several parameters via telemetry allowed detection of changes associated with rejection as well as other complications at an early stage, allowing prompt intervention, treatment, and possibly reversal of rejection.

Fig 1

Direct view of the monitor, displaying continuous measurement of graft function by telemetry. Readings from 2 transplanted pig cardiac xenografts and recipient baboons are shown. The parameters include left ventricular peak-systolic pressure (PEAK_1, PEAK_2), end-diastolic pressure (END_1, END_2), heart rate (LVHR_1, LVHR_2), and recipient temperature (MEAN_1, MEAN_2).

Fig 2

Telemetry interpretations of normal and rejected cardiac xenografts: A. Normal LVP and ECG readings. B. Loss of graft function indicated by abnormal LVP and ECG readings.

Fig 3

Representative telemetry recordings from 1 baboon with long-term surviving cardiac xenograft. A. LVHR, PEAK, and END recordings of the graft function over 6 months. B. Temperature recording over 6 months.