Platelet Activation in Ovines Undergoing Sham Surgery or Implant of the Second Generation PediaFlow Pediatric Ventricular Assist Device

Abstract

The PediaFlow™ pediatric ventricular assist device (VAD) is a magnetically levitated turbodynamic pump under development for circulatory support of small children with a targeted flow rate range of 0.3 - 1.5 L/min. As the design of this device is refined, ensuring high levels of blood biocompatibility is essential. In this study we characterized platelet activation during the implantation and operation of a second generation prototype of the PediaFlow VAD (PF2) and also performed a series of surgical sham studies to examine purely surgical effects on platelet activation. In addition, a newly available monoclonal antibody was characterized and shown to be capable of quantifying ovine platelet activation. The PF2 was implanted in 3 chronic ovine experiments of 16, 30, and 70 days, while surgical sham procedures were performed in 5 ovines with 30 d monitoring. Blood biocompatibility in terms of circulating activated platelets was measured by flow cytometric assays with and without exogenous agonist stimulation. Platelet activation following sham surgery returned to baseline in approximately 2 weeks. Platelets in PF2 implanted ovines returned to baseline activation levels in all three animals, and showed an ability to respond to agonist stimulation. Late term platelet activation was observed in one animal corresponding with unexpected pump stoppages related to a manufacturing defect in the percutaneous cable. The results demonstrated encouraging platelet biocompatibility for the PF2 in that basal platelet activation was achieved early in the pump implant period. Furthermore, this first characterization of the effect of a major cardiothoracic procedure on temporal ovine platelet activation provides comparative data for future cardiovascular device evaluation in the ovine model.

Modern Outcomes of Mechanical Circulatory Support as a Bridge to Pediatric Heart Transplantation

“…Given the known thromboembolic, bleeding, and infectious complications associated with the use of ECMO [19, 20], it raises the question of whether the observed early mortality in the ECMO BTT group would be markedly reduced if durable VAD support were made available to the smallest children requiring MCS as a BTT. A number of devices currently under development [21], including the infant Jarvik 2000 [22] and PediaFlow [23], could help to answer this question if brought to clinical trial.…”

Platelet Activation After Implantation of the Levitronix PediVAS in the Ovine Model

“…Recently, in the ovine model pediatric VAD biocompatibility has been characterized with flow cytometric assays that could detect platelet activation. [6, 15–17] In several of these studies the assays demonstrated sensitivity in responding to animal and pump complications. [16–17] Ovine sham studies were also previously performed to mimic the surgical insult for a VAD implant and demonstrated that the effects of surgery on platelet activation dissipate within approximately two weeks.…”

Experimental Study of Micro‐Scale Taylor Vortices Within a Co‐Axial Mixed‐Flow Blood Pump

“…In turn, decreased exposure will poten- tially mitigate the activation or destruction of cells, and thereby could potentially reduce hemolysis and thrombosis-a known serious adverse event associated with rotodynamic blood pumps. (7).…”