Platelet activation, aggregation, and life span in calves implanted with axial flow ventricular assist devices

Snyder, Trevor A.; Watach, Mary J.; Litwak, Kenneth N.; Wagner, William R.

doi:10.1016/s0003-4975(02)03549-x

Cited by 50 publications

(51 citation statements)

References 18 publications

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“…The relative health of the animal makes it possible to elucidate device effects on platelet activation once the effects of the implantation surgery have dissipated. This has previously been demonstrated in comparing platelet activation between calves receiving a rotary VAD and those receiving a sham surgery (15). Platelet activation associated with the sham surgery could be discounted to show that there was ongoing platelet activation in the VAD-implanted calves.…”

Section: Discussionmentioning

confidence: 79%

“…In fact, flow cytometric assays to detect circulating activated platelets were able to discern trends in platelet activation between calves having uneventful VAD implantation periods and calves experiencing thrombotic obstruction of the VAD (15). Flow cytometric assays were also sensitive enough to detect significant differences in levels of circulating activated platelets for different blood-contacting surface coatings in VAD-implanted calves (18).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we have described several flow cytometric assays to quantify circulating activated bovine platelets and platelet microaggregates (14). These assays have been applied to assess circulating activated platelets in calves implanted with rotary VADs (14,15). The results demonstrate the ongoing presence of circulating activated platelets after the effects of surgery (without extracorporeal circulation) have diminished, indicating a level of platelet activation that can be attributed to the VAD (15).…”

mentioning

confidence: 99%

“…These assays have been applied to assess circulating activated platelets in calves implanted with rotary VADs (14,15). The results demonstrate the ongoing presence of circulating activated platelets after the effects of surgery (without extracorporeal circulation) have diminished, indicating a level of platelet activation that can be attributed to the VAD (15). The application of similar assays in ovines can yield a greater understanding of device effects on ovine platelet activation during preclinical testing when design changes may be made at a time of reduced regulatory and economic burden.…”

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confidence: 99%

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Flow Cytometric Assays for Quantifying Activated Ovine Platelets

et al. 2007

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Ovines are a common animal model for preclinical evaluation of cardiovascular devices including heart valves, endovascular grafts, and ventricular assist devices. Biocompatibility is essential to the success of these devices; however, tools to assess biocompatibility in ovines are limited. To address this need, antibodies that bind to activated human and bovine platelets and annexin V protein were evaluated for potential cross-reactivity to activated ovine platelets. These candidate markers were incubated with stimulated and quiescent ovine whole blood, and binding to platelets was quantified by flow cytometry. Several antihuman CD62P antibodies including one polyclonal antibody, three monoclonal antibodies, and annexin V selectively bound to activated ovine platelets. An assay to quantify platelet microaggregates was also developed. The availability of assays to quantify ovine platelet activation can increase the quality of biocompatibility data obtainable during preclinical development of artificial organs in the ovine model, potentially aiding in the evaluation of design refinements to enhance device biocompatibility. KeywordsBiocompatibility; Flow cytometry; Ovine platelets; Cardiovascular devices; Platelet activation Ovines are a common animal model for preclinical testing of blood-contacting cardiovascular devices including mechanical heart valves, endovascular grafts, and ventricular assist devices (VADs) (1-4). A critical aspect in the design of these devices is the evaluation of their blood biocompatibility. Yet, the biocompatibility data that can be obtained in ovine studies is limited due to a paucity of available assays for evaluating circulating blood elements during the implant period. In particular, there has only been one report on the use of flow cytometry to evaluate ovine platelet activation in platelet-rich plasma, and there have been no reports in the literature using such techniques to assess temporal platelet activation in ovines implanted with cardiovascular devices (5).Flow cytometry permits surface expression of platelet activation-dependent epitopes to be quantified, providing insight on circulating platelets not obtainable with platelet aggregometry and plasma assays for β-thromboglobulin and platelet factor 4 (6). Circulating activated platelets have been measured in patients with stents, mechanical heart valves, and VADs as well as in patients suffering from acute myocardial infarction and ischemic stroke [7][8][9][10][11][12][13]. The presence of circulating activated platelets has been suggested as a marker for increased risk of thrombotic complications (10). Previously, we have described several flow cytometric assays to quantify circulating activated bovine platelets and platelet microaggregates (14). These assays have been applied to assess circulating activated platelets in calves implanted with rotary VADs (14,15). The results demonstrate the ongoing presence of circulating activated platelets after the effects of surgery (without extracorporeal circulation) have di...

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Flow Cytometric Assays for Quantifying Activated Ovine Platelets

et al. 2007

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“…Circulating activated platelets were quantified with flow cytometric detection of annexin V (BDPharmingen, La Jolla, CA, USA) binding as previously described (9). Circulating platelet microaggregates, small aggregates consisting of a few to several platelets or platelet-leukocyte microaggregates, were quantified using antibovine CD41/61 (VMRD, Pullman, WA, USA) (10).…”

Section: Platelet Assaysmentioning

confidence: 99%

Blood Biocompatibility Assessment of an Intravenous Gas Exchange Device

et al. 2006

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Abstract:To treat acute lung failure, an intravenous membrane gas exchange device, the Hattler Catheter, is currently under development. Several methods were employed to evaluate the biocompatibility of the device during preclinical testing in bovines, and potential coatings for the fibers comprising the device were screened for their effectiveness in reducing thrombus deposition in vitro. Flow cytometric analysis demonstrated that the device had the capacity to activate platelets as evidenced by significant increases in circulating platelet microaggregates and activated platelets. Thrombus was observed on 20 ± 6% of the surface area of devices implanted for up to 53 h. Adding aspirin to the antithrombotic therapy permitted two devices to remain implanted up to 96 h with reduced platelet activation and only 3% of the surface covered with thrombus. The application of heparin-based coatings significantly reduced thrombus deposition in vitro. The results suggest that with the use of appropriate antithrombotic therapies and surface coatings the Hattler Catheter might successfully provide support for acute lung failure without thrombotic complications.

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Skin Tissue Engineering for Regeneration

Harley

Yannas

2006

Encyclopedia of Medical Devices and Instrumentation

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Skin wounds, particularly burns, affect a large population each year. The injury response to skin wounds depends both of the severity of the wound and the animal affected. The typical organismic response to an injury at the organ‐scale is cell‐mediated wound contraction and synthesis of nonphysiologic tissue (scar); this process is termed repair. Regeneration of lost or damaged tissue describes a process marked by synthesis of physiologic (normal, functional) tissue in the wound site. With increasing organism development, wound closure depends increasingly less on regeneration and correspondingly more on contraction and scar formation. A variety of tissue engineering constructs have been utilized to prevent contraction and scar formation and induce regeneration following skin wounds. Experimental experience has identified a number of specific criteria to maximize the bioactivity of such a graft, leading to maximal regeneration. These criteria as well as the morphology, functionality, and regenerative capacity of the three tissues that comprise skin will be detailed. In addition to the description of the organismic response to skin injuries and the current and historical clinical treatments for such injuries, five specific devices developed to treat severe skin injuries, including the design and manufacture of each device as well as the attendant experimental and clinical successes, will be detailed.

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Platelet activation, aggregation, and life span in calves implanted with axial flow ventricular assist devices

Cited by 50 publications

References 18 publications

Flow Cytometric Assays for Quantifying Activated Ovine Platelets

Flow Cytometric Assays for Quantifying Activated Ovine Platelets

Blood Biocompatibility Assessment of an Intravenous Gas Exchange Device

Skin Tissue Engineering for Regeneration

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