In vivo evaluation of the biocompatibility of the totally implantable ventricular assist device (HeartSaver VAD).

A series of multicenter in vivo studies have been conducted to assess the biocompatibility and device performance of the HeartSaver VAD, a totally implantable pulsatile ventricular assist device (VAD). The experiments (n = 23) were conducted in calves with a mean weight of 101 (75-152) kg. Implants took place at four centers using two different surgical procedures of implantation (one with cardiopulmonary bypass and one without). Three anticoagulation regimens were used (one with continuous intravenous heparin, one with oral warfarin, and one with oral warfarin combined with antiplatelet clopidogrel therapy). Device function and biochemistry were monitored during the study, and organs and device analysis were conducted at explant. There were six nonsurvivors because of early surgical complications (during the first week of support). The postoperative courses in the remaining 17 (74%) calves were uneventful. Hemodynamic and biocompatibility indicators were monitored throughout the study. The mean duration of device support for those cases was 48 (13-92) days. Mean device flow was 7.15 (+/- 1.68) L/min. There were no deaths caused by infection; however, two animals developed endocarditis believed to be caused by the percutaneous instrumentation lines used for the study. No severe bleeding requiring reoperation occurred during the study. The mean plasma free hemoglobin was within normal limits at 6.8 +/- 2.6 mg/dl. Renal and hepatic functions were normal with a mean creatinine of 0.6 +/- 0.1 mg/dl and a mean aspartate aminotransferase of 68.7 +/- 42.6 mg/dl. Several device related improvements were identified and have now been implemented. Additional bovine implants with an optimized device are currently underway in preparation for human trials.

The monkey (Macaca fascicularis) heart neural structures and conducting system: an immunochemical study of selected neural biomarkers and glutamate receptors.

The neural markers, protein gene product 9.5 (PGP 9.5), neurofilaments (NF) and glutamate receptors (GluRs) were visualized by immunohistochemistry in the monkey heart. PGP 9.5 showed the greatest affinity for intramural ganglia cells and nerve fibres. Structural components of the conducting system were also stained, particularly the bundle of His, AV node and Purkinje fibres. Anti-NF 200 and NF 160 showed strong, preferential affinity to nerve fibres and ganglia throughout the heart. Further studies concentrated on the presence and the distribution of glutamate receptors: NMDAR 1, GluR 1, GluR 2/3, GluR 5/6/7, mGluR 2/3, and mGluR 5. Positive immunoreactivity of GluRs was evident in nerve terminals within the atrium, myocardium, intramural ganglia and elements of the conducting system. The intensity of the stain varied for each antibody according to the anatomical distribution within neural structures and conducting system. The specificity of immunolabelling was confirmed by absorption studies with each corresponding peptide. There is preferential affinity to and differential distribution of staining with PGP 9.5, NFs and several subtypes of GluRs in the various components of the cardiac conducting system in adult monkeys. The expression of specific neural markers and glutamate receptors common to nerve fibers and ganglia cells is consistent to our previous report in rodents. These expressions suggests that such structures in the heart share common characteristics with a variety of neural tissues and hence are potential targets for neurotoxins. Furthermore, the strong affinity and specific distribution of several subtypes of GluRs in the monkey heart fosters our view that these receptors may be able to influence the physiology and pathophysiology of cardiac rhythm and excitation. Hence as in the brain, the GluRs may be involved in the mediation of excitatory effects in the heart.