Hemodynamic and left ventricular pressure-volume responses to counterpulsation in mock circulation and acute large animal models.

Alternative therapies for treating heart failure patients are being explored to provide effective options for patients with progressive heart failure. Cardiac assist devices that promote myocardial recovery may be a potential solution. Ventricular assist devices (VAD) have demonstrated long-term efficacy and intraaortic balloon pumps (IABP) have shown short-term successes. In this paper, testing of a hybrid counterpulsation device (CPD) that couples the attributes of device longevity (VAD) with less invasive surgery (IABP) is presented. Hemodynamic and ventricular pressure-volume responses to a 40 ml CPD and 40 ml IABP were evaluated in vitro in an adult mock circulation and in vivo in a large animal heart failure model. The CPD is a flexing diaphragm ventricle with a controlled stroke volume up to 85 cc through a single, valveless cannula. In this study, the CPD was cannulated to the brachiocephalic artery to provide 40 ml of counterpulsation support. The CPD effectively provided diastolic augmentation increasing coronary flow and afterload reduction. These results were comparable to IABP. These preliminary studies suggest that CPD may be an effective therapy for treating patients with early stage heart failure.

HeartMate II left ventricular assist system: from concept to first clinical use.

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): an animal model of human non-insulin-dependent diabetes mellitus.

To further characterize spontaneous diabetes mellitus in cynomolgus macaques (Macaca fascicularis) as a model for human non-insulin-dependent diabetes mellitus (NIDDM), we evaluated the morphologic characteristics of the endocrine pancreas of 4 diabetic and 12 age-matched nondiabetic cynomolgus macaques. In addition, the cDNA-predicted amino acid sequence for islet amyloid polypeptide (IAPP) of this species was determined. Islet amyloid deposits exhibiting typical congophilia and green birefringence were found in 4/4 diabetic animals and in 8/12 nondiabetics. Islet amyloid deposits were significantly more extensive in the diabetic macaques (P = 0.001), in which they occupied a mean of 60% of the islet area. In contrast, in the nondiabetic group the maximum islet area occupied by amyloid was 24% (group mean = 6.8%), with four animals having no detectable islet amyloid. Amyloid deposits consistently showed immunoreactivity for IAPP but not for insulin. Comparisons between group means for diabetic versus nondiabetic macaques showed significantly greater islet area (P = 0.01, 85,390 versus 36,540 microns 2) and significantly greater islet area fraction (P = 0.02, 0.065 versus 0.032) for the diabetic group. The cDNA-predicted amino acid sequence for cynomolgus IAPP was identical to that previously reported for pig-tail macaques (M. nemestrina) and had 92%, 86%, and 84% amino acid sequence identity with human, domestic cat, and murine IAPPs, respectively. These findings support the use of cynomolgus macaques as an animal model of human NIDDM.