Does cognition improve following LVAD implantation?

BACKGROUND: Studies of cognition after LVAD surgery have produced mixed results. To explore whether cognition would improve, decline, or remain stable after LVAD surgery, we examined cognition before and 1- and 3-months after LVAD surgery. Patients with post-surgical stroke were excluded. METHODS: 28 subjects (mean age = 54.31 ± 12 years) comprised an observational case series from the DuraHeart LVAS device® trial. Cognitive testing was performed at baseline, 1-month, and 3-month post-surgery, and included tests of attention, memory, language, visualmotor speed (TMT) and visualconstruction. RESULTS: No difference in cognition was found between baseline and 1-month exams (means z score improvement = 0.06, p = 0.43) but cognition improved significantly between baseline and 3-month exams (mean z score improvement = 0.34, p < 0.00001). Examination of individual test scores found, after correction for multiple comparisons, only the TMT variable was significantly different at the 3-month exam. CONCLUSIONS: We found significantly improved cognition 3 months after LVAD surgery in a subset of patients without post-surgical stroke. The reasons for the lack of cognitive improvement at the 1-month post-surgical assessment may include ongoing medical and physiological disruptions in the immediate post-operative period. Further research into the sources of delayed improvement is warranted. Cognitive assessments performed immediately after surgery should be interpreted with caution because the results may not reflect longer term cognitive outcomes. LVAD patients may require additional support to successfully manage their health in the weeks immediately following surgery but assistance needs may decrease over time.

Development of standard tests to examine viscoelastic properties of blood of experimental animals for pediatric mechanical support device evaluation.

We investigated the applicability of measuring the viscoelasticity of bovine, ovine, and porcine whole blood for the evaluation of sublethal damage to red blood cells (RBCs). An increase in blood viscosity and elasticity without changes in hematocrit and plasma viscosity would signify a decrease in RBC deformability. Blood viscoelasticity was assessed using a Vilastic Scientific viscoelastometer. Due to the natural absence of RBC aggregation and small RBC size in normal bovine and ovine blood, viscoelastic properties are less readily detected. However, we found that adjustment of blood hematocrit to a standard level of 40-50% allows for sensitive assessment of viscoelasticity in these blood types demonstrating a marked non-Newtonian behavior mostly related to RBC deformability. Porcine blood showed a pronounced non-Newtonian behavior at all tested hematocrit values, which makes it rheologically comparable to human blood. Both viscosity and elasticity were elevated after blood exposure to a uniform mechanical stress. RBCs rigidified by heat exposure demonstrated a loss of viscoelasticity dependence on shear rate. Measurements of blood viscoelasticity can be meaningful in bovine, ovine, and, especially, porcine blood, and can be used for evaluation of sublethal blood damage during in vitro and animal trials of heart-assist devices.

Lessons learned from the first fully magnetically levitated centrifugal LVAD trial in the United States: the DuraHeart trial.

BACKGROUND: The DuraHeart is a continuous centrifugal-flow left ventricular assist device that uses active magnetic levitation for impeller positioning designed for improved hemocompatibility and durability. This study reviews the results of the US trial with specific attention to hemolysis, thrombotic complications, and pump failure. METHODS: The US SUSTAIN trial was a multicenter, prospective, single-arm observational study in advanced heart failure patients listed for transplantation. Follow-up was complete in 100% of the patients at 6 months. RESULTS: Sixty-three patients were enrolled at 23 centers. Forty-six patients (73%) reached the primary end points of survival to transplantation, alive on the original device at 180 days and listed for transplantation, or explant for recovery. Median duration of support was 267 days (range, 10 to 952 days) with a total support time of 46 patient-years. There was no clinical hemolysis reported during the study. Mean lactate dehydrogenase values peaked at day 4 and significantly decreased during support (435±236 U/L and 297±142 U/L on day 3 and day 180, respectively). There were no cases of pump thrombosis reported, and 3 cases of pump thrombus "in transit" (0.06 events/patient-year) were observed. There were 6 (10%) cases of magnetic levitation system failure, all secondary to cable wire fractures (0.12 events/patient-year). All patients were hemodynamically stable with the backup hydrodynamic mode. Major adverse events included gastrointestinal bleeding (0.52 events/patient-year), ischemic and hemorrhagic strokes (0.17 events/patient-year and 0.09 events/patient-year, respectively), and driveline infections (0.67 events/patient-year). CONCLUSIONS: The DuraHeart demonstrated good hemocompatibility; however, the reliability of full magnetic levitation systems should be a high priority in future pump designs.

Drag-reducing hyaluronic acid increases survival in profoundly hemorrhaged rats.

We tested the hypothesis that the infusion of a small volume of a drag-reducing polymer (DRP) solution can prolong survival in rats subjected to lethal hemorrhagic shock (HS; shed 51% of estimated blood volume) in the absence of complete resuscitation with fluids or blood. In this set of experiments, we used a newly designed mixture of hyaluronic acid (molecular weight, approximately 2.0 x 10 d; 0.4 mg/mL) and polyethylene oxide (molecular weight, approximately 4 x 10 d; 0.05 mg/mL) dissolved in sterile phosphate-buffered saline. Anesthetized rats were subjected to a volume-controlled HS. During the first 20 min, blood (21.7 mL/kg) was withdrawn. During the next 40 min, additional blood (14 mL/kg) was withdrawn, and during the final 20 min, saline vehicle or saline + DRP (2.8 mL/kg) was simultaneously infused. The survival rate of the rats treated with the hyaluronic acid/polyethylene oxide was significantly higher (P < 0.01). The mean survival times for control and DRP-treated animals were 100.4 +/- 9.5 vs. 154.8 +/- 7.0 min (P < 0.001). MAP was higher (P < 0.005) and skin perfusion was significantly improved in the DRP-treated group after the end of the DRP infusion. These results support the use of nanomolar concentrations of DRP to prolong survival in rats after lethal HS in the absence of fluid resuscitation. The DRP formulation studied here warrants further evaluation for the amelioration of critical illness associated with profound shock when access to resuscitation fluids may not be possible or delayed.

Intravenous injections of soluble drag-reducing polymers reduce foreign body reaction to implants.

We tested whether soluble viscoelastic drag-reducing polymers (DRPs), which modify blood flow in the macro- and microcirculation, affect host response to implanted biomaterials and control biodegradation and tissue ingrowth processes. Porous poly(L-lactate) (PLLA) implants, which are naturally hydrolyzed by foreign body giant cells, were used to evaluate differences in host response. Intravenous DRPs, high-molecular weight poly(ethylene oxide) (PEO) or poly(mannose) (PMNN), were given biweekly at 0.3-0.4 nM in saline (equivalent volumes of saline in controls) to rats with subcutaneous PLLA implants. After 7 weeks, there was no difference in weight gain or behavior between control and DRP-injected groups. Implanted PLLA scaffolds in controls were almost totally degraded and replaced by giant cell granulomas. On the contrary, PEO- or PMNN-treated animals retained a significant part of the implanted scaffold (p < 0.0001 vs. controls). The foreign body reaction was markedly decreased, and there was an increase in well-oriented collagen deposition within the implanted scaffold area in the animals treated with DRPs. The DRP-mediated effects observed in this study potentially reflect alteration in inflammatory events in response to implanted bioengineered materials, and, thus, warrant further investigation.

Poly(N-vinylformamide)-A drag-reducing polymer for biomedical applications.

Water-soluble drag-reducing polymers (DRPs) were previously demonstrated to significantly increase blood flow, tissue perfusion, and tissue oxygenation when injected intravenously at nanomolar concentrations in various animal models. Turbulent flow drag-reducing ability was proven to be the most important factor defining the potential of polymers to favorably affect blood circulation. Several DRPs were applied in previous in vivo tests, but the search continues for suitable DRPs for biomedical applications. We demonstrated that poly(N-vinylformamide) (PNVF) with a molecular weight of 4.5 x 10(6) Da significantly reduced resistance to turbulent flow in a pipe and thus presents a DRP. We also found that the PNVF mechanical degradation is much slower than that of the most commonly used DRP, poly(ethylene oxide). PNVF is known to have low toxicity. Furthermore, our pilot in vivo study showed that PNVF had acceptable biocompatibility and hemodynamic effectiveness and thus could be considered as a DRP candidate for potential clinical use.