John P. Kerrigan

An intraventricular axial flow blood pump integrated with a bearing purge system

The future development of implantable axial flow blood pumps must address two major issues: mechanically induced hemolysis and shaft seal reliability. The recent revisions to our miniature intraventricular axial flow left ventricular assist device (LVAD) were aimed particularly at addressing these concerns. To improve hemocompatibility, a new impeller has been designed according to the following criteria: 1) gradual pressure rise along the blade chord; 2) minimized local fluid acceleration to prevent cavitation; 3) minimum surface roughness; and 4) radius edges. Subsequent in vitro hemolysis tests conducted with bovine and ovine blood have demonstrated very low hemolysis (normalized index of hemolysis = 0.0051 +/- 0.0047 g/100 L) with this new impeller design. To address the need for a reliable seal, we have developed a purged seal system consisting of a miniature lip seal and ceramic pressure groove journal bearing that also acts as a purge pump. Several spiral grooves formed on the bearing surface provide viscous pumping of the purge fluid, generating more than 3,000 mmHg at 10,000 rpm. This purge flow flushes the lip seal and prevents blood backflow into the bearing. We have found this purge pump to offer several advantages because it is simple, compact, durable, does not require separate actuation, and offers a wide range of flow, depending upon the groove design. In vivo animal tests demonstrated the potential of the purged seal system.

Dynamic systemic vascular resistance in a sheep supported with a Nimbus AxiPump.

Changes in systemic vascular resistance (SVR) in response to diminished pulse perfusion were analyzed over a dynamic range of flow conditions. An axial flow LVAD (Nimbus AxiPump, Rancho Cordova, CA) was implanted in a sheep for 28 days, during which time SVR was determined over several conditions of posture and excitability. Total arterial resistance (TR) was calculated dynamically as an index of SVR by analysis of pump flow in diastole, and systemic pressure estimated from the characteristic pressure-flow-speed relation of the AxiPump. TR was evaluated over a range of flow rates, including maximum flow--for which the pressures and flows were essentially nonpulsatile. Throughout the course of support, and independent of pulsatility, TR dropped when the sheep stood and was significantly lower than that in the sitting position (P < 0.01). Response to excitement followed the same trend: TR was significantly higher during agitation than during normal temper (P < 0.01). In spite of changes in pulse pressure and flow rate, SVR changes occurred according to expected physiologic responses for pulsatile perfusion. Because pump flow and pressure are sensitive to afterload, the results of these studies suggest that pump speed control must compensate for changes in SVR to maintain acceptable perfusion.

In vivo evaluation of the Nimbus axial flow ventricular assist system. Criteria and methods.

Continuing in vivo trials are being conducted at the University of Pittsburgh using the Nimbus axial flow blood pump (AxiPump). To date, 14 sheep experiments have been performed to address several issues related to short-term support. Six acute experiments (< 6 hr) have been performed to assess hemodynamics related to speed regulation and to determine anatomic placement of the pump and cannulae. Eight short-term survival studies lasting up to 6 days have been performed to evaluate biocompatibility and system reliability, and to establish clinical management protocols. The AxiPump has been used as a left ventricular assist device (LVAD), right ventricular assist device (RVAD), and biventricular assist device (BiVAD) with left ventricular and right atrial cannulation. The AxiPump has demonstrated the ability to assume complete support of either the pulmonary or systemic circulation, or both. We have determined that sufficient surgical access may be obtained through left lateral thoracotomy for both LVAD and RVAD insertion. In the absence of post operative anticoagulation therapy, we have detected subclinical renal cortical infarctions in 6 of 8 short-term animals. Thrombus deposition has been observed at the ventricular cannula tip in 4 of 8 cases--necessitating design changes. Two short-term experiments have been terminated because of bleeding--one due to inflow cannula obstruction and one due to cannula failure. Plasma free hemoglobin levels were all below 15 mg/dl, except for one case complicated by inflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

High‐Resolution Fluorescent Particle‐Tracking Flow Visualization within an Intraventricular Axial Flow Left Ventricular Assist Device

Flow visualization is typically applied in blood pump development to both confirm the design expectations and identify regions that may be predisposed to blood element deposition and trauma. Rotary pumps, in particular, place high demands on the technique chosen to visualize the flow given the limited visual accessibility of the flow path and the high impeller speeds. Fluorescent image-tracking velocimetry currently is used at the University of Pittsburgh Medical Center to visualize flow accurately inside of these pumps both qualitatively and quantitatively. Flow patterns under steady conditions within an intraventricular axial flow, left ventricular assist pump (prototype No. 7, SUN Medical Technology Research Corporation, Nagano, Japan) were investigated using this technique. The flow fields at the impeller-stator interface and at the pump outlet were given specific attention. This allowed the assessment of the fluid dynamics throughout the hydrodynamic design limits of the pump.

Effect of perfluorochemical emulsion on blood trauma and hemorheology

One of the major problems of development and improvement of heart assist devices is the reduction of blood cell damage. The extremely high levels of shear stress, turbulence, prolonged contact between blood and foreign surfaces, and other abnormal hydrodynamic circumstances have been shown to cause hemolysis, activation of platelets, and changes in mechanical properties of red blood cells. Hemolysis, in turn, can drastically increase red blood cell aggregation at low shear conditions. A new pharmacologic approach to reduce blood trauma and improve rheologic properties of blood subjected to mechanical stress was investigated. These experiments showed that the replacement of 20% of the plasma volume with Fluosol (Alpha Therapeutic Corp., Los Angeles, CA), a perfluorochemical that transports oxygen, reduced mechanical fragility of human (P < 0.01) and ovine (P = 0.054) red blood cells by approximately 30%. The same replacement of plasma with Fluosol reduced hemolysis (plasma free Hb) by approximately 40% compared to control (P < 0.05) during in vitro pumping of blood with a centrifugal pump. A 20% replacement of plasma volume with Fluosol remarkably reduced low shear blood viscosity (from 31.9 +/- 6.1 to 18.2 +/- 4.8 cP, for shear rate gamma = 0.277 sec-1) and erythrocyte sedimentation rate (from 16.7 +/- 9.2 to 3.1 +/- 3.1) mm/hr) in human blood. Decrease of these parameters indicates the reduction of red blood cell aggregation. Results of this study demonstrate the potential feasibility of Fluosol to improve mechanical properties of blood in patients with heart assist devices.

Fluorescent image tracking velocimetry of the Nimbus AxiPump.

High shear rates and extended residence times causing hemolysis and platelet activation can develop in an assist pump or cannula when inferior flow conditions exist. The high volume output of a miniature axial flow pump presents challenges in avoiding these adverse conditions. To assess the hemodynamics within the continuous flow Nimbus Axi-Pump, vector flow fields inside a translucent inflow cannula and a modified 12 mm AxiPump were mapped. Fluorescent image tracking velocimetry was used to track the motion of neutrally buoyant fluorescent particles (30 microns) using pulsed laser light, high resolution video cameras, and computer image analysis. An acrylic pump housing and cannula were integrated into a mock circulatory loop filled with a Newtonian, optically clear blood analog fluid. The flow parameters were controlled to yield known, physiologic loading conditions, including varying degrees of pulsatility. Cannula flow visualization results exhibited critical recirculation patterns at the bend. These results will be used to further optimize the design of the inflow. Particle impact was seen at the pump inlet in the inducer region of the rotor. Very good attachment of flow from the rotor to stator was observed when the pump operated at normal operating speeds. Intermittent regurgitant flow fields were evident in the presence of increased pulsatility and low pump speed. These results have lead to improvements in impeller design and speed control criteria to avoid potential deleterious flows.

Effect of pulsatility and hemodynamic power on recovery of renal function.

Circulatory assist devices are used to treat patients awaiting cardiac transplantation to preserve life as well as to permit recovery of end-organ function. The efficacy of pulseless perfusion versus pulsatile perfusion in the recovery of end-organ function has not been fully determined. In this study, the efficacy of pulseless perfusion compared to pulsatile perfusion on the recovery of renal function after a 30 min period of normothermic ischemia was examined. Pigs were randomly assigned to four groups. In all groups, acute renal ischemia was induced by clamping both renal arteries for 30 min. Reperfusion for 120 min was performed using either pulsatile perfusion or pulseless perfusion at 65 +/- 1.6 mm Hg (Groups I [pulsatile] and II [pulseless]) and at 40 +/- 1.1 mm Hg (Groups III [pulsatile] and IV [pulseless]). After reperfusion, renal blood flow, hemodynamic power (pressure * flow: hemodynamic power), oxygen consumption (VO2), tissue ATP, and urine output (UO) in Groups I, II, and III were significantly higher than in Group IV (p < .01 by ANOVA). Histopathologic examinations were not significantly different between groups. Under hypotensive conditions, pulsatile perfusion improves hemodynamic power delivery to the organ compared to pulseless perfusion. These results suggest that a pulseless pump is acceptable as an assist device when normal flow or perfusion pressure is maintained.

The Pittsburgh experience: Biomechanics and testing of total artificial hearts and ventricular assist devices

Since 1985, the University of Pittsburgh has maintained one of the world’s most active clinical programs in mechanical circulatory support (MCS) as a bridge to cardiac transplantatm of this number, 53 patients were discharged (82%). An even higher percentage of the Novacor LVAS patients who were transplanted (n=37) were ultimately discharged home (n=33,89%).

Bearing Seizure in a Rotational Blood Pump: Mechanism and Potential Solutions

A critical issue facing the development of an implantable, rotational blood pump is the maintenance of an effective seal at the rotating shaft while preventing seizure of the bearing gap. Pump failure due to occlusion of the bearing gap was hypothesized to be related to the adhesion and aggregation of blood proteins that diffuse into this space. To determine the protein responsible for this occlusion and possible means to prevent this effect, a series of isolated bearing experiments were conducted in vitro, using physiologic solutions of albumin, globulin, and fibrinogen. The annular journal bearing used in these studies incorporated several spiral grooves which provided viscous pumping of the purge fluid through the bearing annulus. Protein denaturation in the bearing gap was evaluated by analyzing the effluent that was pumped out of the bearing. Of the proteins studied, only fibrinogen was found to induce bearing seizure. Spectrophotometric and microscopic examination indicated that bearing seizure was due to the adhesion and aggregation of heat-denatured fibrinogen onto the bearing surface. Such quasi-polymerized fibrinogen generates critical friction, which seizes the bearing. This finding is supported by earlier work demonstrating fibrinogen aggregation via interactions of D-domains of fibrinogen upon exposure to temperatures in excess of 50°C. To prevent bearing seizure, three techniques are suggested: (1) we demonstrated that the peptide GPRP which binds to the fibrinogen D-domain, raised the temperature of denaturation by 3.5°C and thus could be beneficial if added to the purge fluid; (2) we also found that the addition of thermostable proteases from thermophilic bacteria, which profeases degrade fibrinogen, was remarkably effective in preventing bearing seizure; and (3) the device could be redesigned in the future to provide greater heat radiation efficiency and to maintain the temperature in the bearing gap below 50°C.

Low Hemolytic Intraventricular Axial Flow Blood Pump Integrated with Totally Implantable Bearing Purge System

Future development of implantable axial flow blood pumps must address two major issues: mechanically induced hemolysis and shaft seal reliability. Recent revisions of the design of our miniature intraventricular axial flow left ventricular assist device (LVAD) were aimed particularly toward addressing these concerns. To improve hemocompatibility, a new impeller (13.5-mm diameter) has been designed according to the following criteria: (1) gradual pressure rise along the blade chord, (2) minimized local fluid acceleration to prevent cavitation, (3) minimum surface roughness, and (4) radiused edges. Subsequent in-vitro hemolysis tests conducted with bovine and ovine blood have demonstrated very low hemolysis (normalized index of hemolysis, 0.005 ± 0.002 g/1001) with this new impeller design. These studies were conducted for 4h at 37°C, with an impeller speed maintained between 10000 and 11 000 rpm, providing a flow rate of 4–51/min against a 90–100 mmHg afterload. To address the need for a reliable seal system, we have recently developed an implantable purge system consisting of a miniature lip seal and a ceramic pressure-groove journal bearing (7 × 10mm). Several spiral grooves formed on the bearing surface provide viscous pumping of the purge fluid, generating over 3000 mmHg at 10000 rpm. This purge flow flushes the lip seal and prevents blood back-flow into the bearing. We have found this purge pump to offer several advantages, since it is simple, compact, durable, and does not require separate actuation. These recent developments with our device provide additional promise towards realizing a totally implantable purged axial flow LVAD.