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Research

Strain Controlled LVAD Unloading and Cardiac Remodeling in Heart Failure

Funded By National Heart, Lung and Blood Institute (R01 HL 081106, PI: Dr. BP Griffith)

Research - surgeon

Acute cardiac remodeling appears to be an adaptive process of hypertrophy in response to increased LV-loading conditions and stretch with loss of contractility. It becomes maladaptive as the scar expands, LV geometry becomes spherical and normally perfused zones progressively become hypocontractile.

The goal of this project is to relate the amount of strain and reduction with unloading to post MI hypertrophy and impaired EC coupling and apoptosis.

In order to accomplish this goal, we are:

  • Developing an animal model
  • Using sonomicrometry array localization to measure LV regional function
  • Determining biomechanical characterization of the LV using strain mapping
  • Characterizing global LV function with echocardiographic imaging as well as pressure/volume measurements
  • Using molecular biology to study tissue level structure and function
  • Conducting a single cell study to measure myocycte level structure and function

Overview

In spite of new medical therapies and intervention treatments, long-term sequelae of infarction remain a major clinical problem. In the United States, more than a million patients sustain LV injury from infarct annually, and more than five million suffer with heart failure (HF). Acute cardiac remodeling after infarction appears to be an adaptive process of hypertrophy in response to increased LV loading conditions and stretch with loss of contractility. As the scar expands, LV geometry becomes spherical, and normally perfused zones progressively become hypocontractile.

The objectives of this study are to:

  • Predict remodeling after MI using sonomicrometry array localization (SAL) strain maps
  • Show how reduction of LV strain by mechanical unloading using a left ventricular assist device (LVAD) reduces infarct size and remodeling
  • Show how post MI hypertophy and impaired EC coupling and apoptosis is regionally related to strain and reduced with unloading.

Read more about this study.

Integrated Artificial Pump Lungs for Respiratory Failure

Funded By National Heart, Lung and Blood Institute (R01 HL082631, PI: Dr. BP Griffith, R41 HL083621, PIs: B Biancucci (MC3, Inc.), Dr. ZJ Wu (UMB),  R41/42 HL084807, PIs:  Dr. KA Dasse (LEVITRONIX, LLC), Dr. ZJ Wu (UMB))

The goal of this project is to combine biomedical disciplines in new approaches in an effort to design ambulatory wearable artificial pump lungs (APL). The APL will provide for the total respiratory needs of adults with acute and chronic lung failure.

In order to accomplish this goal, we are:

  • Using computational modeling to measure fluid flow field, mass transport and blood damage in the APL
  • Determining design optimization of the APL using multi-objective optimization algorithm
  • Measuring biocompatibility, hemolysis, and platelet and white cell function assay
  • Using digital particle image velocimetry to conduct flow visualization studies of the APL
  • Using rapid prototyping techniques to construct the APL
  • Conducting extensive bench testing and evaluation
  • Developing an in-vivo evaluation of the APL
  • Completing full system integration and control of the APL

Overview

Nearly 344,000 Americans die of lung disease yearly. It is the number three killer in the US. Lung disease costs the American economy $148 billion in total expenditures. While progress for heart disease and cancer, the number one and number two causes of death, have been marked by a significant fall in their rates of death (36.6% for heart disease since 1979), the rate of death from lung disease rose by 19.3%.

Adult respiratory distress syndrome (ARDS) afflicts approximately 150,000 US patients annually, and despite advances in critical-care medicine, ARDS mortality remains between 40% and 50%. Currently available therapies using mechanical ventilation and extracorporeal membrane oxygenation (ECMO) have not been effective and have even proven harmful to some patients. While lung transplantation has become an effective treatment over the past twenty years, fewer than 1000 lung transplants are performed in the United States annually due to the shortage of organ donors.

In our research, we are working to present novel active-mixing pump lungs (AMPL), with the goal of providing total respiratory support to an ambulatory patient.

Our objectives were:

  • To develop computational fluid dynamics (CFD), based on multidisciplinary modeling, to optimize the function and flow field related biocompatibility of the artificial pump lung (APL).
  • To validate the computationally predicted flow characteristics of the APL design in a circulatory flow loop using a glycerol/water solution.
  • To evaluate the function and flow-field biocompatibility of the APL in a circulatory loop using fresh ovine blood and 8-hour in-vivo animal studies.
  • To reduce in-vitro and in-vivo fibrin generation, platelet activation and thrombosis by modifying blood-contacting polymer surfaces on the APL device.
  • To perform 30-day in-vivo ovine experiments to assess the long-term function, biocompatibility and durability of the APL device and its effect on the animal.

Read more about this study.

Pediatric Ventricular Assist Devices

Funded By National Heart, Lung and Blood Institute (NIH/HHSN268200448190C PIs: Dr. R Jarvik (Jarvik Heart), Dr. BP Grifith (UMB))

The goal of this project is to design, develop and test a child- and infant-size model of the Jarvik 2000 heart.

In order to accomplish this goal, we are:

  • Using computational modeling to measure the fluid flow field characteristics
  • Determining design optimization using multi-objective optimization
  • Measuring biocompatibilty – hemolysis, platelet and white cell function assay - in order to optimize rotary blade geometries
  • Using flow visualization techniques (DPIV) to quantify the flow field under steady and pulsatile conditions
  • Developing bench testing methods to characterize the pediatric and infant Jarvik 2000 blood pumps under conditions representative of normal left ventricular myocardial contractility and of severe impairment
  • Conducting long term in-vivo testing and evaluation

Read more about this study.  

Multiscale Dynamics of Shear-Induced Blood Damage and CFD Modeling

Funded By National Heart, Lung and Blood Institute (R01 HL 088100, PI: Dr. ZJ Wu)

The long-term goal of these studies is to develop accurate, robust, and physiologically realistic numerical models capable of predicting the functional characteristics and bio/hemo-compatibility of cardiovascular devices. The models can aid in the development of new designs in order to improve the functional characteristics and bio/hemo-compatibility of the devices.

The specific aims of the proposed project are:

  • Identify the correlation between CFD-derived fluid-dynamic variables (shear stress, exposure time, flow pattern) and blood damage data (platelet activation, thrombosis, and hemolysis) obtained from human patients and animals implanted with ventricular assist devices (VADs).
  • Develop multi-scale in-vitro experimental platforms to investigate the influence of specific fluid dynamic characteristics on blood cell damage. Using these platforms, generate comprehensive databases of flow-induced blood damage.
  • Based on the collective databases of blood damage, develop and implement a validated CFD model of flow-induced blood damage in a biomedical device.