The Ins and Outs of Using ECMO and VAD in Preclinical Studies

• Spinning tube-based system that requires ~3ml of blood per sample
• In our experience, I-Stat generally records slightly lower ACT values comparatively, but has much more consistent value
• Makes tracking ranges simpler between animals
• Not specifically tied to individual animal baselines
• The hemochron system records slightly higher values, but can vary in value range more dramatically from sample to sample
  
  

  Target Range

  1) This is defined in the GLP protocol. There are two common methods: 1) Set the range to 1.5x to 2.0x baseline ACT value for each animal

  • Specifically set for each animal

  • Highly dependent on initial baseline reading

  • Makes tracking ranges between multiple animals more challenging
  
  

  2) Set range (e.g. 200 seconds to 350 seconds)
  

• Monitored by manual hematocrits, clinical pathology, and plasma-free hemoglobin

• Reducing or halting heparin CRI can often reverse some anemia, but increases the risk or clotting

Blood donation from a naive animal, if allowed, in protocol and an emergency condition can be helpful

Challenges of the ICU Model 

Projects of this scope are some of the most challenging undertakings a preclinical laboratory can assume. 24-hour ICU care run at a GLP-compliant lab can be a costly and extensive use of staff and resources. Example: 12-animal, 21-day study.

• Requires 42, 12-hour shifts with 4 staff members per shift
• Totals a minimum of 2,016 skilled labor hours while maintaining GLP compliance and ensuring the welfare of the animals
• Remember to add in time for a study director, veterinarian, quality assurance, etc.
  
  

Potential Clinically Adverse Effects

1. Anemia - due to prolonged circuit therapy, numerous blood samples or anticoagulation

2. Hemorrhaging/Hematomas – at vascular access sites

• More common in jugular or carotid access sites with anticoagulation running compared to retroperitoneal or thoractomy
• Treatable in most cases with pressure bandages or manual draining

3. Infections

• More common in retroperitoneal or thoractomy access sites

• Despite best efforts, these surgical accesses are not 100% sealed to bacterial ingress along the tubing/drive lines

• Access sites are cleaned daily

• Temperature and SOAP exams are typical first signs

• Antibiotics are typically given for ~3 days post-operatively

• Antibiotics could be given continuously, but calves and sheep with prolonged antibiotics can have digestive issues and the study should not mask potential GLP safety issues by blanketing antibiotics without clinical indicators

4. Clotting – in the tubing, oxygenator, pump, or other parts of the circuit

• Although certain parts may be replaceable, some are not or would be considered failed endpoints by the GLP protocol

• Some fibrinous growth in tubing and oxygenator is often expected and typical as long as it does not hinder or occlude flow and does not break off as it would be later found in downstream organs

5. Thrombus – resulting in stroke, cardiac arrest, or pulmonary embolism - Very few treatment options, typically resulting in an early mortality or early termination

6. Acute Interstitial Pulmonary Emphysema – also known as interstitial pneumonia (AIP)

• Common cause of sudden respiratory distress in cattle

• Sudden onset of clinical signs with minimal coughing and severe difficulty breathing similar to an asthma attack

• Affected animals often die despite supportive treatment

• Bubble-like appearance of lungs is an indication at necropsy

Are you pursuing an ECMO/VAD device? Veranex' team of industry leading preclinical professionals have deep experience in cardiovascular preclinical studies, GLP and non-GLP. Collectively the team has supported over 100 regulatory submissions returned with no questions asked.