Calves chronically implanted with a total artificial heart as a pharmacological model

Area of Science:

• Cardiovascular Pharmacology
• Medical Device Technology
• Animal Models in Research

Background:

• Congestive heart failure (CHF) pharmacotherapy often involves drugs with combined inotropic and vasoactive properties.
• Distinguishing between inotropic and vasoactive drug effects can be challenging in standard models.
• Myocardial influence complicates the assessment of pure vascular responses to vasoactive agents.

Purpose of the Study:

• To evaluate the utility of a total artificial heart (TAH) animal model for studying drug vasoactive effects.
• To investigate the isolated vascular responses to commonly used vasoactive drugs in a TAH model.
• To assess the sensitivity of the TAH model to changes in preload and afterload.

Main Methods:

• Four instrumented calves with implanted total artificial hearts (TAHs) were utilized.
• Vasoactive drugs including epinephrine, dopamine, isoproterenol, and nitroprusside were administered.
• Vascular resistance changes (Systemic Vascular Resistance - SVR, Pulmonary Vascular Resistance - PVR) were measured and compared to control conditions.

Main Results:

• Epinephrine administration resulted in a significant increase in Systemic Vascular Resistance (SVR).
• Dopamine administration led to a significant increase in Pulmonary Vascular Resistance (PVR).
• Isoproterenol administration caused a significant decrease in Pulmonary Vascular Resistance (PVR).

Conclusions:

• Total artificial heart (TAH) implanted calves provide a viable model for isolating and studying drug vasoactive effects.
• This model allows for the investigation of vascular responses independent of myocardial function.
• The TAH model's sensitivity to preload and afterload changes enhances its utility for pharmacological research in cardiovascular diseases.