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Calves chronically implanted with a total artificial heart as a pharmacological model
S D Everett1, G M Pantalos, I F Goldenberg
1Department of Surgery, University of Utah, Salt Lake City.
Insights
Total artificial heart (TAH) models in calves effectively isolate drug vasoactive effects, crucial for congestive heart failure research. This study demonstrated TAH calves
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.
Abstract:
Pharmacological therapy for congestive heart failure includes drugs that have both inotropic and vasoactive effects, although it is sometimes difficult to differentiate between the two effects. An animal with an implanted total artificial heart (TAH) allows the investigation of the vascular effect of these drugs in the absence of the effect on the myocardium. An advantage of the TAH model is its sensitivity to changes in right and left ventricular preload and afterload. Four instrumented TAH calves were given vasoactive drugs and the response was compared to control. Epinephrine, dopamine, isoproterenol, and nitroprusside were selected because of the predictability of their responses. Epinephrine caused a significant increase in systemic vascular resistance (SVR), and dopamine caused a significant increase in Pulmonary vascular resistance (PVR) and Isoproterenol caused a significant decrease in PVR. TAH implanted calves can thus serve as a pharmacological model to study the vascular response, which may be useful in investigation of new agents with inotropic and vascular effects.