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[Dose-dependent vasodilator effect of dobutamine in calves with a constant cardiac output artificial heart]
Insights
This study used an artificial heart in calves to isolate dobutamine's vascular effects from its cardiac actions. Results help determine dobutamine's direct impact on peripheral vascular resistance.
Area of Science:
- Cardiovascular pharmacology
- Surgical innovation
- Animal research models
Context:
- Differentiating drug effects on myocardium versus vasculature is challenging.
- Dobutamine is primarily known for myocardial action.
- Artificial hearts offer a novel model to isolate drug effects.
Purpose:
- To determine the peripheral vascular effects of dobutamine.
- To separate dobutamine's vascular actions from its myocardial effects.
- To establish a research model for drug evaluation post-artificial heart implantation.
Summary:
- Calves with implanted artificial hearts received stepwise infusions of dobutamine (5-30 mcg/kg/min).
- Cardiac output was maintained at a fixed 7.85 L/min.
- Right atrial pressure and femoral arterial pressure were recorded to calculate total peripheral resistance.
Impact:
- Provides a method to assess drug vascular effects independently of native cardiac function.
- Contributes to understanding dobutamine's haemodynamic profile.
- Informs future pharmacological studies in patients with mechanical circulatory support.
Abstract:
The haemodynamic effect of any drug being the resultant of its myocardial and vascular actions, it is often difficult to separate what is due to each of these components. Dobutamine is regarded as having an almost exclusive effect on the myocardium in therapeutic doses (1); its administration after implantation of an artificial heart would enable its peripheral vascular effects to be determined by exclusion of the native ventricles. Experiments were conducted on three calves weighing about 90 kg each. The artificial heart, two central venous catheters and a femoral arterial catheter were implanted under general anaesthesia. The study began on the first post-implantation day, the animals being awake, in stable haemodynamic status and with normal temperature. Dobutamine was infused through one of the venous catheter placed in the native atrium, in 6 stepwise doses of 5, 10, 15, 20, 25 and 30 mcg/kg/min, each dose being given over 10 min and separated from the other dose by a 10 min interval. The order in which these doses were administered was determined at random. By adjusting the propulsion pressure of the two ventricles and the heart rate, the cardiac output was set at a fixed value of 7.85 L/min throughout the study, this value being controlled by a computer-assisted unit. Right atrial pressure and femoral arterial were recorded during each step of the infusion. Total peripheral resistance was calculated over a stable period of the last 5 min of each dosing and before administration of dobutamine. This procedure was repeated 4 times in each calf, at intervals of 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)