Feedback control of multiple hemodynamic variables with multiple cardiovascular drugs

The ultimate goal of disease treatment is to control the biological system beyond the native regulation to combat pathological process. To maximize the advantage of drugs, we attempted to pharmacologically control the biological system at will, e.g., control multiple hemodynamic variables with multiple cardiovascular drugs. A comprehensive physiological cardiovascular model enabled us to evaluate cardiovascular properties (pump function, vascular resistance, and blood volume) and the feedback control of these properties. In 12 dogs, with dobutamine (5plusmn3 mugmiddotkg^-1middotmin^-1), nitroprusside (4plusmn2 mugmiddotkg^-1middotmin^-1), dextran (2plusmn2 mlmiddotkg^-1), and furosemide (10 mg in one, 20 mg in one), rapid, sufficient and stable control of pump function, vascular resistance and blood volume resulted in similarly quick and stable control of blood pressure, cardiac output and left atrial pressure in 5plusmn7, 7plusmn5, and 12plusmn10 minutes, respectively. These variables remained stable for 60 minutes (RMS 4plusmn3 mmHg, 5plusmn2 mlmiddotmin^-1middotkg^-1, 0.8plusmn0.6 mmHg, respectively).