Clonidine Modulation of Hemodynamic and Catecholamine Responses Associated with Hypoxia or Hypercapnia in Dogs

Background: Hypoxia or hypercapnia elicits cardiovascular responses associated with increased plasma catecholamine concentrations, whereas clonidine, an alpha2 -adrenergic agonist, decreases plasma catecholamine concentrations. The authors examined whether systemic clonidine administration would alter the hemodynamic and catecholamine responses to hypoxia or hypercapnia in anesthetized dogs.

Methods: Pentobarbital-anesthetized dogs whose lungs were mechanically ventilated were instrumented for measurement of mean arterial pressure, heart rate, mean pulmonary artery pressure, right atrial pressure, cardiac output, left ventricular end-diastolic pressure, and the peak of first derivative of left ventricular pressure. The dogs were randomly assigned to receive an intravenous bolus injection of 10 micro gram/kg clonidine followed by continuous infusion at a rate of 1 micro gram *symbol* kg sup -1 *symbol* min sup -1 (clonidine-10 group, n = 7), an intravenous bolus injection of 5 micro gram/kg clonidine followed by continuous infusion at a rate of 0.5 micro gram *symbol* kg sup -1 *symbol* min sup -1 (clonidine-5 group, n = 7), or an equivalent volume of 0.9% saline (control group, n = 7). Each dog underwent random challenges of hypoxia (PaO2 30, 40, and 50 mmHg) and hypercapnia (PaCO sub 2 60, 80, and 120 mmHg). Measurements of hemodynamic and plasma norepinephrine and epinephrine concentrations were made during each period of hypoxia or hypercapnia, and measurements of plasma clonidine concentrations were made after the loading dose of clonidine and the first and the second exposure of hypoxia or hypercapnia.

Results: Although significant increases from prehypoxic values in mean arterial pressure (39+/-10 mmHg) and plasma norepinephrine (291+/-66 pg/ml) and epinephrine (45+/-22 pg/ml) concentrations were noted during hypoxia of PaO2 30 mmHg in the control group (P < 0.05), such changes were absent in both clonidine groups. During hypercapnia of PaCO2, 120 mmHg, changes from prehypercapnic values in mean arterial pressure, mean pulmonary artery pressure, the peak of first derivative of left ventricular pressure, and plasma norepinephrine and epinephrine concentrations in the clonidine-10 and clonidine-5 groups were significantly less than those in the control group. Plasma clonidine concentrations in the clonidine-10 and clonidine-5 groups were 16.8+/-1.7 and 8.9+/-1.0, 42.5+/- 2.9 and 21.5+/-1.5, and 51.1+/-3.2 and 26.7+/- 1.0 ng/ml after the loading dose of clonidine and the first and the second exposure of hypoxia or hypercapnia, respectively.