OBJECTIVE: alpha 2-adrenergic agonists decrease central sympathetic outflow and maintain normal transmural myocardial blood flow distribution, but intravenous bolus doses of these agents can also induce excessive coronary vasoconstriction and myocardial ischemia. The hypothesis of the present study was that a rapid intravenous bolus of dexmedetomidine, a specific alpha 2-adrenergic agonist, will cause coronary vasoconstriction and accompanying myocardial ischemia in young pigs. DESIGN: Prospective, controlled study on experimental animals. SETTING: Animal laboratory of a university cardiorespiratory research center. PARTICIPANTS: Twelve domestic 8-week-old open-chest pigs, anesthetized with high-dose fentanyl. Another six pigs served as controls. INTERVENTIONS: Sequential intravenous dexmedetomidine boluses of 3, 10, and 30 mg/kg were administered, and responses were measured during peak changes (2 minutes after injection) and during recovery after each dose. MEASUREMENTS AND MAIN RESULTS: Left anterior descending coronary artery blood flow, calculated regional coronary vascular resistance, myocardial extraction of oxygen and lactate, plasma catecholamine levels, and conventional central hemodynamic parameters were measured. The two higher doses of dexmedetomidine induced 21% and 29% immediate increases in left anterior descending coronary artery blood flow. At the same time mean systemic blood pressure and pulmonary capillary wedge pressure increased, and calculated regional coronary vascular resistance increased. Myocardial extraction of oxygen and lactate remained unchanged. CONCLUSIONS: Large intravenous doses of dexmedetomidine caused moderate regional coronary vasoconstriction without metabolic signs of myocardial ischemia in young domestic pigs at the same time as a marked vasoconstrictive response in the systemic circulation.
OBJECTIVE: alpha 2-adrenergic agonists decrease central sympathetic outflow and maintain normal transmural myocardial blood flow distribution, but intravenous bolus doses of these agents can also induce excessive coronary vasoconstriction and myocardial ischemia. The hypothesis of the present study was that a rapid intravenous bolus of dexmedetomidine, a specific alpha 2-adrenergic agonist, will cause coronary vasoconstriction and accompanying myocardial ischemia in young pigs. DESIGN: Prospective, controlled study on experimental animals. SETTING: Animal laboratory of a university cardiorespiratory research center. PARTICIPANTS: Twelve domestic 8-week-old open-chest pigs, anesthetized with high-dose fentanyl. Another six pigs served as controls. INTERVENTIONS: Sequential intravenous dexmedetomidine boluses of 3, 10, and 30 mg/kg were administered, and responses were measured during peak changes (2 minutes after injection) and during recovery after each dose. MEASUREMENTS AND MAIN RESULTS: Left anterior descending coronary artery blood flow, calculated regional coronary vascular resistance, myocardial extraction of oxygen and lactate, plasma catecholamine levels, and conventional central hemodynamic parameters were measured. The two higher doses of dexmedetomidine induced 21% and 29% immediate increases in left anterior descending coronary artery blood flow. At the same time mean systemic blood pressure and pulmonary capillary wedge pressure increased, and calculated regional coronary vascular resistance increased. Myocardial extraction of oxygen and lactate remained unchanged. CONCLUSIONS: Large intravenous doses of dexmedetomidine caused moderate regional coronary vasoconstriction without metabolic signs of myocardial ischemia in young domestic pigs at the same time as a marked vasoconstrictive response in the systemic circulation.
Authors: Francis Lam; Chase Ransom; Jeffrey M Gossett; Aaron Kelkhoff; Paul M Seib; Michael L Schmitz; Janet C Bryant; Elizabeth A Frazier; Punkaj Gupta Journal: Pediatr Cardiol Date: 2012-10-09 Impact factor: 1.655