An intact animal model for the assessment of coronary blood flow regulation “Coronary blood flow regulation”

• Published in: Physiological reports 2020-07, Vol.8 (14), p.e14510-n/a
• Main Authors: Boudart, Céline, Su, Fuhong, Herpain, Antoine, Creteur, Jacques, Naeije, Robert, Brimioulle, Serge, Dewachter, Laurence, Van Obbergh, Luc
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine - pharmacology; Animal models; Animal research; Animals; autoregulation; Blood flow; Blood Flow Velocity; Blood pressure; Bradykinin; Bradykinin - pharmacology; Carotid arteries; Catheters; coronary blood flow; Coronary Circulation - drug effects; Coronary Circulation - physiology; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - physiology; endothelial function; Endothelium; Heart rate; Hemodynamics - physiology; Hogs; Hyperemia; Ischemia; metabolic regulation; Metabolism; microvascular function; Models, Animal; Original; Physiology; Pulmonary arteries; Swine; Ultrasonic imaging; Vasodilator Agents - pharmacology; Vasodilators; Veins & arteries
• ISSN: 2051-817X
• DOI: 10.14814/phy2.14510

Coronary blood flow adapts to metabolic demand ("metabolic regulation") and remains relatively constant over a range of pressure changes ("autoregulation"). Coronary metabolic regulation and autoregulation are usually studied separately. We developed an intact animal experimental model to explore both regulatory mechanisms of coronary blood flow. Coronary pressure and flow‐velocities were measured in four anesthetized and closed‐chest pigs using an intracoronary Doppler wire. Metabolic regulation was assessed by coronary flow reserve defined as the ratio between the maximally vasodilated and the basal flow, with hyperemia achieved using intracoronary administration of adenosine (90 µg) or bradykinin (10–6 M) as endothelium‐independent and ‐dependent vasodilators respectively. For both vasodilators, we found a healthy coronary flow reserve ≥ 3.0 at baseline, which was maintained at 2.9 ± 0.2 after a 6‐hr period. Autoregulation was assessed by the lower breakpoint of coronary pressure‐flow relationships, with gradual decrease in coronary pressure through the inflation of an intracoronary balloon. We found a lower limit of autoregulation between 42 and 55 mmHg, which was stable during a 6‐hr period. We conclude that this intact animal model is adequate for the study of pharmacological interventions on the coronary circulation in health and disease, and as such suitable for preclinical drug studies. Metabolic regulation adapts the coronary blood flow (CBF) to the myocardial demand. Autoregulation maintains CBF constant over a wide range of pressure. These CBF regulation mechanisms were to date studied separately. We developed here a new method to comprehensively assess CBF regulation in an intact large animal experimental model.