Norepinephrine Release is Increased in the Hibernating Heart, Studied in a Chronic Canine Model of Myocardial Hibernation

Abstract

We examined the change in cardiac sympathetic function in the hibernating heart. To induce hibernating hearts in dogs, we placed a nylon tube via the carotid artery in the left circumflex artery (LCx) and obstructed the LCx flow. The plasma norepinephrine (NE) and epinephrine (E) concentrations in the coronary sinus and the aorta were measured before and 1 week after the tube placement to evaluate the catecholamine release from the heart. The wall motion was followed by echocardiography and. 1 week after the tube placement, regional myocardial blood flow (RBF) was measured using colored microspheres. Also. the restorability of myocardial dysfunction was examined in other dogs by extracting the LCx tube 1 week after the placement. Finally, the heart was removed for pathological observation and dogs showing myocardial infarction were excluded. One week after placing the tube, wall thickening was reduced in the LCx area, but was not in the left anterior descending (LAD) area. Compared with the LAD area, RBF in the LCx area was decreased in the endocardium (p < 0.05), but was not in the epicardium. In other dogs, the reduced wall thickening in the LCx area was restored to normal levels 1 or 2 weeks after the tube extraction. Thereby, our dogs with the tube placed were considered to be models of myocardial hibernation. The plasma NE and E concentrations were not significantly changed by placing the tube, but NE release from the heart was increased after the tube placement (p < 0.05). E uptake from the heart did not differ. Therefore, it is suggested that NE release is increased in the hibernating heart and may contribute to its mechanism.

Dobutamine responsiveness, PET mismatch, and lack of necrosis in low-flow ischemia: is this hibernation in the isolated rat heart?

“…This phenomenon has been previously described as "perfusion-contraction matching," and it seems likely that the decrease in flow induces the heart to downregulate its contraction, establishing a new balance between energy supply and demand, thus conserving viability. Low-flow ischemic models of acute hibernation via perfusion-contraction matching have been demonstrated in a number of other species, including pigs (31), dogs (22), and rats (30).…”

Effects of Carvedilol Treatment in Dogs with Chronic Mitral Valvular Disease

“…2,[4][5][6][7][8][9][10][11][12][13][14][15][16] This activation stimulates tachycardia and arrhythmias and also causes malfunction and necrosis of cardiomyocytes. [13][14][15][16][17][18] Analysis of these results suggests that the use of beta-blockers to prevent sympathetic action on cardiomyocytes would be especially helpful in reducing progression of heart disease in dogs. Beta-blockers have become an established treatment for human patients with HF.…”

A porcine model of ischemic heart failure produced by chronic placement of a tube in a coronary artery

“…This procedure needs fluoroscopy, but does not need thoracotomy or an additional procedure and is a relatively easy procedure. The position of the tube in the LCx artery was determined based on previous findings in dogs [6] and preliminary findings in pigs. When we previously used the placement of the tube in the LCx artery in dogs, we intended not to induce myocardial infarction but to induce myocardial hibernation.…”

“…The tube was placed in the LCx artery, as the distal end of the tube was positioned at about the distal two thirds of the main stream of the LCx artery. The depth of the tube in the LCx artery was determined based on a previous study in dogs [6] and a preliminary study in pigs. The cervical incision was sutured and the pigs of MI group were also allowed to recover.…”