Duration of ischemia is vital for collateral development: repeated brief coronary artery occlusions in conscious dogs.

Abstract

The effects of two types of repeated transient coronary artery occlusions on collateral development were examined in chronically instrumented, conscious dogs. A 2-minute coronary occlusion at 32-minute intervals (group 1, n = 11) or a 15-second occlusion at 4-minute intervals (group 2, n = 7) were repeated day and night without interruption. In both groups, the total duration of coronary occlusions each day was the same (90 minutes). Before and after repetitive occlusions of either group, effects of transient 2-minute coronary occlusion on regional segment shortening in the ischemic area were examined to assess the functional state of the collateral vessels. In group 1, systolic segment shortening in the area rendered ischemic was reduced to -97.8 +/- 17.7% of the preocclusive control value during 2 minutes of coronary occlusion. After 125-478 repetitive occlusions (3-11 days), the degree of hypokinesia during the 2-minute occlusion was significantly improved to -0.6 +/- 4.6% of the preocclusive value (p less than 0.001 vs. before the repetition). In group 2, it remained unchanged even after 3,500-5,450 repetitive occlusions (11-16 days): -111.8 +/- 8.2% before and -111.4 +/- 13.8% after the repetition of 15-second occlusions (NS). The ratio of peripheral coronary arterial pressure to aortic pressure during transient-coronary occlusion, measured by selective catheterization, was significantly higher in group 1 than in group 2 (64.4 +/- 5.3% vs. 20.7 +/- 1.3%, p less than 0.001). These findings suggest that myocardial ischemia of 2 minutes but not 15 seconds is vital to provide effective stimuli for angiogenesis.

Redox-sensitive Akt and Src regulate coronary collateral growth in metabolic syndrome

“…Our results supporting the idea that RI is an important driving force for CCG are in agreement with multiple studies (7,10,14,17,23,42,46). Elevated fluid shear stress, resulting from occlusion-induced pressure gradients across the coronary circulation, has also been proposed to drive collateral remodeling (13,27,34,35).…”

“…In that study (46), three different occlusion protocols produced exactly the same pressure gradient across preexisting collaterals but strikingly different increases in blood flow and cardiac function recovery; thus, this study strongly suggests that pressure gradients by themselves cannot sufficiently dilate preexisting collaterals and demonstrates a critical importance for ischemia in CCG. Furthermore, ischemic periods of 2 min but not 15 s stimulated CCG in dogs (23), providing further evidence for ischemia as a critical factor for CCG.…”

“…None of these studies have definitively excluded ischemia as the contributing factor to collateral growth. The suggestion that ischemia is not a driving force for CCG rests on a single study (24) in a model of canine coronary occlusion, which observed only epicardial vascular growth while the subendocardium became ischemic.Several studies now support the view that RI is an important driving force for CCG (7,10,14,17,23,42,46). RI induced CCG, as evident by increased collateral-dependent blood flow and cardiac function recovery, in a model of coronary occlusion in dogs (14), pigs (17), and rats (42).…”

“…Several studies now support the view that RI is an important driving force for CCG (7,10,14,17,23,42,46). RI induced CCG, as evident by increased collateral-dependent blood flow and cardiac function recovery, in a model of coronary occlusion in dogs (14), pigs (17), and rats (42).…”

Late preconditioning against myocardial stunning. An endogenous protective mechanism that confers resistance to postischemic dysfunction 24 h after brief ischemia in conscious pigs.

“…Thus, a highly reproducible degree of ischemia was observed over a period of 3 wk, which is an indispensable requisite for longitudinal studies comparing the response of the heart to coronary occlusions repeated on different days. Such a result probably could not have been obtained in the dog, in which new collaterals develop rapidly in response to cardiac instrumentation as well as brief (2-min) coronary occlusions (32). Finally, the coronary circulation of the pig is anatomically and physiologically similar to that of humans (26,29) and like the human heart (33), the porcine heart has minimal xanthine oxidase activity (34).…”