Bradycardia Stimulates Vascular Growth During Gradual Coronary Occlusion

Abstract

Objective-In cultured endothelium, stretch induces release of growth factors that contribute to angiogenesis. We tested the hypothesis that bradycardia, which prolongs ventricular diastolic filling time and volume, promotes collateral vessel growth. Methods and Results-An ameroid occluder was placed on coronary arteries of dogs with normal heart rates (AM) or bradycardia (55 bpm; AMϩBC). A third group had normal heart rates and no ameroid (control [CON]). Four weeks after occluder placement, myocardial blood flow at rest and maximal vasodilation (adenosine) at equivalent heart rates and vascular morphometry of hearts were measured. In AM dogs, conductance (myocardial flow/diastolic pressure) of collateral-dependent myocardium was similar to collateral-independent myocardium during rest but increased to only one third of CON during maximal vasodilation. In contrast, in AMϩBC dogs, conductance was similar in collateral-dependent and -independent regions during maximal vasodilation. Arteriolar length density in collateraldependent myocardium was 80% greater in AMϩBC than AM dogs. Capillary length density in collateral-dependent region of AM dogs was lower than CON but normal in AMϩBC dogs. The angiopoietin receptor Tie-2 increased in collateral-dependent regions of AM and AMϩBC groups, whereas vascular endothelial growth factor increased in collateral-dependent and -independent regions only in AMϩBC dogs. Conclusion-Chronic

Postinfarction healing dynamics in the mechanically unloaded rat left ventricle

“…This process could be further accentuate when the LV is unloaded by reducing wall stress transmission-induced compression to intramyocardial collateral vessels (5). In the granulation phase of infarct healing, our results are in agreement with previous work showing that heart rate reduction could enhance postinfarction angiogenesis by upregulating proangiogenic factors (28,30,56). Moreover, pharmacologically induced chronic heart rate reduction could give rise to a dramatic improvement of infarct size and myocardial survival in rats (55).…”

Landiolol Hydrochloride Normalizes Diminished Levels of Cardiac Vascular Endothelial Growth Factor (VEGF) Signaling System Components in Lipopolysaccharide-Induced Sepsis Independent of Inflammatory Markers

“…*p<0.05 vs. control, #p<0.05 vs. 3 h LPS-administered rats. been demonstrated to enhance coronary reserve, as well as capillary and arteriolar growth in normal [39] and in the post-MI (myocardial infarction) hearts [40,41]. Thus, collectively, data from the present and previous studies indicate that adrenergic receptor blockers, including landiolol, may enhance angiogenesis through the induction of VEGF signaling in various disease conditions.…”

Assessment of the Human Coronary Collateral Circulation

“…5,25 Because of prolongation of diastole, bradycardia prolongs the period of longitudinal stretch of endothelial cells, increasing the expression of various proarteriogenic signaling pathway components. 26 Indicators of repolarization heterogeneity have been documented to be valuable for assessing the collateral circulation: ECG U-wave appearance at rest or during exercise is known to point to CAD with critical arterial narrowing. 27 In stable effort angina pectoris, patients with exercise-induced U-wave changes exhibit fewer ischemic ECG ST changes and less chest pain during coronary occlusion than those without.…”