Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart

Abstract

Background-We tested the hypothesis that induction of chronic bradycardia would trigger an upregulation of key growth factors and receptors, which would then lead to angiogenesis and improve coronary reserve in the left ventricle after myocardial infarction. Methods and Results-Bradycardia was induced in rats by administering alinidine via osmotic pumps beginning 1 day after coronary artery ligation. Echocardiographic analysis was conducted before and after treatment. Morphometric analysis was used in perfusion-fixed hearts to document arteriolar and capillary growth. Western blots were used to evaluate growth factor and receptor changes. During the first week of treatment, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), and basic fibroblast growth factor proteins were higher in the treated group, whereas VEGF receptor 2 (Flk-1), angiopoietin-1, and angiopoietin-2 were not affected by treatment. After 3 weeks, VEGF protein remained elevated, and bradycardia was associated with a higher capillary length density in the border (40%) and remote (14%) regions and a higher arteriolar length density in the septum (62%), despite a greater increase in left ventricular mass. Although arteriolar length density increased in all size classes, the greatest increase occurred in the smallest (terminal) arterioles. This vascular growth was associated with a 23% greater coronary reserve. Echocardiography revealed a smaller increase in ventricular volume and a greater preservation of ejection fraction in rats treated with bradycardia. Conclusions-Pharmacologic induction of bradycardia enhances vascularity and coronary reserve, preserves function of surviving myocardium, and therefore, is a noninvasive, therapeutic avenue that provides an alternative to gene therapy.

Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure

“…Previous studies have shown that drug-induced bradycardia enhances vascularity and coronary reserve, preserving the function of the surviving myocardium (10,35). This angiogenic response is dependent on VEGF (35,74). It has been documented that after myocardial infarction the VEGF is increased in the surviving myocardium (29,39,64,66) as observed in the current study.…”

“…Previous studies have shown that drug-induced bradycardia enhances vascularity and coronary reserve, preserving the function of the surviving myocardium (10,35). This angiogenic response is dependent on VEGF (35,74).…”

“…HR reduction in HF rats is associated with angiogenesis in postinfarcted hearts (10,35). Previous studies have shown that drug-induced bradycardia enhances vascularity and coronary reserve, preserving the function of the surviving myocardium (10,35).…”

“…In the present study, PYR augmented the VEGF protein level, suggesting increased angiogenesis in the surviving myocardium. The expansion of the capillary bed in the affected vasculature of the heart can prevent cardiac remodeling and support better pumping capacity (10,35).…”

β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation

“…Various guidelines for primary and secondary therapies are about β-receptor blockers, whose administration is one of the secondary prevention strategies employed for people with acute coronary syndrome or who have had an acute MI. β-receptor blockers reduce heart rate and improve left ventricular filling and coronary perfusion by prolonging diastolic time, reducing myocardial oxygen consumption, and elevating the threshold for ventricular fibrillation, thereby reducing the incidence of malignant arrhythmia (Lei et al, 2004). However, a multinational survey at 134 sites in 19 countries discovered that 78% of patients with acute coronary syndrome used β-receptor blockers.…”