Ischemia generally has been assumed to cause maximal vasodilation of the coronary resistance vessels. However, recent observations have demonstrated that during ischemia, the coronary microvessels can retain some degree of vasodilator reserve and remain responsive to vasoconstrictor stimuli. Traditional understanding of coronary blood flow regulation envisioned an array of resistance vessels that respond homogeneously to local myocardial metabolic needs. Although coronary arterioles (<100 μm) do respond to myocardial metabolic activity, recent studies have demonstrated that up to 40% of total coronary resistance resides in small arteries 100-400 μm in diameter. Vasoconstriction of these small arteries is capable of decreasing blood flow, but they are minimally responsive to the metabolic effects of the resultant flow reduction. The lack of metabolic vasoregulation of the resistance arteries explains, at least in part, the observation that myocardial ischemia does not predictably cause maximal resistance vessel dilation. In addition, vasoconstrictor influences can compete with metabolic vasodilator activity in coronary arterioles. These findings suggest that pharmacologic vasodilators acting at the microvascular level might be therapeutically useful in patients with ischemic heart disease. Unfortunately, when myocardial ischemia results from a flow-limiting coronary stenosis, nonselective pharmacologic vasodilation of the resistance vessels can worsen subendocardial ischemia by decreasing intravascular pressure to produce coronary steal and by worsening of stenosis severity. Selective dilation of small arteries in ischemic regions might have potential for enhancing blood flow. A critical property of an effective agent is that it not interfere with metabolic vasoregulation at the arteriole level, so that dilation of small arteries in adequately perfused regions would be countered by compensatory vasoconstriction of the arterioles to prevent coronary steal. Copyright (C) 2000 Elsevier Science Inc.
- Blood flow
- Resistance vessels