Coronary vasoregulation in health and disease

Abstract

E arly interests of clinical researchers at the Quebec HeartInstitute focused on various aspects of cardiac physiology, biochemistry (ie, metabolism) and pathology. In the late 1970s, the Quebec Heart Institute recruited Dr Jacques Rouleau, a cardiologist whose primary research interests focused on biophysical mechanisms that regulate the distribution of blood flow across the ventricular wall. The later addition to this laboratory of Dr John Kingma, whose research focused on mechanisms involved in myocardial protection following ischemia-reperfusion injury, created a basic scienceclinical research collaboration that continues today.The principal function of the heart is to supply the different organs in the body with blood containing essential nutrients and oxygen required for their proper functioning. In addition, the heart is essential for the transport of metabolic waste products, the accumulation of which would influence organ function. Mechanical work necessary to pump blood is performed by the myocardium. Proper functioning of the myocardium depends on blood flow in the coronary circulation, which comprises large epicardial conductance vessels originating from the coronary ostia. These large vessels branch into smaller vessels that supply the capillary network responsible for the transport of oxygen and nutrients to the myocytes. Comprehension of mechanisms responsible for regulation of the coronary circulation requires the interpretation of information from several disciplines, including cardiology, physiology, biochemistry and physics; this list is far from exclusive because new information regarding interactions of molecular and mechanical signals is consistently being added to the equation. The present review summarizes several achievements resulting from this research collaboration over the past two decades. REGULATION OF THE DISTRIBUTION OF MYOCARDIAL BLOOD FLOWControl of the coronary circulation involves a host of interactions among mechanical factors, such as arterial pressure, blood flow, ventricular contraction and myocardial wall tension. Suffice it to say that coronary blood flow is never constant but rather adaptive in relation to the metabolic and oxygen requirements of the myocardium; approximately 70% of oxygen transported is extracted from blood flowing in arterial vessels. This intrinsic capacity of arterial vessels to adjust in calibre and maintain constant perfusion over a range of arterial pressures is referred to as 'coronary autoregulation' (Figure 1). Principal mechanisms involved in the control of coronary blood flow include metabolic mediator(s) between myocytes and vascular cells, myogenic tone (induced by stretch) and neurogenic stimulation. However, studies on flow control mechanisms in the coronary circulation are limited because function of intramyocardial resistance vessels cannot be investigated with the currently available techniques. Exercise-induced increases in myocardial oxygen demand are accommodated by increases in coronary blood flow, the latter being controlled by ...

Ventricular cycle length irregularity affects the correlation between ventricular rate and coronary flow in isolated, Langendorff perfused guinea pig hearts

“…13 nutrient demand (Duncker, et al, 2012;Kingma & Rouleau, 2007). One interesting implication from the present study is confirmation that autoregulation is largely autonomicindependent (Langendorff hearts are denervated).…”

“…One interesting implication from the present study is confirmation that autoregulation is largely autonomicindependent (Langendorff hearts are denervated). In vivo, the autonomic nervous system may influence autoregulation (Kingma & Rouleau, 2007), but the relationship is preserved in autonomically denervated dogs (Kingma & Rouleau, 2007;Rouleau, Simard, Rodrigue, Blouin, & Kingma, 2002), and in isolated, denervated, Langendorff-perfused rat hearts (Bernier, et al, 1989). The present data confirm that autoregulation is intrinsic to the heart.…”

“…In in vivo conditions coronary flow is regulated by a combination of i) intramural pressure in coronary arteries caused by wall stress during the cardiac cycle, ii) the autonomic nervous system, iii) and work-induced autoregulation via local metabolites (Duncker, Bache, & Merkus, 2012;Kingma & Rouleau, 2007). Additionally, irregular rhythm affects the work of the myocardium independently of rate and load (Cooper, 1993).…”

Impaired Coronary Autoregulation Is Associated With Long-term Fatal Events in Patients With Stable Coronary Artery Disease

“…Preclinical studies suggest a role of hypertension-associated left ventricular hypertrophy, [20][21][22] diabetes mellitus, 23,24 and acute renal failure, 25 although the latter condition was an exclusion criterion in the present study. Disturbance of coronary autoregulation may arise from a wide variety of pathophysiological mechanisms, 1,3,26,27 and larger cohorts of patients with disturbed coronary autoregulation are necessary to elucidate the origin of such dysfunction in patients with stable CAD.…”

Hypoxic conditioning in blood vessels and smooth muscle tissues: effects on function, mechanisms, and unknowns

“…Ever since its initial discovery around 30 yr ago, there has been great interest and much literature in the field of ischemic conditioning. From the initial discoveries around contractility in isolated hearts, ischemic conditioning has been shown to be protective against myocardial infarcts, myocardial stunning, and arrhythmias (63,96).…”