Neuronal control of coronary blood flow

Controversies on acetylcholine-induced increases or decreases in coronary blood flow arise from obvious species differences, the role of endothelium in mediating vascular smooth muscle responses, and the marked negative chronotropic and inotropic effects of acetylcholine. In man, there appears to be a predominant dilation of intact epicardial coronary arteries and a constriction of artherosclerotic segments. However, at present there is no evidence for a vagal initiation of myocardial ischemia. Coronary vascular β-adrenergic receptors mediate dilation, but appear to be functionally insignificant during sympathetic activation. The β-adrenergic mechanism contributing to myocardial ischemia are indirect, mediated by a tachycardia-related redistribution of blood flow away from the ischemic myocardium. α-Adrenergic receptors mediating epicardial coronary artery constriction in experimental studies appear not to be responsible for the initiation of ischemia in patients with angina at rest. However, α-adrenergic constriction of coronary resistance vessels resulting in the precipitation of poststenotic myocardial ischemia was demonstrated in experimental studies and recently confirmed in patients with effort angina. Non-adrenergic, non-cholinergic neurotransmitters exist; however, their role in regulating coronary blood flow remains entirely unclear.     

Vagal control of coronary blood flow in dogs

Summary The experiments were performed on open-chest mongrel dogs, the hearts being paced at a constant rate. Both vagi were cut in the neck and the peripheral ends were stimulated with frequencies of 1, 5, 10, 15, 20, 25, 30, 35, 40 and 50 cycles per sec (30 sec, 8V, 2 msec). Adrenergic beta-receptors were blocked with propranolol and adrenergic alpha-receptors with dihydroergotamine. Coronary flow was measured with electromagnetic flowmeters on the descending branch of the left coronary artery. A significant increase in coronary flow was observed with rising frequency of stimulation. This increase was 15 percent with 30 Hz and decreased with higher frequencies. The total coronary resistance reached its lowest level at the frequency of 30 cycles per sec. The results clearly indicate the parasympathetic control of myocardial blood flow.

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Die vagale Regelung der Koronardurchblutung beim Hund

Zusammenfassung Die Versuche erfolgten an Bastardhunden mit offenem Thorax bei künstlich konstant gehaltener Herzfrequenz. Beide Halsvagi wurden durchtrennt und ihre peripheren Stümpfe parallel mit Rechteckimpulsen von 2 msec Dauer, 8–10 V und Frequenzen von 1, 5, 10, 15, 20, 25, 30, 35, 40 und 50 Hz über jeweils 30 sec gereizt. Die adrenergen Beta-Rezeptoren wurden durch Propranolol und die adrenergen Alpha-Rezeptoren mit Dihydroergotamin blockiert. Der Koronardurchfluß wurde mit einem elektromagnetischen Durchflußmesser am Ramus descendens der linken Koronararterie ermittelt.Mit zunehmender Reizfrequenz wurde ein signifikanter Anstieg der Koronardurchblutung mit einem Maximum der Zunahme von 15% bei 30 Hz gefunden. Bei höheren Frequenzen zeigte sich wieder eine abnehmende Tendenz. Der Gesamtwiderstand in den Koronargefäßen erreichte seinen niedrigsten Wert bei ebenfalls 30 Hz. Die Ergebnisse sprechen für eine direkte vagale Beeinflussung der myokardialen Durchblutung.

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With 3 figures and 2 tables

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Supported by the Ministry of Health of the German Dem. Rep.

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A preliminary report was given at the 27th Int. Congress of Physiol. Sciences, Paris, 1977.     

Carotid sinus reflex control of coronary blood flow in human subjects

Systemic and coronary hemodynamics were assessed before and during a reduction in carotid transmural pressure. This reduction was induced by means of a pneumatic neck chamber in 15 normal subjects and 15 hypertensive patients with a normal coronary arteriogram. A reduced baroreflex responsiveness was demonstrated in hypertensive patients as compared with normal subjects by evaluating both the reflex bradycardia evoked by intravenous administration of phenylephrine and the reflex increase in blood pressure during carotid sinus hypotension. In normal subjects, the reduction in carotid transmural pressure induced a significant increase in mean blood pressure, total peripheral resistance, cardiac output, heart rate, coronary vascular resistance, coronary blood flow assessed by the continuous thermodilution method and myocardial oxygen consumption. In hypertensive patients, the same stimulus significantly increased mean blood pressure, cardiac output, heart rate and coronary blood flow while no significant change was detected in coronary vascular resistance and myocardial oxygen consumption. The increase in mean blood pressure, total peripheral resistance and cardiac output was significantly higher in normal subjects than in hypertensive patients. These results suggest that in normal subjects carotid sinus hypotension evokes reflex coronary vasoconstriction, whereas this response is blunted in hypertensive patients with reduced baroreflex sensitivity.     

Impact of blood pressure control on coronary flow reserve in hypertensive patients

<正>Objective To investigate the impacts of blood pressure control on coronary flow reserve(CFR)in hypertensive patients.Methods A total of 236 patients without significant coronary stenosis(defined as50%luminal narrowing confirmed by coronary angiography or coronary artery CT scan)between January 2011 and July 2015were retrospectively enrolled in this study.CFR was     

Regulation of coronary blood flow

A very schematic summary of possible factors that affect coronary vascular resistance is illustrated in Fig. 11. These factors are mechanical, myogenic, metabolic, and neural.⁶⁴ Mechanical influence is passive and is essentially determined by the extravascular compression which is important only during systole and particularly in the subendocardial layers of the left ventricular myocardium. With respect to the myogenic factor it is controversial whether it plays a role in adjustments of coronary vascular tone. Metabolic processes are possibly integrated at the level of the myocardial cell P_O2 which is the resultant of oxygen supply and need, which in turn depend on the myocardial contractile activity as well as other biochemical processes. A decrease in myocardial P_O2 gives rise to the release of the vasodilator metabolite adenosine. Nevertheless, other chemical factors (H⁺, K⁺, osmolarity) known to be released by the heart (which by themselves are poor and transient coronary vasodilators and whose release does not correspond with changes in coronary resistance) may play a role by modulating the coronary sensitivity to adenosine and other factors.     

Changes in coronary blood flow produced by the coronary artery occlusion

The influence of the occlusion of one coronary artery on coronary blood flow in an intact myocardium was investigated in narcotised dogs with open chest by using the crossed circulation method. Interruption of blood inflow to one of the branches of the left coronary artery under autoperfusion of the coronary bed led to a drop in the blood flow rate in the intact branch of the same artery, which was caused by decreased perfusion pressure. Stabilization of coronary perfusion pressure made it possible to detect the dilatatory reaction of the intact coronary bed to the occlusion of one of the coronary arteries. On the basis of an analysis of the dilatatory reaction, conclusions are drawn about the reflex nature of the observed phenomenon. The results of experiments with selective pharmacological blockade of both parts of the autonomous nervous system suggest that the afferent and efferent pathways run in the sympathetic nervous system.     

Microcirculation and coronary blood flow

The microcirculation of the coronary vasculature functions as a penetrating vascular network running from epicardium to endocardium with direct communications of both arterioles and venules with the ventricular chambers. The degree of capillary flow and utilization reflect the fact that the heart is a constantly functioning muscle. The cyclical compression of this vascular system also sets it apart from the conditions in the remainder of the systemic circulation. There are considerable species differences in the number of collateral vessels. Response to stress, such as hypoxia or arterial narrowing, involves conversion of collateral microvessels into communicating arteries, a reaction which can be seen to occur within days of the initial stimulus.     

Relationship between coronary blood flow velocity waveform and transmural distribution of myocardial blood flow in coronary artery

It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Time-velocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId + TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (r = 0.57) between the endo/epi ratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.