The following points highlight the seventeen important factors which influences coronary circulation in human beings. The factors are: 1. Mean Aortic Pressure 2. Cardiac Output 3. Metabolic Factors 4. CO2 and O2 5. Ions 6. Polypeptiedes 7. Adenine Nucleotides 8. Cardiac Sympathetic and Parasympathetic Nerves 9. Heart Rate 10. Hormones 11. Temperature 12. Muscular Exercise and Excitement 13. Anaemia and Few Others.
1. Mean Aortic Pressure:
It is the chief motive force for driving blood into the coronary vessels. Any alteration of aortic pressure will, therefore, because parallel changes in coronary circulation. In a denervated heart-lung preparation of dog, it is observed that a rise of blood pressure from 50 to 130 mm of Hg increases the coronary inflow from 20 to 250 ml per minute.
In partial clamping of the aorta or in coarctation of the aorta, the central aortic pressure is increased and the coronary flow is also increased. But if this state is kept for some time then the blood flow is not maintained at the same degree.
It has been observed that if the aorta remains in a state of partial occlusion, then the work load of the left heart is increased as the peripheral resistance is increased. This increased work load of the heart ultimately becomes the cause of the congestive heart failure.
2. Cardiac Output:
Obviously, the coronary inflow is directly proportional to the cardiac output.
Increased output raises coronary inflow in two ways:
(a) By raising the aortic pressure, and
(b) By reflex inhibition of the vagal vasoconstrictor tone (Anrep).
3. Metabolic Factors:
With the increased metabolism of heart, the O2 requirement is increased and the circulation is greatly increased. There is a causal relationship between the myocardial metabolic activity, oxygen consumption and coronary blood flow. In the normal heart blood oxygen content of coronary sinus is low under a variety of physiological conditions which supports the view of metabolic regulation of coronary blood flow (CBF) by reactive hyperaemia. Adenine nucleotide may be responsible for this reactive hyperaemia.
4. CO2 and O2:
It has been observed by Katz and also by others that if O2 requirement of the heart is increased then the coronary circulation is increased. Furthermore if the O2 supply to the heart muscle is decreased then the coronary flow is increased. But if the O2 is supplied more than it is required, then the coronary circulation is decreased. Similarly, CO2 stimulates the coronary flow. During asphyxia or inhalation of CO2, concentration in the blood is increased; coronary flow is also increased at the first stage in order to maintain the total O2 requirement of the cardiac muscle.
5. Ions:
It has been observed by Katz that K+ in low concentration dilates the coronary vessel, whereas K+ in higher concentration constricts. Calcium in therapeutic doses increases the flow and O2 consumption of the cardiac muscle.
6. Polypeptiedes:
Bradykinin has been claimed to have vasodilating effect on coronary vessels but its normal physiological role is not yet fully known. Angiotensin II is an active octapeptide which causes arteriolar constriction in the skin, kidney, and brain and also in coronary vessels.
7. Adenine Nucleotides:
Adenine nucleotides have been known to be potent coronary vasodilators. ATP and ADP are equally potent vasodilators. AMP is a bit weaker vasodilator than those of ATP and ADP. ATP is not permeable to cell membrane, but adenosine can easily pass through the cell membrane.
Berne has described that adenosine, the breakdown product of ATP during hypoxia, permeates through the cell membrane to dilate the coronary vessels. Possible metabolic regulation of coronary blood flow by adenosine has been presented schematically by Berne (1963) (Fig. 7.101).
8. Cardiac Sympathetic and Parasympathetic Nerves:
Stimulation of cardiac sympathetic fibres from the stellate ganglion or the ganglion itself produces increased coronary inflow. This is mainly due to the influence of the cardiac sympathetic on coronary blood vessels resulting from the release of norepinephrine which causes vasodilatation of the coronary vessels and increases the coronary inflow.
It has been observed under different experimental conditions that stimulation of sympathetic cardiac nerves causes increase of coronary flow. But the mechanism by which the coronary flow is increased is not yet settled. From the observations of increased flow following intracoronary administration of adrenaline or noradrenaline it is claimed that liberation of noradrenaline from the postganglionic sympathetic nerve ending following stimulation is the probable cause.
Gregg (1963) has described that acute metabolic changes or the cardiac muscle due to increase of cardiac work following sympathetic stimulation is possibly the cause of increased coronary flow. Furthermore, the mediator released at sympathetic postganglionic endings of the cardiac muscle following stimulation increases the O2 consumption and this state causes the cardiac muscle hypoxia, a condition favourable for increasing blood flow through reactive hyperaemia.
Regarding the role of vagus on coronary flow there was conflicting opinion. But recent studies claim that the vagal stimulation, produce; vasodilatation of the coronary vessels through liberation of acetylcholine. It is quite unlikely that the vagus will be coronary vasoconstrictor since its chemical mediator acetylcholine is a coronary vasodilator.
9. Heart Rate:
When the heart rate is increased, minute cardiac output, aortic blood pressure may increase but the stroke volume decreases. The phasic coronary inflow and O2 consumption per beat decrease, but minute coronary flow and O2 consumption per minute are increased. With the increase of heart rate, O2 requirement of the heart muscle is increased and is maintained normally through increase of minute flow. It has been observed that with the increase of heart rate the extra-vascular resistance is increased, but the intravascular resistance is actually decreased causing a decrease of resistance, hence increase of minute flow.
10. Hormones:
a. Thyroid:
In thyrotoxicosis metabolism is increased along with increased coronary inflow and O2 consumption per minute. In hypothyroidism the flow is decreased which is possibly related with the altered metabolism of the cardiac muscle.
b. Adrenaline and Noradrenaline:
These cause increased coronary inflow along with increased O2 consumption per minute. These produce the relaxation of the coronary vessels by acting on the β-receptor of the vessel. Nicotine also increases the coronary flow through the liberation of noradrenaline. Relaxation of coronary blood vessels is prohibited by β-adrenergic blockers.
c. Pitressin:
It causes increased coronary resistance and diminution of coronary inflow. In the open chest or closed chest dog, pitressin causes decrease of coronary flow all throughout the cardiac cycle in the presence of an increased central coronary pressure. This decreased flow is presumably due to direct vasoconstrictor effect on the coronary vascular bed. This vasoconstrictor effect is not due to metabolic effect or due to increase of intracellular and extracellular K+ values. It possibly constricts the vessels at arteriolar level.
d. Acetylcholine:
It increases coronary inflow due to dilatation of the coronary vessels. This increased flow response is completely abolished by atropine. It increases the mean diameter of the coronary vessels.
11. Temperature:
With the rise of body temperature, the metabolism is increased and for the maintenance of normal O2 need the coronary circulation is increased. But with the fall of body temperature, as in the case of hypothermia, the coronary circulation is greatly decreased along with the decreased metabolic need of the cardiac muscle. The coronary vessels are dilated greatly at that state.
With the increase of body temperature by fever or by external application of heat (hyperthermia), though the heart rate, cardiac output and work of the heart are increased, yet coronary flow possibly remains unchanged. In heart- lung preparation if the myocardial temperature is increased, coronary flow is also increased but if the temperature of blood is increased, then the flow remains unaltered.
12. Muscular Exercise and Excitement:
As mentioned above, coronary inflow is adjusted according to the work done by heart. During heavy exercise the inflow rises about ten times. This is due to the fact that almost all the factors which increase coronary inflow come into action during muscular exercise, viz., O2 lack, CO2 excess, increased H-ion concentration, metabolites, increased temperature, adrenaline secretion, raised blood pressure, etc. During excitement, as the heart rate is increased, the coronary blood flow is also increased greatly, although the diastolic phase is decreased.
13. Anaemia:
In anaemia, the coronary flow is increased sharply in order to maintain the normal O2 need of the cardiac muscle, because the O2 carrying capacity of the blood is decreased under such state. The increase in the coronary flow is related partly to the decreased viscosity of blood and mostly to the active vasodilatation (Reactive hyperaemia) resulting.
(a) Anaemic hypoxia, and
(b) Metabolic hypoxia due to compensatory increased heart rate.
14. Intraventricular Pressure:
The increase of intraventricular pressure also alters the coronary flow. The increase of the right ventricular pressure (due to mitral stenosis, emphysema, atelectasis, etc.) affects coronary flow greatly as this pressure is reflected in the coronary venous bed of the right ventricle.
In case of the left ventricle, the coronary flow through this side is initially increased with the rise of intraventricular pressure (due to coarctation of the aorta or increase of peripheral resistance by any means). Under such state the left ventricular work load is increased greatly and ultimately the heart muscle is hypertrophied and coronary flow is gradually decreased. Ultimate fate of the heart is the degeneration of cardiac muscle fibres leading to congestive heart failure.
15. Transfusion:
During transfusion, ventricular load is increased due to rapid venous return; and the systolic and diastolic heart size, ventricular stroke volume and work and also arterial blood pressure are all increased. Under such state the heart rate decreased causing greater increase of stroke volume, diastolic pause and thus the coronary flow per beat and per minute is increased.
16. Extravascular Pressure:
This is an important determinant of the coronary flow as the coronary vascular resistance is increased due to rhythmical compression of the myocardial vessels during contraction.
17. Viscerocardiac Reflex:
The coronary flow is markedly altered during visceral distention and it is often encountered in a patient with ischaemic heart disease. Anginal pain, following a meal in such cardiac patient, is the consequence of decreased coronary flow. The reflex pathways for the manifestation of this pain following visceral distention are possibly lying in the vagi and the sympathetic. Thorough works in this line are required.