Autoregulation

Autoregulation has been defined as "the intrinsic tendency of an organ to maintain constant blood flow despite changes in arterial perfusion pressure".95 Using a more operational definition, autoregulation is a proportional change in vascular resistance in response to a change in perfusion pressure. This active change in vascular resistance constitutes an

Fig 4.3 Regulation of vasomotor tone by neuromodulation, vascular receptors, and endothelium. NA = noradrenaline. A II = angiotensin II. TGF-ß = transforming growth factor ß. Thr = thrombin. Ach = acetylcholine. Bk = bradykinin. ET-1 =endothelin-l. EDRF = endothelium-derived relaxing factor. NO = nitric oxide. GC = guanylyl cyclase. Circles represent receptors: ETA = endothelin-A receptor. M =

muscarinic. P = purinergic. = Excitatory effect. Ö = Inhibitory effect.

(Modified from Opie LH. The heart, 3rd edn. Philadelphia: Lippincott-Raven, 1998: 270.)

intrinsic mechanism that is independent of extrinsic neurohumoral factors.

Perfusion is autoregulated mainly by arterioles that are larger than 150 p,m in diameter. As perfusion pressure continues to decline, however, smaller arterioles are recruited.96 There are lower and upper limits of autoregulation beyond which CBF will (pressure-dependently) decrease or increase, respectively.

Such a mechanism requires immediate adjustment of vasomotor tone in response to alterations in perfusion pressure. Autoregulatory changes in coronary vasomotor tone behave in a dynamic fashion. If metabolic demand is kept constant, a sudden change in coronary perfusion pressure results in an immediate directionally identical change in CBF which returns to normal over 10-30 s46 (Fig 4.4). As, at rest, the coronary vasculature appears to be under greater vasoconstrictor tone than other vascular beds, this greater vasodilatory reserve provides the capacity to increase flow remarkably.

The definition of autoregulation assumes that organ metabolism and venous pressure do not change as arterial perfusion pressure is altered. As aortic pressure is a major determinant of left ventricular afterload, and as developed left ventricular systolic pressure correlates with left ventricular (MFO^si ¡t ¡s impossible to study coronary autoregulation simply by a) b)

Mean aortic pressu re (mm Hg)

Phasic coronary pressure (mm Hg)

Phasic coronary flow

Mean coronary flow (ml/miri)

10s 10s

Fig 4.4 Dynamic coronary flow response to a sudden change in perfusion pressure in the left circumflex artery in the dog. (a) Flow response to a step decrease in pressure; (b) response to a step increase in pressure. (Reproduced with permission from Dole WP. Autoregulation of the coronary circulation. Prog Cardiovasc Dis 1987;29:293-323.)

changing aortic pressure because this would lead to marked changes in myocardial metabolism. This problem can be overcome by cannulating a coronary artery and perfusing it with a pump. Nevertheless, low perfusion pressures may cause myocardial ischaemia with subsequent decreases in myocardial metabolism and increases in venous pressure. On the other hand, higher than normal perfusion may increase cardiac contractility and myocardial metabolism, secondary to the increase in CBF. Doubling of the resting CBF may increase the strength of cardiac contraction by 15%.98 This phenomenon is referred to as the "Gregg effect", after its discoverer99 (see below). Either increasing CBF by increasing cannulated coronary artery pressure or increasing it by pharmacological vasodilation at constant coronary perfusion pressure will elicit this effect, thus changing myocardial metabolism simultaneously. As autoregulation constitutes a flow response to changes in perfusion pressure, a Gregg effect will always be involved in autoregulatory investigations. Such simultaneous changes in will complicate the interpretation of acquired data on autoregulation.

Adenosine

The precise mechanism(s) responsible for maintaining CBF in the presence of decreasing coronary perfusion pressure remain (s) controversial.46 100 Autoregulation is largely unrelated to the release of adenosine.101 Furthermore, intracoronary infusion of adenosine deaminase or adenosine receptor antagonists that blunt reactive hyperaemia does not affect coronary autoregulation,47 101 and interstitial levels of adenosine do not change with decreases in coronary perfusion pressure within the autoregulatory range.47 These data would suggest that adenosine plays at best a minor role in coronary autoregulation.

EDRF/NO

Endothelium-dependent production of NO in coronary vessels appears to be an important mechanism in the regulation of myocardial perfusion only during hypoperfusion.102 Inhibiting NO synthase with L-NAME increased the critical pressure at which myocardial ischaemia began (lower autoregulatory break point) from 45±3 mm Hg under control conditions to 61 ± 2 mm Hg after L-NAME (Fig 4.5). In addition, both the slope of the coronary pressure-flow relation below the autoregulatory point, and the peak reactive hyperaemic flow response were reduced, reflecting impaired capability to minimise coronary vascular resistance. On the other hand, flow recruitment in response to increased metabolic demand (that is, a twofold increase in heart rate) was not affected by L-NAME. These findings would suggest that both initial autoregulatory adjustments to decreases in

Fig 4.5 Plots summarising pressure-flow relationships under control conditions (open circles) and following inhibition of nitric oxide synthesis by ^-nitro-L-arginine (l-NAME) (hatched triangles). l-NAME had no significant effect on flow regulation over the autoregulatory plateau. The lower autoregulatory break point (arrows) as well as the pressure-flow relationship during ischaemia were, however, shifted to the right after inhibition of nitric oxide production. (Reproduced with permission from Smith TP, Canty JM Jr. Modulation of coronary autoregulatory responses by nitric oxide. Circ Res 1993;73:232-40.)

Fig 4.5 Plots summarising pressure-flow relationships under control conditions (open circles) and following inhibition of nitric oxide synthesis by ^-nitro-L-arginine (l-NAME) (hatched triangles). l-NAME had no significant effect on flow regulation over the autoregulatory plateau. The lower autoregulatory break point (arrows) as well as the pressure-flow relationship during ischaemia were, however, shifted to the right after inhibition of nitric oxide production. (Reproduced with permission from Smith TP, Canty JM Jr. Modulation of coronary autoregulatory responses by nitric oxide. Circ Res 1993;73:232-40.)

coronary perfusion pressure and flow recruitment in response to increased metabolic demand are probably mediated by metabolic factors independent of NO production. During hypoperfusion, however, endothelium-dependent production of NO is importantly involved in minimising coronary vascular resistance.

O2 and CO2 tension

Changes in myocardial O2 and CO2 tensions may mediate coronary autoregulation.103 104

There appears to be a strong inverse relationship between coronary venous O2 tension and coronary autoregulation. Good autoregulation was observed when coronary venous O2

tension was 25 mm Hg(3 3 kPa) and autoregulation was lost when venous O2 tension was more than 32 mm Hg(4 3 kPa).104 This, again, would indicate that the dominant mechanism of coronary autoregulation is metabolic. The normal resting coronary sinus PO2 of 18-25

mm Hg(2-4-3.3 kPa) indicates a tight coupling between and myocardial 02

delivery.

Changes in PaO2 (arterial O2 tension) itself induce variations in coronary vasomotor tone, independent of O2 content and metabolic regulation of CBF. A high PaO2 constricts coronary arteries, possibly mediated by closure of ^ATP channels.125

Although possibly involved in the phenomenon of autoregulation, the effect of CO2 tension is probably small at venous O2 tension (PVO2) of more than 20 mm Hg(2-7 kPa).103 It remains unclear whether coronary auto-regulation is mediated directly by changes in

tissue 02 tension or by some mediating factors, such as ATP channels.

ATP sensitive K+ channels

Glibenclamide, a putative blocker of ^ATP channels, abolishes auto-regulation in the

canine heart perfused with blood in situ.126 ATP channels open when intracellular ATP concentration falls in myocardial and vascular smooth muscle cells.53 56 107 It has been suggested that a decrease in myocardial tissue O2 tension may be sensed by the vascular smooth muscle cell. By regulation of the generation of ATP, this decrease may

Was this article helpful?

0 0
Reducing Blood Pressure Naturally

Reducing Blood Pressure Naturally

Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.

Get My Free Ebook


Post a comment