INGRESO PERCIBIDO DEL TRABAJO REMUNERADO DE LAS

1.12.1 Acute hypoxaemia

1.12.1.1 Reflex responses

The fetal cardiovascular reflex responses to hypoxaemia have been recently reviewed by Giussani et al. (1994). It has been found that prior to 110 d GA acute hypoxaemia causes a rise in heart rate, which is maintained, and a fall in blood pressure (Iwamoto et a i, 1989), but after 110 d GA the response is the opposite (Iwamoto et a i, 1989). There is an initial bradycardia, within 2-3 minutes after the onset of hypoxaemia, and a transitory rise in blood pressure, the magnitude of each being dependent on the extent to which the blood gases and pH change.

In the more mature fetus, the initial bradycardia is due to a carotid (not aortic) chemoreflexly mediated increase in vagal activity, and the peripheral vasoconstriction is partly due to a carotid chemoreflexly mediated increase in sympathetic activity operating on the a-adrenergic receptors (Giussani et a i,

1993). Part of the vasoconstriction is also non-reflex in nature and is the result of elevated levels of circulating hormones (see section 1.12.1.iii). The decrease in heart rate is thought to be chemoreflexly, rather than baroreflexly, mediated, because heart rate drops before the increase in pressure.

1.12.1.ÎI Changes in blood flow

CVO is maintained during acute hypoxaemia (Court et a i, 1984; Jensen & Berger, 1993), but it is redistributed in favour of those organs that are essential for keeping the fetus alive. There is a decrease in vascular resistance in the heart, brain and adrenals, such that blood flow to those organs is increased (Court et a i, 1984). At the same time, there is an intense vasoconstriction of the peripheral arterioles (starting within 5 minutes of the onset of hypoxaemia), kidneys, gut, spleen, liver, carcass and lungs (Court et a i, 1984), so blood flow to those organs decreases.

Court et al. (1984) observed a decrease in placental vascular resistance, whereas Jensen & Lang (1992) saw an increase. However, despite the increase in placental resistance observed by Jensen & Lang (1992), the percent of cardiac output to the placenta was increased and blood flow

Chapter 1 INTRODUCTION

remained the same. Thus, in response to acute hypoxaemia, there appears to be a maintenance of blood flow to the placenta.

1.12.1.Hi Endocrine responses

There is an increase in the concentration of circulating plasma catecholamines during acute hypoxaemia due to the direct effects of hypoxaemia on the adrenal medulla (Cheung, 1989), and through chemoreflexly mediated sympathetic stimulation of the adrenals (Jensen & Hanson, 1995).

Hypoxaemia also causes an increase in the release of A VP (Iwamoto et a i,

1989; R aff et al., 1991; Giussani et a i , 1994), and release is further augmented by acidaemia (Wood & Chen, 1989; Raff et a i, 1991), through mechanisms that are not mediated by cortisol (Akagi et a i, 1990), or by the peripheral baroreceptors (Wood et a i, 1989) or chemoreceptors (Raff et a i,

1991), contrary to the adult animal. It has been shown, however, that adenosine mediates the release of A VP in response to acute hypoxaemia, probably through the stimulation of central adenosine receptors in the brain (Koos et a i, 1994).

In the fetus, hypoxaemia is an extremely potent stimulus for the release of ANP (Cheung & Brace, 1988), with increases in ANP concentration during hypoxaemia being greater in the immature (110-119 d G A) than mature (130- 135 d G A) fetal lamb (Cheung, 1992). It has been suggested that ANP release in response to hypoxaemia may be caused by direct effects on the heart and by the rise in plasma catecholamines (Cheung & Brace, 1988), and it has been demonstrated that the rise in ANP concentration during hypoxaemia is modulated by A VP and the autonomic nervous system (Cheung, 1992). Endothelin also regulates the release of ANP, perhaps by m ediating its release from atrial cardiocytes, though its role during hypoxaemia is not understood (Cheung, 1994).

The rise in plasma concentrations of cortisol and ACTH during acute hypoxaemia is by now well established (Boddy et a i, 1975; Jackson et a i,

1989; Giussani et a i, 1994b). The elevation in ACTH concentration is greater in young (125-129 d G A) than older (134-147 d G A) fetal sheep, possibly due to the negative feedback effects of cortisol on ACTH (Akagi et a i, 1990). Cortisol concentrations rise during late gestation (see section 1.10.2.iv). A functional fetal hypothalamic-pituitary connection is essential for the ACTH stimulated rises in cortisol in response to hypoxaemia (Ozolins et a i, 1992).

Chapter 1 INTRODUCTION

ACTH release is stimulated by acidaemia (Wood, Chen & Bell, 1989; Wood & Chen, 1989), which suggests that the response is chemoreceptor mediated, though the relative contributions of central and peripheral chemoreceptors are unknown. Recently it has been shown that the rise in plasma cortisol concentration is delayed in response to carotid sinus nerve section, but ACTH concentration is still increased significantly, suggesting a possible role of the carotid chemo- and baroreceptors in the release of cortisol (Giussani et a i,

1994b).

All levels increase during acute hypoxaemia concurrently with a rise in plasma renin concentrations (Broughton-Pipkin et a i, 1974), and contribute to the rise in blood pressure that is observed during hypoxaemia. We may speculate that impaired development of renal nephrons, such as has been observed in babies with lUGR (Hinchliffe et a i, 1992), may affect the fetal angiotensin response to hypoxaemia. The arterial chemoreceptors are involved in mediating the release of renin, which has been demonstrated by the fact that hypercapnia is a more potent stimulus to renin secretion than hypoxaemia (Wood, 1995).

Factors acting at the local level are also released in response to hypoxaemia. Both in vitro and in vivo studies show that NO is released in response to hypoxaemia (Busse et a l , 1993) and it is also released in the fetus (Green et a l, 1996). In response to fetal hypoxaemia, NO is important in regulating the increase in myocardial blood flow (Relier et a l, 1995), carotid blood flow (Green et a l, 1996) and cerebral blood flow (Iwamoto et a l, 1992).

Chapter 1 INTRODUCTION