I. M. James

Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity.

Cerebral blood flow (CBF) was studied at normocapnia and after a challenge with 5% CO2 in 59 diabetic patients and 28 controls. There was a significant age-related decline in CBF in both groups, which suggests that diabetes does not affect the rate of decrease of CBF with age. After CO2 challenge CBF increased in most of the controls; in the patients CBF increased in 23, decreased in 26, and remained stable in 10. Thus the reactivity of cerebral blood vessels in diabetics is altered. Diabetics have diminished cerebrovascular reserve and are thus at increased risk of cerebrovascular disease because they are unable to compensate when necessary with an increased CBF.

INSTABILITY OF CEREBRAL BLOOD-FLOW IN INSULIN-DEPENDENT DIABETICS

Cerebral blood-flow (CBF) was measured in 23 insulin-dependent diabetics before and 2--3 h after insulin/breakfast. In 10 of these patients CBF changed significantly during the day, with a significant fall in 9. In 3 patients who had the greatest falls in CBF there was a concomitant sensation of an impending faint. Thus CBF is unstable in insulin-dependent diabetics in contrast to control subjects in who there is little or no variation. Sudden falls in CBF in insulin-dependent diabetics may explain the symptoms of impending faint without hypoglycaemia; such falls would also be relevant to the pathogenesis of strokes in these patients.

Muscle Blood Flow in Diabetes Mellitus: Evidence of Abnormality After Exercise

Objective To determine whether muscle blood flow before and after exercise is abnormal in patients with diabetes mellitus. Research Design and Methods Muscle blood flow (MBF) was measured with the 133Xe clearance technique in 15 nondiabetic subjects, 10 patients with insulin-dependent diabetes mellitus (IDDM), and 11 patients with non-insulin-dependent diabetes (NIDDM) at rest and after exercise. None of the patients had neuropathy. Results The median resting MBF was similar in all three groups. The median postexercise MBF was significantly greater in nondiabetic subjects (40.1 ml· min−1·100 g−1 of tissue) than in patients with IDDM (25.7 ml· min−1·100 g−1 of tissue; P <0.01) or NIDDM (14 ml· min−1·100 g−1 of tissue; P <0.01). The difference between IDDM and NIDDM was not significant. Conclusions Diabetic patients have abnormalities of MBF in response to exercise. This abnormality occurs in the absence of clinical diabetic neuropathy.

EFFECT OF INDUCED METABOLIC ALKALOSIS IN HEPATIC ENCEPHALOPATHY

Abstract 500 ml. of 5% sodium bicarbonate given to five patients in hepatic coma caused a striking improvement in their clinical condition and increases in their cerebral blood-flow, cerebral oxygen consumption, and oxygen/glucose index. Similar changes were noted in flow and oxygen consumption in five patients with chronic porto-systemic encephalopathy.

FACTORS AFFECTING THE CEREBROVASCULAR RESPONSE TO NORADRENALINE IN THE DOG

1 Noradrenaline infused into the internal carotid artery of the dog (0.01–1 μg kg−1 min−1) constricts the blood vessels of the cortex. This constriction is mediated by the action of noradrenaline on α‐adrenoceptors of the cerebral arteries. 2 Intravenous (1 μg kg−1 min−1) or intra common carotid arterial (0.01–1 μg kg−1 min−1) infusions of noradrenaline cause an increase in cortical blood flow that can be dissociated from changes in blood pressure. 3 The effect of intravenous noradrenaline on the cortical blood vessels and metabolism is blocked by high PaCO2 levels, or by the prior administration of (±)‐propranolol. (+)‐Propranolol is without such effect. 4 Following section of both vagi and both sinus nerves, intravenous noradrenaline fails to cause an increase in cortical blood flow. 5 In another series of animals the area of the carotid bifurcation was vascularly isolated and perfused with blood from a second dog. Chemoreceptor and baroreceptor activity was shown to be intact. 6 Administration of 5% CO2 to the donor dog caused an increase in cerebral blood flow in the recipient dog. 7 Administration of intravenous noradrenaline (1.0 μg kg−1 min−1) to the donor animal caused an increase in cerebral blood flow, cerebral O2 and glucose utilization of the recipient. 8 Administration of 5% CO2 and intravenous (—)‐noradrenaline (1.0 μg kg−1 min−1) caused a further increase in flow and metabolism. 9 This evidence suggests that the cerebrovasodilatation observed following intravenous noradrenaline is reflex and is triggered by chemoreceptor activity. 10 The evidence also suggests that the antagonism of the cortical dilatory effects of intravenous noradrenaline by raised PaCO2 in the intact animal must be at a site different from the peripheral chemoreceptors.

Effect of ornithine alpha ketoglutarate on disturbances of brain metabolism caused by high blood ammonia

The administration of ammonium salts to free ventilated dogs causes an increase in the anaerobic consumption of glucose. Prior and simultaneous administration of the drug ornithine alpha ketoglutarate not only attenuates the rise in blood ammonia but also favourably affects these changes in brain metabolism.

The Effect of Clomipramine (Anafranil) on Brain Metabolism

Cerebral blood flow in healthy adult subjects is about 54 ml per 100 g tissue per minute (Kety & Schmidt 1948). Such high perfusion is related to an equally high metabolic rate. In fact the oxygen metabolic requirement of the brain is about 3-3 ml per 100 g tissue per minute (Kety & Schmidt 1948) which means that the brain consumes approximately a quarter of the total oxygen used by the body at rest. It has been known for some time that glucose is the principal substrate used by the brain and that the ability of the brain to use other substances is, at most, extremely limited. Since the normal cerebral glucose consumption is about 4-8 mg per 100 g tissue per minute it can be calculated that some 8 5 % of glucose breakdown is aerobic in the brain.

The effect of five per cent carbon dioxide on the response of muscle blood flow to isoproterenol in man

Heart rate, muscle blood flow, and blood pressure were measured in 10 subjects. The administration of 5 per cent CO2 caused a fall in blood flow and an increase in mean arterial pressure without significant change in heart rate. An infusion of isoproterenol at a dose of 2 ug per minute caused an increase in flow, heart rate, and pulse pressure but no change in mean arterial blood pressure. The administration of 5 per cent CO2 during the isoproterenol infusion abolished the increase in muscle blood flow, produced an increase in mean arterial blood pressure, and caused an attenuation of the chronotropic effect of isoproterenol. These results suggest that certain cardiovascular effects of isoproterenol are altered during respiratory acidosis.