SUMMARY Autonomic function was assessed in subjects with acute intermittent porphyria and age-and sex-matched controls using five different bedside tests of cardiovascular reflexes. During the acute attack both parasympathetic and sympathetic tests were impaired, but subsequently improved during remission. Early parasympathetic dysfunction was also detected during remission and in latent asymptomatic acute intermittent porphyria.Acute intermittent porphyria is an autosomal dominant inborn error of metabolism characterised by a partial deficiency in the activity of the haem biosynthetic enzyme, porphobilinogen deaminase (PBG). Consequently the porphyrin precursors delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG) accumulate in blood and are excreted in excessive amounts in the urine.' 2The clinical manifestations of acute intermittent porphyria have been attributed to a widespread neurological dysfunction caused by the block in haem biosynthesis.34 Abdominal pain is the commonest and often the most troublesome symptom which occurs in more than 90% of cases.5 It has been explained on the basis of splanchnic autonomic dysfunction, thus providing a mechanism for the intestinal dilatation and stasis occasionally noted radiologically and at laparotomy in patients suffering from an acute attack.6 Indeed, many of the accompanying features of an acute attack are suggestive of autonomic neuropathy; namely, the inappropriate sinus tachycardia, labile hypertension, postural hypotension, excessive sweating, severe vomiting, constipation and occasional diarrhoea and sphincteric bladder problems.5 78 Ridley et al have reported that tachycardia invariably preceded the development of peripheral neuropathy and respiratory paralysis, and they postulated that the tachycardia of porphyria might be due to autonomic cardioneuropathy.5 The transient and labile hypertension which commonly accompanies the acute attack has also been given a neurogenic explanation follow-

Conduction velocity is dependent on two main factors: intercellular electrical coupling and cellular electrical excitability. There is significant redundancy, 'conduction reserve', in these parameters such that significant reduction in the conduction velocity of the action potential requires either a severe change in one of these parameters or a combined change in both parameters. Studies in diabetic rat hearts have shown a significant reduction in the conduction reserve and it was hypothesized that this is mainly due to the lateralization of the gap junction protein connexin 43 (Cx43). To gain a better understanding of the effect of reduced intercellular coupling, a rat ventricle myocyte model was used to simulate propagation along a strand of cells. Simulations were performed to assess the effect of reduction of intercellular conductance on the conduction velocity. As the conductance of the gap junction decreased a significant reduction in the conduction velocity was observed. The relationship between conduction velocity and intercellular coupling became steeper with decreasing coupling, such that conduction velocity became increasingly sensitive to further uncoupling. This is consistent with experimental results, in which application of the gap junction uncoupler heptanol caused a larger conduction slowing in diabetic hearts than in controls.