THE HEMODYNAMIC ABNORMALITIES IN SHORT-TERM INSULIN DEFICIENCY - THE ROLE OF PROSTAGLANDIN INHIBITION

It has been suggested that the hemodynamic derangements present in dia betic ketoacidosis are the results not only of profound volume depleti on but also of the effects of increased production of vasodilating pro staglandins (PGs), principally PGI(2), released by adipose tissue, In animal and in vitro models, prostaglandin synthesis is increased durin g insulin deficiency, We assessed the effects of short-term ketosis on the metabolic and hemodynamic variables of 10 IDDM patients free from long-term complications and of 9 normal control subjects after a 7-da y randomized double-blind indomethacin (INDO) (50 mg q.i.d.) or placeb o treatment period, Calf blood flow (CBF), postocclusive reactive hype remia (PORH), and recovery half-time (an index of overall perfusion) a fter PORH were measured by plethysmography, Left ventricular and myoca rdial functions were also studied in each different condition during p lacebo and lNDO treatment in IDDM patients, During placebo treatment, the increase in CBF during ketosis was higher (1.75 +/- 0.29 ml . min( -1) . 100 ml muscle(-1)) than during INDO (0.85 +/- 0.17 ml . min(-1) . 100 ml muscle(-1): P = 0.007), PORH was similar in baseline conditio ns, during ketosis, and in recovery in both the placebo and INDO arms, Recovery half-time significantly increased during placebo (10 +/- 2; 200%; P < 0.01) but not during INDO (1 +/- 1; 106%; NS) treatment, In normal control subjects, insulin deficiency did not induce any signifi cant effect on hemodynamic variables, In IDDM patients, during placebo treatment, ketosis increased both the cardiac index (from 3.4 +/- 0.7 to 4.1 +/- 0.81 . min(-1) . m(-2); P < 0.01) and the stroke index (fr om 42 +/- 8 to 49 +/- 7 ml/m(2); P < 0.01) without changes in left ven tricular ejection fraction but with a significant increase in both lef t and right ventricular end-diastolic volumes, Metabolic recovery indu ced a normalization of these parameters, INDO treatment significantly blunted these alterations, In summary, we showed that during acute ins ulin deficiency, INDO-sensitive mechanisms mediate vascular disturbanc es, Moreover, INDO treatment was capable of completely preventing the cardiac venous return and the left ventricular alterations, INDO does not interfere with the overall ketogenetic process or with insulin-ind uced metabolic recovery.