MYOCARDIAL CHANGES IN RATS WITH LITHIUM‐INDUCED URAEMIA

The possible effects of lithium on myocardial morphology were studied at the light‐microscopic level in three different rat models: (i) rats with chronic renal failure due to lithium administration for 8–16 weeks after birth, (ii) normal, adult rats treated with lithium for 16 weeks, and (iii) new‐born rats exposed to lithium in their prenatal life. Morphological changes were found in 57% of the male rats with lithium‐induced uraemia after lithium administration for 16 weeks postnatally. The changes comprised myocytic degeneration and necrosis associated with infiltration of lymphocytes, histiocytes and plasma cells. This morphological picture is different from the myocardial changes associated with chronic renal failure. Male rats with chronic uraemia after withdrawal of lithium 8 weeks postnatally showed no myocardial changes after 16 weeks. Also, male rats with normal renal function had no myocardial changes after 16 weeks on lithium, but these rats had a significantly lower plasma level of lithium than the lithium‐uraemic rats (0.8 vs. 1.4 mmol/1). It is suggested that myocarditis was a consequence of persistent high plasma levels of lithium maintained in the lithium‐uraemic rats and that cardiotoxic effects of lithium may be potentiated by concomitant renal failure.