THE EFFECT OF VERAPAMIL AND DILTIAZEM ON ALVEOLAR TYPE-II CELLS DURING WARM AND COLD METABOLIC ISCHEMIA

The alteration of cytosolic free calcium concentration is an important event during cellular ischaemia. Calcium channel blockers have been s hown to be beneficial during experimental ischaemic organ protection. To investigate the mechanisms of this protection, the behaviour of typ e II pneumocyte cultures, subjected to warm and cold metabolic ischaem ia (6 h), was studied. The cells were incubated in electrolytic soluti ons and treated with high doses of verapamil (10 mg/l) or diltiazem (1 00 mg/l). Alveolar type II epithelial cells were removed from adult ra t lungs using the modified Dobbs' method. Cell viability was determine d by analysis of the total protein content, and from the rate of prote in synthesis as indicated by the [S-35]methionine uptake assay. The re sults show that verapamil does not have a direct cytoprotective or cyt otoxic effect on the incubated cells, but diltiazem seems to be toxic to the cells, especially during cold ischaemia when the toxicity is si gnificant (P < 0.05). Thus, the protection from ischaemia previously a ttributed to calcium channel blockers is ascribed to action on the blo od vessels resulting in vasodilatation, rather than to a direct influe nce on cytosolic free calcium homeostasis.