Increased calcium levels alter cellular and molecular events in wound healing

Surgical morbidity is dictated directly by wound healing. We have studied the effects of elevated calcium levels using cultured keratinocytes in vitro on two of the rate-limiting steps of wound healing, chemotaxis (directed migration) and adhesion. We found that the increased calcium (10 mmol/L) significantly inhibited both keratinocyte chemotaxis and adhesion (p less than 0.05). The calcium effect on adhesion could be partially reversed by pretreatment with the calcium channel blocker verapamil. Based on these data, an animal model was formulated in which topical calcium (5 mmol/L/day) was added to linear incision wounds. This resulted in significantly (p less than 0.05) delayed wound contraction characteristic of a chronic or impaired wound. Wound contraction depends on the presence of fibroblasts that synthesize collagen. The chronic wound was characterized by increased collagenase activity (p less than 0.05) but little alteration in collagen I synthesis. The addition of verapamil to these chronic wounds resulted in improved wound closure. These studies define the molecular and cellular events occurring as a result of the addition of elevated levels of calcium both in vitro and in vivo. Calcium may play a key role in the pathogenesis of chronic wounds.