Topical and systemic calcium channel blockers in the prevention and treatment of microvascular spasm in a rat epigastric island skin flap model.

ABSTRACT

Vasospasm is a frustrating problem commonly encountered in microvascular surgery. Extreme arterial vasoconstriction usually occurs intraoperatively, shortly after release of the vascular clamps, but can be a problem for 48 to 72 hours postoperatively. Failure to alleviate vasospasm can have disastrous consequences in replanted and revascularized tissues, ultimately resulting in microsurgical failure. The authors investigated the efficacy of topical and systemic administration of two commonly prescribed calcium channel blockers-nifedipine and verapamil-in both the prevention and treatment of vasospasm in a rat epigastric island skin flap model. Superficial epigastric island skin flaps were elevated in 60 Sprague-Dawley rats. Femoral vessels were isolated from the inguinal ligament to a point 1 cm distal to the origin of the epigastric vessels, and the feeding vessels were ligated. The flap was returned to its natural anatomic bed and was sutured into place, leaving the femoral vessels exposed. The femoral artery and vein were transected, and anastomoses were performed under the operating microscope. A block of ice was then applied directly to the anastomotic site for 1 minute to induce additional vasospasm. Groups I through III received topical application of solutions of 0.5 ml of either 0.9% normal saline (control), verapamil (2.5 mg per milliliter), or nifedipine (5 mg per milliliter) directly to the anastomotic site immediately prior to release of the vascular clamps. Groups IV through VI received intraperitoneal injections of 1.0-ml solutions of either 0.9% normal saline (control), verapamil (2.5 mg per milliliter), or nifedipine (5 mg per milliliter) at 30 minutes prior to performing the anastomoses. Thermocouple temperature probes reflecting blood flow were placed at the center of the skin flap in a subcutaneous position, at the proximal femoral artery, and at the takeoff of the epigastric artery. Accurate, direct temperature measurements of the isolated skin flap and femoral vessels were recorded at 10, 20, and 30 minutes after release of the vascular clamps. Topical and systemic administration of verapamil and nifedipine moderated significantly the temperature declines observed at 10 minutes at the level of the femoral artery proximally and distally compared with controls. Following this decline, groups I through III (topical) demonstrated significant recovery of temperature toward baseline, with verapamil and nifedipine showing significantly better recovery of temperature than controls. Groups IV through VI (systemic) demonstrated a stabilization of temperature without any significant additional recovery of temperature toward baseline. Verapamil was more effective than nifedipine in its actions when administered topically or systemically. The authors' results suggest a potential role for topical and systemic administration of verapamil and nifedipine in preventing, or at least minimizing, the deleterious effects of vasospasm on flap survival, as demonstrated by its temporizing effect on temperature change across the anastomosis in their model.