Drug-Induced Vasodilation: The Effects of Sodium Nitroprusside, Hydralazine, and Cromakalin on the Rabbit Carotid Artery: In Vitro and in Vivo Study

ABSTRACT

Extreme arterial and venous constrictions are common problems in microvascular surgery, often leading to tissue injury and flap failure. The ideal pharmacologic tool to counteract ischemia should exert its action both locally and distally in the microcirculation of the flap. In this study, the vascular properties of sodium nitroprusside, hydralazine, and cromakalin were evaluated and compared in in vitro and in vivo models in the rabbit carotid artery. In the in vitro study, 20 rings from the rabbit carotid artery were bathed in Krebs-Ringers solution, stretched progressively to an optimal tension of 3.7 to 4.2 gm, and their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 μM) and a dose-response curve was established by adding cumulatively either sodium nitroprusside (n = 7), cromokalin (n = 7), or hydralazine (n = 7) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 19 animals using 9-0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride, and served as control. The other side was treated blindly with the topical application of 1 ml of either sodium nitroprusside (10 mg/ml, n = 5), hydralazine (20 mg/ml, n = 5), or cromakalin (25 mg/ml, n = 4), during and after the anastomoses. Blood-flow changes in the vessels were continuously monitored with the transonic Doppler applied to both carotid arteries for 60 min after the procedure.

Sodium nitroprusside and cromakalin elicited a concentration-dependent relaxation of norepinephrine-precontracted carotid artery rings in vitro. Sodium nitroprusside was significantly more effective than cromakalin in inducing relaxation. Hydralazine elicited a biphasic response, with low concentrations (1.5 × 10^-5 to 1.5 × 10^-3 M) potentiating the norepinephrine-induced contraction, and high concentrations relieving this contraction. Microsurgical anastomosis in the rabbit carotid artery-produced a significant decrease of blood flow through the vessel as measured by the transonic Doppler for 30 min. Topical application of heparinized saline did not significantly change the blood flow after the microvascular anastomosis. Topical application of sodium nitroprusside and cromakalin significantly increased the blood flow in the vessel after the anastomosis; however, the topical hydralazine did not significantly alter blood flow, but demonstrated a trend toward increased flow values.

The data support the conclusion that sodium nitroprusside and cromakalin could be used to relieve vascular constriction. It is suggested that further studies on the clinical use of these drugs in microsurgery is warranted.