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(Circulation. 2004;110:79-83.)
© 2004 American Heart Association, Inc.

Original Articles

Extracellular Calcium and Vascular Responses After Forearm Ischemia

Virginia A. Imadojemu, MD; Kenneth Mooney, MD; Cindy Hogeman, BA, BSN, RN; Mary E.J. Lott, PhD; Allen Kunselman, BS, MA; Lawrence I. Sinoway, MD

From the Division of Pulmonary, Allergy, and Critical Care (V.A.I., K.M.) and the Division of Cardiology (C.H., M.E.J.L., L.I.S.) and Department of Health Evaluation Sciences (A.K.), The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pa; and Lebanon VA Medical Center (L.I.S.), Lebanon, Pa.

Correspondence to Lawrence I. Sinoway, MD, Division of Cardiology, MC H047, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, PO Box 850, Hershey, PA 17033. E-mail lsinoway{at}psu.edu

Received July 1, 2003; de novo received January 26, 2004; accepted March 13, 2004.

Background— The myogenic response is a phenomenon in which blood vessels respond to increases and decreases in transmural pressure with constriction and dilation, respectively. Despite intense investigation into the signaling mechanisms underlying this response, the precise mechanisms remain unclear. It has been suggested that the myogenic response occurs when pressure or stretch evokes increases in vessel wall tension that results in vessel smooth muscle cell depolarization. This causes Ca²⁺ entry through voltage-gated Ca²⁺ channels. Of note, in vitro studies demonstrate that the magnitude of the myogenic response is dependent on the extracellular Ca²⁺. We tested the hypothesis that in conscious humans, physiological changes in extracellular Ca²⁺ concentrations would be an important determinant of the myogenic response.

Methods and Results— Venous blood ionized calcium was used as an index of interstitial calcium and was measured 5, 15, and then every 15 seconds for 75 seconds, then every 30 seconds for 90 seconds, then finally at the 300-second mark. Forearm blood pressure and flow velocity were determined after 10 minutes of forearm ischemia. We found that the rate of change in serum calcium levels varied as a function of transmural pressure (r=0.96). Moreover, the calcium concentration was inversely proportional to forearm blood velocity (r=0.99).

Conclusions— We hypothesize that muscle stretch caused by a rise in transmural pressure raises interstitial calcium by unknown mechanisms and this in turn acts to lower limb flow velocity.

Key Words: blood flow • calcium • vasoconstriction

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