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Two patients in whom the bispectral index (BIS) decreased to zero following cardiac arrest during cardiothoracic surgery are described. The BIS value decreased to zero after cardiac arrest, and the value remained low for the remainder of the anesthetic despite successful cardiopulmonary resuscitation. Both patients were found to have severe brain injuries in the postoperative period.

Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human coronary arteries, we determined if VEGF could stimulate VSMC migration and the intracellular signals involved. VEGF induced VSMC migration but had no significant activity on proliferation. VEGF increased intracellular reactive oxygen species (ROS), NF-kappaB activation and IL-6 expression. Blockade of the generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-kappaB activation, IL-6 expression, and cell migration indicating that generation of ROS was required for NF-kappaB activation and the chemotactic activity of VEGF. Expression of a mutated, nondegradable form of inhibitor of NF-kappaB (IkappaB-alphaM) suppressed VEGF-triggered activation of NF-kappaB and upregulation of IL-6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly attenuated the migration stimulated by VEGF. Collectively, our data provide the first evidence that intracellular ROS and NF-kappaB are required for VEGF-mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved in the ability of the growth factor to stimulate migration., (Copyright 2001 Academic Press.)

A-type natriuretic peptide (ANP) is found primarily in the heart and is released into the circulation. C-type (CNP) is found principally in the brain and has also been detected in the systemic circulation. When injected, both peptides produce vasodilatation most likely by elevation of guanosine 3'5'-cyclic monophosphate (cGMP) in smooth muscle cells via two distinct receptors, NPR-A and NPR-B. In this present study, we determined the effects of these two peptides on intracellular cGMP in smooth muscle cells cultured from pig cerebral and peripheral arteries. In smooth muscle cells cultured from the left anterior descending coronary artery, ANP and CNP increased cGMP with equal potency and efficacy (EC50 for ANP and CNP, 3.6 +/- 0.2 x 10(-8) M and 6.7 +/- 0.8 x 10(-8) M, respectively). In contrast, in smooth muscle cells from cerebral arteries, ANP was without effect while CNP increased cGMP in a concentration dependent manner (EC50: 9.6 +/- 1.7 x 10(-8) M). Stimulation of the soluble guanylyl cyclase with either nitroglycerin or nitroprusside was equivalent in the two cell types. The pattern of response of intracellular cGMP to CNP and ANP in isolated intact arteries from brain and heart was similar to that found in the cultured cells. These results suggest that smooth muscle cells in cerebral arteries express only NPR-B while cells from peripheral arteries can express both NPR-A and NPR-B.

Atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) increase cGMP in vascular smooth muscle cells and act as vasodilators in some, but not all, blood vessels. In this present study, we attempted to correlate the ability of these two agents to dilate blood vessels with the ability to increase cGMP in cultured vascular smooth muscle cells. In the isolated guinea pig heart, SNP dose-dependently increased coronary flow while ANP was ineffective. In smooth muscle cells cultured from the coronary system, SNP increased intracellular cGMP in a dose-dependent manner while ANP had no effect on cGMP in these cells. In isolated guinea-pig thoracic aorta, precontracted with K+, both ANP and SNP produced relaxation and ANP was the more potent. In smooth muscle cells cultured from the aorta, ANP and SNP increased cGMP and the potency relationship was similar to the intact vessel. These results support the view that phenotypic properties of vascular smooth muscle cells can account for differences in the response of blood vessels to vasodilators.