Mathematical model for describing cerebral oxygen desaturation in patients undergoing deep hypothermic circulatory arrest.

BACKGROUND: Surgical treatment for aortic arch disease requiring periods of circulatory arrest is associated with a spectrum of neurological sequelae. Cerebral oximetry can non-invasively monitor patients for cerebral ischaemia even during periods of circulatory arrest. We hypothesized that cerebral desaturation during circulatory arrest could be described by a mathematical relationship that is time-dependent. METHODS: Cerebral desaturation curves obtained from 36 patients undergoing aortic surgery with deep hypothermic circulatory arrest (DHCA) were used to create a non-linear mixed model. The model assumes that the rate of oxygen decline is greatest at the beginning before steadily transitioning to a constant. Leave-one-out cross-validation and jackknife methods were used to evaluate the validity of the predictive model. RESULTS: The average rate of cerebral desaturation during DHCA can be described as: Sct(o(2))[t]=81.4-(11.53+0.37 x t) (1-0.88 x exp (-0.17 x t)). Higher starting Sct(o(2)) values and taller patient height were also associated with a greater decline rate of Sct(o(2)). Additionally, a predictive model was derived after the functional form of a x log (b+c x delta), where delta is the degree of Sct(o(2)) decline after 15 min of DHCA. The model enables the estimation of a maximal acceptable arrest time before reaching an ischaemic threshold. Validation tests showed that, for the majority, the prediction error is no more than +/-3 min. CONCLUSIONS: We were able to create two mathematical models, which can accurately describe the rate of cerebral desaturation during circulatory arrest at 12-15 degrees C as a function of time and predict the length of arrest time until a threshold value is reached.

The integrin-mediated cyclic strain-induced signaling pathway in vascular endothelial cells.

The irregular distribution of plaque in the vasculature results from the interaction of local hemodynamic forces with the vessel wall. One well-characterized force is cyclic circumferential strain, the repetitive pulsatile pressure distention on the arterial wall. This review summarizes current research, which has aimed to elicit the signal transduction pathway by which cyclic strain elicits functional and structural responses in endothelial cells; specifically, it summarizes the signaling pathway that begins with the reorganization of integrins. One method by which these extracellular matrix receptors affect signal transduction is through their ability to initiate the process of phosphorylation on tyrosine residues of cytoplasmic protein kinases, including focal adhesion kinase. The strain-induced pathway appears to also involve ras and the mitogen-activated protein kinase family of enzymes, and preliminary data suggests a role for src as well. Ultimately, it is the regulation of gene expression through the modulation of transcription factors that allows endothelial cells to respond to changes in local hemodynamics.

Vascular smooth muscle cell effect on endothelial cell endothelin-1 production.

Endothelin-1 (ET-1) is a potent mitogen secreted by endothelial cells (ECs) in culture and is a putative factor in vascular lesion development. The purpose of this study was to examine whether smooth muscle cells (SMCs) inhibit EC secretion of ET-1. The effect of SMCs on EC ET-1 and constitutively expressed nitric oxide (NO) synthase activity was examined by using a bilayer co-culture model. SMCs inhibited both EC ET-1 protein and RNA levels, compared with ECs cultured alone. SMCs increased EC NO production when compared with ECs cultured alone. In addition, SMC inhibition of EC ET-1 production could be blocked by the NO synthase inhibitor N(G)-nitro-L-arginine-methyl ester. ECs stimulated SMC proliferation, and the ET-1 AB and B receptor blockers inhibited EC stimulation of SMC proliferation. The ET-1 A blocker had no effect on SMC proliferation. We conclude that SMCs regulate EC ET-1 and ecNOS synthase transcript levels and protein levels. SMC inhibition of ET-1 production by ECs may be mediated through SMC-modulated changes in EC NO activity. Finally, EC stimulation of SMC proliferation in bilayer co-culture is mediated by ET-1 through the ET-1 B receptor.