Physiologic Effects of Xenon in Xenon-CT Cerebral Blood Flow Studies on Comatose Patients.

Despite more than 30 years of clinical use, questions remain about the safety of xenon gas in Xenon-CT cerebral blood flow (XeCTCBF) studies. In particular, xenon's effect on brain oxygen (PbtO2) in comatose patients is not well defined. Our objective was to assess the effect of a 4.5-min inhalation of 28 % stable xenon on several physiologic variables, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO2 in comatose patients (Glasgow Coma Scale [GCS] ≤ 8). Thirty-seven comatose patients who underwent 73 XeCTCBF studies were identified retrospectively from a prospective observational database. Changes in MAP, HR, SaO2, EtCO2, ICP, CPP, and PbtO2 measured at the start of xenon administration and every minute for 5 min thereafter were assessed. The maximum change in each variable also was determined for each scan to tabulate clinically relevant changes. Statistically, but not clinically significant changes in MAP, HR, and EtCO2 were seen. Xenon had no effect on ICP, and a small, but clinically insignificant decrease in CPP and PbtO2, was observed. There was a varied response to xenon in most measured variables. Clinically significant changes in each were infrequent, and readily reversed with the cessation of the gas. We conclude that xenon does not appear to have a clinically significant effect on ICP, CPP, and PbtO2 and so appears safe to evaluate cerebral blood flow in comatose patients.

Cyclic strain activates the pro-survival Akt protein kinase in bovine aortic smooth muscle cells.

BACKGROUND: Pulsatile pressure induced by the beating heart causes cyclic strain on arterial endothelial cells and smooth muscle cells (SMCs). This study examined whether Akt, a serine/threonine protein kinase known to promote cell survival by inhibiting apoptosis, is activated by cyclic strain in bovine aortic SMCs. METHODS: Bovine aortic SMCs were cultured on flexible-bottomed membranes and then serum-starved for 24 to 36 hours. The cells were then exposed to 150-mm Hg repetitive deformations, which created an average of 10% strain on the monolayer SMCs at a frequency of 60 cycles/minute for 0 (negative control) and 30 minutes. Platelet-derived growth factor (PDGF)--stimulated SMCs were used as positive controls. Phosphorylation of Akt was determined by means of Western blot analysis. An apoptosis assay (TUNEL) was also performed on SMCs exposed to cyclic strain. RESULTS: Akt phosphorylation was significantly increased over that of the negative control after 30 minutes of cyclic strain and in the PDGF group. Cyclic strain did not increase the prevalence of apoptosis in SMCs over the control. CONCLUSIONS: Cyclic strain activated the pro-survival Akt kinase. The pro-survival function was supported by the fact that cyclic strain did not increase apoptosis in bovine aortic SMCs. This experiment suggests that cyclic strain may induce arterial wall thickening by tipping the balance toward arterial SMC proliferation through the inhibition of apoptosis.

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.

Intermittent pneumatic compression devices -- physiological mechanisms of action.

There are many reports of how IPC is used effectively in the clinical setting; including the prevention of deep venous thrombosis, improvement of circulation in patients with lower extremity arterial diseases, reduction of lymphoedema, and the healing of venous ulcers. However, despite the widely accepted use of IPC, it is still unclear how IPC actually exerts its beneficial effects. The exact physiological mechanisms of action are unknown. The clinical utility of IPC and the putative mechanisms by which IPC could exert its therapeutic effect will be reviewed. The paper will examine the mechanical effects of IPC exerted on the lower extremity, and the subsequent biochemical changes in the circulation. In vitro studies of the effects of mechanical stress such as compressive strain and shear on cultured endothelial cells, and their clinical relevance to IPC will also be reviewed.

Gender does not impact infrainguinal vein bypass graft outcome.

BACKGROUND: The percentage of women requiring infrainguinal bypass graft operations continues to increase, whereas the effect of gender on postoperative outcome remains unclear. The purpose of this study was to assess the influence of gender on patient selection and outcome in patients requiring infrainguinal vein bypass grafting procedures. METHODS: This retrospective study reviewed 217 infrainguinal vein bypass grafts performed over an 8-year period. Medical records and patient interviews were used to determine study measures and outcomes. Gender and multiple covariables affecting patient survival were analyzed; postoperative complications and graft patencies were examined. Bivariate and life-table analyses were conducted, followed by multivariate analysis with the Cox proportional hazards model. RESULTS: No statistical differences existed between men and women for age, diabetes, cardiac disease, tobacco use, hypertension, stroke, renal disease, or prior contralateral bypass or major amputation. Women were more likely to be black (P =.014) and have a spliced vein graft (P =.035). No differences were noted between the 2 groups for 30-day morbidity rates-except women had more incisional complications (P =.01)-or for survival (P =.45), primary-patency (P =.57), secondary-patency (P =. 79), or limb-salvage rates (P =.40). Multivariate analysis showed that gender had no role in affecting survival rates. CONCLUSIONS: Gender does not affect graft patency, limb salvage, or survival rates. There should be no introduction of a gender bias into management of infrainguinal occlusive disease.

Localization of atherosclerosis: role of hemodynamics.

Atherosclerosis is a chronic disease attributed to risk factors that are systemic in nature. Yet the lesions involved do not occur in random fashion. The coronary arteries, the major branches of the aortic arch, and the abdominal aorta and its visceral and major lower extremity branches are particularly susceptible sites. Hemodynamic forces interacting with an active vascular endothelium are responsible for localizing lesions in a nonrandom pattern of distribution. Shear stress and cyclic circumferential strain are the predominant forces that have been characterized. The modification of endothelial cell structure and function by these mechanical forces sheds insight into the vasculature's propensity for atherogenesis.