Pulse Decomposition Analysis of the digital arterial pulse during hemorrhage simulation

Background

Markers of temporal changes in central blood volume are required to non-invasively detect hemorrhage and the onset of hemorrhagic shock. Recent work suggests that pulse pressure may be such a marker. A new approach to tracking blood pressure, and pulse pressure specifically is presented that is based on a new form of pulse pressure wave analysis called Pulse Decomposition Analysis (PDA). The premise of the PDA model is that the peripheral arterial pressure pulse is a superposition of five individual component pressure pulses, the first of which is due to the left ventricular ejection from the heart while the remaining component pressure pulses are reflections and re-reflections that originate from only two reflection sites within the central arteries. The hypothesis examined here is that the PDA parameter T13, the timing delay between the first and third component pulses, correlates with pulse pressure. T13 was monitored along with blood pressure, as determined by an automatic cuff and another continuous blood pressure monitor, during the course of lower body negative pressure (LBNP) sessions involving four stages, -15 mmHg, -30 mmHg, -45 mmHg, and -60 mmHg, in fifteen subjects (average age: 24.4 years, SD: 3.0 years; average height: 168.6 cm, SD: 8.0 cm; average weight: 64.0 kg, SD: 9.1 kg).

Results

Statistically significant correlations between T13 and pulse pressure as well as the ability of T13 to resolve the effects of different LBNP stages were established. Experimental T13 values were compared with predictions of the PDA model. These interventions resulted in pulse pressure changes of up to 7.8 mmHg (SE = 3.49 mmHg) as determined by the automatic cuff. Corresponding changes in T13 were a shortening by -72 milliseconds (SE = 4.17 milliseconds). In contrast to the other two methodologies, T13 was able to resolve the effects of the two least negative pressure stages with significance set at p < 0.01.

Conclusions

The agreement of observations and measurements provides a preliminary validation of the PDA model regarding the origin of the arterial pressure pulse reflections. The proposed physical picture of the PDA model is attractive because it identifies the contributions of distinct reflecting arterial tree components to the peripheral pressure pulse envelope. Since the importance of arterial pressure reflections to cardiovascular health is well known, the PDA pulse analysis could provide, beyond the tracking of blood pressure, an assessment tool of those reflections as well as the health of the sites that give rise to them.     

Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling

In certain epithelial tissues, activation of transient receptor potential (TRP) vanilloid subtype 1 (TRPV1) by noxious stimuli induces pro-inflammatory cytokine release, which helps to mitigate the challenge. While the corneal epithelium elicits such responses to a variety of challenges, it remains unknown whether TRPV1 mediates pro-inflammatory cytokine secretion. Accordingly, we probed for TRPV1 expression and function in human (HCEC) and rabbit corneal epithelial cell (RCEC) lines, in their primary counterparts, and in human and mouse corneal epithelium in situ. Cell membrane and perinuclear TRPV1 expression was detected in all preparations and its identity verified by Western blot analysis. Capsaicin (CAP) (1-10 microM) increased nonselective cation channel whole cell currents (2.5-fold +/- 0.5-fold between -60 and 130 mV), resulting in calcium transients that were fully blocked by the TRPV1 antagonists capsazepine (CPZ) and ruthenium red, or removal of extracellular calcium. Another signaling event involved transient activation of global mitogen-activated protein kinase (MAPK) superfamily, which was followed by up to 3.3- and 9-fold increases in interleukins (IL)-6 and -8 release, respectively. Such increases in inflammatory mediators' release were suppressed by exposure to CPZ or MAPK inhibitors, or removal of Ca2+. Taken together, TRPV1 receptors may play a role in mediating corneal epithelial inflammatory mediator secretion and subsequent hyperalgesia.     

Cannabinoids inhibit HIV-1 Gp120-mediated insults in brain microvascular endothelial cells

HIV-1 infection has significant effect on the immune system as well as on the nervous system. Breakdown of the blood-brain barrier (BBB) is frequently observed in patients with HIV-associated dementia (HAD) despite lack of productive infection of human brain microvascular endothelial cells (HBMEC). Cellular products and viral proteins secreted by HIV-1 infected cells, such as the HIV-1 Gp120 envelope glycoprotein, play important roles in BBB impairment and HIV-associated dementia development. HBMEC are a major component of the BBB. Using cocultures of HBMEC and human astrocytes as a model system for human BBB as well as in vivo model, we show for the first time that cannabinoid agonists inhibited HIV-1 Gp120-induced calcium influx mediated by substance P and significantly decreased the permeability of HBMEC as well as prevented tight junction protein down-regulation of ZO-1, claudin-5, and JAM-1 in HBMEC. Furthermore, cannabinoid agonists inhibited the transmigration of human monocytes across the BBB and blocked the BBB permeability in vivo. These results demonstrate that cannabinoid agonists are able to restore the integrity of HBMEC and the BBB following insults by HIV-1 Gp120. These studies may lead to better strategies for treatment modalities targeted to the BBB following HIV-1 infection of the brain based on cannabinoid pharmacotherapies.