The impact of temperature on vascular function in connection with vascular laser treatment.

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.

Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review.

With the introduction of endovascular thrombectomy (EVT), a new era for treatment of acute ischemic stroke (AIS) has arrived. However, despite the much larger recanalization rate as compared to thrombolysis alone, final outcome remains far from ideal. This raises the question if some of the previously tested neuroprotective drugs warrant re-evaluation, since these compounds were all tested in studies where large-vessel recanalization was rarely achieved in the acute phase. This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. A literature search was performed using the search terms "ischemic stroke brain" in title/abstract, and additional filters. After exclusion of papers using pre-defined selection criteria, a total of 89 trials were eligible for review which reported on 56 unique compounds. Trial compounds were divided into 6 categories based on their perceived mode of action: systemic haemodynamics, excitotoxicity, neuro-inflammation, blood-brain barrier and vasogenic edema, oxidative and nitrosative stress, neurogenesis/-regeneration and -recovery. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy. Finally, possible theories behind individual and group effects are discussed and recommendation for promising treatment strategies are described.

Impact of Intracranial Aneurysm Morphology and Rupture Status on the Particle Residence Time.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics play an important role in aneurysm growth and subsequent rupture. Within the available hemodynamic characteristics, particle residence time (PRT) is relatively unexplored. However, some studies have shown that PRT is related to thrombus formation and inflammation. The goal of this study is to evaluate the association between PRT and aneurysm rupture and morphology. METHODS: We determined the PRT for 113 aneurysms (61 unruptured, 53 ruptured) based on computational fluid dynamic models. Virtual particles were injected into the parent vessel and followed during multiple cardiac cycles. PRT was defined as the time needed for 99% of the particles that entered an aneurysm to leave the aneurysm. Subsequently, we evaluated the association between PRT, rupture, and morphology (aneurysm type, presence of blebs, or multiple lobulations). RESULTS: PRT showed no significant difference between unruptured (1.1 seconds interquartile range [IQR .39-2.0 seconds]) and ruptured aneurysms (1.2 seconds [IQR .47-2.3 seconds]). PRT was influenced by aneurysm morphology. Longer PRTs were seen in bifurcation aneurysms (1.3 seconds [IQR .54-2.4 seconds], P = .01) and aneurysms with blebs or multiple lobulations (1.92 seconds [IQR .94-2.8 seconds], P < .001). Four of five partially thrombosed aneurysms had a long residence time (>1.9 seconds). CONCLUSIONS: Our study shows an influence of aneurysm morphology on PRT. Nevertheless, it suggests that PRT cannot be used to differentiate unruptured and ruptured aneurysms.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.

Intracranial blood-flow velocity and pressure measurements using an intra-arterial dual-sensor guidewire.

Hemodynamics is thought to play a role in the growth and rupture of intracranial aneurysms. In 4 patients, we obtained local pressure and BFV by using a dual-sensor pressure and Doppler velocity wire within and in vessels surrounding unruptured aneurysms. Local BFVs can serve as boundary conditions for computational fluid dynamics, whereas pressure recordings provide direct information on the mechanical load imposed on the aneurysm. Both measurements may thus add to patient-specific rupture-risk assessment.