Vascular Response after Directional Coronary Atherectomy for Left Main Bifurcation Lesion

Aims. To evaluate the vascular response after directional coronary atherectomy (DCA) for left main (LM) bifurcation lesion. Methods. This study was a retrospective, single-center study enrolling 31 patients who underwent stentless therapy using DCA followed by drug-coated balloon (DCB) angioplasty for LM bifurcation lesion. We compared intravascular ultrasound (IVUS) findings before and after DCA. Results. After DCA, the lumen and vessel areas significantly increased, whereas the plaque area (PA) and %PA were significantly reduced. When the lesions were divided into small vessel and large vessel groups using the median value of the vessel area, the maximum balloon pressure of the DCA catheter was greater in the large vessel group. Changes in the lumen and vessel areas were also significantly greater in the large vessel group. On the other hand, the changes in PA and %PA were similar between groups. Conclusions. The main vascular responses associated with lumen enlargement after DCA were plaque reduction and vessel expansion. Contribution of vessel expansion to lumen enlargement was larger than the effect of plaque reduction in large vessel lesions.

342 Cardiorespiratory fitness and systemic vascular resistance: oxygen pressure as a novel marker of peripheral vascular response during cardiopulmonary exercise testing

Aims The key role of systemic vascular resistance (SVR) in cardiovascular performance during exercise has been invasively demonstrated, however no data have been non-invasively obtained by analysing SVR response using cardiopulmonary exercise testing (CPET). To investigate the relationship between SVR at peak, maximum oxygen uptake (VO2 peak), and its determinants using CPET. Methods and results 1130 consecutive subjects were enrolled; according to physiology, SVR was determined as the ratio between mean arterial pressure (MAP) and cardiac output (CO). A novel parameter, named oxygen pressure (MAP peak/VO2 peak) was also created. Mean age was 61 ± 12 years and male gender was prevalent (61%); 66% of patients had arterial hypertension, 74% dyslipidaemia, 19% diabetes, 20% had smoking habit, and 26% previous history of cardiovascular (CV) disease. Significant inverse correlations between SVR peak and VO2/kg peak (P < 0.001), oxygen pulse (P < 0.001), CV efficiency (P < 0.001), chronotropic response (P < 0.001), and oxygen uptake exaction slope (P < 0.001) were found. Moreover, positive correlation between SVR peak and VE/VCO2 slope (P < 0.001) was observed. After multivariate analysis, the inverse correlation between peak SVR and peak VO2 remained significant (P < 0.001). Similar results were found considering oxygen pressure. Conclusions Low values of SVR at peak exercise, non-invasively evaluated with CPET, are associated with high levels of cardiorespiratory fitness. Oxygen pressure may represent a novel and simple CPET marker of peripheral vascular response to exercise, thereby representing a promising field of research in exercise medicine.

Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing

Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor expression in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.

Retinal Vascular Response to Hyperoxia in Patients with Diabetes Mellitus without Diabetic Retinopathy

Purpose. To evaluate the retinal vascular response to hyperoxia in patients with diabetes at the preclinical stage of diabetic retinopathy (DR) and to quantify the changes in comparison with normal subjects using optical coherence tomography angiography (OCTA). Methods. In this prospective study, 40 eyes of 20 participants comprising 10 diabetic patients with no diabetic retinopathy (NDR) and 10 normal subjects were recruited. OCTA images were acquired in the resting position and were repeated after a hyperoxic challenge using a nasal mask connected to a reservoir bag supplying 100% oxygen at the rate of 15 L per minute for 5 minutes. The changes of mean parafoveal vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the foveal avascular zone (FAZ) size, and the outer retina flow index were compared between two conditions in each group and between the two study groups. The statistical significance of differences in the means was evaluated using Student’s t-test for unpaired samples with consideration of the generalized estimating equations (GEE) for intereye correlation. Results. At baseline, the mean parafoveal VD of SCP and DCP were significantly lower in the NDR participants compared to the healthy subjects (P < 0.001 and P = 0.006, respectively). After induction of the hyperoxic challenge in healthy participants, mean parafoveal VD reduced at both the SCP and DCP, but reached a statistical significance only in DCP (P = 0.006). However, following induction of hyperoxic challenge in patients with NDR, no significant decline was noticed in mean parafoveal VD of SCP and DCP. The degree of change in mean parafoveal VD of DCP was statistically significantly more pronounced in healthy subjects compared to the NDR group (P = 0.034). The change in FAZ size and the outer retina flow index were comparable between the two study groups. Conclusion. Retinal capillary layers responded differently to hyperoxia-induced challenge, and in normal subjects, the autoregulatory mechanism was mostly effective in the parafoveal DCP. Retinal vascular reactivity was impaired in SCP and DCP at the preclinical stage of DR. OCTA as a noninvasive modality was able to quantify the retinal vascular response to the hyperoxic challenge.

Direct Deviations in Astrocyte Free Ca2+ Concentration Control Multiple Arteriole Tone States

Astrocytes elicit bidirectional control of microvascular diameter in acutely isolated brain slices through vasoconstriction and vasodilation pathways that can be differentially recruited via the free Ca2+ concentration in endfeet and/or the metabolic status of the tissue. However, the Ca2+-level hypothesis has not been tested using direct manipulation. To overcome this, we used Ca2+-clamp whole-cell patching of peri-arteriole astrocytes to change astrocyte-free Ca2+ to different concentrations and examined the vascular response. We discovered that clamping Ca2+ at the approximate resting value (100 nM) had no impact on arteriole diameter in a pre-constricted arteriole. However, a moderate elevation to 250 nM elicited sustained vasodilation that was blocked by the COX-1 antagonist SC-560 (500 nM). The vasodilation to 250 nM Ca2+ was sensitive to the metabolic state, as it converted to vasoconstriction when oxygen tension was dramatically elevated. In normal oxygen, clamping astrocyte Ca2+ well above the resting level (750 nM) produced sustained vasoconstriction, which converted to vasodilation in the 20-HETE blocker HET0016 (1 μM). This response was fully blocked by the addition of SC-560 (500 nM), showing that 20-HETE-induced vasoconstriction dominated the dilatory action of COX-1. These data demonstrate that direct changes in astrocyte free Ca2+ can control multiple arteriole tone states through different mediators.

Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity

The Spaceflight Associated Neuro-ocular Syndrome (SANS), associated with the headward fluid shifts incurred in microgravity during long-duration missions, remains a high-priority health and performance risk for human space exploration. To help characterize the pathophysiology of SANS, NASA’s VESsel GENeration Analysis (VESGEN) software was used to map and quantify vascular adaptations in the retina before and after 70 days of bed rest at 6-degree Head-Down Tilt (HDT), a well-studied microgravity analog. Results were compared to the retinal vascular response of astronauts following 6-month missions to the International Space Station (ISS). By mixed effects modeling, the trends of vascular response were opposite. Vascular density decreased significantly in the 16 retinas of eight astronauts and in contrast, increased slightly in the ten retinas of five subjects after HDT (although with limited significance). The one astronaut retina diagnosed with SANS displayed the greatest vascular loss. Results suggest that microgravity is a major variable in the retinal mediation of fluid shifts that is not reproduced in this HDT bed rest model.

The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia

Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.