Comparison of embolization strategies for mixed plexiform and fistulous brain arteriovenous malformations: a computational model analysis of theoretical risks of nidus rupture

BackgroundHigh-flow fistulas related to plexiform nidi are found in 40% of large brain arteriovenous malformations (AVMs). Endovascular occlusion of intranidal fistulas before plexiform components is empirically considered safe, but potential ensuing dangerous re-routing of flow through plexiform vessels may in theory raise their rupture risk. It remains unclear whether it is safer to embolize plexiform or fistulous vessels initially. We used a novel biomathematical AVM model to compare theoretical hemodynamic changes and rupture risks on sequential embolizations of both types of nidus vessels.MethodsWe computationally modeled a theoretical AVM as an electrical circuit containing a nidus consisting of a massive stochastic network ensemble comprising 1000 vessels. We sampled and individually simulated 10 000 different nidus morphologies with a fistula angioarchitecturally isolated from its adjacent plexiform nidus. We used network analysis to calculate mean intravascular pressure (Pmean) and flow rate within each nidus vessel; and Monte Carlo analysis to assess overall risks of nidus rupture when simulating sequential occlusions of vessel types in all 10 000 nidi.ResultsWe consistently observed lower nidus rupture risks with initial fistula occlusion in different network morphologies. Intranidal fistula occlusion simultaneously reduced Pmean and flow rate within draining veins.ConclusionsInitial occlusion of AVM fistulas theoretically reduces downstream draining vessel hypertension and lowers the risk of rupture of an adjoining plexiform nidus component. This mitigates the theoretical concern that fistula occlusion may cause dangerous redistribution of hemodynamic forces into plexiform nidus vessels, and supports a clinical strategy favoring AVM fistula occlusion before plexiform nidus embolization.

Adaptation to 5 weeks of intermittent local vascular pressure increments; mechanisms to be considered in the development of primary hypertension?

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150 mmHg in healthy men (n=11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressure-distension determinations were conducted by exposing the subjects arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (p<0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (Ang-II) and endothelin-1 (ET-1) (p<0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (p<0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension.

Therapeutic and functional approach for the treatment of patients with bone marrow edema in Rehabilitation Medicine

Bone marrow edema (BME) represents an imaging finding in various diseases, and often causes pain and significant dysfunction. Although few data are available about its etiology, several hypotheses have been developed to explain the pathogenetic mechanisms of BME. Increased intravascular pressure and capillary leakage within the bone marrow would lead to nerve irritation, causing pain. Bone turnover would increase locally, due to proinflammatory molecules driven by the primary cause of BME (trauma, ischemia, arthritis, etc.). In addition to imaging findings, the clinical evaluation of a subject affected by BME should rely on an accurate functional assessment, as this condition often leads to transient disability. As regards therapeutic approaches, recent research works have reported benefits from the extracorporeal shock wave treatment (ESWT) and above all bisphosphonates. A deeper knowledge of the pathophysiological bases of the BME combined with the classic physiatric approach can allow to select the subjects affected by BME who can benefit from therapies such as bisphosphonates and ESWT, and evaluate their clinical and functional effects.

Forward blood flow provoked by changing intravascular pressure using an extracorporeal circulation during cardiopulmonary resuscitation

Since both “cardiac pump” and “thoracic pump” theories have been proved during cardiopulmonary resuscitation (CPR), the mechanism of forward blood flow during closed chest compression still remains open to question. The cardiac pump seems to work by the direct compression of the cardiac ventricles between the sternum and vertebral column. A pressure gradient created between the ventricle and aorta generates systemic blood flow. However, the thoracic pump mechanism presumes chest compression causes a rise in intrathoracic pressure which generates a blood flow from the thoracic cavity to the systemic circulation. Retrograde blood flow from the right heart into the systemic veins is prevented by a concomitant collapse of veins at the thoracic inlet. We hypothesize that the intrinsic decrease of vascular resistance from the aorta to peripheral arteries and the existence of competent venous valves enable blood to flow unidirectionally by the fluctuation of intravascular pressures during closed chest compression. The purpose of this study is to prove an antegrade arterial blood flow without cardiac compression and intrathoracic pressure changes in an animal cardiac arrest model. We demonstrate that arterial pulses can be developed by using an extracorporeal circuit, resulting in forward blood flow from the aorta through the systemic vasculature. It can be suggested that changes in intravascular pressure provoked by either cardiac or thoracic pump generate systemic blood flow during closed chest compression, while systemic vascular patency and valve function may be required for successful CPR.

SUMO1 modification of PKD2 channels regulates arterial contractility

PKD2 (polycystin-2, TRPP1) channels are expressed in a wide variety of cell types and can regulate functions, including cell division and contraction. Whether posttranslational modification of PKD2 modifies channel properties is unclear. Similarly uncertain are signaling mechanisms that regulate PKD2 channels in arterial smooth muscle cells (myocytes). Here, by studying inducible, cell-specificPkd2knockout mice, we discovered that PKD2 channels are modified by SUMO1 (small ubiquitin-like modifier 1) protein in myocytes of resistance-size arteries. At physiological intravascular pressures, PKD2 exists in approximately equal proportions as either nonsumoylated (PKD2) or triple SUMO1-modifed (SUMO-PKD2) proteins. SUMO-PKD2 recycles, whereas unmodified PKD2 is surface-resident. Intravascular pressure activates voltage-dependent Ca2+influx that stimulates the return of internalized SUMO-PKD2 channels to the plasma membrane. In contrast, a reduction in intravascular pressure, membrane hyperpolarization, or inhibition of Ca2+influx leads to lysosomal degradation of internalized SUMO-PKD2 protein, which reduces surface channel abundance. Through this sumoylation-dependent mechanism, intravascular pressure regulates the surface density of SUMO-PKD2−mediated Na+currents (INa) in myocytes to control arterial contractility. We also demonstrate that intravascular pressure activates SUMO-PKD2, not PKD2, channels, as desumoylation leads to loss of INaactivation in myocytes and vasodilation. In summary, this study reveals that PKD2 channels undergo posttranslational modification by SUMO1, which enables physiological regulation of their surface abundance and pressure-mediated activation in myocytes and thus control of arterial contractility.