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Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome. Guidance regarding the optimal management of patients with SCAD has been published over the past 10 years, but the impact on clinical practice has not been evaluated. The present study aims to examine if approaches to invasive management, medical therapy, and vascular imaging have changed over time. Methods: This is a retrospective cohort study of 157 patients treated for SCAD between 2005 and 2019 at an academic health system in Philadelphia, Pennsylvania. We aimed to examine change in management over time, including rates of coronary revascularization, discharge medications, and vascular imaging. Results: Conservative management of SCAD increased over time from 35% before 2013 to 89% in 2019, p < 0.001. Revascularization was associated with younger age, pregnancy-associated SCAD, and lesions of the left main artery, left anterior descending artery, and multiple vessels, p < 0.05 for all. Partial imaging for extracoronary vascular abnormalities ranged from 33% before 2013 to 71% in 2018, p = 0.146. The rate of comprehensive vascular imaging (cross-sectional head to pelvis imaging) remained low in all time categories (10–18%) and did not change over time. Patients who underwent comprehensive imaging were more likely to be diagnosed with fibromuscular dysplasia (FMD) compared to those with partial imaging (63% vs 15%, p < 0.001). Conclusion: Management of spontaneous coronary artery dissection has changed over time. More patients are being managed conservatively and undergo screening for extracoronary vascular abnormalities such as FMD. Future efforts should focus on improving rates of comprehensive vascular screening.

Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood–brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood–retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib. These findings suggest that chronic diabetes mellitus and hypercholesterolaemia induces increased blood–retina barrier permeability that may be linked to altered expression of blood–retina barrier–associated tight junction proteins, claudin and occludin, leading to structural changes in the retina consistent with diabetic retinopathy. Additionally, results suggest that drugs with vascular anti-inflammatory properties, such as Darapladib, may have beneficial effects on eye diseases strongly linked to vascular abnormalities such as diabetic retinopathy and age-related macular degeneration.

Although clinical studies are underway to evaluate the effectiveness of angiogenesis, there are no validated, non-invasive methods to assess peripheral collateral development. This study was performed to validate a novel ultrasound-based method of assessing collateral formation in a pig model of hindlimb ischemia. Ultrasonography of predefined ultrasound planes was performed on 12 pigs immediately after ligation of the right common femoral artery, and 7, 14, 28 and 42 days thereafter. A custom software program was used to evaluate both color Doppler (CD) and power Doppler (PD) images to generate flow indices. Collateral development was observed with ultrasound as early as 7 days post-arteriectomy and increased dramatically by 28 days. Areas of persistent ischemia resulting from inadequate collateral formation were easily quantified in all images. Collaterals detected on ultrasound were confirmed by angiography and histology, and tissue perfusion by a fluorescent microsphere method. As demonstrated with color and power Doppler measurements, collateral formation is initiated early after ischemic injury in this large juvenile animal model of angiogenesis. This non-invasive method is useful to quantify blood flow, visualize angiogenesis and determine areas of persistent lower limb ischemia, and may have an important role in evaluating new approaches to modulate angiogenesis.

Background: Catheter-based local vascular delivery results in concentrated quantities of pharmaceutical agents or genes into focal areas of the arterial wall. However, intramural retention is short and has reduced the potential efficacy of this approach. It was postulated that agents that possess increased intramural binding would show increased intramural reten tion. Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were models of agents with increased cellular and extracellular matrix binding properties. Methods and Results: The delivery efficiency and intramural retention of 2 mL of saline containing I125 labeled PDGF (n = 35 arteries) and bFGF (n = 24) were compared with albumin (n = 21) after local delivery into porcine coronary arteries. Animals were sacrificed at three or more prespecified timepoints: immediately after delivery, 1 day, or 3 days after delivery and if necessary at 5 or 7 days to document prolonged retention. Autoradiograms of the arterial sections were evaluated for the extent of delivery. Delivery efficiency, defined as the amount leaving the catheter and retrieved from the arterial wall, was 0.60% ± 0.42% for albumin, 1.98% ± 0.88% for PDGF ( P = .001), and 0.31% ± 0.11% for bFGF. The calculated intramural half-life of albumin was 7.4 hours, 56.2 hours for PDGF, and 14.9 hours for bFGF ( P = .0001 for PDGF). Infusate covering >50% of the medial area was observed in 85% of arteries immediately after delivery. Although myocardial delivery was similar for albumin, PDGF, and bFGF, myocardial retention was significantly longer for bFGF ( P < .001). Conclusions: Molecules that exhibit preferential intramural binding show a longer intra mural residence duration than solutes without such binding properties. In addition, delivery and subsequent prolonged retention in the myocardium can be obtained by local delivery via the arterial lumen of solutions with preferential binding properties.