Lerman, Amir

Hypercholesterolemia (HC) is characterized by increased circulating 8- epi-prostaglandin-F2α(isoprostane), a vasoconstrictor, marker, and mediator of increased oxidative stress, whose vascular effects might be augmented in HC. Anesthetized pigs were studied in vivo with electron beam computed tomography after a 12-wk normal ( n = 8) or HC ( n = 8) diet. Mean arterial pressure (MAP), single-kidney perfusion, and glomerular filtration rate (GFR) were quantified before and during unilateral intrarenal infusions of U46619 (10 ng · kg−1· min−1) or isoprostane (1 μg · kg−1· min−1). Basal renal perfusion and function were similar, and isoprostane infusion elevated its systemic levels similarly in normal and HC (333 ± 89 vs. 366 ± 48 pg/ml, respectively, P < 0.01 vs. baseline). Both drugs markedly and comparably decreased cortical perfusion and GFR in both groups, whereas medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in HC (+9 ± 3 and +11 ± 3 mmHg, respectively, P≤ 0.05). Hence, in HC, renal functional responses to high-dose isoprostane are largely similar to normal, but the systemic circulation exhibits augmented sensitivity to pathophysiological levels of isoprostane and U46619 , which may potentially play a role in development of hypertension and vascular injury associated with increased oxidative stress.

SummaryCoronary endothelial‐dependent microvascular dysfunction, an early reversible stage of coronary artery disease (CAD), is associated with poor clinical outcome. The current study investigated whether coronary artery distensibility index (CDI) is associated with: (i) coronary endothelial‐dependent microvascular dysfunction and (ii) vulnerable plaque composition among subjects with non‐obstructive CAD. Seventy‐four subjects with non‐obstructive CAD (luminal stenosis <30%) were studied. In 20 subjects with and without coronary endothelial‐dependent microvascular dysfunction, coronary flow reserve (CFR) of target segment during intracoronary (IC) infusion of acetylcholine (Ach) and bolus injection of adenosine as well as CDI at rest of corresponding target segment were measured. In 54 subjects, plaque compositions and CDI at rest of 154 non‐obstructive coronary segments as well as proximal segment without disease were measured by intravascular ultrasound (IVUS). CDI was defined as: [(Early‐diastolic cross‐sectional‐area (CSA) – End‐diastolic CSA of target segment)/(end‐diastolic CSA of target segment × coronary‐pulse‐pressure) × 103]. There is a direct association between endothelial dysfunction and impaired CDI of a coronary segment both in the given coronary segment and corresponding microvessels in which a strong agreement between CDI and CFR Ach (r2 = 0·85, P = 0·0001) was observed. Multivariable regression‐analysis showed that CDI was an independent predictor of the vulnerable plaque characteristics. The risk of impaired CDI was 125% higher in segments with necrotic core and 60% higher in segments with fibrofatty components as compared to normal segments (P = 0·001). In conclusions, the current study reveals that impaired CDI is an endothelial‐dependent process of both given coronary segment and corresponding microvessels and is associated with vulnerable plaque composition.

Background— Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome for which optimal management remains undefined. Methods and Results— We performed a retrospective study of 189 patients presenting with a first SCAD episode. We evaluated outcomes according to initial management: (1) revascularization versus conservative therapy and (2) percutaneous coronary intervention (PCI) versus conservative therapy stratified by vessel flow at presentation. Demographics were similar in revascularization versus conservative (mean age, 44±9 years; women 92% both groups), but vessel occlusion was more frequent in revascularization (44/95 versus 18/94). There was 1 in-hospital death (revascularization) and 1 late death (conservative). Procedural failure rate was 53% in those managed with PCI. In the subgroup of patients presenting with preserved vessel flow, rates of PCI failure were similarly high (50%), and 6 (13%) required emergency coronary artery bypass grafting. In the conservative group, 85 of 94 (90%) had an uneventful in-hospital course, but 9 (10%) experienced early SCAD progression requiring revascularization. Kaplan–Meier estimated 5-year rates of target vessel revascularization and recurrent SCAD were no different in revascularization versus conservative therapy (30% versus 19%; P =0.06 and 23% versus 31%; P =0.7). Conclusions— PCI for SCAD is associated with high rates of technical failure even in those presenting with preserved vessel flow and does not protect against target vessel revascularization or recurrent SCAD. A strategy of conservative management with prolonged observation may be preferable.