BACKGROUND To determine the effect of vasovagally mediated syncope on the cerebral circulation, transcranial Doppler sonography was used to assess changes in cerebral blood flow velocity during head-upright tilt-induced syncope. METHODS AND RESULTS Thirty patients (17 men and 13 women; mean age, 43 +/- 22 years) with recurrent unexplained syncope were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of intravenous isoproterenol (1-4 micrograms/min), in an attempt to provoke bradycardia, hypotension, or both. Transcranial Doppler sonography was used to assess middle cerebral artery systolic velocity (Vs), diastolic velocity (Vd), ratio of systolic to diastolic velocities, pulsatility index (PI = Vs-Vd/Vmean), and resistance index (RI = Vs-Vd/Vs) before, during, and after tilt. Syncope occurred in six patients (20%) during the baseline tilt and 14 (46%) during isoproterenol infusion (total positives, 66%). In the tilt-positive patients, concomitant with the development of hypotension and bradycardia, transcranial Doppler sonography showed a 75 +/- 17% decrease in diastolic velocity, unchanged systolic velocity, a 46 +/- 17% decrease in mean velocity, a 295 +/- 227% increase in pulsatility index, and a 73 +/- 34% increase in resistance index. CONCLUSIONS These findings reflect increased cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery. This is paradoxic because the expected response of the cerebral circulation to hypotension is vasodilation. We conclude that abnormal baroreceptor responses triggered during vasovagal syncope result in a derangement of cerebral autoregulation with paradoxic vasoconstriction in the face of increasing hypotension.

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Background-Preservation of renal function is an important objective of renal artery stent procedures. Although atheroembolization can cause renal dysfunction during renal stent procedures, whether adjunctive use of embolic protection devices or glycoprotein IIb/IIIa inhibitors improves renal function is unknown. Methods and Results-One hundred patients undergoing renal artery stenting at 7 centers were randomly assigned to an open-label embolic protection device, Angioguard, or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor, abciximab, in a 2ϫ2 factorial design. The main effects of treatments and their interaction were assessed on percentage change in Modification in Diet in Renal Disease-derived glomerular filtration rate from baseline to 1 month using centrally analyzed creatinine. Filter devices were analyzed for the presence of platelet-rich thrombus. With stenting alone, stenting and embolic protection, and stenting with abciximab alone, glomerular filtration rate declined (PϽ0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2ϫ2 design (PϽ0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0Ϯ27% versus Ϫ10Ϯ20%; PϽ0.05), embolic protection was not (Ϫ1Ϯ28% versus Ϫ10Ϯ20%; Pϭ0.08). An interaction was observed between abciximab and embolic protection (PϽ0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (PϽ0.01). Conclusions-Renal artery stenting alone, stenting with embolic protection, and stenting with abciximab were associated with a decline in glomerular filtration rate. An unanticipated interaction between Angioguard and abciximab was seen, with combination therapy better than no treatment or either treatment alone. (Circulation. 2008;117:2752-2760.)

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Transcranial Doppler (TCD) ultrasonography done during head-upright tilt induced neurocardiogenic syncope has demonstrated that cerebral vasoconstriction occurs concomitant with (or precedes) loss of consciousness. This article demonstrates evidence that cerebral blood flow changes alone (vasoconstriction), in the absence of systemic hypotension, may result in syncope. Five patients (4 men, 1 woman; mean age 41 +/- 17 years) with recurrent unexplained syncope were evaluated by use of an upright tilt table test for 45 minutes with or without an infusion of low dose isoproterenol. TCDoppler ultrasonography was used to assess middle cerebral artery systolic velocity (Vs); diastolic velocity (Vd); mean velocity (Vm); and pulsatility index (PI = Vs = Vd/Vmean). Syncope occurred in five patients during the baseline tilt and in one patient during isoproterenol infusion. During tilt induced syncope, at an average mean arterial pressure of 89 +/- 16 mmHg, TCD sonography showed a 2% +/- 10% increase in systolic velocity; a 51% +/- 27% decrease in diastolic velocity; and a 131% +/- 87% increase in pulsatility index. One patient underwent continuous electroencephalographic recording during tilt, which demonstrated diffuse slow wave activity (indicating cerebral hypoxia) at the time of syncope concomitant with the aforementioned TCD changes in the absence of systemic hypotension. These findings reflect an increase in cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery, that occurred concomitant with loss of consciousness and in the absence of systemic hypotension. We conclude that in some individuals abnormal baroreceptor responses triggered during orthostatic stress may result in a derangement of cerebral autoregulation leading to cerebral vasoconstriction with resultant cerebral hypoxia in the absence of systemic hypotension.

Liquid biopsies have advanced rapidly in recent years for use in diagnostic and prognostic applications. One important aspect of this advancement is the growth in our understanding of microRNA (miRNA) biology. The measurement of miRNAs packaged within exosomes, which are constantly released into the blood stream, may reflect pathological changes within the body. The current study performed miRNA profiling using plasma and plasma-derived exosome samples from two animal models of kidney disease, the 5/6th partial nephrectomy (PNx) and two-kidney-one-clip (2K1C) models. The RT-qPCR-based profiling results revealed that the overall miRNA expression level was much higher in plasma than in plasma-derived exosomes. With 200 µl of either plasma or exosomes derived from the same volume of plasma, 629 out of 665 total miRNAs analyzed were detectable in plasma samples from sham-operated rats, while only 403 were detectable in exosomes with a cutoff value set at 35 cycles. Moreover, the average miRNA expression level in plasma was about 16-fold higher than that in exosomes. We also found a select subset of miRNAs that were enriched within exosomes. The number of detectable miRNAs from plasma-derived exosomes was increased in rats subjected to PNx or 2K1C surgery compared to sham-operated animals. Importantly, we found that the changes of individual miRNAs measured in plasma had very poor concordance with that measured in plasma-derived exosomes in both animal models, suggesting that miRNAs in plasma and plasma-derived exosomes are differentially regulated in these disease conditions. Interestingly, PNx and 2K1C surgeries induced similar changes in miRNA expression, implying that common pathways were activated in these two disease models. Pathway analyses using DIANA-miRPath v3.0 showed that significantly changed exosomal miRNAs were associated with extracellular matrix (ECM) receptor interaction and mucin type-O-glycan synthesis pathways, which are related with tissue fibrosis and kidney injury, respectively. In conclusion, our results demonstrated that due to the differential changes in miRNAs, the measurement of exosomal miRNAs cannot be replaced by the measurement of miRNAs in plasma, or vice versa. We also showed that a set of miRNAs related with kidney injury and organ fibrosis were dysregulated in plasma-derived exosomes from animal models of kidney disease.

Guidelines for management of normotensive patients with acute pulmonary embolism (PE) emphasize further risk stratification on the basis of right ventricular (RV) size and biomarkers of RV injury or strain; however, the prognostic importance of these factors on long-term mortality is not known. We performed a retrospective cohort study of subjects diagnosed with acute PE from 2010 to 2015 at a tertiary care academic medical center. The severity of initial PE presentation was categorized into three groups: massive, submassive, and low-risk PE. The primary endpoint of all-cause mortality was ascertained using the Centers for Disease Control National Death Index (CDC NDI). A total of 183 subjects were studied and their median follow-up was 4.1 years. The median age was 65 years. The 30-day mortality rate was 7.7% and the overall mortality rate through the end of follow-up was 40.4%. The overall mortality rates for massive, submassive, and low-risk PE were 71.4%, 44.5%, and 28.1%, respectively ( p < 0.001). Landmark analysis using a 30-day cutpoint demonstrated that subjects presenting with submassive PE compared with low-risk PE had increased mortality during both the short- and the long-term periods. The most frequent causes of death were malignancy, cardiac disease, respiratory disease, and PE. Independent predictors of all-cause mortality were cancer at baseline, age, white blood cell count, diabetes mellitus, liver disease, female sex, and initial presentation with massive PE. In conclusion, the diagnosis of acute PE was associated with substantial long-term mortality. The severity of initial PE presentation was associated with both short- and long-term mortality.

Radial access and closure devices are associated with improved quality of life (QOL) after cardiac catheterization. Whether this is related to the access site or time to ambulation is unknown. Seventy-five patients undergoing cardiac catheterization were randomized to femoral 6 Fr with AngioSeal closure (F+C), femoral 4 Fr without closure, and radial (R) access. All patients were ambulated at 1 hr. QOL was measured utilizing visual analogue scales and Short Form-36 at baseline, 1 day, and 1 week. Time to ambulation and discharge were equivalent, as was postprocedure QOL. However, angiographic quality was lower in the 4 Fr group (P < 0.0001) and catheterization costs were higher in the F+C group (P < 0.0001). Ambulation 1 hr after catheterization can be accomplished utilizing radial, femoral 6 Fr with closure device, or femoral 4 Fr access with equivalent outcomes and QOL. However, this is achieved at a higher cost with a closure device, or lesser angiographic quality with 4 Fr catheters.