Search tips
Search criteria

Results 1-6 (6)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal 
Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation.
Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety.
Seventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost.
Based on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa.
PMCID: PMC3996494  PMID: 24731393
Anticoagulation; Hemorrhage; Trauma; Prothrombin complex concentrate; Recombinant factor VIIa; Warfarin
2.  A prospective study of the role of sleep related disordered breathing as a risk factor for motor vehicle crashes and the development of systemic complications in non-commercial drivers 
Sleep related disordered breathing (SRDB), is an established risk factor for motor vehicle crashes (MVCs) involving commercial drivers. The role of SRDB in motor vehicle crashes involving non-commercial drivers is not well established.
Drivers involved in MVCs who were admitted to an American College of Surgeons accredited Level I trauma center for treatment of their injuries, and who could give informed consent and provide verbal responses to screening questionnaires were eligible for enrolment in this study. Two questionnaires previously validated for screening patients at risk for sleep disturbances (The Epworth Sleepiness Scale (ESS) and The Berlin Questionnaire (BQ)) were administered. Questionnaire results associated with an 85% sensitivity for predicting obstructive sleep apnea were considered positive. In this study we tested the hypothesis that patients at risk for SRDB, as measured by validated questionnaires, are at an increased risk being involved in MVCs.
Between March and October 2010, 71 consecutive patients were offered enrolment in this study with 56 agreeing to participate in this study. Six were previously diagnosed with SRDB with only one being compliant and effectively treated at the time of their MVC. Forty-two patients (75%) had responses to the questionnaires that indicated that the patients were at high risk for SRDB. Six patients suffered systemic complications, including pleural effusions, pneumonia and arrhythmias, during their hospitalization with five (83%) having abnormal questionnaire responses indicating that the patient was at high risk for SRDB.
The high incidence of positive responses to the sleep questionnaires is consistent with the hypothesis that SRDB is potentially a significant risk factor for MVCs. Furthermore the observation that systemic complications were seen more commonly in those with SRDB, while not unexpected, is a novel observation. Further studies are needed to validate these findings in a larger cohort of patients as well as determining if these patients are truly at a greater risk for systemic complications. If replicated these observations would suggest that effective therapy for disordered sleep could play a significant role in an injury prevention process.
PMCID: PMC3933287  PMID: 24397859
Sleep related disordered breathing; Motor vehicle crashes
3.  Renal Responses to Chronic Suppression of Central Sympathetic Outflow 
Hypertension  2012;60(3):749-756.
Chronic electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated as hypertension therapy for patients with resistant hypertension. However, the chronic changes in renal function associated with natural suppression of sympathetic activity are largely unknown. In normotensive dogs we investigated the integrative cardiovascular effects of chronic baroreflex activation (2 weeks) alone and in combination with the calcium channel blocker amlodipine, which is commonly used in the treatment of resistant hypertension. During baroreflex activation alone, there were sustained decreases in mean arterial pressure (17 ± 1 mm Hg) and plasma [norepinephrine] (NE, ~35%), with no change in plasma renin activity (PRA). Despite low pressure, sodium balance was achieved due to decreased tubular reabsorption, because GFR and renal blood flow decreased 10–20%. After 2 weeks of amlodipine, arterial pressure was also reduced 17 mm Hg, but with substantial increases in NE and PRA, and no change in GFR. In the presence of amlodipine, baroreflex activation greatly attenuated neurohormonal activation and pressure decreased even further (by 11 ± 2 mm Hg). Moreover, during amlodipine administration the fall in GFR with baroreflex activation was abolished. These findings suggest that the chronic blood pressure lowering effects of baroreflex activation are due, at least in part, to sustained inhibition of renal sympathetic nerve activity and attendant decreases in sodium reabsorption prior to the macula densa. Tubuloglomerular feedback constriction of the afferent arterioles may account for reduced GFR, a response abolished by amlodipine, which dilates the preglomerular vasculature.
PMCID: PMC3501271  PMID: 22753216
arterial pressure; baroreflex; sympathetic nervous system; renal nerves; renal function; renin-angiotensin system
4.  Systemic and Renal-Specific Sympathoinhibition in Obesity Hypertension 
Hypertension  2011;59(2):331-338.
Chronic pressure-mediated baroreflex activation suppresses renal sympathetic nerve activity. Recent observations indicate that chronic electrical activation of the carotid baroreflex produces sustained reductions in global sympathetic activity and arterial pressure. Thus, we investigated the effects of global and renal specific suppression of sympathetic activity in dogs with sympathetically-mediated, obesity-induced hypertension by comparing the cardiovascular, renal, and neurohormonal responses to chronic baroreflex activation and bilateral surgical renal denervation. After control measurements, the diet was supplemented with beef fat while sodium intake was held constant. After 4 weeks on the high-fat, when body weight had increased ~a 50%, fat intake was reduced to a level that maintained this body weight. This weight increase was associated with an increase in mean arterial pressure from 100±2 to 117±3 mm Hg and heart rate from 86±3 to 130±4 bpm. The hypertension was associated with a marked increase in cumulative sodium balance despite ~ a 35% increase in GFR. The importance of increased tubular reabsorption to sodium retention was further reflected by ~ a 35% decrease in fractional sodium excretion. Subsequently, both chronic baroreflex activation (7 days) and renal denervation decreased plasma renin activity and abolished the hypertension. However, baroreflex activation also suppressed systemic sympathetic activity and tachycardia and reduced glomerular hyperfiltration while increasing fractional sodium excretion. In contrast, GFR increased further after renal denervation. Thus, by improving autonomic control of cardiac function and diminishing glomerular hyperfiltration, suppression of global sympathetic activity by baroreflex activation may have beneficial effects in obesity beyond simply attenuating hypertension.
PMCID: PMC3277854  PMID: 22184321
obesity; hypertension; baroreflex; sympathetic nervous system; renal nerves; renal function; renin-angiotensin system
5.  Chronic Electrical Stimulation of the Carotid Sinus Baroreflex Improves LV Function and Promotes Reversal of Ventricular Remodeling in Dogs with Advanced Heart Failure 
Circulation. Heart failure  2010;4(1):65-70.
Autonomic abnormalities exist in heart failure (HF) and contribute to disease progression. Activation of the Carotid sinus baroreflex (CSB) has been shown to reduce sympathetic outflow and augment parasympathetic vagal tone. This study tested the hypothesis that long-term electrical activation of carotid sinus baroreflex improves left ventricular (LV) function and attenuates progressive LV remodeling in dogs with advanced chronic HF.
Methods and Results
Studies were performed in 14 dogs with coronary microembolization-induced HF (LV ejection fraction, EF ~25%). Eight dogs were chronically instrumented for bilateral CSB activation using the Rheos® System (CVRx® Inc., Minneapolis, MN) and 6 were not and served as controls. All dogs were followed for 3 months and none received other background therapy. During follow-up, treatment with CSB increased LV EF 4.0 ± 2.4 % compared to a reduction in control dogs of −2.8 ± 1.0% (p<0.05). Similarly, treatment with CSB decreased LV end-systolic volume −2.5 ± 2.7 ml compared to an increase in control dogs of 6.7 ± 2.9 ml (p<0.05). Compared to control, CSB activation significantly decreased LV end-diastolic pressure and circulating plasma norepinephrine, normalized expression of cardiac β1-adrenergic receptors, β-adrenergic receptor kinase and nitric oxide synthase and reduced interstitial fibrosis and cardiomyocyte hypertrophy.
In dogs with advanced HF, CSB activation improves global LV function and partially reverses LV remodeling both globally and at cellular and molecular levels.
PMCID: PMC3048958  PMID: 21097604
heart failure; ventricular remodeling; gene expression; baroreflex function
Hypertension  2009;53(5):833-838.
Previous studies suggest that prolonged electrical activation of the baroreflex may reduce arterial pressure more than chronic blockade of α1-and β1,2-adrenergic receptors. To determine whether central inhibition of sympathetic outflow has appreciable effects to chronically reduce arterial pressure by actions distinct from well established mechanisms, we hypothesized that chronic baroreflex activation would lower arterial pressure substantially even during complete α1-and β1,2-adrenergic receptor blockade. This hypothesis was tested in 6 dogs during adrenergic blockade (18 days) with and without electrical activation of the carotid baroreflex (7 days). During chronic adrenergic blockade alone, there was a sustained decrease in mean arterial pressure of 21±2 mm Hg (control = 95±4 mm Hg) and nearly a 3-fold increase in plasma norepinephrine concentration (control = 138±6pg/mL), likely due to baroreceptor unloading. In comparison, during adrenergic blockade + prolonged baroreflex activation, plasma norepinephrine concentration decreased to control levels and mean arterial pressure fell an additional 10±1 mm Hg. Because of differences in plasma norepinephrine concentration, we also tested the acute blood pressure lowering effects of MK-467, a peripherally acting α2-antagonist. After administration of MK-467, there was a significantly greater fall in arterial pressure during adrenergic blockade (15±3 mm Hg) than during adrenergic blockade + prolonged baroreflex activation (7±3 mm Hg). These findings suggest that reflex-induced increases in sympathetic activity attenuate reductions in arterial pressure during chronic adrenergic blockade and that inhibition of central sympathetic outflow by prolonged baroreflex activation lowers arterial pressure further by previously undefined mechanisms, possibly by diminishing attendant activation of postjunctional α2-adrenergic receptors.
PMCID: PMC2698596  PMID: 19273736
baroreflex; arterial pressure; sympathetic nervous system; α-and β-adrenergic receptors; norepinephrine; renin-angiotensin system

Results 1-6 (6)