Pamela Brewster

Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope. A paradoxic and unexpected response.

BackgroundTo 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 ResultsThirty 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 μg/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. ConclusionsThese 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.

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

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 2×2 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 (P<0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2×2 design (P<0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0±27% versus −10±20%; P<0.05), embolic protection was not (−1±28% versus −10±20%; P=0.08). An interaction was observed between abciximab and embolic protection (P<0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (P<0.01). 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.

Use of sertraline hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents

OBJECTIVES The purpose of our study was to determine whether the serotonin reuptake inhibitor sertraline hydrochloride could prevent neurocardiogenic syncope in children and adolescents resistant to or intolerant of other therapies. BACKGROUND The serotonin reuptake inhibitor fluoxetine hydrochloride has been reported to be effective in preventing neurocardiogenic syncope in adults. METHODS Seventeen consecutive young patients (mean age 15 years, range 10 to 18; 7 male, 10 female) with recurrent syncope and a positive head-upright tilt table test, and in whom standard therapies (fludrocortisone, transdermal scopolamine, beta-adrenergic blocking agents, disopyramide) were ineffectual, poorly tolerated or contraindicated, were referred for study. Sertraline was administered orally at 50 mg daily for 4 to 6 weeks. A head-upright tilt table test was then reperformed, and the clinical effect was noted. RESULTS Three patients (18%, 95% confidence interval [CI] 1 to 44) were intolerant of the drug, and it was discontinued. Nine patients became asymptomatic and tilt negative (53%, 95% CI 26 to 76), and five remained tilt positive (36%, 95% CI 15 to 65). Over a mean follow-up period of 12 +/- 5 months, the tilt-negative patients remained symptom free while taking sertraline. CONCLUSIONS The serotonin reuptake inhibitor sertraline hydrochloride can be effective in preventing recurrent neurocardiogenic syncope in selected patients unresponsive to or intolerant of other therapeutic modalities.

Renal artery angioplasty and stent placement: Predictors of a favorable outcome ☆ ☆☆

BACKGROUND Renal artery stenosis is a common disorder and is an established cause of hypertension and renal insufficiency. Although treatment with renal artery stents has been shown to improve blood pressure and renal function for some patients, the patient population most likely to benefit is unknown. The current study was designed to determine which factors are predictive of improved blood pressure and renal function when patients with renal artery stenosis are treated with renal artery angioplasty and stent placement. METHODS In a prospective evaluation 127 consecutively enrolled patients with renal artery stenosis in 171 vessels were treated with angioplasty and intravascular stents. Blood pressure and serum creatinine concentration were measured before stent placement and during the follow-up period. RESULTS The mean length of the follow-up period was 15 +/- 14 months. Mean systolic blood pressure improved among patients with hypertension (from 177 +/- 26 mm Hg before stent placement to 151 +/- 24 mm Hg 6 months after stent placement (P <.001). The greatest improvement occurred among those with the highest baseline systolic blood pressure. This beneficial effect on blood pressure was sustained for 3 years. Sex, age, diastolic blood pressure, number of vessels into which stents were placed, serum creatinine concentration, presence of bilateral disease, race, and severity of stenosis were not predictive of improved blood pressure. Mean creatinine concentration was not significantly changed for the group as a whole. A significant decrease in serum creatinine concentration occurred among 43% of patients with baseline renal insufficiency. None of the examined variables was predictive of improvement. CONCLUSIONS Renal artery angioplasty and stent placement produced a significantly greater reduction in systolic blood pressure among patients with the highest baseline systolic blood pressure. Other examined variables were not predictive of a significant improvement in blood pressure. No examined variable was predictive of improved renal function. We concluded that management of renal artery stenosis with renal artery angioplasty and stent placement is most likely to result in significant improvement in systolic blood pressure among patients with the highest baseline systolic blood pressure.

Mechanism of cocaine-induced myocardial depression in dogs.

Cocaine causes pronounced depression of left ventricular function in conscious dogs immediately after intravenous administration. To examine this effect, 14 mongrel dogs were anesthetized with pentobarbital sodium (32 mg/kg) and instrumented with arterial and venous catheters and a Doppler blood flow transducer on the left circumflex coronary artery. Two weeks later, heart rate, blood pressure, coronary blood flow, and regional left ventricular ejection fraction (by two-dimensional echocardiography) were measured before and 1, 2, 5, and 10 minutes after cocaine (4 mg/kg i.v.), while the animals were fully conscious. Heart rate, blood pressure, and coronary blood flow were increased significantly at each time after cocaine. Regional ejection fraction, however, was depressed by 50 +/- 7%, 35 +/- 4%, and 21 +/- 4% at 1, 2, and 5 minutes after cocaine treatment, respectively. Ten minutes after cocaine treatment, regional ejection fraction had recovered to a level not significantly different from baseline. Because the observed myocardial depression after cocaine was accompanied by a large increase in the rate-pressure product, and presumably, myocardial oxygen consumption, this depression could have been secondary to increased myocardial oxygen demand not appropriately matched by an increase in coronary blood flow. To minimize the effects of cocaine on myocardial oxygen demand, a subset of six dogs received cocaine (4 mg/kg i.v.) while sedated with pentobarbital (25 mg/kg). In these dogs, cocaine did not significantly alter heart rate or blood pressure; however, regional ejection fraction was significantly depressed by 44 +/- 5% and 36 +/- 6% at 1 and 2 minutes after cocaine treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral syncope : loss of consciousness associated with cerebral vasoconstriction in the absence of systemic hypotension

Transcranial Doppler (TCD) ultrasonography done during headupright 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 fndings 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.

Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state

Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis.

Randomized comparison of rapid ambulation using radial, 4 French femoral access, or femoral access with AngioSeal closure.

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. Catheter Cardiovasc Interv 2004;62:143–149.

Renal Ischemia Regulates Marinobufagenin Release in Humans

Cardiotonic steroids, including marinobufagenin, are a group of new steroid hormones found in plasma and urine of patients with congestive heart failure, myocardial infarction, and chronic renal failure. In animal studies, partial nephrectomy induces marinobufagenin elevation, cardiac hypertrophy, and fibrosis. The objective of this study is to test the effect of renal ischemia on marinobufagenin levels in humans with renal artery stenosis (RAS). To test this, plasma marinobufagenin levels were measured in patients with RAS of the Prospective Randomized Study Comparing Renal Artery Stenting With or Without Distal Protection, non-RAS patient controls who were scheduled for coronary angiography, and normal healthy individuals. Marinobufagenin levels were significantly higher in patients with RAS compared with those of the other 2 groups. Multivariate analysis shows that occurrence of RAS is independently related to marinobufagenin levels. In addition, renal artery revascularization by stenting partially reversed marinobufagenin levels in the patients with RAS (0.77±0.06 nmol/L at baseline; 0.66±0.06 nmol/L at 24 hours; and 0.61±0.05 nmol/L at 1 month). In conclusion, we have found that marinobufagenin levels are increased in patients with RAS, whereas reversal of renal ischemia by stenting treatment reduces marinobufagenin levels. These results suggest that RAS-induced renal ischemia may be a major cause of marinobufagenin release.

Predictors of embolization during protected renal artery angioplasty and stenting: Role of antiplatelet therapy.

Objective: The objective of this study was to identify the predictors of distal embolization (DE) during protected renal artery angioplasty and stenting. Background: DE may contribute to worsening renal function after renal artery stenting. The factors associated with DE, rates of platelet‐rich emboli, and treatments that may prevent DE during renal stenting have not been evaluated. Methods: The current study evaluated patients randomized to receive an embolic protection device (EPD) in the RESIST trial. Forty‐two patients were identified for inclusion in this study. These patients were further randomized to abcizimab (N = 22) or placebo (N = 20). Modification in Diet in Renal Disease glomerular filtration rate (GFR) was used as the primary measure of renal function. Creatinine was measured by a modified Jaffe reaction using the IDMS‐traceable assay. The primary endpoint was capture of platelet rich emboli in the angioguard basket. Results: DE occurred in 15/42 (35%) of the patients and platelet rich DE in 10 (24%) of the patients who received an EPD. Of the angiographic characteristics only lesion length was significantly higher in patients with DE (16 ± 7 mm vs. 10 ± 5 mm, P = 0.04). Preprocedural abciximab reduced DE from 42 to 8% (P = 0.02). The rate of platelet rich emboli was 50% with neither abciximab nor a thienopyridine, 36% with thienopyridine only, 15% abciximab only, and 0% in patients who received both a thienopyridine and abciximab. Only Abciximab use was associated with improved renal function at 1‐month, thienopyridine was not. Angiographic characteristics including percent stenosis, minimal luminal diameter (MLD), reference diameter, change in MLD, contrast volume, and procedure time were not predictors of DE during renal stenting. Conclusion: Capture of DE and specifically platelet DE are common during protected renal stenting using a filter‐type EPD. Abciximab use, and potentially combined thienopyridine and abciximab use, decreased the rate of platelet rich DE; however, only abciximab improved renal function at 1‐month.