Spontanous periodic breathing is associated with sympathetic hyperreactivity and baroreceptor dysfunction in hypertension.

OBJECTIVES: Intermittent periods of hypoxemia such as during periodic breathing are associated with hypertension and increased sympathetic activity. In patients with sleep apnea syndrome, hypertension is common. Treating apnea improves hypertension and reduces sympathetic outflow. The aim of the present study was to investigate the phenomenon and mechanisms of spontaneous periodic breathing in patients with hypertension. METHOD: We examined 43 hypertensive patients with untreated hypertension without left-ventricular dysfunction, heart failure or sleep apnea syndrome. Muscle sympathetic nerve activity (MSA), heart rate (HR), blood pressure (BP) and respiration were continuously recorded at rest and during cold-pressor testing. Oxygen and a CO2-enriched gas were used to test central and peripheral chemoreceptors, respectively. Baroreceptor gain was measured using the alpha method. RESULTS: Seven out of 43 patients showed spontaneous periodic breathing while awake. No difference in MSA, HR and BP was seen between patients with and without periodic breathing at rest except the breathing pattern. However, the cold-pressor test caused a larger increase of MSA in patients with periodic breathing (203 +/- 62 vs. 62 +/- 8%, P < 0.0001 by ANOVA), as well as systolic (46 +/- 6 vs. 25 +/- 3 mmHg, P = 0.002) and diastolic BP (26 +/- 5 vs. 12 +/- 1 mmHg, P = 0.004, ANOVA). Baroreceptor gain was markedly higher in patients with periodic breathing. Chemoreceptor sensitivity was comparable. CONCLUSION: Spontaneous periodic breathing is relatively common in patients with hypertension and is associated with greatly enhanced responses to cold-pressor testing. We suggest increased baroreceptor gain and sympathetic outflow as a cause for the oscillatory respiration pattern via barorespiratory coupling.

Predictors of appropriate implantable cardioverter-defibrillator therapy during long-term follow-up of patients with coronary artery disease.

Indications for implantable cardioverter defibrillators (ICDs) are expanding. Defining long-term predictors of ICD therapies might help to identify those patients who will benefit most from implantation of an ICD. The objective of this study was to examine long-term predictors of appropriate ICD therapy among patients with coronary disease at high risk of sudden cardiac death. An analysis of 245 patients with coronary disease, who had been implanted with an ICD for primary or secondary prevention of sudden cardiac death, was performed. Time to appropriate ICD therapy, defined as antitachycardia pacing or shock, was evaluated by the Kaplan-Meier method. Cox regression analysis was performed to determine hazard ratios for factors predicting appropriate ICD therapies. During a mean (SD) follow-up of 41 (33) months, 115 patients (53%) experienced appropriate ICD therapy. Independent predictors of appropriate ICD therapy included advanced age, left ventricular ejection fraction (LVEF) < 35%, and impaired renal function, with covariate-adjusted hazard ratios of 1.36 per 10 years (95% CI, 1.11 - 1.66; P = 0.003), 1.78 (95% CI, 1.21 - 2.63; P = 0.004), and 1.59 (95% CI, 1.00 - 2.54; P = 0.050), respectively. Remote myocardial infarction (> 6 months prior to ICD implantation) was associated with higher probability of appropriate ICD therapy among patients with LVEF > 35% (adjusted HR 2.68 [95% CI, 1.05 - 6.86; P = 0.04]), but not among patients with LVEF < 35% (adjusted HR 1.09 [95% CI, 0.58 - 2.04; P = 0.79]). Left ventricular ejection fraction, advanced age, and renal impairment are long-term predictors of appropriate ICD therapy in patients with coronary disease at high risk of sudden cardiac death. Patients with an ejection fraction above 35% have few arrhythmic events early after the myocardial infarction but appropriate therapies become more frequent late after the myocardial infarction, possibly due to progression of the disease.

Long-term predictors of mortality in ICD patients with non-ischaemic cardiac disease: impact of renal function.

BACKGROUND: Randomized trials have demonstrated that implantable cardioverter defibrillator (ICD) therapy may reduce the risk of death in patients with non-ischaemic cardiomyopathy (CMP). In this study, we aimed at determining the long-term benefit of ICD therapy among patients with dilated CMP (DCM) and among those with other non-ischaemic cardiac diseases (NICDs). METHODS AND RESULTS: We performed a single-centre longitudinal study to assess the outcomes of 176 patients with NICDs who were implanted with an ICD for primary or secondary prevention of cardiac death. The cumulative survival rate after 1, 2, 5, and 10 years was 91, 87, 78, and 65%, respectively. Mortality risk did not differ significantly between patients with DCM and those with other NICDs. Atrial fibrillation, recurrent ventricular arrhythmias requiring ICD therapy, and right ventricular pacing, but not delayed intrinsic ventricular conduction, were associated with higher risk. New York Heart Association (NYHA) functional class > or =III was an independent predictor of adverse outcome among patients with DCM [hazard ratio (HR) 5.27, P = 0.01], whereas reduced left ventricular function with ejection fraction <35% (HR 12.1, P < 0.001) and anti-arrhythmic drug use (HR 4.82, P = 0.03) were independent predictors among those with other NICDs. Renal insufficiency with estimated glomerular filtration rate <60 mL/min/1.73 m(2) (HR 5.9, P < 0.001) was a strong independent predictor of mortality among all patients with NICD, irrespective of underlying cardiac condition. CONCLUSION: In ICD patients with DCM, higher NYHA functional class is associated with adverse outcomes. Impaired left ventricular function and anti-arrhythmic drug use predict higher mortality among patients with non-dilated, NICDs. Impaired renal function is a strong predictor of mortality in all patients with NICD.

[Anticoagulation in atrial fibrillation]. / Antikoagulation bei Vorhofflimmern.

Atrial fibrillation is the most common arrhythmia in the elderly and is associated with substantial morbidity and mortality, mostly due to the consequences of thromboembolism. Anticoagulation reduces the risk of stroke and death considerably, the risk reduction depending on the patient's absolute risk. Although there is modest benefit from acetylsalicylic acid, randomized trials have shown that it is consistently and substantially less effective than vitamin K antagonists. These benefits must be balanced against an increased risk of bleeding. In addition, warfarin therapy imposes a variety of lifestyle constraints, including frequent blood test monitoring and, possibly, dietary modification, and is associated with a number of drug interactions. Careful assessment of the absolute risk of stroke on the one hand and bleeding complications on the other hand will guide the use of appropriate prophylaxis against thromboembolism and its consequences.

Anxiolytic therapy with alprazolam increases muscle sympathetic activity in patients with panic disorders.

Anxiolytic therapy with the benzodiazepine alprazolam is an established therapy in patients with panic disorder. Normally, panic-like anxiety and its concomitant physical symptoms quickly disappear under such treatment. Therefore we investigated whether there is a difference in sympathetic nervous system in patients with panic disorder compared to healthy controls. Three groups of subjects were included: ten patients with panic disorder, who received alprazolam and 20 healthy control subjects who were given either alprazolam (n=10) or matching placebo (n=10). Muscle sympathetic nerve activity (MSNA) and heart rate did not differ at baseline but significantly increased both in patients and healthy controls after intake of alprazolam (1 mg). However, in both groups both MSNA and heart rate were significantly elevated when compared to both baseline and the placebo control group. This study demonstrates (1) that anxiolytic therapy with alprazolam increases muscle sympathetic nerve activity and heart rate not only in patients with panic disorder but also in healthy controls and (2) that a significant difference in sympathetic nervous system activity between patients and controls, at baseline and during the therapy with alprazolam could not be demonstrated.

Potential interference of small neodymium magnets with cardiac pacemakers and implantable cardioverter-defibrillators.

BACKGROUND: Magnetic fields may interfere with the function of cardiac pacemakers and implantable cardioverter-defibrillators (ICDs). Neodymium-iron-boron (NdFeB) magnets, which are small in size but produce strong magnetic fields, have become widely available in recent years. Therefore, NdFeB magnets may be associated with an emerging risk of device interference. OBJECTIVE: We conducted a clinical study to evaluate the potential of small NdFeB magnets to interfere with cardiac pacemakers and ICDs. METHODS: The effect of four NdFeB magnets (two spherical magnets 8 and 10 mm in diameter, a necklace made of 45 spherical magnets, and a magnetic name tag) was tested in forty-one ambulatory patients with a pacemaker and 29 patients with an ICD. The maximum distance at which the magnetic switch of a device was influenced was observed. RESULTS: Magnetic interference was observed in all patients. The maximum distance resulting in device interference was 3 cm. No significant differences were found with respect to device manufacturer and device types. CONCLUSION: Small NdFeB magnets may cause interference with cardiac pacemakers and ICDs. Patients should be cautioned about the interference risk associated with NdFeB magnets during daily life.

Wavelet-based tachycardia discrimination in ICDs: Impact of posture and electrogram configuration.

BACKGROUND: Inappropriate therapy delivery is an important concern in the management of patients with implantable cardioverter defibrillators (ICDs). Recently, a morphology-based algorithm (wavelet feature) has been introduced for differentiation of ventricular and supraventricular tachycardia. In this study, we evaluated the performance of the wavelet algorithm using various electrogram (EGM) configurations during different body positions. METHODS: Patients with a single-chamber Medtronic model 7230 ICD (Minneapolis, MN, USA) and a double-coil lead were included. EGM templates were collected during baseline rhythm in supine position for different EGM sources (right ventricular [RV] coil-can, RV coil-superior vena cava [SVC] coil, tip-ring, SVC coil-can). For each EGM configuration, morphologic similarity (match percentage) of EGMs obtained during different body positions (supine, left and right lateral, sitting, standing, walking) were compared with the templates. RESULTS: Twenty-eight patients (24 males; age 58 +/- 17 years) were studied. A total of 9,775 intracardiac EGMs were analyzed. Median match percentage (interquartile range) was 88% (85-94), 88% (82-94), 82% (76-88), and 73 (58-85) for the RV coil-can, RV coil-SVC coil, tip-ring, and SVC coil-can configurations, respectively. Correct classification rates, as defined by match percentage of 70% or higher, were significantly higher with the RV coil-can, RV coil-SVC coil, and tip-ring EGM configurations, as compared to the SVC coil-can configuration (95, 91, and 91 vs 58% > or =70% match percent, P < 0.001). CONCLUSION: Wavelet-based morphology scores in ICDs may change with various body positions. These variations are relatively minor using the nominal configuration (RV coil-can), as well as by using RV coil-SVC coil and tip-ring. However, morphology scores can vary considerably when SVC coil-can is used; therefore, this configuration should be avoided while using the wavelet algorithm.

Coffee blunts mental stress-induced blood pressure increase in habitual but not in nonhabitual coffee drinkers.

Coffee is widely consumed, especially during mental stress conditions. Cardiovascular impact of coffee remains debated because the underlying mechanisms of action are complex. We reported previously differential cardiovascular stimulation of coffee at rest depending on habitual consumption. The present study was designed to evaluate the effects of coffee on cardiovascular response to mental stress. In 15 healthy volunteers (6 habitual, 9 nonhabitual coffee drinkers), we assessed the effect of mental stress on blood pressure (BP), heart rate (HR), and muscle sympathetic activity (MSA) before and after a triple espresso, intravenous caffeine, and placebo in the same subjects. Under baseline conditions, mental stress significantly increases MSA (+2.5+/-0.7 volts per minute; +14.1+/-10.3%), systolic (+11.6+/-4.1 mm Hg) and diastolic BP (+6.4+/-2.0 mm Hg), and HR (+9.6+/-1.8 minutes(-1)). In nonhabitual coffee drinkers, a triple espresso but not caffeine induced an additional increase in systolic BP (+9+/-6.3 mm Hg; P=0.003) during mental stress, whereas in habitual drinkers, the stress-induced BP increase was blunted (+4+/-3.9 mm Hg; P=NS). As a result, nonhabitual coffee drinkers experienced significantly higher BP during mental stress than habitual drinkers (151+/-17.9/83+/-5.6 mm Hg versus 130+/-7.8/74+/-6.7 mm Hg; P<0.05). Caffeine induced similar effects in habitual and nonhabitual coffee drinkers at rest and during mental stress. The response to the cold pressor test was not influenced by coffee drinking in both groups. In conclusion, in nonhabitual coffee drinkers, coffee enhances the cardiovascular response to mental stress with an additional increase in systolic BP, whereas in habitual drinkers, the response is blunted. Caffeine alone does not exert any potentiating effect, confirming that ingredients other than caffeine are partially responsible for the stimulating effect of coffee on the cardiovascular system.

Rapid progression of atherosclerotic coronary artery disease in patients with human immunodeficiency virus infection.

We describe the case of a 39-year-old human immunodeficiency virus (HIV)-infected man with angiographically documented rapid progression of coronary artery disease. Over a time course of only 2 months, he developed high-grade stenosis of the left anterior descending coronary artery. The risk of myocardial infarction is increased in patients with HIV infection receiving antiretroviral therapy. However, the absolute risk is small and the marked overall benefits of antiretroviral therapy are evident. Patients receiving HIV protease inhibitors should be screened for hyperlipidemia, hyperglycemia, and hypertension. They may be candidates for lipid-lowering therapies depending on their long-term prognosis and individual risk of cardiovascular disease. Care is need because of possible drug interactions between lipid-lowering drugs and antiretroviral therapy. Invasive treatment of acute myocardial infarction does not differ from that in patients not infected with HIV. The rate of progression of coronary artery disease and the restenosis rate, however, are often unexpectedly high in these patients.

Cardiovascular effects of coffee: is it a risk factor?

Intake of coffee, one of the most common beverages worldwide, is often reported as a cardiovascular risk factor; however, definitive data are lacking. Acute intake of coffee or beverages containing caffeine can increase blood pressure, heart minute volumes, and cardiac index, as well as activate the sympathetic nervous system in nonhabitual coffee drinkers. Interestingly, this is not observed in habitual coffee drinkers. Restriction of coffee or caffeinated beverages is no longer indicated in the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines for the treatment of hypertension. In fact, no clear association between coffee and the risk of hypertension, myocardial infarction, or other cardiovascular diseases has been demonstrated. In contrast to early studies, recent research indicates that habitual moderate coffee intake does not represent a health hazard and may even be associated with beneficial effects on cardiovascular health.

Endogenous estrogens increase postischemic hyperemia in the skin microcirculation.

Estrogens have been recognized as a major regulator of vascular tone and structure, particularly in the skin. The objective of this study was to investigate the effects of endogenous estrogens on the skin microcirculation. Skin blood flow was measured at the forearm at rest and during postischemic hyperemia using laser Doppler flowmetry in 32 healthy women (mean age 34.5 +/- 3.9 years) involved in an in-vitro fertilization program. Women were treated for 10 to 12 days with gonadotropin-releasing hormone agonist (total dose 40.3 +/- 3.3 mg) and human menopausal gonadotropin (1942 +/- 801 IE) or follicle-stimulating hormone (2544 +/- 1071 IE) according to individual estrogen levels. Plasma estrogen levels increased from 132 +/- 90 pmol/L (36 +/- 25 pg/mL) to 8471 +/- 4386 pmol/L (2308 +/- 1195 pg/mL) during treatment (P < 0.0001). Maximal hyperemic blood flow increased from 353 +/- 81% before treatment to 516 +/- 144% after hormonal stimulation (P < 0.0001), whereas basal skin flow was not altered. This study shows that endogenous estrogens enhance the postischemic hyperemic response of the skin microcirculation.

Induction ovens and electromagnetic interference: what is the risk for patients with implantable cardioverter defibrillators?

Electromagnetic fields may interfere with normal implantable cardioverter defibrillator (ICD) function. Although the devices are effectively shielded and use exclusively bipolar leads, electromagnetic interference (EMI) remains a concern when patients are exposed to several household appliances. The aim of this study was to evaluate potential EMI risk of induction ovens, which are increasingly common in private households. In vitro measurements of an induction oven for private households GK 43 TI (V-Zug, Inc., Zug, Switzerland) showed that heating is regulated by increasing operating time from level 1 (100 ms/sec) to 5 (continuous operation). From levels 5 to 9 the magnetic field increases. Nineteen patients with left-sided implants of single- and dual-chamber ICD systems (8 Medtronic, 7 Guidant, and 4 St. Jude Medical) (18 males, 1 female), age (mean +/- SEM) 58 +/- 3 years, were included in this study. All patients were examined in standing position, bent over the cooking pot (minimal distance to the induction coil 25 cm), and with the cooking pot put eccentrically over the induction field at three different cooking levels (level 2, 5, and 9). The tests were repeated touching the cooking pot with one hand. Ventricular sensitivity was left unchanged. Ventricular tachycardia therapies were turned off in Medtronic and Guidant devices and ventricular sensing was continuously monitored in St. Jude Medical devices during testing. Interrogation of the devices after exposure did not show any inappropriate tachycardia detection, oversensing, or reprogramming. In conclusion, ICD patients can be reassured that EMI is unlikely to affect their devices if induction ovens are used in their kitchens.

Statins enhance postischemic hyperemia in the skin circulation of hypercholesterolemic patients: a monitoring test of endothelial dysfunction for clinical practice?

OBJECTIVES: The present study aims to investigate whether laser Doppler flowmetry can be used to monitor improvements in vascular function during statin therapy. BACKGROUND: Endothelial dysfunction is an early feature of atherosclerosis in hypercholesterolemic patients and can be improved by statins. There are several methods to assess endothelial function in vivo, none of them being feasible in everyday practice. METHODS: Skin perfusion, measured by laser Doppler flowmetry, was assessed at rest and during reactive hyperemia. Nineteen hypercholesterolemic patients (age 42 to 73 years, total cholesterol 5.4 to 9.6 mmol/l) were studied before and during statin therapy. To further investigate the mechanisms, postischemic skin hyperemia was measured before and after intradermal injection of the nitric oxide synthase inhibitor L-NAME and its inactive isoform D-NAME (0.5 micromol/10 microl each). On a separate day, the healthy volunteers were reexamined before and 2 h after 1,000 mg aspirin. RESULTS: Postischemic skin blood flow was markedly reduced in hypercholesterolemic patients (45 +/- 11%) compared with healthy controls (238 +/- 20%, p < 0.0001) and improved after statin therapy (113 +/- 15%, p = 0.0005 vs. pre-treatment). In the healthy volunteers, the hyperemic responses were not significantly different after L-NAME and D-NAME. Aspirin reduced hyperemia from 274 +/- 49% to 197 +/- 40% (p = 0.025). CONCLUSIONS: Reactive hyperemia of the skin microcirculation can be easily and reproducibly assessed by laser Doppler flowmetry. Vasodilator prostaglandins are the major mediators of postischemic skin hyperemia, which is impaired in hypercholesterolemic patients and can be enhanced by cholesterol-lowering therapy. Thus, laser Doppler flowmetry may represent a tool to assess and monitor vascular function during therapy in everyday practice.

Dysfunctional baroreflex regulation of sympathetic nerve activity in patients with vasovagal syncope.

BACKGROUND: The interplay of resting muscle sympathetic nerve activity (MSA) and the baroreceptor reflex in patients with vasovagal syncope remains elusive. Hence, the aim of the present study was to investigate MSA, baroreceptor sensitivity, heart rate, and blood pressure under resting conditions and during orthostatic stress in patients with a history of vasovagal syncope. METHODS AND RESULTS: MSA was measured using microneurography at rest and during lower body negative pressure (LBNP) to mimic orthostatic stress in patients with a history of vasovagal syncope (n=10) and in age-matched healthy controls (n=8). Heart rate and blood pressure were simultaneously recorded. Cardiac baroreceptor sensitivity was calculated with the spectral technique (alpha coefficient). Resting MSA in the patients with syncope was significantly increased as compared with controls (42.4+/-2.3 versus 26.5+/-3.6 bursts/min, P=0.001), whereas activation of MSA during orthostatic stress in the patient group was significantly blunted (5.1+/-1.6 versus 15.2+/-2.1 bursts/min at LBNP -50 mm Hg, P=0.002). In the patients with syncope, cardiac baroreceptor sensitivity was significantly reduced under supine resting conditions (8.5+/-0.7 versus 13.0+/-1.1 ms/mm Hg, P=0.001), as well as under orthostatic stress (7.3+/-0.7 versus 13.4+/-1.5 ms/mm Hg, P=0.003). CONCLUSIONS: This study shows that in patients with vasovagal syncope, resting MSA is increased and baroreflex regulation during orthostatic stress is blunted, thus leading to impaired MSA adaptation. These results provide new insights into mechanisms of vasovagal syncope and suggest that pharmacological modulation of baroreceptor sensitivity may represent a promising treatment of neuromediated syncope.

Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking.

BACKGROUND: Coffee is the most abundantly consumed stimulant worldwide. However, its cardiovascular safety remains controversial. Possible health hazards have been related to its main ingredient, caffeine. Activation of the sympathetic nervous system by coffee may enhance cardiovascular risk; however, it is unclear whether this effect of coffee is related to caffeine or other substance(s) also contained in decaffeinated coffee. METHODS AND RESULTS: In 15 healthy volunteers (6 habitual and 9 nonhabitual coffee drinkers) arterial blood pressure (BP), heart rate, and muscle sympathetic nervous activity (MSA) were continuously recorded before and after drinking a triple espresso or a decaffeinated triple espresso or after intravenous administration of caffeine (250 mg) or placebo (saline) in the same subjects. There was a significant time x condition interaction for the intravenous caffeine and placebo conditions for MSA, with caffeine showing a significant increase in MSA at 60 minutes (53.2+/-14.1% total activity) and the placebo group showing no effect. A similar significant time effect was found for coffee drinking (54.1+/-22.5% total activity). Habitual and nonhabitual coffee drinkers demonstrated similar changes in MSA and BP after intravenous caffeine, whereas coffee drinking increased BP in nonhabitual drinkers only, despite comparable increases of MSA and plasma caffeine levels. Nonhabitual coffee drinkers showed similar activation of MSA and BP after caffeine infusion, coffee, or decaffeinated coffee. CONCLUSIONS: Acutely, coffee and caffeine induced comparable increases in MSA and BP in nonhabitual coffee drinkers, whereas habitual coffee drinkers exhibited lack of BP increase despite MSA activation to coffee. Because decaffeinated coffee also increases BP and MSA in nonhabitual drinkers, ingredients other than caffeine must be responsible for cardiovascular activation.

Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension.

The sympathetic nervous system (SNS) is an important regulator of the circulation. Its activity is increased in hypertension and heart failure and adversely affects prognosis. Although certain drugs inhibit SNS, dihydropyridine calcium antagonists may stimulate the system. Phenylalkylamine calcium antagonists such as verapamil have a different pharmacological profile. We therefore tested the hypothesis of whether amlodipine, nifedipine, or verapamil differs in the effects on muscle sympathetic nerve activity (MSA). Forty-three patients (31 men, 12 women) with mild to moderate hypertension were randomly assigned to 1 drug for 8 weeks. Blood pressure, heart rate, and MSA (by microneurography) were measured at baseline and after 8 weeks of treatment. All calcium antagonists led to a similar decrease in blood pressure of 5.0+/-1.5 to 6.4+/-1.4 mm Hg at 8 weeks (P<0.001 versus baseline). There were no significant differences in MSA between groups. With amlodipine, MSA averaged 49+/-3 bursts/min (3 versus baseline); with nifedipine, 48+/-3 bursts/min (2 versus baseline); and with verapamil, 49+/-2 bursts/min (all, P=NS). With verapamil, norepinephrine decreased by 4% but tended to increase by about one third with amlodipine or nifedipine (P=NS). Thus, in hypertension slow release forms of verapamil, nifedipine, and amlodipine exert comparable antihypertensive effects and do not change MSA, although there was a trend toward decreased MSA and plasma norepinephrine with verapamil.

High-density lipoprotein restores endothelial function in hypercholesterolemic men.

BACKGROUND: Hypercholesterolemia is a risk factor for atherosclerosis-causing endothelial dysfunction, an early event in the disease process. In contrast, high-density lipoprotein (HDL) cholesterol inversely correlates with morbidity and mortality representing a protective effect. Therefore, we investigated the effects of reconstituted HDL on endothelial function in hypercholesterolemic men. METHODS AND RESULTS: Endothelium-dependent and -independent vasodilation to intraarterial acetylcholine and sodium nitroprusside (SNP), respectively, was measured by forearm venous occlusion plethysmography in healthy normo- and hypercholesterolemic men. In hypercholesterolemics, the effects of reconstituted HDL (rHDL; 80 mg/kg IV over 4 hours) on acetylcholine- and SNP-induced changes in forearm blood flow were assessed in the presence or absence of the nitric oxide (NO) synthase inhibitor L-NMMA. Hypercholesterolemics showed reduced vasodilation to acetylcholine but not to SNP compared with normocholesterolemics (P<0.0001). rHDL infusion increased plasma HDL cholesterol from 1.3+/-0.1 to 2.2+/-0.1 mmol/L (P<0.0001, n=18) and significantly enhanced the acetylcholine-induced increase in forearm blood flow without affecting that induced by SNP. rHDL infusion also improved flow-mediated dilation of the brachial artery (to 4.5+/-0.9% from 2.7+/-0.6%, P=0.02). NO synthase inhibition prevented the improvement in acetylcholine-induced vasodilation while leaving the response to SNP unchanged. Albumin infusion in an equivalent protein dose had no effect on vasomotion or lipid levels. CONCLUSIONS: In hypercholesterolemic patients, intravenous rHDL infusion rapidly normalizes endothelium-dependent vasodilation by increasing NO bioavailability. This may in part explain the protective effect of HDL from coronary heart disease and illustrates the potential therapeutic benefit of increasing HDL in patients at risk from atherosclerosis.

The Beauty and the Beast: Aspects of the Autonomic Nervous System.

Sympathetic nerve activity is altered and is a prognostic factor for many cardiovascular diseases such as hypertension, coronary syndromes, and congestive heart failure. Therefore, the selection of vasoactive drugs for the treatment of these diseases should also take into consideration their effects on the sympathetic nervous system.