Boutaina Najem

Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension

Background—This study tested the hypothesis that sympathetic nerve activity is increased in pulmonary artery hypertension (PAH), a rare disease of poor prognosis and incompletely understood pathophysiology. We subsequently explored whether chemoreflex activation contributes to sympathoexcitation in PAH. Methods and Results—We measured muscle sympathetic nerve activity (MSNA) by microneurography, heart rate (HR), and arterial oxygen saturation (Sao2) in 17 patients with PAH and 12 control subjects. The patients also underwent cardiac echography, right heart catheterization, and a 6-minute walk test with dyspnea scoring. Circulating catecholamines were determined in 8 of the patients. Chemoreflex deactivation by 100% O2 was assessed in 14 patients with the use of a randomized, double-blind, placebo-controlled, crossover study design. Compared with the controls, the PAH patients had increased MSNA (67±4 versus 40±3 bursts per minute; P<0.0001) and HR (82±4 versus 68±3 bpm; P=0.02). MSNA in the PAH patients was correlated with HR (r=0.64, P=0.006), Sao2 (r=−0.53, P=0.03), the presence of pericardial effusion (r=0.51, P=0.046), and NYHA class (r=0.52, P=0.033). The PAH patients treated with prostacyclin derivatives had higher MSNA (P=0.009), lower Sao2 (P=0.01), faster HR (P=0.003), and worse NYHA class (P=0.04). Plasma catecholamines were normal. Peripheral chemoreflex deactivation with hyperoxia increased Sao2 (91.7±1% to 98.4±0.2%; P<0.0001) and decreased MSNA (67±5 to 60±4 bursts per minute; P=0.0015), thereby correcting approximately one fourth of the difference between PAH patients and controls. Conclusions—We report for the first time direct evidence of increased sympathetic nerve traffic in advanced PAH. Sympathetic hyperactivity in PAH is partially chemoreflex mediated and may be related to disease severity.

Acute cardiovascular and sympathetic effects of nicotine replacement therapy.

Sympathetic overactivity is implicated in the increased cardiovascular risk of cigarette smokers. Excitatory nicotinic receptors are present on peripheral chemoreceptor cells. Chemoreceptors located in the carotid and aortic bodies increase ventilation (Ve), blood pressure (BP), heart rate (HR), and sympathetic nerve activity to muscle circulation (MSNA) in response to hypoxia. We tested the hypothesis that nicotine replacement therapy (NRT) increases MSNA and chemoreceptor sensitivity to hypoxia. Sixteen young healthy smokers were included in the study (8 women). After a randomized and blinded sublingual administration of a 4-mg tablet of nicotine or placebo, we measured minute Ve, HR, mean BP, and MSNA during normoxia and 5 minutes of isocapnic hypoxia. Maximal voluntary end-expiratory apneas were performed at baseline and at the end of the fifth minute of hypoxia. Nicotine increased HR by 7±3 bpm, mean BP by 5±2 mm Hg, and MSNA by 4±1 bursts/min, whereas subjects breathed room air (all P<0.05). During hypoxia, nicotine also raised HR by 8±2 bpm, mean BP by 2±1 mm Hg, and MSNA by 7±2 bursts/min (all P<0.05). Nicotine increased MSNA during the apneas performed in normoxia and hypoxia (P<0.05). Nicotine also raised the product of systolic BP and HR, a marker of cardiac oxygen consumption, during normoxia, hypoxia, and the apneas (P<0.05). Ve, apnea duration, and O2 saturation during hypoxia and the apneas remained unaffected. In conclusion, sympathoexcitatory effects of NRT are not because of an increased chemoreflex sensitivity to hypoxia. NRT increases myocardial oxygen consumption in periods of reduced oxygen availability.

Arterial Stiffness and Wave Reflections in Patients With Sickle Cell Disease

We tested the hypothesis that lower blood pressure and increased vasodilatation reported in sickle cell disease (SCD) patients with hemoglobin SS genotype (SS) are translated by lower arterial stiffness determined by pulse wave velocity (PWV) and wave reflections assessed by augmentation index (AI). We enrolled 20 SS (8 females; 12 male) patients closely matched for age, gender, height, and body mass index to 20 subjects with hemoglobin AA genotype (AA). Carotid–femoral PWV (PWVCF) and carotid–radial PWV (PWVCR) were recorded with the Complior device. Aortic AI was derived from pressure wave analysis (SphygmocoR). PWVCF and PWVCR were lower in SS than in AA (4.5±0.7 m/s versus 6.9±0.9 m/s, P<0.0001 and 6.6±1.2 m/s versus 9.5±1.4 m/s, P<0.0001, respectively). AI was lower in SS than in AA (2±14% versus 11±8%, P=0.02). Multivariate analysis revealed that both PWVCF and PWVCR were negatively associated with hemoglobin SS type and positively related to mean arterial pressure (MAP), whereas AI was positively associated with MAP and total cholesterol (all P<0.0001). Multivariate analysis restricted to SS indicated a positive association between PWVCF and PWVCR with age but a negative association with MAP (R2=0.57 and 0.51, respectively, both P<0.001), whereas MAP and heart rate were independently associated with AI (R2=0.65, P<0.001). This study provides the first evidence that SCD is associated with both lower arterial stiffness and wave reflections. SS patients have a paradoxical negative association between PWV and MAP, suggesting that low MAP does not protect them against arterial stiffness impairment.

Arteriovenous fistula closure after renal transplantation: A prospective study with 24-hour ambulatory blood pressure monitoring

We prospectively evaluated the effects of arteriovenous fistula closure on 24-hour ambulatory blood pressure measurements and on left ventricular geometry assessed by echocardiography. Sixteen kidney transplant recipients were studied before and 1 month after surgical fistula closure. The mean of 24-hour diastolic blood pressure increased from 77+/-7 mmHg to 82+/-8 mmHg (P=0.003) without systolic changes. The diastolic blood pressure increase correlated with the reduction in left ventricular mass (P=0.0034). In multivariate analysis, the diastolic blood pressure increase best correlated with preoperative cardiac index (P=0.01). After a similar time delay between two studies, blood pressure remained unchanged in 14 kidney transplant controls with a patent fistula not scheduled for closure. Because the increase in diastolic blood pressure after arteriovenous fistula closure occurred regardless of the preoperative level of diastolic pressure, we suggest that blood pressure should be monitored after fistula closure, particularly when preoperative diastolic blood pressure is borderline or elevated.