The Left Atrial Septal Pouch as a Possible Risk Factor for Stroke.

BACKGROUND: The left atrial septal pouch (LASP) is formed by the caudal fusion of the area of overlap of the septum primum and the septum secundum, leaving an opening toward the left atrium. The association between LASP and stroke has not been validated by the previous studies. METHODS: The prevalence of the LASP was determined in 223 ischemic stroke patients and 223 control subjects with other cardiac pathologies, in a monocentric retrospective case-control study design. Stroke subtypes were defined according to the modified TOAST criteria. RESULTS: The mean age was 66 ± 15, 54% males, with a high prevalence of cardiovascular risk factors. The prevalence of the LASP was 81 (18%), irrespective of age or pathology. The number of LASP was similar in the stroke and control groups (18% vs. 19%, P = 0.7), as well as in the cryptogenic stroke subgroup (16%, P = 0.6). LASP was not associated with ischemic stroke on univariate (OR = 1.095; 95% CI = 0.676-1.772; P = 0.7) and multivariate logistic regression analysis (OR = 1.004; 95%CI = 0.574-1.758, P = 0.98). There was no statistical association between LASP and cryptogenic stroke on univariate (OR = 1.26; 95%CI = 0.526-3.016; P = 0.6) or multivariate analysis (OR = 0.705; 95%CI = 0.193-2.577, P = 0.6). The association of LASP to AF, left ventricular dysfunction, and thrombophilia did not lead to a higher incidence of stroke (OR = 0.99; 95%CI = 0.37-2.66; P = 0.99). CONCLUSION: Our study did not show any association between LASP and ischemic stroke. A septal pouch was present in 18% of the population. Other associated risk factors need to be considered to incriminate the septal pouch as the etiology of a stroke.

Effects of digoxin on muscle reflexes in normal humans.

Blockade of the skeletal muscle Na(+)-K(+)-ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise, which in turn could stimulate the mechano- and metaboreceptors. In a randomized, double-blinded, placebo-controlled, and cross-over-design study, we measured mean blood pressure (MBP), heart rate (HR), ventilation (V(E)), oxygen saturation (SpO(2)), muscle sympathetic nerve activity (MSNA), venous plasma potassium and lactic acid during dynamic handgrip exercises, and local circulatory arrest in 11 healthy subjects. Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR, V(E), SpO(2), and MSNA. Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na(+)-K(+)-ATPase blockade. We conclude that digoxin increased MBP during dynamic exercise in healthy humans, independently of changes in potassium and lactic acid. A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms, independent of muscle reflexes and related to the inotropic effects of digoxin, might be implicated.

Sympathetic baroreceptor regulation during hypoxic hypotension in humans: new insights.

BACKGROUND: Baroreceptor activation by a continuous infusion of phenylephrine selectively abolishes the muscle sympathetic nerve activity (MSNA) response to hypoxia in humans. Baroreceptor deactivation enhances the MSNA rise during hypoxia in animals. Whether this is true in humans is unknown and was tested in the present study. METHODS: We assessed MSNA responses elicited by isocapnic hypoxia (10% O2 in N2) during baroreflex loading and unloading with phenylephrine and nitroprusside, respectively, in 19 healthy volunteers. The study was randomized and placebo-controlled. RESULTS: Phenylephrine and nitroprusside increased and decreased, respectively, blood pressure during normoxia and hypoxia, whereas the reverse occurred for heart rate and MSNA (all P < 0.001 vs. placebo). As compared with normoxia, cardiac barosensitivity decreased during the infusion of placebo and nitroprusside in the presence of hypoxia, as well as sympathetic barosensitivity during the infusion of nitroprusside (all P < 0.05). Three patients even disclosed a reduction in arterial pressure, which became apparent at the third minute of hypoxia and worsened steadily thereafter (SBP: 91 ±â€Š7 mmHg; DBP 47 ±â€Š9 mmHg), in spite of a gradual rise in heart rate of 20 ±â€Š4 bpm. Changes in baroreceptor loading conditions did not affect ventilation during normoxia and hypoxia. CONCLUSION: Cardiac and sympathetic baroreceptor sensitivity decrease during baroreceptor unloading in the presence of peripheral chemoreceptor activation. Normal humans have limited reflex capabilities to sustain simultaneous reductions in oxygen and pressure, and may experience hemodynamic instability episodes in such condition.

Endothelin contributes to the blood pressure rise triggered by hypoxia in severe obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is strongly correlated with an increased risk of systemic hypertension. However, the link between systemic hypertension and nocturnal apneas remains incompletely understood. Animal studies suggest an implication of the endothelin system. The aim of the present study is to determine if endogenous endothelin plays a role in the increase in blood pressure observed during hypoxic episodes in OSA patients, in addition to peripheral chemoreflex and neural sympathetic activation. METHODS: We assessed the effects of the nonspecific endothelin antagonist bosentan (500 mg; Tracleer; Actelion; Basel, Switzerland) on ventilation, hemodynamics, and muscle sympathetic nerve activity (MSNA) during normoxia and isocapnic hypoxia using a randomized, crossover, double-blinded, placebo-controlled study design, and in 13 severely untreated sleep apneic patients (age 50 ±â€Š9 years, apnea-hypopnea index 35 ±â€Š21/h). RESULTS: Hypoxia increased blood pressure, MSNA, and minute ventilation as oxygen saturation decreased. Bosentan suppressed completely the increase in SBP during a 5-min hypoxic challenge (143 ±â€Š5 mmHg during hypoxia vs. 133 ±â€Š5 mmHg during normoxia with placebo and 127 ±â€Š3 mmHg during hypoxia vs. 125 ±â€Š3 mmHg during normoxia under bosentan, P = 0.023). DBP as well as the rise in MSNA and ventilation during isocapnic hypoxia did not differ between bosentan and placebo. CONCLUSION: Endothelin contributes to the rise in SBP in response to acute hypoxia in patients with severely untreated OSA. This was not due to lower chemoreflex activation with bosentan.

Effects of hunter-gatherer subsistence mode on arterial distensibility in Cameroonian pygmies.

We aimed to assess whether arterial distensibility estimated by pulse wave velocity (PWV) and augmentation index (AI) differs between Cameroon traditional pygmies (TPs) on hunter-gather subsistence mode, contemporary pygmies who migrated to semiurban area, and the Bantou farmers (BFs) sharing the same environment. For that purpose, we recorded carotid-femoral PWV (ComplioR) in age and sex carefully matched 20 TPs, 20 contemporary pygmies, and 22 BFs. Aortic AI corrected for heart rate and blood pressures were generated from pressure wave analysis (SphygmoCor). Lipid profile was determined in TP and BF participants. TPs were shorter (P=0.02) with lower body weight (P<0.01) in comparison with contemporary pygmies and BFs. TPs had lower low-density lipoprotein cholesterol but higher high-density lipoprotein cholesterol than BFs (P<0.01). Their PWV (5.81±0.21 m/s) was slower (P=0.006) than that of contemporary pygmies (6.82±0.36 m/s) or BFs (6.93±0.29 m/s); however, after its adjustment for age, mean arterial pressure, and heart rate, the difference was slightly attenuated (P=0.051). PWV adjusted for weight did not differ between groups (P=0.10). In the whole study population but not in TPs taken separately, multivariate regression analysis revealed that PWV was independently associated with mean arterial pressure, age, and TP status (P<0.001), whereas age, mean arterial pressure, and height emerged as independent determinants of aortic AI corrected for heart rate (P<0.001). Aortic AI corrected for heart rate did not differ in the 3 groups. In conclusion, hunter-gather lifestyle is associated with low atherosclerosis risk translated by lower aortic stiffness attributed at least partly to low weight and blunted effects of aging and blood pressures on TP arterial structure and function.

Intensified large artery and microvascular response to cold adrenergic stimulation in African blacks.

BACKGROUND: Arterial stiffening is more accelerated in blacks than in whites. Whether this is attributed to an enhanced vascular reactivity to environmental stress stimulation remains unknown. We therefore decided to test the hypothesis that cold pressor test (CPT) elicits a greater increase in arterial stiffness and an enhanced sympathetic skin vasoconstriction in African blacks than in whites normotensives. METHODS: A total of 17 young normotensive African blacks and 17 normotensive whites were recruited. All underwent continuous assessment of blood pressure (BP), heart rate, and carotid-femoral pulse wave velocity (PWVc-f) at rest, during and after hand immersion in iced water (CPT). Concomitantly, skin microvascular blood flow was monitored by laser Doppler flowmetry on the opposite hand. RESULTS: At baseline, African blacks exhibited higher values of PWVc-f than whites (7.2 +/- 0.3 vs. 6.5 +/- 0.2 m/s, respectively, P = 0.04). During CPT the increases in systolic BP and PWVc-f were greater in African blacks than in whites (systolic BP 17 +/- 2 mm Hg vs. 9 +/- 3 mm Hg, P < 0.001 and PWVc-f 0.62 +/- 0.1 m/s vs. 0.26 +/- 0.1 m/s, P = 0.03, respectively). However, there was no significant difference in the PWVc-f responses among the groups during CPT after adjustment for the increments in mean BP. Finally, CPT induced a more pronounced skin microvascular vasoconstriction in African blacks than in whites (-54.4 +/- 5 % vs. -31.3 +/- 6 %, P < 0.001). CONCLUSIONS: CPT provokes a more pronounced increase in PWVc-f in normotensive African blacks than in whites, that appears to be due to a greater increase in mean BP. Additionally, African blacks present an intensified skin microvascular response to the CPT as compared to their whites counterparts.

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.