Biomedical subjects

V K Somers

Publications and source records attributed to V K Somers.

At least 19 recordsLinked to original sources

PubMed2006

Obesity-related cardiovascular disease: implications of obstructive sleep apnea.

Obesity and obstructive sleep apnea (OSA) often coexist. OSA has been linked to cardiovascular disease. Thus, OSA may contribute to the cardiovascular consequences of obesity. In this review, we explore clinical and pathophysiological interactions between obesity, cardiovascular disease and OSA. We discuss the mechanisms whereby OSA may contribute to hypertension, atherosclerosis, insulin resistance and atrial fibrillation associated with obesity, and emphasize the potential implications for understanding why only a subgroup of obese patients develop cardiovascular disease. Identification of the OSA-dependent and OSA-independent pathways in the cardiovascular pathophysiology of obesity may hold clinical and therapeutic promise.

Atherosclerosis↗

PubMed2005

Recognition, diagnosis and management of obesity after myocardial infarction.

OBJECTIVE: We investigated the documentation of obesity as a medical problem, and subsequent management recommendations, in patients after myocardial infarction (MI). DESIGN: We performed a cross-sectional analysis of a randomly selected sample of 627 patients discharged after an MI, from five US teaching hospitals between 1/1/01 and 12/31/02. Information was extracted from clinical notes using standardized definitions. RESULTS: Mean body mass index (BMI) was 31+/-13 kg/m2, which was documented in only 14% of patients and had to be calculated post hoc in the rest. Waist circumference and waist/hip ratio were not documented at all; 83% of patients were overweight, 55% obese, and 8% morbidly obese. In only 20% of patients with BMI> or =30 kg/m2 was the diagnosis of obesity documented either as a current medical problem, as part of past medical history or as a final diagnosis. A dietary counseling was carried out in 61% of patients with BMI> or =25 kg/m2 and in 61% of patients with BMI<25 kg/m2, P=0.96. Weight loss was described as part of the goals/plan at discharge in 7% of overweight and 9% of obese patients. There was no change in either the level of recognition of obesity (22 vs 19%, P=0.3) or in the proportion of obese patients for whom weight loss was described as part of the goals/plan at discharge (8 vs 10%, P=0.7) before (n=301) compared to after (n=326) the Call to Action in Obesity by the Surgeon General in December 2001. CONCLUSION: Obesity is underecognized, underdiagnosed and undertreated in persons with acute MI.

Aged↗

PubMed2004

Sleep apnea and hypertension.

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing and frequently coexists with obesity. Almost 15 million Americans are affected by this disorder. This prevalence is likely increasing, given the current epidemic of obesity. Recent data confirm an association between sleep apnea and several cardiovascular disease conditions, suggesting that OSA may be a new risk factor for coronary artery disease, heart failure, heart rhythm disturbances and hypertension, independent of body mass index. In this review, the authors focus on the nature of the association between OSA and hypertension, the evidence suggesting a causal interaction, and discuss the potential pathophysiologic mechanisms responsible. These mechanisms include activation of the sympathetic and renin-angiotensin-aldosterone systems (RAAS), oxidative stress, and systemic and vascular inflammation, all of which could link OSA to a sustained increase in blood pressure. The authors also review potential therapeutic strategies for the hypertensive patient with OSA.

Humans↗

PubMed2003

Non-invasive model-based estimation of the sinus node dynamic properties from spontaneous cardiovascular variability series.

A non-invasive model-based approach to the estimation of sinus node dynamic properties is proposed. The model exploits the spontaneous beat-to-beat variability of heart period and systolic arterial pressure and the sampled respiration, thus surrogating the information from direct measures of neural activity. The residual heart period variability not related to baroreflex, to direct effects of respiration and to low frequency influences independent of baroreflex, is interpreted as the effect of the dynamic properties of the sinus node and modelled as a regression of the RR interval over its previous value. Therefore the sinus node transfer function is modelled by means of a filter with a real pole z = mu (and a zero in the origin). It was found that: first, in young healthy subjects the nodal tissue responded as a low-pass filter with mu = 0.76 +/- 0.12 (mean +/- SD); secondly, ageing did not significantly modify either its shape or gain at 0 Hz; thirdly, in heart transplant recipients, the dynamic transduction properties were lost (all-pass filter, p = 0.06 +/- 0.16, p < 0.001); fourthly, low-dose atropine left the sinus node dynamic properties unmodified; fifthly, high-dose atropine affected the dynamic transduction properties by increasing the gain at 0 Hz and rendering steeper its roll-off (the percent increase of mu with respect to baseline was 18.3 +/- 22.3, p < 0.05).

Adult↗

PubMed2003

Chemoreflexes--physiology and clinical implications.

The chemoreflexes are important modulators of sympathetic activation. The peripheral chemoreceptors located in the carotid bodies respond primarily to hypoxaemia. Central chemoreceptors located in the region of the brainstem respond to hypercapnia. Activation of either the hypoxic or hypercapnic chemoreflex elicits both hyperventilation and sympathetic activation. During apnoea, when the inhibitory influence of stretch of the pulmonary afferents is eliminated, there is a potentiation of the sympathetic response to both hypoxia and hypercapnia. This inhibitory influence of the pulmonary afferents is more marked on the sympathetic response to peripheral compared with central chemoreceptor activation. The arterial baroreflexes also have a powerful inhibitory influence on the chemoreflexes. This inhibition is again more marked with respect to the peripheral compared with central chemoreflexes. In patients with hypertension, there is a marked increase in the sympathetic and ventilatory response to hypoxaemia. During apnoea, with elimination of the inhibitory influence of breathing, the sympathetic response in untreated mild hypertensive patients is strikingly greater than that seen in matched normotensive controls. This potentiated peripheral chemoreflex sensitivity in hypertension may be explained in part by impaired baroreflex function in these patients. Enhanced peripheral chemoreflex sensitivity is also evident in patients with obstructive sleep apnoea. This peripheral chemoreflex enhancement is not explained by obesity, as obese individuals have a selective potentiation of the central chemoreceptors with peripheral chemoreflex responses similar to those seen in lean controls. Increased sensitivity to hypoxaemia has important implications in patients with obstructive sleep apnoea who experience repetitive and severe hypoxaemic stress. Tonic activation of the chemoreflex may also contribute to the high levels of sympathetic activity evident even during normoxic daytime wakefulness in sleep apnoea patients. Administration of 100% oxygen in patients with sleep apnoea results in reductions in heart rate, blood pressure and central sympathetic outflow. In patients with heart failure, the central chemoreflex response to hypercapnia is markedly and selectively enhanced. This increased central chemoreflex sensitivity may contribute to the development of central sleep apnoea in heart failure patients. Administration of 100% oxygen does not lower sympathetic activity in patients with heart failure, providing further evidence against any peripheral chemoreflex potentiation. The peripheral and central chemoreflexes have powerful effects on sympathetic activity in both health and disease and may contribute importantly to disease pathophysiology, particularly in conditions such as hypertension, obstructive sleep apnoea and heart failure.

Blood Pressure↗

PubMed2003

Sympathetic nerve activity in obstructive sleep apnoea.

The mechanisms underlying the link between obstructive sleep apnoea (OSA) and cardiovascular disease are not completely established. However, there is increasing evidence that autonomic mechanisms are implicated. A number of studies have consistently shown that patients with OSA have high levels of sympathetic nerve traffic. During sleep, repetitive episodes of hypoxia, hypercapnia and obstructive apnoea act through chemoreceptor reflexes and other mechanisms to increase sympathetic drive. Remarkably, the high sympathetic drive is present even during daytime wakefulness when subjects are breathing normally and no evidence of hypoxia or chemoreflex activation is apparent. Several neural and humoral mechanisms may contribute to maintenance of higher sympathetic activity and blood pressure. These mechanisms include chemoreflex and baroreflex dysfunction, altered cardiovascular variability, vasoconstrictor effects of nocturnal endothelin release and endothelial dysfunction. Long-term continuous positive airway pressure treatment decreases muscle sympathetic nerve activity in OSA patients. The vast majority of OSA patients remain undiagnosed. Unrecognized OSA may contribute, in part, to the metabolic and cardiovascular derangements that are thought to be linked to obesity, and to the association between obesity and cardiovascular risk. Furthermore, acting through sympathetic neural mechanisms, OSA may contribute to or augment elevated levels of blood pressure in a large proportion of the hypertensive patient population.

Baroreflex↗

PubMed2001

Differential characteristics of neural circulatory control: early versus late after cardiac transplantation.

BACKGROUND: Reappearance of low-frequency (LF) (+/-0.10 Hz) oscillations in RR interval (RR) after cardiac transplantation is indicative of sympathetic efferent reinnervation. We hypothesized that restored LF oscillations in RR in heart transplant recipients (HTRs) are linked to oscillations in muscle sympathetic nerve traffic (MSNA). METHODS AND RESULTS: RR, RR variability, and MSNA were recorded 5+/-2 months (n=7, short-term HTRs) and 138+/-8 months (n=7, long-term HTRs) after heart transplantation and compared with matched hypertensive patients (n=7). A coherence function determined the coupling between LF oscillations in MSNA and RR. RR variance did not differ between short-term and long-term HTRs. However, LF variability was only 1+/-0.5 ms(2) in the short-term HTRs but was 15+/-8 ms(2) in the long-term HTRs (P<0.05). Normalized LF variability was also higher in the long-term HTRs (40+/-14 normalized unites) versus the short-term HTRs (6+/-3 normalized united, P<0.05) but did not differ from the LF variability of the hypertensive patients. Long-term HTRs were taking less cyclosporine (P<0.01) but had higher MSNA than the short-term HTRs (62+/-7 versus 31+/-7 burst/min, respectively, P<0.05). Coherence between LF oscillations in MSNA and RR was similar in the long-term HTRs (0.59+/-0.11) and the hypertensive patients (0.60+/-0.07) and was 3-fold greater than in the short-term HTRs (0.20+/-0.06, P<0.05). CONCLUSIONS: Cardiac reinnervation after long-term heart transplantation is characterized by a restoration of the coherence between LF oscillations in RR and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time elapsed after cardiac transplantation may be a major determinant of sympathetic excitation in heart transplant recipients.

Biological Clocks↗

PubMed2001

Predisposition to vasovagal syncope in subjects with blood/injury phobia.

BACKGROUND: Most subjects with blood/injury phobia experience syncope or presyncope as part of the phobic response. We tested the hypothesis that these subjects have a constitutional autonomic dysregulation that predisposes them to vasovagal syncope during head-up tilt. METHODS AND RESULTS: We studied 11 subjects (9 females, 2 males) who had a history of syncope or presyncope only in response to a blood or injury stimulus and 11 healthy matched controls (10 females, 1 male) without a history of syncope. Blood pressure (BP) and heart rate (HR) were measured during a 15-minute baseline period with subjects in the supine position and then during 45 minutes of head-up tilt to 70 degrees. Measurements at rest did not differ between the blood phobic and control subjects. During tilt, 9 (82%) of the 11 blood phobic subjects experienced presyncope or syncope, leading to termination of the study after 22+/-17 minutes of tilt. Only 1 (9%) of the 11 control subjects experienced presyncope (chi(2)=11.7, P=0.001). Hemodynamic responses to tilt were consistent with a vasovagal mechanism in the blood phobic subjects, with simultaneous decreases in BP and HR during tilt. During tilt, systolic BP fell by 21+/-15 mm Hg (P=0.001), and HR fell by 22+/-25 bpm (P=0.01). By contrast, BP and HR were very stable in the control group. CONCLUSIONS: Subjects with syncope related to blood/injury phobia have an underlying autonomic dysregulation predisposing them to neurally mediated syncope, even in the absence of any blood or injury stimulus. Fainting related to these stimuli may in large part be due to dysfunction in neural circulatory control, which may secondarily lead to the phobia because of repeated syncopal events.

Adult↗

PubMed2001

Obstructive sleep apnea and vascular disease.

There is emerging evidence linking obstructive sleep apnea (OSA) to vascular disease, including hypertension. This relationship may be independent of co-morbidity, such as obesity. Even apparently healthy OSA patients have evidence of subtle functional vascular abnormalities that are known to occur in patients with hypertension and atherosclerosis. Untreated OSA may possibly contribute to the initiation and/or progression of pathophysiologic mechanisms involved in hypertension, heart failure, cardiac ischemia and stroke. This brief commentary will examine the evidence and mechanisms linking OSA to vascular disease.

Animals↗

PubMed2001

Independent association between plasma leptin levels and heart rate in heart transplant recipients.

BACKGROUND: Leptin, the protein product of the ob gene, has been linked to a faster heart rate in animal and human studies. The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. METHODS AND RESULTS: We studied 32 male patients (mean age, 56.5+/-9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All subjects underwent a physical examination, anthropometric measurements, blood chemistry analysis, and office blood pressure measurements. A blood sample was collected from each subject while fasting. In univariate analysis, heart rate was related to leptin levels (r=0.47, P=0.007) but heart rate was not related to systolic or diastolic blood pressure, mean arterial pressure, body mass index, or catecholamines. Leptin levels were only strongly associated with heart rate and body mass index (r=0.73, P<0.0001). In multivariate analysis, heart rate was independently and positively associated with leptin levels (F=2.61, P=0.017). We also observed a strong, independent association between leptin levels and body mass index (F=5.8, P<0.00001). CONCLUSIONS: We show an independent association between leptin levels and heart rate in heart transplant recipients. We speculate that this may be due, in part, to a direct effect of leptin on heart rate, conceivably mediated through cardiac leptin receptors.

Adult↗

PubMed2001

Rhythms, rhymes, and reasons--spectral oscillations in neural cardiovascular control.

Cardiovascular neural regulation is an integrated response to a continuous interaction of inhibitory and excitatory stimuli. Neural control of the circulation appears to be coded simultaneously in different modalities as amplitude (strength of signal or tonic activity) and frequency (oscillatory or phasic activity). Changes in tonic activity appear to be accompanied by tightly linked modulations in oscillatory characteristics. This is true within a narrow range of physiologic conditions, and the relationship is eliminated in extreme cardiovascular pathophysiology. Nevertheless, the oscillatory patterns in cardiovascular neural control appear to be widespread so that low and high frequency oscillatory patterns are evident even in sympathetic traffic to skin (Cogliati et al., 2000). Thus, it is likely that there is a functional significance to these oscillations. Recent data from Nafz et al. (1999) suggest that the presence of LF oscillatory characteristics in renal perfusion may attenuate renin-angiotensin activation during renal hypotension. These findings may have direct relevance to poorer outcomes observed in heart failure patients in whom an absence of LF oscillatory power was observed in RR interval and sympathetic traffic (Van de Borne et al., 1997a).

Blood Pressure↗

PubMed2001

Cardiovascular variability characteristics in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular disease. Altered cardiovascular variability is a prognostic indicator for cardiovascular events. This review examines the evidence that OSA is accompanied by alterations in cardiovascular variability. This alteration is evident even in the absence of hypertension, heart failure or other disease states, and may be linked to the severity of OSA. The presence of clear-cut abnormalities in time and frequency-domain measures of blood-pressure and heart-rate variability in normotensive OSA patients provides intriguing evidence for the concept of an etiologic interaction between sleep apnea and cardiovascular disease. Mechanisms that could contribute to altered cardiovascular variability in patients with sleep apnea include abnormalities in chemoreflex, baroreflex and endothelial function.

Blood Pressure↗

PubMed2001

Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects.

OBJECTIVE: Administration of leptin to animals increases sympathetic nerve activity and heart rate. We therefore tested the hypothesis that plasma leptin is linked independently to muscle sympathetic nerve activity (MSNA) and heart rate in healthy humans. METHODS: We measured plasma leptin, plasma insulin, body mass index (BMI), percent body fat, waist: hip ratio, MSNA, heart rate and blood pressure in 88 healthy individuals (50 men and 38 women). RESULTS: In men, plasma leptin concentration correlated significantly with BMI (r = 0.75, P < 0.001), percent body fat (r = 0.70, P< 0.001), waist: hip ratio (r = 0.69, P < 0.001), insulin (r = 0.37, P = 0.009), and age (r = 0.38, P = 0.006). Only BMI and waist: hip ratio were linked independently to plasma leptin concentration (r = 0.78, P < 0.001). Plasma leptin concentrations also correlated with heart rate (r = 0.39, P = 0.006) and mean arterial pressure (MAP; r = 0.38, P = 0.007), but not with MSNA (r = 0.17, P = 0.24). After adjustment for BMI and waist: hip ratio, plasma leptin concentration correlated significantly only with heart rate (r = 0.29, P = 0.04), and not with MAP (r = 0.21, P = 0.14). Individuals were divided into high-leptin and low-leptin subgroups on the basis of plasma leptin concentrations adjusted for BMI and waist: hip ratio. Those with high leptin concentrations had significantly faster heart rates than those with low leptin. MAP and MSNA were similar in both subgroups. No relationship between leptin and either heart rate or MSNA was evident in women. CONCLUSIONS: In normal men, heart rate, but not MSNA, is linked to plasma leptin concentration. This sex-specific relationship between heart rate and plasma leptin is independent of plasma insulin, BMI, waist:hip ratio and percentage body fat.

Adult↗

PubMed2001

Sleep disordered breathing and hypertension.

Patients with sleep apnea may be at increased risk for cardiovascular disease. Recently, the link between hypertension and sleep apnea has been strengthened by findings of two large epidemiologic studies. Neurohumoral and hemodynamic responses to repetitive episodes of hypoxemia and apnea may offer a pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension. Sympathetic, humoral, and cellular responses to sleep apnea over the long term may cause vascular dysfunction and consequent hypertension. These responses may be exacerbated by sleep deprivation, which occurs commonly in patients with sleep apnea because of poor sleep architecture. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to cardiovascular risk in this patient population. Alleviation of sleep disordered breathing may be accompanied by lower blood pressure in hypertensive patients with sleep apnea.

Humans↗

PubMed2001

Cardiorespiratory interactions in neural circulatory control in humans.

The reflex mechanisms and interactions described in this overview provide some explanation for the range of neural circulatory responses evident during changes in breathing. The effects described represent the integrated responses to activation of several reflex mechanisms, including peripheral and central chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and ventricular mechanoreceptors. These interactions occur on a dynamic basis and the transfer characteristics of any single interaction are, in all likelihood, also highly dynamic. Nevertheless, it is only by attempting to understand individual reflexes and their modulating influences that a more thorough understanding of the responses to complex phenomena such as hyperventilation, apnea, and obstructive sleep apnea can be better understood.

Baroreflex↗

PubMed2001

Importance of ventilation in modulating interaction between sympathetic drive and cardiovascular variability.

Chemoreflex stimulation elicits both hyperventilation and sympathetic activation, each of which may have different influences on oscillatory characteristics of cardiovascular variability. We examined the influence of hyperventilation on the interactions between changes in R-R interval (RR) and muscle sympathetic nerve activity (MSNA) and changes in neurocirculatory variability, in 14 healthy subjects. We performed spectral analysis of RR and MSNA variability during each of the following interventions: 1) controlled breathing, 2) maximal end-expiratory apnea, 3) isocapnic voluntary hyperventilation, and 4) hypercapnia-induced hyperventilation. MSNA increased from 100% during controlled breathing to 170 +/- 25% during apnea (P = 0.02). RR was unchanged, but normalized low-frequency (LF) variability of both RR and MSNA increased markedly (P < 0.001). During isocapnic hyperventilation, minute ventilation increased to 20.2 +/- 1.4 l/min (P < 0.0001). During hypercapnic hyperventilation, minute ventilation also increased (to 19.7 +/- 1.7 l/min) as did end-tidal CO(2) (both P < 0.0001). MSNA remained unchanged during isocapnic hyperventilation (104 +/- 7%) but increased to 241 +/- 49% during hypercapnic hyperventilation (P < 0.01). RR decreased during both isocapnic and hypercapnic hyperventilation (P < 0.05). However, normalized LF variability of RR and of MSNA decreased (P < 0.05) during both isocapnic and hypercapnic hyperventilation, despite the tachycardia and heightened sympathetic nerve traffic. In conclusion, marked respiratory oscillations in autonomic drive induced by hyperventilation may induce dissociation between RR, MSNA, and neurocirculatory variability, perhaps by suppressing central genesis and/or inhibiting transmission of LF cardiovascular rhythms.

Adult↗

PubMed2001

Contrasting effects of phentolamine and nitroprusside on neural and cardiovascular variability.

The relative contributions of a central neural oscillator and of the delay in alpha-adrenergic transmission within the baroreflex loop in the predominance of low-frequency (LF) cardiovascular variability during sympathetic activation in humans are unclear. We measured R-R interval (RR), muscle sympathetic nerve activity (MSNA), blood pressure (BP), and their variability in 10 normal subjects during sympathetic activation achieved by BP lowering with sodium nitroprusside (SNP) and alpha-adrenergic blockade using phentolamine. SNP and phentolamine induced comparable reductions in BP (P > 0.25). Despite tachycardia and sympathetic activation with both SNP and phentolamine, LF variability in RR, MSNA, and BP increased during SNP and decreased during phentolamine (SNP: RR +20 +/- 6%, MSNA +3 +/- 5%, systolic BP +9 +/- 6%, diastolic BP +7 +/- 5%; phentolamine: RR -2 +/- 7%, MSNA -34 +/- 6%, systolic BP -16 +/- 8%, diastolic BP -13 +/- 4%, P < 0.05 except systolic BP, where P = 0.09). Thus LF variability is reduced when sympathetic activation is induced by alpha-adrenergic blockade. This suggests that alpha-adrenergic transmission within the baroreflex loop may contribute importantly to the predominance of LF cardiovascular variability associated with sympathetic excitation in humans.

Adrenergic alpha-Antagonists↗

PubMed2000

Sympathetic activation by sildenafil.

BACKGROUND: Sildenafil citrate is an effective and widely prescribed therapy for erectile dysfunction. Little is known about the effects of sildenafil on neural control of the circulation or about the effects of sildenafil on neurocirculatory stress responses. METHODS AND RESULTS: We studied 14 normal volunteers (age 32+/-7 years) who were randomized in a double-blind crossover fashion to receive a single oral dose of sildenafil 100 mg or placebo on 2 separate study days. Blood pressure, heart rate, forearm vascular resistance, muscle sympathetic nerve activity, and plasma catecholamines were measured at baseline and at 30 and 60 minutes after sildenafil and after placebo administration. The effects of sildenafil and placebo on neural and circulatory responses to stressful stimuli (sustained handgrip, maximal forearm ischemia, mental stress, and the cold pressor test) were also evaluated. Blood pressure, heart rate, and forearm vascular resistance after sildenafil and placebo were similar. However, muscle sympathetic nerve activity increased strikingly after sildenafil (by 141+/-26%, mean+/-SEM) compared with placebo (3+/-8%) (P=0.006); plasma norepinephrine levels also increased by 31+/-5% after sildenafil administration (P=0.004). Sympathetic nerve traffic during mental, physical, and cold stresses was 2- to 8-fold higher after sildenafil than with placebo (P<0.05). CONCLUSIONS: Sildenafil causes a marked increase in sympathetic activation, evident both at rest and during stressful stimuli. Sympathetic activation by sildenafil may have implications for understanding cardiovascular events associated with sildenafil use.

3',5'-Cyclic-GMP Phosphodiesterases↗