Alterations In Cardiovascular Function Research Articles

Cardiovascular function in the heat‐stressed human

Heat stress, whether passive (i.e. exposure to elevated environmental temperatures) or via exercise, results in pronounced cardiovascular adjustments that are necessary for adequate temperature regulation as well as perfusion of the exercising muscle, heart and brain. The available data suggest that generally during passive heat stress baroreflex control of heart rate and sympathetic nerve activity are unchanged, while baroreflex control of systemic vascular resistance may be impaired perhaps due to attenuated vasoconstrictor responsiveness of the cutaneous circulation. Heat stress improves left ventricular systolic function, evidenced by increased cardiac contractility, thereby maintaining stroke volume despite large reductions in ventricular filling pressures. Heat stress-induced reductions in cerebral perfusion likely contribute to the recognized effect of this thermal condition in reducing orthostatic tolerance, although the mechanism(s) by which this occurs is not completely understood. The combination of intense whole-body exercise and environmental heat stress or dehydration-induced hyperthermia results in significant cardiovascular strain prior to exhaustion, which is characterized by reductions in cardiac output, stroke volume, arterial pressure and blood flow to the brain, skin and exercising muscle. These alterations in cardiovascular function and regulation late in heat stress/dehydration exercise might involve the interplay of both local and central reflexes, the contribution of which is presently unresolved.

RELATIONSHIP BETWEEN ARTERIAL STIFFNESS AND DIASTOLIC FUNCTION IN POST-MENOPAUSAL WOMEN: PP.31.228

Objective: Cardiovascular risk in post-menopausal women is related not only to the prevalence of traditional risk factors but also to the incidence of alterations in cardiovascular function and structure. Arterial stiffness can represent a mechanism involved in development of cardiac alterations. The aim of this study is to evaluate the relationship between arterial stiffness and left ventricular diastolic function in a group of post-menopausal women entering the prevention program “Woman and Heart”. Design and Methods: In 149 women with no previous cardiovascular events (age 56 ± 6 years, blood pressure-BP 129 ± 17/76 ± 9 mmHg, 38% hypertensives, 30% smokers, 27% hypercholesterolemic, 20% obese, 8% with impaired glucose tolerance or diabetes), carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry (Sphygmocor, Atcor Medical). Moreover, a trans-toracic echocardiographic study was carried out to measure mitral inflow pattern, left ventricular mass index (LVMI) and relative wall thickness (RWT). Results: In the total population, carotid-femoral PWV was 7.2 ± 1.3m/s. Left ventricular hypertrophy (LVMI >51 g/m2,7) was found in 30% of the population, RWT was>0.42 in 12%, while impaired left ventricular relaxation (E/A ratio < 0.8, deceleration time>200ms) was found in 24%. An increased PWV was associated with the presence of impaired left ventricular relaxation (PWV 7.72 vs 7.15 m/s, p<0.01), but not with left ventricular hypertrophy or concentric remodeling. The only risk factors associated with increased PWV were age, hypertension and altered glucose tolerance. Logistic regression analysis, adjusted for these 3 risk factors, showed that a PWV greater than the median value of 7.1 m/sec was associated with a 2.9-fold greater risk (confidence limits 5–95% 1.11–7.79) of having impaired left ventricular relaxation. Conclusions: In a post-menopausal female population, evaluated in a primary prevention setting, carotid to femoral PWV is associated to mild diastolic dysfunction even after correction for the most important confounders. These data suggest that an increased aortic stiffness could contribute to left ventricular diastolic dysfunction and possibly to diastolic heart failure in post-menopausal women.

Cardiovascular Adaptations to Long-Duration Head-Down Bed Rest

Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 d of bed rest and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 min or until presyncopal symptoms intervened. Plasma volume was significantly reduced (15%) by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49 (6% from pre-bed rest). Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Anterior tibial artery intimal-medial thickness markedly decreased at bed rest days 21 (21%), 35 (22%), and 49 (19%). Several cardiac functional parameters, including isovolumic relaxation time (73 ms to 85 ms at day 7) and myocardial performance index, were significantly increased (0.41 to 0.49 by day 7 of bed rest; indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 d of bed rest (P = 0.1). Our data suggest that bed rest altered cardiovascular structure and function in a pattern similar to short-duration spaceflight. Additionally, the vascular alterations were primarily seen in the lower body, while vessels of the upper body were unaffected.

The Effects Of Reduced Blood Volumes On Oxygen Uptake Kinetics In Trained Athletes

The Effects of reduced blood volumes on Oxygen Uptake Kinetics PURPOSE: The purpose of this study was to test the hypothesis that a reduced total blood volume will influence the (VO2) on-kinetic response during both moderate (MOD) and heavy (HVY) intensity exercise. METHOD: Following University Institutional ethics approval twelve subjects volunteered and agreed to participate (age, 21 ± 2 yrs; height, 175.2 ± 5.1 cm; weight, 66.4 ± 2.8 kg; VO2max, 53.0 ± 4.1 ml.kg-1·min-1). The subjects completed two exercise trials, un-bled (UBL) and bled (BLL) which were interspersed by a period of 48h. The trials consisted of an initial phase of 4-min of unloaded cycling followed by 2 bouts of 6-min constant load cycling at D 80% base-line VO2 - VO2 at ventilatory threshold (MOD), which were separated by 10-min of recovery unloaded cycling. Following the same recovery phase the subjects completed a third bout of 6-min constant load cycling at D50% ventilatory threshold - VO2max (HVY). Between the two exercise trials the subjects donated 500ml3 of blood. For both the UBL and BL trials VO2 was recorded on a breath-by breath basis using a pre-calibrated metabolic cart, haemodynamic responses were recorded throughout the trials and haematological variables were recorded pre-exercise. For both UBL and BLL trials the VO2 on-kinetic response data were fitted with a 3-component exponential model for analysis of the primary time component and mean response times. RESULTS: There were significant differences between UBL and BLL for Hb g·dl-1 (p< 0.005), HcT % (p< 0.001) and RBC·μl-1 (p< 0.013) with Hb showing a decrease of 9.7% from 14.5 ± 5.5 g·dl-1 to 13.1 ± 14.9 g·dl-1. There were non-significant differences between UBL and BLL for either the time constant or the amplitude of the phase II/III VO2 responses in both the MOD and HVY conditions (p >0.05). However there was a significant increase in the D pulse pressure for phase II between UBL and BLL in both MOD (10.4 ± 24.1mmHg) (p< 0.037) and HVY domains (21.2 ± 4.1mmHg) (p< 0.042). CONCLUSION: The data highlights the capability of the cardiovascular system in compensating for a reduction in the O2 carrying capacity of the blood through central alterations of cardiovascular function suggesting that exercise in the MOD and HVY domains does not appear to be limited by O2 delivery in healthy young individuals.

Hepatic and vascular mRNA expression in adult zebrafish ( Danio rerio) following exposure to benzo-a-pyrene and 2,3,7,8-tetrachlorodibenzo- p-dioxin

Developmental exposure to aryl hydrocarbon receptor (AhR) agonists in fish causes severe defects in the cardiovascular system. However, the effects of acute AhR agonist exposure on the adult fish cardiovascular system are not clear. We hypothesized that AhR-mediated changes in adult vascular tissue gene expression would differ from that of hepatic tissue. Therefore, zebrafish ( Danio rerio) were intraperitoneally injected with the AhR agonists benzo-a-pyrene (BaP; 1 mg/kg) or 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD; 20 μg/kg) alone and in combination with the AhR antagonists resveratrol (Res; 10 mg/kg) or α-naphthoflavone (ANF; 50 mg/kg). Hepatic and mesenteric artery cytochrome P450 enzyme (subtypes 1A, 1B1, 1C1, and 1C2) and cyclooxygenase enzyme (subtypes 1, 2a, and 2b) mRNA expression was quantified using real-time reverse transcriptase PCR. TCDD exposure significantly increased ( p ≤ 0.05 in Tukey's posteriori test after 1-way ANOVA; n = 4–6/group) CYP1A, CYP1C1, and COX-2b mRNA expression in hepatic tissue (105 ± 21, 12 ± 2, and 2 ± 0.3 fold-increase, mean ± SEM respectively). TCDD also increased CYP1A, CYP1B1, CYP1C1, CYP1C2, and COX-1 mRNA expression in mesenteric artery (121 ± 23, 5 ± 1, 28 ± 6, 7 ± 1, and 3 ± 0.3, respectively). Importantly, while BaP exposure elicited no significant alterations in hepatic CYP mRNA expression, it increased COX-1 and COX-2b in liver tissues (3 ± 1 and 2 ± 0.1, respectively), as well as CYP1A, CYP1B1, CYP1C1, CYP1C2, and COX-1 expression in mesenteric artery (2 ± 0.3, 4 ± 0.3, 5 ± 1, 5 ± 1, and 2 ± 0.3, respectively). Resveratrol was able to antagonize TCDD-induced CYP1C2 in mesenteric artery but was without effect in all other treatments in both liver and mesenteric artery. In contrast, ANF antagonized TCDD and BaP-induced COX-2b and TCDD-induced CYP1C1 expression increases, as well as reduced baseline CYP1B1 and COX-2a expression in liver, while failing to affect BaP and TCDD-induced hepatic CYP1A increases. However, in mesenteric artery, ANF alone acted instead as an agonist to increase expression of CYP1A, CYP1B1, CYP1C1, CYP1C2, COX-2a and COX-2b. Thus, there are important differences in response to both AhR agonists and antagonists between liver and mesenteric artery in adult zebrafish. The vascular-specific changes in gene expression will be linked to future studies examining alterations in cardiovascular function produced by acute AhR agonist exposure in adult fish.

Effects of tetrahydrobiopterin on venous bubble grade and acute diving‐induced changes in cardiovascular function

Self-contained underwater breathing apparatus diving reduces cardiovascular function and increases pulmonary artery pressure (PAP) up to 3 days after a single dive. Acute antioxidants partially attenuated arterial endothelial dysfunction, whereas cardiac and PA functions were unaffected. We tested the hypothesis that acute tetrahydobiopterin (BH(4)), as a cofactor of endothelial nitric oxide (NO) synthase, reduces bubble grade (BG) and attenuates alteration in cardiovascular function after diving because of increased NO bioavailability. Mean PAP (mPAP), PA acceleration time and right ventricle ejection time, left ventricle ejection fraction (LV-EF) and BG were measured after oral placebo (P), vitamin C (C) or a combination of vitamin C and BH(4) (BH(4)) in a randomized, placebo controlled trial before and after field dive to 30 m of sea water for 30 min bottom time. Eight recreational divers performed three dives with a 3-days period between them. Regarding the primary hypothesis, no difference was observed between post-dive changes in BG (2.1 +/- 2.2 bubbles cm(-2) for P, 3.4 +/- 3.9 for C and 3.6 +/- 2.1 for BH(4)), mPAP (25.6 +/- 6.5 mmHg for P, 25.9 +/- 8.6 for C and 22.6 +/- 3.5 for BH(4)) and LV-EF (62.6 +/- 4.6% for P, 61.4 +/- 3.9 for C and 61.6 +/- 3.7 for BH(4)) with all three conditions. This suggests that co-administration of BH(4) and vitamin C does not improve heart and pulmonary artery function after diving.

Relationships between vascular resistance and energy deficiency, nutritional status and oxidative stress in oestrogen deficient physically active women

Oestrogen deficiency contributes to altered cardiovascular function in premenopausal amenorrheic physically active women. We investigated whether other energy deficiency-associated factors might also be associated with altered cardiovascular function in these women. A prospective observational study was completed at a research facility at the University of Toronto. Thirty-two healthy premenopausal women (18-35 years old) were studied; 9 sedentary and ovulatory; 14 physically active and ovulatory; and 8 physically active and amenorrheic. We measured calf vascular resistance, resting heart rate, dietary energy intake, resting energy expenditure and serum measures of homocysteine, high-sensitivity C-reactive protein, oxidized low-density lipoproteins, total T(3), ghrelin, leptin and insulin. Groups were similar (P > 0.05) in age (25.1 +/- 0.8 years; mean +/- SEM), weight (57.3 +/- 1.1 kg), and BMI (21.4 +/- 0.3 kg/m(2)). Resting vascular resistance and ghrelin were highest (P < 0.05, main effect), and total T(3) and energy expenditure adjusted for fat free mass lowest (P < 0.05, main effect) in oestrogen deficient women. Using pooled data for stepwise multiple regression modelling: ghrelin and resting energy expenditure adjusted for fat free mass were associated with resting vascular resistance (R(2) = 0.398, P = 0.018); adjusted dietary energy intake was associated with peak-ischaemic vascular resistance (R(2) = 0.231, P = 0.015). Adjusted resting energy expenditure (r = 0.624, P < 0.001) and total T(3) correlated (r = 0.427, P = 0.019) with resting heart rate. Homocysteine, high-sensitivity C-reactive protein and oxidized low-density lipoproteins were similar (P > 0.05, main effect) among the groups, and were unrelated to cardiovascular measures. Altered resting vascular resistance in premenopausal oestrogen deficient physically active amenorrheic women is not associated with vascular inflammation or oxidative stress, but rather with parameters that reflect metabolic allostasis and dietary intake, suggesting a potential role for chronic energy deficiency in vascular regulation.

Age and Lateral Sleep Position: A Pilot Study

Purpose: Previous research, undertaken using a Super 8 camera and non-continuous data, has reported that with increasing age, people are more likely to sleep in the right lateral position. It has been postulated that this is due to age related alterations in cardiovascular function. This pilot study was undertaken to determine if collection and analysis of continuous sleep data was a feasible method for further investigation of this topic and to determine the sample size required for an adequately powered study. Increased understanding of age related changes in sleep position may provide valuable information to improve sleep quality and nursing care of the elderly person. Method: Research at the Centre for Sleep Research, University of South Australia, investigated the association between age and sleep position. Infra-red illumination and video cameras recorded the sleep patterns of 12 subjects for two nights. Videos were examined and the amount of time spent in each sleep position was calculated in seconds. Results: In a one-way analysis of variance, sample sizes of 19, 19, and, 19 are necessary from the three age groups whose means are to be compared. The expected means are 20, 25 and 45 for the three age groups respectively. The total sample of 57 subjects achieves 82% power to detect differences among the means versus the alternative of equal means using an F test with a 0.05 significance level.Conclusions: The results of this pilot study support further investigation of the relationship between age and lateral sleep position preference, and particularly the physiological parameters which may underpin the adoption of different sleep positions with increasing age. The described method is appropriate and modifications are suggested to further improve future studies.

Should we treat all subjects with subclinical thyroid disease the same way?

Overt hypothyroidism and hyperthyroidism are associated with an increased cardiovascular risk (1). Despite the high prevalence of subclinical thyroid disease and the potential progression to overt disease, the risk associated with this condition is debated (2, 3). The potential cardiovascular risk in subclinical thyroid disease is an important factor that can affect decisions about the screening and treatment of patients (4, 5). Alterations of cardiovascular function have been reported in young and middle-aged individuals with persistent subclinical hyperthyroidism (SHyper) (4, 5). Moreover, the atherosclerotic risk was found to be higher in SHyper patients with decreased serum thyrotrophin (TSH) levels (6). In elderly individuals, SHyper is associated with an increased prevalence of atrial fibrillation, and the hypercoagulable state could predispose these subjects to an increased thromboembolic risk (7). SHyper has been linked to several important independent cardiovascular risk factors, and if left untreated could, in the long term, increase morbidity andmortality due to coronary heart disease, stroke, heart failure, and sudden death, especially in the elderly. Three studies have assessed cardiovascular mortality in patients with endogenous SHyper (7–9). No adverse outcome and no increased cardiovascular mortality was observed by Cappola et al. (7) and Walsh et al. (9) in patients with endogenous SHyper as a whole, or in the subgroup with serum TSH less than 0.1 mIU/l and serum TSH between 0.1 and 0.4 mIU/l. On the contrary, in another study, survival was poorest in subjects with low serum TSH (!0.5 mIU/l) (8), and there was no difference in survival between patients with a low but detectable TSH and undetectable serum TSH. The increased mortality was due to cardiovascular diseases. Interestingly, thyroid hormone use was not related to cardiovascular mortality among women with baseline TSH below the normal range in the community dwelling study by Bauer et al. (10). The epidemiological studies of endogenous SHyper have several limitations, subclinical thyroid dysfunction may not be stable over time and not all studies provided information about: 1) the pre-diagnosis duration of SHyper; 2) the diagnosis of SHyper; and3) the progression or treatment of thyroid dysfunction of the members of some cohorts. Lastly, the analysiswas not always adjusted for associated cardiovascular risk factors.

Perinatal iron deficiency results in increased visceral adiposity in male Wistar rats

Perinatal iron deficiency (ID) has adverse programming effects in adult offspring manifested as alterations in cardiovascular function as well as glucose and lipid metabolism. Given the importance of increased visceral adipose tissue (VAT) as a likely mediator of these sequalae, in the present study we determined the effect of perinatal ID on VAT in male wistar rats, and its association with other obesity‐related disturbances, such as salt sensitive arterial pressure (AP). Dams were fed a low iron diet (&lt;10ppm Fe) prior to and throughout gestation. At delivery, dams were fed a normal iron diet (270ppm Fe). ID offspring had lower body weights (−11%) and markedly reduced hematocrits (−40%) at birth compared to controls. At 16 weeks of age, these animals had 20% more VAT (normalized to body weight) than controls. Furthermore, the elevation of AP (assessed by radiotelemetry) in response to increased sodium intake was 79% greater in the ID offspring compared to controls. In summary, perinatal ID resulted in a persistent increase in visceral adiposity associated with an enhanced hypertensive response to dietary salt. Supported by the Canadian Institutes of Health Research and the Bickell Foundation of Canada.

Beta‐2 adrenergic receptor haplotype and echocardiographic indices in heart failure patients

We recently reported altered cardiovascular structure and function in heart failure (HF) patients based on the Arg16/Gly and Gln27/Glu beta‐2 adrenergic receptor (ADRB2) polymorphisms. The purpose of this study was to extend the echocardiographic analysis based on haplotype combination of ADRB2 at nucleotides −654, 46 79, 252, 491, 523, in a larger database of HF patients (n=126, age 56±1yr, LV ejection fraction, LVEF 29±1%, BMI 28±0.4kg/m2, mean±SEM) and healthy controls (n=100, age 50±2yr, LVEF 63±0.7%, BMI 25±0.3kg/m2). The most common haplotypes in both HF and control were 2, 8, and 12 (2=AACGCC, 8=GGCACA, and 12=GGGGCC, for nucleotides −654, 46, 79, 252, 491, and 523). Cardiac function did not differ according to haplotype pairs in the control subjects. In HF, the widest discrepancies were between haplotype pair 2/2 (which includes the Arg16+Gln27 homozygotes) and haplotype pair 12/12 (which includes the Gly16+Glu27 homozygotes), respectively: 2/2 displayed lower cardiac index (2.3±0.1 v 2.7±0.1 l/min/m2), greater left atrial diameter (53±2 v 47±2 mm), shorter LV decel time (185±11 v 224±14 msec), and greater right ventricular pressure (44±2 v 33±2 mmHg) p&lt;0.05 for all). These data suggest that in HF, haplotype variation of the ADRB2 is associated with differences in cardiac function, and SNP positions 16 and 27 remain major loci of interest.Support: K23RR‐17520, HL‐71478.

Spontaneously occurring differences in fetal weight do not affect blood pressure, the hypothalamic-pituitary-adrenal axis or the renin-angiotensin system in the late-gestation ovine fetus

Fetal growth restriction (FGR) has been associated with an increased incidence of cardiovascular disease in adult life. Animal models of restricted fetal growth often cause FGR over discrete periods of gestation and hence may not be applicable to individuals with low birthweight but who are not clinically growth-restricted. Our aim was to determine whether spontaneously occurring differences in fetal growth influence the functional development of the hypothalamic-pituitary-adrenal (HPA) axis or the renin-angiotensin system (RAS), both of which are involved in arterial pressure regulation. Using sheep, arterial pressure and heart rate were monitored in chronically catheterised singleton and twin fetuses at 130, 134 and 137 days of gestation (term approximately 147 days). Fetuses were challenged, at different times, with exogenous angiotensin (Ang) II, combined administration of arginine vasopressin and corticotrophin releasing hormone (AVP+CRH) and adrenocorticotrophic hormone (ACTH); fetal cardiovascular responses and circulating cortisol concentrations were measured. In all fetuses Ang II and AVP+CRH altered cardiovascular function (increase in mean arterial pressure and decrease in heart rate); both AVP+CRH and ACTH increased circulating cortisol concentrations. Responses were not related to fetal bodyweight. We conclude that naturally occurring differences in growth do not influence the development of the HPA axis or RAS function in fetal sheep.

Increased secretory capacity of mouse adrenal chromaffin cells by chronic intermittent hypoxia: involvement of protein kinase C

Previous studies have shown that catecholamine secretion from the adrenal medulla plays a critical role in chronic intermittent hypoxia (CIH)-induced alterations in cardiovascular function. In the present study we examined the cellular mechanisms associated with the effects of CIH on adrenal chromaffin cell catecholamine secretion. Experiments were performed on adult male mice (C57/BL6) that were exposed to 1-4 days of CIH or to normoxia. Perforated patch electrical capacitance recordings were performed on freshly prepared adrenal medullary slices that permit separating the chromaffin cell secretion from sympathetic input. CIH resulted in a significant increase in the readily releasable pool (RRP) of secretory granules, and decreased stimulus-evoked Ca(2+) influx. Continuous hypoxia (CH) either for 2.5 h (equivalent to hypoxic duration accumulated over 4 days of CIH) or for 4 days were ineffective in evoking changes in the RRP and Ca(2+) influx. CIH activated PKC in adrenal medullae as evidenced by increased phosphorylation of PKC at Thr(514) and PKC inhibitors prevented CIH-induced increases in the RRP and restored stimulus-evoked attenuation of Ca(2+) influx. CIH resulted in elevated thio-barbituric acid reactive substances (TBARSs, an index of oxidized proteins) and an antioxidant prevented CIH-induced changes in the RRP, suggesting the involvement of reactive oxygen species (ROS). These results demonstrate that CIH increases the RRP in adrenal chromaffin cells via ROS-mediated activation of PKC and suggest that CIH can directly affect the secretory capacity of chromaffin cells and contribute, in part, to elevated catecholamine levels.

Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 +/- 2 vs. 20 +/- 4 mGU/ml, P < 0.05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P < 0.05) accompanied by a 25% reduction in systolic blood pressure (BP, 110 +/- 4 vs. 147 +/- 3 mmHg, P < 0.001) compared with WT mice. Aldosterone levels were unchanged, whereas the plasma potassium concentration was elevated by 14% (P < 0.05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice (P < 0.05), and cardiac dimensions as analyzed by echocardiography were similarly reduced. Myograph studies revealed a reduced maximum contractile response in the aorta to norepinephrine (NE) and K(+) (P < 0.05), and aorta media thickness was decreased in GHR KO (P < 0.05). However, contractile force was normal in mesenteric arteries, whereas sensitivity to NE was increased (P < 0.05). Maximal acetylcholine-mediated dilatation was similar in WT and GHR KO mice, whereas the aorta of GHR KO mice showed an increased sensitivity to acetylcholine (P < 0.05). In conclusion, loss of GHR leads to low BP and decreased levels of renin in plasma as well as increase in aortic eNOS expression. Furthermore, GHR deficiency causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size. These data suggest an important role for an intact GH/IGF-I axis in the maintenance of a normal cardiovascular system.

Short-acting NO donor and decompression sickness in humans

to the editor: In the December issue of the Journal of Applied Physiology, Mollerlokken at al. ([3][1]) describe the beneficial effect of a short-acting nitric oxide (NO) donor on the formation of venous gas bubbles after decompression in anesthetized pigs. It is accompanied by the editorial by Dr

Response to Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

We thank Drs Schlaich and Schmieder1 for their interest in our research2 and for providing us with an opportunity to put our results in context. Given the dominant effect of the autonomic nervous system in counteracting alterations in cardiovascular function, we are not surprised that Schlaich and Schmieder1 were unable to show significant changes in renal plasma flow during systemic administration of NO synthase inhibitors, hence our effort to …

Autonomic Alterations in Cocaine-Exposed Neonates Following Orthostatic Stress

We investigated the effects of prenatal cocaine exposure (PCE) on heart rate (HR) and heart rate variability (HRV) in the presence of orthostatic stress among near- and full-term neonates. PCE infants (n = 21) and controls (n = 23) were enrolled within 120 h of birth. ECG was recorded for an hour during quiet sleep, 30 min in supine position and then 30 min in an inclined position. Linear mixed models were used to analyze HR and HRV in the time domain and wavelet and power spectrum analyses in the frequency domain. PCE infants had tachycardia both before (p = 0.091) and after tilting (p = 0.015), but with a clear interaction between PCE and orthostatic stress (p = 0.049). Compared with controls, PCE infants had a delayed and prolonged reaction to orthostatic stress. There was also a pronounced interaction with regard to log-transformed SDDRR, a measure of HRV (p = 0.049). Controls experienced an instantaneous increase in log (SDDRR) followed by a prompt return to normal levels, while PCE infants had a gradual increase that did not dissipate quickly. Frequency-domain analyses also distinguished between the cocaine-exposed infants and the controls. Results suggest that the effects of PCE on the development of sympathetic and parasympathetic systems could lead to altered cardiovascular function.

The effects of acute oral antioxidants on diving‐induced alterations in human cardiovascular function

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (approximately 2-3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24-48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

Exercise training-induced remodeling of paraventricular nucleus (nor)adrenergic innervation in normotensive and hypertensive rats

Activation of oxytocin (OT)ergic projections from the hypothalamic paraventricular nucleus (PVN) to the nucleus tractus solitarii contributes to cardiovascular adjustments during exercise training (EXT). Moreover, a deficit in this central OTergic pathway is associated with altered cardiovascular function in hypertension. Since PVN catecholaminergic inputs, known to be activated during EXT, modulate PVN cardiovascular-related functions, we aimed here to determine whether remodeling of PVN (nor)adrenergic innervation occurs during EXT and whether this phenomenon is affected by hypertension. Confocal immunofluorescence microscopy and tract tracing were used to quantify changes in (nor)adrenergic innervation density in PVN subnuclei and in identified dorsal vagal complex (DVC) projecting neurons (PVN-DVC) in EXT normotensive [Wistar-Kyoto rat (WKY)] and hypertensive [spontaneously hypertensive rat (SHR)] rats. In WKY, EXT increased the density of PVN dopamine beta-hydroxylase immunoreactivity (DBHir) (160%). Furthermore, the number and density of DBHir boutons overlapping PVN-DVC OTergic neurons were also increased during EXT (130%), effects that were blunted in SHR. Conversely, while DBHir in the medial parvocellular subnucleus (an area enriched in corticotropin-releasing hormone neurons) was not changed by EXT in WKY, a diminished DBHir was observed in trained SHR. Overall, these data support the concept that the PVN (nor)adrenergic innervation undergoes plastic remodeling during EXT, an effect that is differentially affected during hypertension. The functional implications of PVN (nor)adrenergic remodeling in relation to the central peptidergic control of cardiovascular function during EXT are discussed.

Elderly patients with unexplained syncope: What should be considered a positive tilt test response?

Introduction Syncope is a common problem and can lead to serious consequences in the elderly. Tilt test is useful to investigate recurrent syncope, but few studies have investigated the hemodynamic responses of this population to tilt test. Objective To describe the tilt test responses of elderly patients with recurrent syncope of unknown origin and to determine the occurrence of altered cardiovascular autonomic function in a subset of those with the diagnosis of dysautonomic pattern to the tilt test. Methods Elderly patients ( n = 165; > 60 years old) who sought medical assistance because of recurrent syncope during 18 months were initially enrolled and submitted to a two-stage, nitroglycerin-potentiated tilt test. A subset of patients who presented with dysautonomic response to tilt test performed clinical autonomic tests. Results The most frequent cause of syncope during tilt test was the dysautonomic pattern (43%), followed by mixed type neurocardiogenic syncope (35%). Most patients who remained asymptomatic during tilt test showed clear abnormal hemodynamic response during the exam. Conclusion Autonomic dysfunction, which can be found during tilt test, is probably an important cause of syncope in the elderly, regardless of the occurrence of symptoms during the tilt test.