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Biomedical subjects

F Boomsma

Publications and source records attributed to F Boomsma.

At least 55 records · Page 3Linked to original sources
PubMed2000

Time course and mechanism of myocardial catecholamine release during transient ischemia in vivo.

BACKGROUND: Elevated concentrations of norepinephrine (NE) have been observed in ischemic myocardium. We investigated the magnitude and mechanism of catecholamine release in the myocardial interstitial fluid (MIF) during ischemia and reperfusion in vivo through the use of microdialysis. METHODS AND RESULTS: In 9 anesthetized pigs, interstitial catecholamine concentrations were measured in the perfusion areas of the left anterior descending coronary artery (LAD) and the left circumflex coronary artery. After stabilization, the LAD was occluded for 60 minutes and reperfused for 150 minutes. During the final 30 minutes, tyramine (154 nmol. kg(-1). min(-1)) was infused into the LAD. During LAD occlusion, MIF NE concentrations in the ischemic region increased progressively from 1. 0+/-0.1 to 524+/-125 nmol/L. MIF concentrations of dopamine and epinephrine rose from 0.4+/-0.1 to 43.9+/-9.5 nmol/L and from <0.2 (detection limit) to 4.7+/-0.7 nmol/L, respectively. Local uptake-1 blockade attenuated release of all 3 catecholamines by >50%. During reperfusion, MIF catecholamine concentrations returned to baseline within 120 minutes. At that time, the tyramine-induced NE release was similar to that seen in nonischemic control animals despite massive infarction. Arterial and MIF catecholamine concentrations in the left circumflex coronary artery region remained unchanged. CONCLUSIONS: Myocardial ischemia is associated with a pronounced increase of MIF catecholamines, which is at least in part mediated by a reversed neuronal reuptake mechanism. The increase of MIF epinephrine implies a (probably neuronal) cardiac source, whereas the preserved catecholamine response to tyramine in postischemic necrotic myocardium indicates functional integrity of sympathetic nerve terminals.

Animals↗
PubMed2000

Chronic administration of moxonidine suppresses sympathetic activation in a rat heart failure model.

Excessive sympathetic activity contributes to cardiovascular abnormalities, which negatively affect the prognosis of heart failure. The present study evaluated the effects of moxonidine, an imidazoline I(1) receptor agonist, on sympathetic activation and myocardial remodelling in a rat heart failure model. Rats were subjected to coronary artery ligation, and treated with moxonidine, 3 or 6 mg/kg/day, from 1 to 21 days after myocardial infarction. After 21 days, heart rate and blood pressure were measured in conscious, chronically instrumented rats. Plasma catecholamine levels were determined by high-performance liquid chromatography. Effects on post-myocardial infarction remodelling were evaluated from the ventricular weight body weight ratio and interstitial collagen deposition, measured morphometrically in the interventricular septum remote from the infarcted area. Moxonidine dose-dependently decreased myocardial infarction induced tachycardia but did not affect myocardial infarction reduced blood pressure. Plasma noradrenaline levels, which were elevated after myocardial infarction, decreased below sham-values with 6 mg/kg/day moxonidine. Ventricular weight-body weight ratio as well as interstitial collagen were significantly elevated in myocardial infarcted rats, and restored to sham values with 6 mg/kg/day moxonidine. These data suggest that moxonidine suppresses myocardial infarction induced sympathetic activation in a dose-dependent way as indicated by reduced heart rate and plasma noradrenaline levels. Furthermore, post-myocardial infarction remodelling may be attenuated at a higher dose-range of moxonidine as shown by normalisation of ventricular weight body weight ratio and interstitial collagen.

Animals↗
PubMed2000

Chronic beta-blocker treatment in patients with advanced heart failure. Effects on neurohormones.

BACKGROUND: To date, the use of beta-blockers in treating patients with chronic heart failure gains support, this since several large clinical trials reported reduced mortality after chronic beta-blockade. Part of these beneficial effects may result from inhibition of deleterious neurohormone activation that accompanies progression of chronic heart failure. The present study evaluates whether this neurohormone inhibition is preserved after chronic beta-blockade. METHODS: In a retrospective analysis the neurohormonal profiles of patients with moderate to severe chronic heart failure were studied from three treatment subgroups: (1) Without beta-blockers or ACE-inhibitors (n=15), (2) without beta-blockers, with ACE-inhibitors (n=324), (3) with beta-blockers and ACE-inhibitors (n=31). Patients were on beta-blockers for an average period of 3.8 years. Plasma samples were obtained under controlled conditions. RESULTS: Despite uneven group sizes, the groups were well matched for clinical characteristics. Plasma renin levels were significantly lower in patients treated adjunctively with beta-blockers. Plasma aldosterone and endothelin-I levels also tended to be lower after chronic beta-blockade, however, this did not reach statistical significance. CONCLUSIONS: Chronic adjunctive beta-blocker treatment shows significantly lower plasma renin levels when compared to single ACE-inhibition. This persistent reduction of plasma neurohormone activation may concomitantly reduce the chance of neurohormones to escape from inhibition.

Adrenergic beta-Antagonists↗
PubMed2000

Variation in semicarbazide-sensitive amine oxidase activity in plasma and tissues of mammals.

Semicarbazide-sensitive amine oxidase (SSAO) (E.C. 1.4.3.6) is a group of enzymes with as yet poorly understood function which is widely present in nature. The variation in methodology for determination of activity, differences in substrates used and in nomenclature have made it difficult to compare SSAO in different species and tissues. Since SSAO is implicated in the pathophysiology of diabetes mellitus and congestive heart failure, our aim was to analyse the importance and abundance of SSAO in human plasma and tissues compared to other mammals. In plasma of ten different mammals, Vmax values were found to vary more than 10,000-fold, while KM differed much less; in human plasma SSAO activity is relatively low. In some species more than one SSAO entity was present in plasma. SSAO activity was ubiquitous in tissues of human, rat and pig, but varied considerably, both between species and between tissues. In human tissues, SSAO activity is higher than in tissues from rat and pig. Relative to monoamine oxidase-B there is also wide variation in SSAO, with much higher relative activities in human than in rat and pig tissues. We conclude that in plasma, SSAO activity is highest in ruminants, while in tissues, SSAO activity is more prominently present in human than in rat and pig.

Amine Oxidase (Copper-Containing)↗
PubMed2000

Prognostic value of the presence and development of atrial fibrillation in patients with advanced chronic heart failure.

AIMS: To examine whether the presence, or development, of atrial fibrillation in patients with advanced chronic heart failure, is associated with a poorer prognosis, compared to patients with sinus rhythm and chronic heart failure. METHODS AND RESULTS: We examined 409 patients with moderate to severe chronic heart failure, and compared patients with sinus rhythm (n=325) to those with atrial fibrillation (n=84). At baseline, the two groups were similar regarding most indices of severity of chronic heart failure, such as left ventricular ejection fraction (0.23) and New York Heart Association (NYHA) functional class, while they were different for age (70 years for atrial fibrillation vs 67 years for sinus rhythm patients), aetiology of chronic heart failure, blood pressure, concomitant treatment, and plasma neurohormones (all P<0.05). During a mean follow-up of 3.4 years (range 2.0-5.4), 203 patients (50%) died. The majority of deaths was due to progressive chronic heart failure (55%) or was sudden (28%), but there was no difference in mode of death between sinus rhythm and atrial fibrillation patients. Overall mortality was higher in atrial fibrillation patients (60%), than in those with sinus rhythm (47%; risk ratio 1.40, 95% CI 1.01-1.92, P=0. 04). After adjusting for important prognostic variables, such as age, left ventricular ejection fraction, NYHA class, renal function, and blood pressure, the presence of atrial fibrillation was no longer related to increased mortality (risk ratio 0.86, range 0.59-1.24, P=ns). Of the 325 patients who had sinus rhythm at baseline, 30 (9%) developed atrial fibrillation during the study. These patients were older (70 vs 66 years, P<0.007), and had slightly lower blood pressure and plasma norepinephrine concentrations (P<0.05), but were otherwise similar. During follow-up, mortality was similar in these two groups (47% in those with new onset atrial fibrillation, vs 47% in those who had sinus rhythm throughout the study). CONCLUSIONS: The present data do not support the concept that the presence, or the development of atrial fibrillation in patients with advanced chronic heart failure is independently related to an adverse outcome during long-term follow-up. The generally observed higher mortality in patients with atrial fibrillation thus seems to be related to other factors, associated with atrial fibrillation.

Aged↗
PubMed2000

Plasma semicarbazide-sensitive amine oxidase (SSAO) is an independent prognostic marker for mortality in chronic heart failure.

AIMS: Experimental evidence has suggested that semicarbazide-sensitive amine oxidase is involved in vascular endothelial damage and in the process of atherosclerosis, through the formation of reactive aldehydes, hydrogen peroxide and ammonia from endogenous substrates. Recent evidence indicates that semicarbazide-sensitive amine oxidase may be identical with the vascular adhesion protein-1. In patients with diabetes mellitus and chronic heart failure the plasma activity is raised relative to the severity of the disease. The prognostic value of plasma semicarbazide-sensitive amine oxidase is not known. METHODS AND RESULTS: Plasma semicarbazide-sensitive amine oxidase activity was measured at baseline in patients with moderate to severe chronic heart failure who participated in a large European study (PRIME-II). The 372 patients who took part in a pre-defined substudy in The Netherlands were investigated and a survival follow-up (maximum 5.4 years, mean 3.4 years) was carried out. Within the follow-up period 195 patients died. Plasma semicarbazide-sensitive amine oxidase was higher at baseline in those who died than in the survivors (653+/-258 vs 540+/-242 mU. l(-1), P<0.001). Dividing the patients into two groups according to plasma values above or below the median value of 550 mU. l(-1), semicarbazide-sensitive amine oxidase was found to be a prognostic parameter for survival, both in univariate (P<0.0001) and in multivariate (P=0.0106) analysis. Semicarbazide-sensitive amine oxidase values >550 mU. l(-1)had a 1. 50 (95% CI, 1.10-2.04) times increased risk of death. CONCLUSION: The finding that plasma semicarbazide-sensitive amine oxidase is an independent prognostic marker for mortality in chronic heart failure supports the concept that an elevated plasma semicarbazide-sensitive amine oxidase level has deleterious effects, possibly due to vascular endothelial damage.

Aged↗
PubMed2000

The angiotensin-converting enzyme gene polymorphism and responses to angiotensins and bradykinin in the human forearm.

The deletion (D) allele of the angiotensin-converting enzyme (ACE) is associated with high ACE levels. Subjects homozygous for the D allele should therefore exhibit enhanced angiotensin I-induced vasoconstrictor responses and diminished bradykinin-induced vasodilator responses as compared with subjects homozygous for the insertion (I) allele. In eight II and eight DD normotensive male subjects, angiotensin I, bradykinin, and angiotensin II were infused in the forearm. Changes in forearm blood flow were registered with venous occlusion plethysmography. Blood was sampled to quantify angiotensin I to II conversion. Plasma ACE levels were 60% higher, and DD subjects showed an enhanced response to angiotensin I infusion (p < 0.05). No differences in angiotensin I to II conversion, angiotensin H vasoconstriction, and bradykinin vasorelaxation were found. The ACE-inhibitor enalaprilate inhibited angiotensin I-induced vasoconstriction, but did not significantly affect bradykinin-induced vasodilation. The AT1-receptor antagonist losartan (3,000 ng/kg/min) inhibited angiotensin II-induced vasoconstriction. In conclusion, subjects with the DD genotype display an enhanced vasoconstrictor response to angiotensin I, which cannot be explained on the basis of a similarly enhanced angiotensin I to II conversion rate or a difference in vascular reactivity. Possibly therefore, differences in angiotensin I to II conversion occur within the vascular wall only, at a site that does not readily equilibrate with blood plasma.

Adult↗
PubMed2000

Diurnal blood pressure variation in progressive autonomic failure.

To investigate the role of the autonomic nervous system (ANS) in the generation of the circadian blood pressure (BP) variation, the degree of impairment of the ANS was related to the results of ambulatory BP recordings in 212 patients with progressive autonomic failure due to familial amyloid polyneuropathy. On the basis of BP and/or heart rate (HR) responses to the Valsalva maneuver, 60 degrees head-up tilting, deep-breathing tests, and plasma norepinephrine levels, 4 groups of patients were distinguished. In all patients and in 38 age-matched control subjects, ambulatory BP was monitored. Patients of group I (n=40, aged 32+/-3 y), with no evidence yet of impairment of their ANS, had circadian BP and HR variations indistinguishable from controls. Patients of group II (n=41, aged 34+/-5 y) had a variable degree of impairment of their parasympathetic ANS, but their sympathetic ANS was still intact. Twenty-four-hour HR was higher in these patients than in controls (88+/-11 versus 78+/-7 bpm, P<0.01). Their circadian HR variation was maintained, but their circadian BP variation was diminished (10+/-6/11+/-4 versus 17+/-6/16+/-4 mm Hg in controls, P<0.01) because of an attenuation of the nocturnal BP decline. Patients of group III (n=69, aged 36+/-6 y), with parasympathetic failure and intermediate sympathetic dysfunction, had a blunted diurnal BP variation, whereas patients of group IV (n=62, aged 38+/-6 y), with parasympathetic failure and severe sympathetic dysfunction, had an absent diurnal BP variation. In patients of groups III and IV, a decrease in daytime BP accounted for the blunted circadian BP variation. This extensive study in progressive autonomic failure confirms the important role of the ANS in the generation of circadian BP variation. For the maintenance of a normal circadian BP pattern, not only an intact sympathetic but also an intact afferent parasympathetic ANS is a prerequisite.

Adult↗
PubMed1999

Sensitive and specific method for the simultaneous determination of natural and synthetic catecholamines and 3,4-dihydroxyphenylglycol in microdialysis samples.

The relatively new technique of microdialysis provides new possibilities for investigating in vivo the functioning of the sympathetic nervous system. The small sample volumes obtained, however, are a great challenge for analytical chemists. We report here a HPLC method for measuring in one run both natural and synthetic catecholamines [dopamine, (nor)epinephrine, alpha-methylnorepinephrine, isoproterenol and epinine] and the intraneuronal metabolite 3,4-dihydroxyphenylglycol in small microdialysis samples after derivatization with the fluorogenic agent 1,2-diphenylethylenediamine. No prior clean-up step is necessary. N-Ethylmaleimide is necessary for preventing an inhibitory action on derivatization occurring in in vivo microdialysis samples. The method can handle large numbers of samples, is sensitive (on-column detection limits 30 to 200 fg) and reproducible (RSD 1 to 7%). Recovery characteristics of the commercial microdialysis probe used (CMA/20) were extensively investigated both in vitro and in vivo at various perfusion rates; for practical purposes a rate of 2 microl/min and sampling at 10-min intervals was found to be workable and to give good and reproducible recoveries (50 to 70%).

Animals↗
PubMed1999

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure.

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Amlodipine↗
PubMed1999

Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock.

BACKGROUND: The systemic hypotension during human sepsis has been ascribed to increased production of nitric oxide (NO). Therefore, inhibitors of NO synthesis have been used in the treatment of hypotension in patients with septic shock. In addition, NO production may inhibit the synthesis and vasoconstrictor effects of endothelin-1 (ET-1). In this study, we tested whether ET-1 contributed to the vasopressor action of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in patients with severe septic shock. METHODS AND RESULTS: Compared with healthy volunteers, patients with septic shock had increased plasma levels of nitrite/nitrate (37+/-5 [SEM] versus 12+/-5 mmol/L, P<0.01), the stable end products of NO metabolism, and ET-1 (45+/-7 versus 3+/-2 pg/mL, P<0.001). Plasma ET-1 concentration was not related to plasma nitrite/nitrate concentration or blood pressure. Continuous infusion of L-NAME (1 mg. kg-1. h-1 IV) for 12 hours increased mean arterial pressure by 43+/-5% and systemic vascular resistance by 64+/-10% (both P<0.01). The increase in blood pressure and systemic vascular resistance correlated positively with the level of ET-1 (both P<0. 005) but not with plasma nitrite/nitrate level. L-NAME infusion did not result in significant changes in the plasma concentrations of ET-1 or nitrite/nitrate. CONCLUSIONS: NO and ET-1 may both play a role in the cardiovascular derangements of human sepsis. Although L-NAME does not increase ET-1 concentration in patients with septic shock, the vasopressor response induced by L-NAME depends on the plasma level of ET-1. These findings may indicate that inhibitors of NO synthesis unmask a tonic pressor response of ET-1 in human septic shock.

Blood Pressure↗
PubMed1999

Circulating semicarbazide-sensitive amine oxidase is raised both in type I (insulin-dependent), in type II (non-insulin-dependent) diabetes mellitus and even in childhood type I diabetes at first clinical diagnosis.

Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e.g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 +/- 209 and 619 +/- 202 vs 352 +/- 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA1c. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 +/- 300 vs 455 +/- 138 mU/l, p < 0.0001), but not associated with HbA1c. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins.

Adolescent↗
PubMed1999

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure.

BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. AIMS: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. METHODS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. CONCLUSION: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function.

Aged↗
PubMed1999

Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice.

AIMS: Cardiac peptides have diagnostic and prognostic value in heart failure. Their plasma concentrations, however, are sensitive to rapid changes in haemodynamics. As blood sampling under standard conditions is not feasible in clinical practice, it is important to know which peptides are most resistant to change. Therefore, the present study investigated the differences in response to exercise between atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, brain natriuretic peptide and the recently identified N-terminal probrain natriuretic peptide. METHODS AND RESULTS: Fifty-two patients with chronic heart failure performed a symptom-limited graded bicycle exercise. Blood samples for determination of plasma concentrations of cardiac peptides were drawn at rest and at peak exercise. There was a significant difference in percentage increase in response to exercise between the four peptides (P<0.0001). N-terminal proatrial natriuretic peptide increased less than atrial natriuretic peptide (5+/-18% vs 59+/-58%;P<0.0001). The difference in increase between N-terminal probrain natriuretic peptide and brain natriuretic peptide was less distinct but still significant (24+/-24% vs 38+/-52%, P<0.05). CONCLUSIONS: Both N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide increased less in response to exercise than their C-terminal counterparts. This implies that the circumstances under which blood sampling for measurements of N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide should be performed are more favourable than the blood sampling conditions for atrial natriuretic peptide and brain natriuretic peptide.

Atrial Natriuretic Factor↗
PubMed1999

Parasympathetic failure does not contribute to ocular dryness in primary Sjögren's syndrome.

OBJECTIVE: To investigate the sympathetic and parasympathetic cardiovascular function in primary Sjögren's syndrome (SS) and to investigate the possible relation with ocular dryness. METHODS: 41 (40 women) patients with primary SS, mean age 50 years (range 20-80) with a mean disease duration of eight years (range 1-30), were studied. In each patient direct arterial blood pressure (BP), heart rate (HR) and respiration were measured continuously for two hours. The function of the autonomic circulatory regulation was evaluated by measuring the heart rate response to deep breathing (6 cycles/min) and by means of the Valsalva manoeuvre and the responses of BP, HR and plasma noradrenaline (norepinephrine) concentrations to a 10 minute 60 degree head up tilt test. Pupillography was done to evaluate ocular autonomic function. RESULTS: The HR-Valsalva ratio was abnormal in 24% of the patients, and the HR variability during forced respiration was abnormal in 56% of the patients. The HR responses to both the Valsalva manoeuvre and deep breathing, as indicators of parasympathetic function, were abnormally low in 6 of 41 (15%) patients. In only two patients the decrease in systolic BP in response to the head up tilt test, as indicator of sympathetic function, was more than 20 mm Hg. However, increment of plasma noradrenaline concentration during head up tilt test and the overshoot of BP in phase IV of the Valsalva manoeuvre, as indicators of sympathetic function, were normal in both patients. Thus, no evidence for sympathetic dysfunction was found, whereas evidence for parasympathetic failure occurred sometimes. Autonomic pupillary function in patients with primary SS and healthy controls, as well as the Schirmer test in patients with or without evidence for parasympathetic dysfunction as based on the results of the Valsalva and deep breathing tests, were not significantly different. CONCLUSION: Parasympathetic, but not sympathetic dysfunction seems to occur in a subgroup of primary SS. Results show that this does not necessarily contribute to the typical ocular dryness in this condition.

Adult↗
PubMed1999

Catecholamine handling in the porcine heart: a microdialysis approach.

Experimental findings suggest a pronounced concentration gradient of norepinephrine (NE) between the intravascular and interstitial compartments of the heart, compatible with an active neuronal reuptake (U1) and/or an endothelial barrier. Using the microdialysis technique in eight anesthetized pigs, we investigated this NE gradient, both under baseline conditions and during increments in either systemic or myocardial interstitial fluid (MIF) NE concentration. At steady state, baseline MIF NE (0.9 +/- 0.1 nmol/l) was higher than arterial NE (0.3 +/- 0.1 nmol/l) but was not different from coronary venous NE (1.5 +/- 0.3 nmol/l). Local U1 inhibition raised MIF NE concentration to 6.5 +/- 0.9 nmol/l. During intravenous NE infusions (0.6 and 1.8 nmol. kg(-1). min(-1)), the fractional removal of NE by the myocardium was 79 +/- 4% to 69 +/- 3%, depending on the infusion rate. Despite this extensive removal, the quotient of changes in MIF and arterial concentration (DeltaMIF/DeltaA ratio) for NE were only 0.10 +/- 0.02 for the lower infusion rate and 0.11 +/- 0.01 for the higher infusion rate, whereas U1 blockade caused the DeltaMIF/DeltaA ratio to rise to 0.21 +/- 0.03 and 0.36 +/- 0.05, respectively. From the differences in DeltaMIF/DeltaA ratios with and without U1 inhibition, we calculated that 67 +/- 5% of MIF NE is removed by U1. Intracoronary infusion of tyramine (154 nmol. kg(-1). min(-1)) caused a 15-fold increase in MIF NE concentration. This pronounced increase was paralleled by a comparable increase of NE in the coronary vein. We conclude that U1 and extraneuronal uptake, and not an endothelial barrier, are the principal mechanisms underlying the concentration gradient of NE between the interstitial and intravascular compartments in the porcine heart.

Animals↗
PubMed1999

Role of sympathetic nervous system in cyclosporine-induced rise in blood pressure.

To clarify the role of the sympathetic nervous system in the development of cyclosporine A (CsA)-induced rise in blood pressure (BP), the effects of CsA on 24-hour ambulatory BP (ABP) were studied in patients with familial amyloid polyneuropathy (FAP) who underwent a liver transplantation. On the basis of autonomic function tests, patients with absent or mild-to-moderate sympathetic damage (Group A, n=11, age 29 to 43 years, disease duration 2 to 6 years) and patients with severe sympathetic damage (Group B, n=9, age 27 to 38 years, disease duration 3 to 9 years) were identified. Both groups were followed for 1 year. The daily doses of CsA and the CsA whole blood trough levels between the groups did not differ. Pretransplantation values of daytime and nighttime ABP were, respectively, 117+/-8/76+/-7 mm Hg and 108+/-12/68+/-9 mm Hg in group A and 107+/-6/66+/-4 mm Hg (P<0.05 group A versus group B) and 102+/-6/62+/-4 mm Hg in group B. In response to CsA, BP increased in all patients, but more so in patients of group B than in patients of group A. One year after transplantation, daytime and nighttime ABP had increased by 6+/-9/3+/-11% and 12+/-10/14+/-14% in group A and by 12+/-6/13+/-10% (P<0.05) and 21+/-11/27+/-21% (P<0.01) in group B. In both groups, the increase in nighttime ABP was greater than the increase in daytime ABP, which resulted in an attenuation or, even, a reversal of the diurnal BP rhythm. Because the rise in BP was greater in patients with more advanced sympathetic dysfunction, the sympathetic nervous system appears to counteract the CsA-induced rise in BP rather than causing it. This implies involvement of factors other than sympathetic activation in the pathogenesis of CsA-induced rise in BP in patients with familial amyloid polyneuropathy.

Adult↗