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Biomedical subjects

C Drummer

Publications and source records attributed to C Drummer.

At least 37 records · Page 2Linked to original sources
PubMed1997

Haematocrit, plasma volume and noradrenaline in humans during simulated weightlessness for 42 days.

Previous results from our laboratory demonstrate that changes in haematocrit (Hct) and haemoglobin concentration (Hb) underestimate the relative (%) change in plasma volume (PV) in seated subjects during simulation of weightlessness by water immersion. Therefore, we examined whether changes in Hct and Hb would accurately reflect the changes in PV in seven subjects during simulation of weightlessness by another model, 6 degrees head-down tilted bed rest (HDBR), for 42 days. Since we have previously observed unexpectedly high plasma levels of noradrenaline (NA) in astronauts during space flight, we also took the opportunity to measure this variable. The measurements were compared with those of the supine horizontal position before and after HDBR. During HDBR, PV measured by the Evans blue dye dilution technique decreased by 6.1 +/- 2.8% (P < 0.05) on day 2 and 9.6 +/- 2.2% (P < 0.05) on the 42nd day compared with that of the supine, horizontal position. Based on changes in Hct and Hb, PV decreased similarly by 8.3 +/- 2.8 and 10.2 +/- 3.2% (P < 0.05) respectively. There were no differences comparing the results of the two methods (P > 0.05). Forearm venous plasma NA was unchanged during the whole course of HDBR compared with that of the pre-HDBR supine position. It is concluded that changes in Hct and Hb reliably reflect the changes in PV comparing prolonged HDBR with the pre- and post-HDBR horizontal, supine position. Thus, changes in Hct and Hb might accurately reflect the change in PV during weightlessness in humans provided that the horizontal supine position is used as the ground-based reference. Furthermore, the results of this study, as well as of previous studies from space, confirm that NA release is unchanged or even increased during weightlessness.

Adult↗
PubMed1996

Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.

Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.

Adenosine Diphosphate↗
PubMed1996

Neutral endopeptidase 24.11 inhibition may not exhibit beneficial haemodynamic effects in patients with congestive heart failure.

OBJECTIVES: Inhibition of neutral endopeptidase 24.11 (NEP) prevents degradation of plasma atrial natriuretic peptide (ANP), a substance with vasodilatory and natriuretic properties. The aim of the study was to investigate the haemodynamic and endocrine effects of the NEP inhibitor candoxatril in patients with congestive heart failure (CHF). METHODS: In a randomized double-blind, parallel group study design, 24 patients with CHF received a 10-day oral drug treatment with candoxatril (25, 100 or 400 mg b.i.d.) or placebo. Invasive haemodynamics and laboratory parameters were measured on days 1 and 10. RESULTS: On the first treatment day, candoxatril produced a dose-dependent increase in plasma cyclic GMP, the second messenger of ANP. At doses of 100 and 400 mg, candoxatril induced an increase (!) in systemic vascular resistance (SVR) and a decrease in cardiac index (CI), which was not observed with placebo and the lower candoxatril dose. CONCLUSION: Despite significant activation of the ANP system, reflected by a dose-dependent increase in plasma cyclic GMP concentrations, high doses of candoxatril induced systemic vasoconstrictory rather than vasocilatory effects in patients with CHF. Therefore NEP inhibition by candoxatril may not exhibit beneficial haemodynamic effects in CHF.

Aldosterone↗
PubMed1996

Body fluid metabolism at actual and simulated microgravity.

Recent observations from space missions indicate that weightlessness does not induce an increase in diuresis and natriuresis in astronauts. Rather, both oral fluid and sodium intake as well as renal fluid and sodium output appear reduced compared with the preflight condition. In addition, influences of reduced energy intake may be more important for total body fluid content inflight than generally assumed. Decreases in plasma volume and observations of upper body edema formation inflight indicate, in addition, an increased extravasation as a result of the headward fluid shift in weightlessness. Current simulations models of microgravity for body fluid metabolism are valid for simulations of the central fluid shift occurring in microgravity. Since weightlessness appears to decrease central venous pressure and does not induce an increased renal fluid and sodium excretion, while simulations models have opposite effects, additional models to simulate adaptation of body fluid metabolism to weightlessness might be necessary.

Adaptation, Physiological↗
PubMed1996

Postprandial natriuresis in humans: further evidence that urodilatin, not ANP, modulates sodium excretion.

We examined the effects of a high-salt (100 mmol NaCl) and a low-salt (5 mmol NaCl) meal on the renal excretion of sodium and chloride in 12 healthy male upright subjects. We also measured the urinary excretion of urodilatin [ANP-(95-126)], and the plasma or serum concentrations of atrial natriuretic peptide [ANP-(99-126)], aldosterone, and renin. The high-salt meal produced a postprandial natriuresis (urinary sodium excretion from 59.0 to a peak rate of 204.6 mumol/min in 3rd h after ingestion of meal) and chloride excretion. In parallel, the urinary excretion of urodilatin increased from 35.7 to a peak rate of 105 fmol/min. The effect of high-salt intake on urinary sodium, chloride, and urodilatin excretion was significant (analysis of variance, P < 0.01), and close significant correlations were observed between urodilatin and sodium excretion (mean R = 0.702) as well as between urodilatin and chloride excretion (mean R = 0.776). In contrast, plasma ANP, which was acutely elevated 15 min after high-salt intake, was already back to low-salt values 1 h later. It did not parallel the postprandial natriuretic profile, and no positive correlation between plasma ANP and sodium excretion was observed. These results provide further evidence that urodilatin, not ANP, is the member of this peptide family primarily involved in the regulation of the excretion of sodium and chloride.

Aldosterone↗
PubMed1996

Natriuresis caused by increased carotid Na+ concentration after renal denervation.

The renal effects of a selective estimated 3 mM increase in the concentration of Na+ in blood perfusing the brain was investigated in conscious dogs with surgically denervated kidneys. In split-infusion experiments the concentration of Na+ in carotid plasma was increased by a bilateral carotid infusion of hypertonic NaCl combined with an infusion of distilled water into the caval vein. In control experiments the same load of NaCl and water was administered as an isotonic solution into the carotid and jugular vessels. Peak rate of Na+ excretion was significantly higher during split infusion (156 +/- 19 mumol/min) compared with control (89 +/- 14 mumol/min). Renal excretion of urodilatin increased in both series. Renal excretion of endothelin immunoreactivity increased significantly more during split infusion (20 +/- 6 pg/min) than during control (9 +/- 3 pg/min). It is concluded that the natriuretic response to minute increases in Na+ concentration of carotid plasma is intact after renal denervation. Furthermore, endothelin may be involved in the excess excretion observed.

Animals↗
PubMed1995

The dihydropyridine calcium channel blocker BAY t 7207 attenuates the exercise induced increase in plasma ANF and cyclic GMP in patients with mildly impaired left ventricular function.

In man, chronic antihypertensive calcium antagonist treatment improves cardiac function and reduces plasma ANF concentrations. Physical exercise increases cardiac workload and plasma ANF levels. In the present study, we investigated the effects of acute administration of the dihydropyridine calcium antagonist BAY t 7207 (BAY) during bicycle exercise on plasma ANF and plasma cyclic GMP levels, on mean arterial pressure (MAP), heart rate (HR), and on natriuresis and urinary urodilatin excretion. In a randomized, double-blind placebo controlled cross-over trial, 8 patients (age 56.8 +/- 2.5 y) with documented coronary artery disease and mildly impaired left ventricular function (EF 50.0 +/- 1.3%), received oral BAY (20 mg) or placebo. Forty-five minutes after medication, patients underwent a standardised exercise bicycle test in the supine position (6 min 25 W, 6 min 50 W). Before exercise, MAP was lower after BAY (88.8 +/- 4.1 mmHg) than after placebo (95.7 +/- 3.5 mmHg; p = 0.024), and HR was higher after BAY (76.8 +/- 3.5 bpm) than after placebo (69.5 +/- 3.6 bpm; p = 0.049). Plasma ANF tended to be higher after BAY (31.2 +/- 5.6 pg/ml) than after placebo (26.7 +/- 5.0 pg/ml), and plasma cGMP was not different (BAY 3.4 +/- 0.3, placebo 3.8 +/- 0.3 pmol/ml). During exercise, the relative increases in HR (+43%) and MAP (+17%) were identical after BAY and placebo. In contrast, ANF levels during exercise increased by 130 +/- 28% after placebo but only by 36 +/- 11% after BAY (p = 0.011). In parallel, plasma cyclic GMP increased by 61 +/- 13% after placebo and by 20 +/- 8% after BAY (p = 0.013). At the end of exercise, the BAY-induced reduction in plasma cyclic GMP reflected the reduction in diastolic arterial pressure (r = 0.717; p = 0.045). Compared to placebo, BAY treatment increased the fractional excretion rate of sodium from 0.46 +/- 0.11 to 0.90 +/- 0.22% (p = 0.016), without relation to urinary urodilatin excretion. Thus, the calcium antagonist BAY t 7207 attenuated the exercise-induced increase in plasma ANF and cyclic GMP probably due to its vasodilator effect. The relationship between blood pressure and the ANF system during exercise, which parallels findings during chronic antihypertensive treatment, may open a perspective for early evaluation of long-term therapy with calcium channel blockers.

Atrial Natriuretic Factor↗
PubMed1995

Severe hypotension and bradycardia after continuous intravenous infusion of urodilatin (ANP 95-126) in a patient with congestive heart failure.

The effects of a continuous i.v. infusion of urodilatin at a dose of 30 ng kg-1 min-1 were studied in a patient with congestive heart failure. After 30 min, urodilatin had induced a marked stimulation of plasma cyclic GMP concentrations. In parallel haematocrit increased. No significant diuresis and no change of invasive haemodynamics was observed. After 2 h the patient developed a profuse perspiration. Eighty minutes later he suffered from dizziness due to hypotension (blood pressure 80/40 mmHg) and a sudden bradycardia (50 bpm). Urodilatin was discontinued and symptoms were relieved by bed tilt and rapid infusion of isotonic saline solution. Mechanisms contributing to these adverse effects may be fluid extravasation to the third space and sympathoinhibitory effects known to occur with natriuretic peptide infusion.

Atrial Natriuretic Factor↗
PubMed1995

Renal and endocrine responses in humans to isotonic saline infusion during microgravity.

It was the purpose of this study to investigate how the endocrine and renal mechanisms of fluid volume control in humans (n = 4) adapt to microgravity by applying an intravenous isotonic saline infusion. The acute ground-based supine (Sup) and seated (Seat) positions were chosen as references. During microgravity, renal sodium excretion (UNaV) was doubled during the second and third hours after infusion compared with during Seat (P < 0.05) but blunted during the first hour after infusion compared with during Sup, leading to a reduction in cumulative UNaV (59 +/- 15 vs. 108 +/- 12 mmol/5 h; P < 0.05). Plasma norepinephrine (NE) attained the highest value 3 h after infusion during microgravity (31 +/- 5 x 10(-2) ng/ml vs. 19 +/- 1 and 13 +/- 3 x 10(-2) ng/ml for Seat and Sup, respectively; P < 0.05). Inflight levels of plasma renin and aldosterone were very similar to levels during Seat. In conclusion, 1) the microgravity-adapted renal responses to infusion reflected a condition in between that of ground-based Seat and Sup, respectively, and 2) the plasma levels of NE, renin, and aldosterone were elevated inflight and not related to the changes in UNaV and urinary flow rate. These observations are in contrast to results of ground-based simulation experiments and might partly have been caused by a prior inflight reduction in extracellular fluid volume. The high levels of NE during microgravity warrant further investigation.

Adult↗
PubMed1995

The volume protective natriuretic peptide system in the inner ear. Comparison between vestibular and cochlear compartments.

It has been suggested that the family of natriuretic peptides (NP) has a protective role in volume overloading. Specific binding sites for atrial natriuretic peptide (ANP) and the kidney analog urodilatin (URO) were identified and quantified with computerized autoradiography and biochemical assay in the cryosection in the cochlear and vestibular (utricle/ampulla) tissue. Immunohistochemistry was used to identify and localize NP-like immunoreactive cells. Different levels of specific receptors between and within the inner ear compartments were detected. The presence of specific receptors for NP, as well as unequal distribution of NP-immunoreactivity between the compartments (in certain parts of the cochlea and the endolymphatic sac), may indicate a local autocrine and/or paracrine action of these peptide systems (presumably as a result of the integration of the different peptide effects), independent of their action via the more conventional systemic route, in addition to differences in response of the inner ear compartments to the load. The present results on specific binding of ANP and URO in the inner ear tissue may suggest physiological homology between the inner ear and the kidney. Moreover, a similar role of NP in these organs is suggested.

Atrial Natriuretic Factor↗
PubMed1994

Natriuresis in conscious dogs caused by increased carotid [Na+] during angiotensin II and aldosterone blockade.

The renal response to a selective increase in the Na+ concentration of the blood perfusing the central nervous system was investigated in conscious dogs treated with the converting enzyme inhibitor enalaprilat and the aldosterone antagonist canrenoate. In split-infusion experiments the plasma [Na+] of carotid blood was increased (approx. 6 mM) by bilateral infusion of hypertonic NaC1. Concomitantly distilled water was infused into the v. cava making the sum of the infusions isotonic. In control experiments isotonic saline was infused at identical rates into all three catheters. Na+ excretion increased markedly in both series, 103 +/- 14 to 678 +/- 84 mumol min-1 during split-infusion and 90 +2- 14 to 496 +/- 74 mumol min-1 during the isotonic volume expansion. Peak rate of excretion, peak fractional sodium excretion, and cumulative sodium excretion were all significantly higher (P < 0.05) during split-infusion than during control experiments. Plasma vasopressin increased only during split-infusion (0.68 +/- 0.11 to 2.4 +/- 0.8 pg ml-1) while the increases in plasma atrial natriuretic peptide were similar in the two series. Urinary excretion of urodilatin (ANP95-126) increased significantly more during split-infusion (46 +/- 11 to 152 +/- 28 fmol min-1) than during the isotonic volume expansion (45 +/- 14 to 84 +/- 16 fmol min-1) (P < 0.05). It is concluded that the natriuretic mechanisms activated by a selective increase in the Na+ concentration of carotid blood and associated with increased excretion of urodilatin cannot be eliminated by blockade of the renin-angiotensin-aldosterone system.

Angiotensin II↗
PubMed1994

Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men.

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3',5'-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.

Adenosine Diphosphate↗
PubMed1993

Effects of nitric oxide-containing compounds on increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to determine the modulatory effects of nitric oxide (NO)-releasing compounds on increases in cytosolic ionized calcium ([Ca2+]i) and on aggregation of gel-filtered human platelets induced via diverse agonists. We used various sydnonimines and organic nitrates as donors of NO. Gel-filtered and fura-2-loaded platelets were stimulated with ADP (4-8 microM), collagen (2-10 micrograms/ml) or thrombin (0.02-0.05 IU/ml), respectively. Half-maximal inhibiting effects of sydnonimines on agonist-evoked increases in [Ca2+]i were observed between 30 and 1000 nM, while half-maximal inhibiting effects of the compounds on aggregation were between 3 and 500 nM. The compound C 87-3754, which is the bioactive metabolite of pirsidomine, was a much stronger inhibitor of increases in [Ca2+]i than of platelet aggregation. This was due to an enhanced NO release from this compound exposed to ultraviolet light during Ca2+ measurement. The organic nitrates isosorbide 5-mono-nitrate and nicorandil inhibited both aggregation and increase of cytosolic ionized calcium in stimulated platelets at half-maximal concentrations of approximately 200 microM. The present results suggest that some of the effects of NO on platelets are independent of cytosolic ionized calcium. The results also suggest that some of the inhibitory effects of NO-releasing compounds correspond rather to the presence of the A forms (NO-containing intermediates) than to the presence of free NO.

Calcium↗
PubMed1993

Reduced natriuresis during weightlessness.

The kidney response to weightlessness was measured in one volunteer during a 1-week space mission. Shortly after entering microgravity and later during the mission, consecutive urine sampling periods were monitored, covering in total about 50% of the inflight time. Preflight references were a sequence of ground-based experiments, which evaluated body fluid metabolism with different degrees of standardization. Additional variables, such as circadian rhythms and cortisol-associated stress, were also monitored. In contrast to current hypotheses, the volunteer showed a pronounced reduction in natriuresis and diuresis during the entire space flight, despite a considerable weight loss. For the first time, the urinary excretion of the renal natriuretic peptide urodilatin was also measured. Both, during the preflight experiments and during weightlessness, close correlations between urodilatin excretion and sodium excretion were observed. However, the correlation between natriuresis and urodilatin excretion was considerably altered during weightlessness. We conclude that the loss of body weight during space flight is not related to an increased renal fluid loss and that urodilatin might counteract the decrease in renal excretion observed in weightlessness.

Atrial Natriuretic Factor↗
PubMed1993

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium.

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects ingested 2.8 mequiv sodium (kg body weight)-1 day-1 during the first phase, 5.6 mequiv (kg body weight)-1 day-1 during the second phase, and 8.4 mequiv (kg body weight)-1 day-1 during the third phase. The excretion of both sodium (P < 0.002) and urodilatin (P < 0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P < 0.001). Serum aldosterone levels (P < 0.01) as well as serum renin levels (P < 0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P < 0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.

Adult↗
PubMed1993

Development and application of a urodilatin (CDD/ANP-95-126)-specific radioimmunoassay.

Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [alpha-ANP(99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.

Amino Acid Sequence↗