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Biomedical subjects

P Haberey

Publications and source records attributed to P Haberey.

At least 19 recordsLinked to original sources
PubMed1999

Circulating adrenomedullin is increased after heart transplantation.

OBJECTIVE: Adrenomedullin (ADM), secreted by the failing human heart, is a newly discovered potent endogenous vasorelaxing and natriuretic peptide that may play a role in cardiorenal regulation. No data are available on ADM in heart-transplant recipients (Htx) and the aim of this study was to determine the short- and long-term responses of ADM after heart transplantation. METHODS: Circulating ADM and its relationship with parameters of cardiovascular hemodynamics, humoral factors and renal function were determined in normal subjects and Htx early (1, 2, 4, 8, 15 and 30 days) and late (32 +/- 16 months) after transplantation. Additionally, ADM was obtained in matched hypertensive and renal-transplant patients (n = 9 in each group). RESULTS: Plasma ADM, elevated in heart failure patients, further increased transiently at day 1 after transplantation (from 37.9 +/- 15.9 to 125.8 +/- 15.3 pmol/l, P < 0.01) and, although decreasing thereafter, remained elevated until the 30th day after transplantation (52.1 +/- 25.2 pmol/l). Late after transplantation. ADM concentrations were still increased compared to normal values (31.3 +/- 5.3 vs. 19.4 +/- 2.7 pmol/l, P < 0.001). ADM positively correlated with endothelin, atrial natriuretic peptide (ANP) and cyclosporine. ADM was also correlated with increased diastolic (r = 0.68, P < 0.04) and systolic (r = 0.66, P < 0.05) blood pressure in late Htx. No relationship was observed between ADM and left ventricular mass index, aldosterone and creatinine. ADM elevation was similar in hypertensive, renal-transplant patients and in Htx. CONCLUSIONS: Circulating ADM is increased after heart transplantation, in relation to hypertension, endothelin, cyclosporine and ANP. In view of ADM's biological properties, these results might suggest a compensatory role for ADM against further development of vasoconstriction and fluid retention states after heart transplantation.

Adrenomedullin↗
PubMed1999

Enhanced natriuretic response to neutral endopeptidase inhibition in heart-transplant recipients.

Heart-transplant recipients (Htx) generally present with body fluid and sodium handling abnormalities and hypertension. To investigate whether neutral endopeptidase inhibition (NEP-I) increases endogenous atrial natriuretic peptide (ANP) and enhances natriuresis and diuresis after heart transplantation, ecadotril was given orally to 8 control subjects and 8 matched Htx, and levels of volume-regulating hormones and renal water, electrolyte, and cyclic guanosine monophosphate (cGMP) excretions were monitored for 210 minutes. Baseline plasma ANP, brain natriuretic peptide (BNP), and cGMP were elevated in Htx, but renin and aldosterone, like urinary parameters, did not differ between groups. NEP-I increased plasma ANP (Htx, 20.6+/-2.3 to 33.2+/-5.9 pmol/L, P<0.01; controls, 7.7+/-1. 2 to 10.6+/-2.6 pmol/L) and cGMP, but not BNP. Renin decreased similarly in both groups, whereas aldosterone decreased significantly only in Htx. Enhanced urinary sodium (1650+/-370% versus 450+/-150%, P=0.01), cGMP, and water excretions were observed in Htx and urinary cGMP positively correlated with natriuresis in 6 of the Htx subjects. Consistent with a normal circadian rhythm of blood pressure, without excluding a possible effect of NEP-I, mean systemic blood pressure increased similarly in both groups at the end of the study (6.9+/-2.0% versus 7.4+/-2.8% in controls and Htx). Thus, systemic hypertension, mild renal impairment, and raised plasma ANP levels are possible contributory factors in the enhanced natriuresis and diuresis with NEP-I in Htx. These results support a physiological role for the cardiac hormone after heart transplantation and suggest that long-term studies may be useful to determine the potential of NEP-I in the treatment of sodium retention and water retention after heart transplantation.

Adult↗
PubMed1998

Erythrocytes participate significantly in blood transport of amino acids during the post absorptive state in normal humans.

To investigate the participation of erythrocytes in the blood transport of amino acids during the course of intestinal absorption in humans, erythrocyte and plasma amino-acid concentrations were determined following ingestion of an oral load of amino acids. In addition to baseline plasma and erythrocyte amino acid concentrations in 18 subjects, plasma and erythrocyte amino acids kinetics during the 125 min following an oral amino acid load were further determined in 9 of the 18 subjects. The results showed that human erythrocytes contained most amino acids at similar or higher concentrations than plasma. Furthermore, the correlations observed between plasma and erythrocyte contents clearly indicated that erythrocytes were involved in the transport of amino acids by the blood. For some amino acids erythrocyte transport sometimes exceeded that of plasma. Significant correlation coefficients showed that strong plasma-erythrocyte relationships existed for alanine, valine, methionine, isoleucine, leucine, phenylalanine, and ornithine. In conclusion, our data supported the hypothesis that both blood compartments, plasma and erythrocytes, are involved significantly in the blood transport of amino acids in humans during the postabsorptive state.

Adolescent↗
PubMed1998

Role of the plasma and erythrocytes in veno-arterial portal changes during post prandial state in the rat.

The determination of plasma and whole blood free amino acid concentrations in arterial and portal venous blood during post prandial state in the rat was used to estimate the role of the erythrocytes in amino acid exchanges. The erythrocyte contents were calculated from plasma, whole blood concentrations and the hematocrit. The veno-arterial concentration differences in plasma were significant for all amino acids except a-aminobutyrate and ornithine whereas in the erythrocytes only 8 amino acids exhibit significant differences (ASP, ALA, VAL, MET, ILE, LEU, TYR, PHE). For 6 amino acids, a significant correlation between the plasma and the erythrocyte concentration has been found (VAL, ILE, LEU, TYR, PHE, HIS). These data suggest that in vivo during the time of contact between blood and organ tissues, some amino acids but not all are significantly taken up by the erythrocytes. Thus, it may be concluded that erythrocyte amino acid blood transport in arterio-venous portal exchanges, concerns particularly tyrosine and essential amino acids. The erythrocyte amino acid transport represents quantitatively about 20 per cent of the total blood transport.

Amino Acids↗
PubMed1998

Enhanced brain natriuretic peptide response to peak exercise in heart transplant recipients.

We investigated the atrial (ANP) and brain natriuretic peptides (BNP), catecholamines, heart rate, and blood pressure responses to graded upright maximal cycling exercise of eight matched healthy subjects and cardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP (15.2 +/- 3.7 vs. 4.4 +/- 0.8 pmol/l; P < 0.01) and BNP (14.3 +/- 2. 6 vs. 7.4 +/- 0.6 pmol/l; P < 0.01), were elevated in HTR, but catecholamine levels were similar in both groups. Peak exercise O2 uptake and heart rate were lower in HTR. Exercise-induced maximal ANP increase was similar in both groups (167 +/- 34 vs. 216 +/- 47%). Enhanced BNP increase was significant only in HTR (37 +/- 8 vs. 16 +/- 8%; P < 0.05). Similar norepinephrine but lower peak epinephrine levels were observed in HTR. ANP and heart rate changes from rest to 75% peak exercise were negatively correlated (r = -0.76, P < 0.05), and BNP increase was correlated with left ventricular mass index (r = 0.83, P < 0.01) after heart transplantation. Although ANP increase was not exaggerated, these data support the idea that the chronotropic limitation secondary to sinus node denervation might stimulate ANP release during early exercise in HTR. Furthermore, the BNP response to maximal exercise, which is related to the left ventricular mass index of HTR, is enhanced after heart transplantation.

Adult↗
PubMed1998

Endothelin participates in increased circulating atrial natriuretic peptide early after human heart transplantation.

BACKGROUND: Hemodynamic improvement after heart transplantation is expected to normalize the neuroendocrine balance, but circulating atrial natriuretic peptide (ANP) remains elevated. Endothelin stimulates ANP secretion and its concentration increases after heart transplantation, suggesting a role for this peptide in the cardiovascular adaptative response to heart transplantation. METHODS: To investigate whether endothelin may induce ANP increase in heart transplant recipients, we monitored daily ANP, endothelin, and related hormonal, biologic, and hemodynamic parameters before and during the first week after either heart transplantation (n = 15) or coronary artery bypass grafting (n = 10). RESULTS: Surgery induced a transient secretory peak of arginine vasopressin and endothelin in both groups at day 1. Bypass grafting did not modify normal ANP (11.8 +/- 2.1 pmol/L), endothelin (2.4 +/- 0.3 pmol/L), renin activity (0.11 +/- 0.04 pmol/L/sec), or aldosterone (492 +/- 122 pmol/L) values. Heart transplantation normalized the renin-aldosterone axis, but the early decrease observed for ANP (from 27.2 +/- 4.8 to 21.14 +/- 1.4 pmol/L) was only partial and transient. Endothelin further increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01) after transplantation. Positive correlations were observed between endothelin, isoproterenol dose, creatinine, right atrial pressure, and ANP, but multiple correlation analysis showed the important role of endothelin (r = 0.69, p < 0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001). CONCLUSIONS: Elevated endothelin, suggesting vascular dysfunction, likely contributes to the ANP increase observed early after heart transplantation. Furthermore, ANP, through a cardiac endothelium feedback, may act in the maintenance of circulatory homeostasis in heart transplant recipients.

Adult↗
PubMed1998

Normal short-term renal response to acute volume expansion in heart transplant recipients: a role for atrial natriuretic peptide?

BACKGROUND: The breakdown of blood pressure and body fluid homeostasis observed in heart transplant (Htx) recipients may partly be due, as in heart failure, to a blunted renal response to elevated atrial natriuretic peptide (ANP). METHOD: This possibility was addressed through determination of the relationship between ANP, the urinary cyclic guanosine monophosphate (cGMP), a biologic marker of ANP renal activity, and the early renal responses to 10 mL/kg isotonic saline infusion over 30 minutes in 8 control subjects and 8 matched Htx recipients. RESULTS: Urine flow, natriuresis, and urinary cGMP excretion increased similarly in both groups, resulting in elimination of, respectively, 1/2 and 2/3 of the sodium and the water load during the experiment that lasted 4 hours and 30 minutes. Plasma renin and aldosterone decreases were similar in both groups. Elevated ANP further increased in Htx after saline infusion (from 19.5 +/- 3.7 to 33.8 +/- 5.6 pmol/L, P < .001). Plasma cGMP paralleled ANP in both groups (r = 0.81; P < .001). Significant correlations were observed between plasma ANP and urinary cGMP excretion (r = 0.48, P < .025 and r = 0.43, P < .05 in Htx recipients and control subjects) and between plasma ANP and urinary sodium excretion (r = 0.64, P < .001 in Htx recipients). CONCLUSION: In spite of a relative renal hyporesponsiveness to the cardiac hormone, with higher plasma ANP being not associated with increased renal excretions in Htx recipients, ANP is likely to participate in the appropriate short-term renal response to acute volume expansion in Htx recipients.

Aldosterone↗
PubMed1997

Safety of a new transpulmonary echocontrast agent (Albunex) in repeated echocardiographic studies in patients.

BACKGROUND AND HYPOTHESIS: Multiple contrast-enhanced echocardiographic studies are to be expected in patients with cardiac ischemic disease, but the sonication process used to produce the echocontrast agent Albunex may result in new epitopes that could cause an immunogenic response. METHODS: Repeated exposures to intravenous Albunex over a period of time long enough to allow development of an eventual immune reaction were performed in 12 patients while monitoring for lymphocyte transformation, microsphere specific IgE and IgG antibodies, and systemic, pulmonary artery, capillary wedge, and right atrial pressures, as well as cardiac output, left ventricular fractional shortening, and blood gases. RESULTS: No significant 3H-thymidine incorporation and thus no specific blastic transformation of the patients' lymphocytes were observed either for high or low Albunex concentrations, corresponding to the expected hepatic and plasma concentrations of microspheres. No formation of microsphere-specific IgE and IgG antibodies was observed after the first or second Albunex exposure. Furthermore, no clinically significant hemodynamic or respiratory adverse reactions were observed in any patient. CONCLUSION: These results suggest that repeated exposures to intravenous Albunex induce no adverse effect on the cellular and humoral immune systems and on left and right heart hemodynamics in patients.

Albumins↗
PubMed1997

Contrast echocardiography in coronary artery diseased patients: effect of systemic and pulmonary artery pressures on left heart opacification after intravenous injection of Albunex.

BACKGROUND: Contrast echocardiography is a useful tool for assessing repeatedly patients with coronary artery disease. Nevertheless, elevated pulmonary artery and systemic blood pressures likely to be associated with cardiac ischemia may limit the left ventricular opacification (LVO) because of the microspheres' sensitivity to pressure. OBJECTIVE: To determine the effects of systemic and pulmonary artery blood pressures on LVO. METHODS: We performed 55 intravenous injections (0.08 and 0.22 ml/kg) of a new transpulmonary contrast agent (Albunex), during two separated exposures, into 20 cardiac ischemic patients while monitoring invasively their cardiac indexes, and intracardiac, systemic, and pulmonary artery blood pressures. LVO was graded qualitatively from faint to full. RESULTS: A logistic model with the grade of LVO as the dependent variable and a selection from among the dose, exposure, right and left atrial blood pressures, systolic systemic and pulmonary artery blood pressures (ranges 94-208 and 14-45 mmHg, respectively), cardiac index, stroke index, and pulmonary and systemic vascular resistances as the explanatory variables demonstrated that increasing the dose gives an increasing probability of LVO (P = 0.02) and that increasing the pulmonary artery pressure reduces that probability (P = 0.006). A decreased cardiac index tended also to be associated with decreased LVO. The systemic blood pressure and the pulmonary and systemic vascular resistances had no statistically significant effect on the grade of LVO. CONCLUSIONS: LVO after intravenous administration of Albunex is dose-dependent and limited by an elevated pulmonary artery pressure. These data suggest that one should use higher doses for cardiac ischemic patients with elevated pulmonary artery pressures and that use of Albunex has the potential to detect pulmonary hypertension in patients.

Adult↗
PubMed1996

Atrial natriuretic factor secretion: a role for atrial systolic ejection force?

The increase in plasma concentration of atrial natriuretic factor in heart transplant patients has not been fully elucidated. Besides an eventual pressure or volume overload leading to passive atrial distension, the atrial tension developed during atrial systole, or atrial ejection force, which may be increased by the transplantation procedure, is an important determinant of atrial natriuretic factor release. We therefore determined the plasma concentration of atrial natriuretic factor and the maximal atrial ejection force in 15 heart transplant patients and 8 controls, matched for age and body mass. Atrial ejection force, as defined as the force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, was obtained using combined two-dimensional imaging and doppler echocardiography. Serum creatinin concentrations, heart rate [91.9 (SD 13.2) vs 71.8 (SD 10.9) beats.min-1], mean arterial blood pressure [103.9 (SD 9.8) vs 87.4 (SD 5.8) mmHg, 13.85 (SD 1.31) vs 11.65 (SD 0.77) kPa], left ventricular posterior wall thickness and interventricular septum thickness were higher in heart transplant patients compared to controls. Plasma concentration of atrial natriuretic factor was also elevated in heart transplant patients [63.9 (SD 18.1) vs 34.0 (SD 3.2) pg.ml-1; P < 0.001]. In contrast, although the left atrial area was greater in heart transplant patients [28.2 (SD 4.8) vs 15.8 (SD 2.5) cm2; P < 0.001], mitral area, transmitral Doppler A-wave maximal velocity and atrial ejection force were similar in transplant and in control patients [7.7 (SD 3.5) vs 8.9 (SD 2.8) kdyn, 77 (SD 35) vs 89 (SD 28)mN]. No significant correlation was observed between concentration of atrial natriuretic factor and atrial ejection force, either in heart transplant patients or in controls. Thus, the elevated plasma concentration of atrial natriuretic factor observed in these heart transplant patients was multifactorial in origin, and was considered to depend upon an hypersecretion rather than upon a decreased clearance rate. Moreover, it is suggested that the atrial ejection force was unlikely to have participated in this enhanced release of atrial natriuretic factor.

Adult↗
PubMed1996

Effect of short-term endurance training on exercise capacity, haemodynamics and atrial natriuretic peptide secretion in heart transplant recipients.

Exercise tolerance of heart transplant patients is often limited. Central and peripheral factors have been proposed to explain such exercise limitation but, to date, the leading factors remain to be determined. We examined how a short-term endurance exercise training programme may improve exercise capacity after heart transplantation, and whether atrial natriuretic peptide (ANP) release may contribute to the beneficial effects of exercise training by minimizing ischaemia and/or cardiac and circulatory congestion through its vasodilatation and haemoconcentration properties. Seven heart transplant recipients performed a square-wave endurance exercise test before and after 6 weeks of supervised training, while monitoring haemodynamic parameters, ANP and catecholamine concentrations. After training, the maximal tolerated power and the total mechanical work load increased from 130.4 (SEM 6.5) to 150.0 (SEM 6.0) W (P < 0.05) and from 2.05 (SEM 0.1) to 3.58 (SEM 0.14) kJ.kg-1 (P < 0.001). Resting heart rate decreased from 100.0 (SEM 3.4) to 92.4 (SEM 3.5) beats.min-1 (P < 0.05) but resting and exercise induced increases in cardiac output, stroke volume, right atrial, pulmonary capillary wedge, systemic and pulmonary artery pressures were not significantly changed by training. Exercise-induced decrease of systemic vascular resistance was similar before and after training. After training arterio-venous differences in oxygen content were similar but maximal lactate concentrations decreased from 6.20 (SEM 0.55) to 4.88 (SEM 0.6) mmol.l-1 (P < 0.05) during exercise. Similarly, maximal exercise noradrenaline concentration tended to decrease from 2060 (SEM 327) to 1168 (SEM 227) pg.ml-1. A significant correlation was observed between lactate and catecholamines concentrations. The ANP concentration at rest and the exercise-induced ANP concentration did not change throughout the experiment [104.8 (SEM 13.1) pg.ml-1 vs 116.0 (SEM 13.5) pg.ml-1 and 200.0 (SEM 23.0) pg.ml-1 vs 206.5 (SEM 25.9) pg.ml-1, respectively]. The results of this study suggested that the significant improvement in exercise capacity observed after this short-term endurance training period may have arisen mainly through peripheral mechanisms, associated with the possible decrease in plasma catecholamine concentrations and reversal of muscle deconditioning and/or prednisone-induced myopathy.

Adult↗
PubMed1996

Persistent exercise intolerance following cardiac transplantation despite normal oxygen transport.

UNLABELLED: To define the respective roles of the periphery and central oxygen transport in the exercise limitation of heart transplanted patients (HTR), we compared 11 HTR (15.1 +/- 10.8 months after transplantation) to six age and weight matched normal controls (C), during an incremental exercise test (30 W/3 min steps; supine position), up to peak exercise level. The C stopped between 120 and 240 W (mean = 180 +/- 39 W), whereas the HTR all reached 90 W, with a significantly lower oxygen uptake (VO2), cardiac index (CI) and arterio-venous oxygen difference (AVO2D) values (respectively VO2: 16.6 +/- 2.6 vs 30.0 +/- 9.3 ml.min-1.kig-1 STPD; CI: 6.84 +/- 1.10 vs 10.55 +/- 2.86l.min-1.m-2; AVO2D: 94 +/- 13 vs 109 +/- 9 ml.l-1; all p < 0.05) but with similar lactate (LA) values (respectively 7.25 +/- 1.98 vs 7.71 +/- 1.55 mmol.l-1; p = NS). At the 90 W step which corresponds to the peak level that all the HTR reached, the C were close to their anaerobic threshold and showed similar parameters of oxygen transport (VO2: 17.4 +/- 2.0; CI: 7.50 +/- 0.41; AVO2D:90 +/- 10) but a lower lactate level (LA: 2.93 +/- 4.76; p < 0.002). At the same intermediate exercise levels VO2, CI and AVO2D were similar in both groups, while the closely matched LA and ventilation increased faster in HTR, reaching significantly higher levels as soon at the 30 W step. This evidence for an increased anaerobic exercise energy generation in HTR suggests that the periphery participates significantly in their exercise limitation, a phenomenon that might be improvable by retraining. VALUES: means+/-standard deviation.

Cardiac Output↗