Pierre Blockx

Coronary Flow Reserve During Coronary Angioplasty in Patients With a Recent Myocardial Infarction: Relation to Stenosis and Myocardial Viability

OBJECTIVES In the present study, we examined post-stenotic coronary flow before and after percutaneous transluminal coronary angioplasty (PTCA) in patients with and without a recent myocardial infarction (MI) and related it to stenosis severity and residual viability. BACKGROUND Post-stenotic coronary blood flow velocity reserve (CFVR) has been used with success to estimate functional stenosis severity in patients with stable angina. However, in patients with a recent MI, the impaired coronary vasodilator response of the reperfused myocardium may substantially alter the flow dynamics of the infarct-related artery. METHODS Distal coronary flow velocities were recorded before and after PTCA in 36 patients at day 13 +/- 7 (mean +/- SD) after acute MI and in 38 patients without MI. The CFVR was assessed by the ratio of distal hyperemic to baseline average peak velocity, using a 0.014-in. Doppler guide wire. Stenosis severity was analyzed by quantitative coronary angiography, and infarct size was assessed scintigraphically. RESULTS For similar angiographic stenosis severity, pre- and post-PTCA values of CFVR were significantly lower in patients with than without MI: 1.22 +/- 0.26 versus 1.50 +/- 0.45 before PTCA (p < 0.05) and 1.72 +/- 0.43 versus 2.21 +/- 0.74 after PTCA, respectively (p < 0.01). Although CFVR increased significantly (p < 0.0001) after angiographically successful PTCA in both study groups, abnormal CFVR (< or = 2.0) was still observed in 80% of patients with MI and in 44% of those without MI (MI vs. no MI, p = 0.001). Patients with an extensive infarction (relative infarct size > or = 50%) and those with a small infarction (relative infarct size < 50%) had comparable levels of post-PTCA CFVR (1.6 +/- 0.3 vs. 1.8 +/- 0.5, p = NS). Among a variety of factors, angiographic stenosis severity was the most important determinant of CFVR in both study groups. CONCLUSIONS In patients with a recent MI, CFVR was significantly lower than in those without MI, both before and after PTCA. Besides the presence of this postreperfusion-related impairment of the coronary vasodilating response, CFVR was mainly influenced by stenosis severity and not by residual viability.

Effects of serotonin precursors on the negative feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal axis function in depression

In order to investigate the relationships between brain serotonergic turnover and hypothalamic-pituitary-adrenal (HPA) axis function in unipolar depression, the authors measured intact adrenocorticotropic hormone (ACTH) and cortisol levels in baseline conditions and after combined dexamethasone (1 mg PO) and L-5-hydroxytryptophan (L-5-HTP, 200 mg PO) administration in 13 minor, 17 simple major, and 17 melancholic subjects. L-5-HTP significantly enhanced post-DST ACTH and cortisol secretion in major--but not in minor--depressed subjects. Major depressed subjects with or without melancholia exhibited significantly higher post-DST ACTH and cortisol responses to L-5-HTP than minor depressed subjects. L-5-HTP administration converted some major depressed ACTH or cortisol suppressors into nonsuppressors. L-5-HTP stimulated ACTH or cortisol secretion to the same extent in major depressed HPA-axis suppressors and nonsuppressors. It is concluded that L-5-HTP loading may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major but not in minor depressed subjects. The findings show that serotonergic mechanisms modulate the negative feedback of glucocorticoids on central HPA-axis regulation. It is hypothesized that the higher L-5-HTP-induced post-DST HPA-axis hormone responses in major depression reflect upregulated 5-HT2 receptor-driven breakthrough secretion of pituitary ACTH from suppression by dexamethasone.

Sex‐linked differences in cortisol, ACTH and prolactin responses to 5‐hydroxy‐tryptophan in healthy controls and minor and major depressed patients

ABSTRACT— Some researchers have found that the administration of 5‐hydroxytryptophan (5‐HTP) results in increased cortisol secretion in major depressives but not in healthy controls. Other authors observed gender‐related differences in cortisol responses to 5‐HTP in major depressives. In order to investigate the pituitary/adrenal responsivity to 5‐HTP, the authors measured cortisol, adrenocorticotropic hormone (ACTH) and prolactin (PRL) in 30 healthy controls and in 90 depressed patients; the hormone levels were determined in baseline conditions and 60, 90 and 120 min after 125 ma L‐5‐HTP (orally, non‐enteric coated). We found [hat healthy men had significantly higher cortisol responses to L‐5‐HTP than healthy women. In the major depressives with melancholia and/or psychotic features these differences were reversed: women exhibited significantly higher cortisol and PRL responses than men. In the female group the most severely depressed patients had increased cortisol and PRL responses to L‐5‐HTP. The amplitudes of the cortisol, ACTH and PRL responses to L‐5‐HTP were significantly and positively correlated. It was concluded that the central serotonergic regulation of ACTH and PRL is significantly different between the sexes and between healthy controls, minor depressives and severely depressed patients.

Clinical subtypes of unipolar depression: Part III. Quantitative differences in various biological markers between the cluster-analytically generated nonvital and vital depression classes

The hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-thyroid (HPT) axis, and the availability of L-tryptophan (L-TRP) to the brain were studied in their relationships to (1) 14 depressive symptoms measured by the Structured Clinical Interview for DSM-III-R--Patient Version (SCID) and (2) the cluster-analytically generated vital/nonvital classes. The following biological parameters were measured in 100 depressed females: free thyroxine (FT4), baseline thyroid stimulating hormone (TSH), predexamethasone and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) values, the circulating levels of total L-TRP, and the L-TRP/sum of competing amino acids ratio. We found that the psychopathological correlates of disorders in the HPA/HPT axis and of a decreased availability of L-TRP were vital symptoms, i.e., distinct quality of mood, nonreactivity, early morning awakening, anorexia-weight loss, and psychomotor disorders. There was no significant relationship between those biological markers and the nonvital symptoms of the SCID inventory for depressive symptoms. However, we did not validate our SCID clustering in vital and nonvital classes by qualitative differences in the biological variables. It was concluded that our nonvital/vital clusters should be regarded as continuous categories with regard to the biological markers studied; these clusters constitute relevant stages in the continuum of progressing biological dysfunction.

Adrenocorticotropin hormone, β-endorphin and cortisol responses to oCRF in melancholic patients

Several authors have reported attenuated adrenocorticotropin hormone (ACTH) responses to corticotropin releasing factor (CRF) administration in melancholic patients as compared with healthy controls. In order to explore the integrity of the hypothalamic-pituitary-adrenal (HPA)-axis in melancholics, we examined the following parameters in 98 subjects: the ACTH; beta-endorphin; and cortisol responses to ovine CRF (oCRF) (100 micrograms/i.v.); and the postdexamethasone cortisol values. We found significant lower CRF-induced ACTH responses in melancholic patients as opposed to healthy controls and minor depressives, while major depressives occupied an intermediate position. The psychopathological correlates of the blunted CRF-induced ACTH responses were feelings of worthlessness, self-reproach, or excessive guilt. The CRF-stimulated beta-endorphin and cortisol response did not differ between the study samples. Higher baseline plasma cortisol was associated with attenuated CRF-induced ACTH responses, but these effects were not pertinent to melancholia. There were no relationships between the disordered oCRF test results, and postdexamethasone cortisol values, age, body size, sex and severity of illness. The diagnostic power of the oCRF and the dexamethasone suppression test for melancholia is enhanced when both test results are combined.

Hypothalamic-pituitary-adrenal and -thyroid axis dysfunctions and decrements in the availability of L-tryptophan as biological markers of suicidal ideation in major depressed females

Several neurochemical correlates of suicide were recently detected. Some authors found increased disorders in the hypothalamic‐pituitary‐adrenal (HPA) and ‐thyroid (HPT) axes and disturbances in serotonergic neurotransmission in suicidal patients. In order to investigate the biological correlates of suicidal ideation, we measured the following: basal thyrotropin‐secreting hormone (TSH), free thyroxine (FT4), pre‐ and postdexamethasone cortisol, adrenocorticotropic hormone (ACTH) levels, the circulating concentrations of total L‐tryptophan (L‐TRP) and the ratio between L‐TRP and competing amino acids (CAA). The subjects were 17 suicidal and 17 nonsuicidal major depressed females matched for age and severity of illness. We found no significant differences in any of the above‐mentioned biological data between patients with suicidal ideation and those without.

A further investigation of basal HPT axis function in unipolar depression: Effects of diagnosis, hospitalization, and dexamethasone administration

Hypothalamic-pituitary-thyroid (HPT) axis function was assessed in depressed subjects 1 and 8 days after hospital admission, and after the administration of 1 mg of dexamethasone. Plasma levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by ultrasensitive assays in 16 patients with minor depression, 15 patients with simple major depression, and 13 patients with melancholia. The postdexamethasone adrenocorticotropic hormone (ACTH) (intact 1-39 molecule) and cortisol values were determined. Basal TSH values were significantly lower in melancholic patients than in patients with minor and simple major depression on the day after admission and 1 week later. Basal TSH values determined 1 week after admission were significantly and negatively related to FT4 values and severity of depression. There were no significant differences in basal TSH, FT3, and FT4 values obtained on day 1 and day 8 after hospital admission. Dexamethasone administration had a significant suppressant effect on basal TSH and FT3 values. Patients who failed to suppress cortisol after the dexamethasone suppression test (DST) exhibited significantly less suppression of basal TSH values than did DST cortisol suppressors.

L-5-hydroxytryptophan stimulated cortisol escape from dexamethasone suppression in melancholic patients

The dexamethasone suppression test (DST) was carried out in 62 depressed patients. At 0800 the postdexamethasone cortisol values were determined and 125 mg L‐5‐hydroxytryptophan (L‐5‐HTP) was administered. The second cortisol sample at 0930 revealed a significant enhancing effect for L‐5‐HTP on the postdexamethasone cortisol values in melancholic patients, whereas no effects were detected in minor depressives. Our results show that L‐5‐HTP converts some DST suppressors into nonsuppressors, whereas the escape from dexamethasone in some nonsuppressors is markedly stimulated. The L‐5‐HTP‐stimulated 0930 postdexamethasone cortisol values performed markedly better than the 0800 DST results: at a cut‐off value of ≥ 5 μg/dl the sensitivity for melancholia increased from 46% to 68%, and the specificity remained unchanged (96%).

The decreased availability of L-tryptophan in depressed females: Clinical and biological correlates

1. The plasma levels of L-tryptophan (L-TRP) and the sum of five competing amino acids (CAA) namely tyrosine, phenylalanine, valine, leucine, isoleucine, were determined in 79 depressed females categorized according to the DSM-III. 2. In these patients the authors measured several parameters known to affect the availability of the above amino acids, i.e. triidothyronine (FT3) and thyroxine (FT4), vanilylmandelic acid (VMA), noradrenaline and adrenaline in 24 hr urine, the sex hormonal and nutritional state. 3. The 1 mg dexamethasone suppression test was performed and the pre and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) levels were determined at 8 a.m. 4. L-TRP and the ratio L-TRP/CAA were significantly lower in severely depressed females (296.X3, 296.X4) as compared with minor (300.40, 309.00) and simple major depressives (296.X2). The ratio L-TRP/CAA performed well as a clinical tool separating melancholic from minor depression. 5. FT3, FT4, VMA and noradrenaline were significantly increased in the severely depressed females, but these data did not correlate with the availability of L-TRP. Neither baseline cortisol nor the sex hormonal, nor the nutritional state related to the L-TRP data. The ratio L-TRP/CAA was significantly and negatively correlated with the postdexamethasone cortisol and ACTH values.

Pituitary and adrenal hormone responsiveness to synachten in melancholic subjects versus subjects with minor depression

Increased adrenal cortex responsiveness to adrenocorticotropic hormone (ACTH) has been suggested to contribute to increased cortisol secretion in dexamethasone nonsuppression and melancholia. To further examine this hypothesis, the following variables were examined in 68 patients with unipolar depression (minor, n = 24; simple major, n = 25; melancholic, n = 19): basal or post-Synacthen [ACTH(1-24), 250 micrograms IV] intact ACTH(1-39), beta-endorphin/beta-lipotropin, cortisol, and androstenedione concentrations, as well as the postdexamethasone (DST) plasma ACTH(1-39) and cortisol values. Melancholic subjects showed significantly higher baseline ACTH(1-39), beta-endorphin/beta-lipotropin, and androstenedione values compared with subjects with minor depression. No significant differences in post-Synacthen cortisol or androstenedione secretion between any of the groups or between [ACTH(1-39) or cortisol] DST nonsuppressors and suppressors were found. No significant relationships between DST and ACTH test results were observed. Abnormally increased post-DST cortisol values in melancholic subjects were highly predicted (> 68% of the variance) by post-DST intact ACTH levels. ACTH(1-39) values were significantly lower after Synacthen administration in melancholic subjects than in subjects with minor depression. These results are not consistent with the hypothesis that melancholia is characterized by an increased adrenocortical responsivity to exogenous ACTH compared with minor depression or that DST nonsuppression is due to adrenal hyperresponsiveness.