Michel Staroukine

Increased angiotensin II in ascites during severe ovarian hyperstimulation syndrome: role of early pregnancy and ovarian gonadotropin stimulation

OBJECTIVE To investigate the implications of the ovarian renin-angiotensin system (RAS) in the pathophysiology of the ovarian hyperstimulation syndrome (OHSS) in relation to gonadotropin stimulation and early pregnancy. DESIGN A controlled clinical study comparing blood and simultaneously sampled peritoneal fluid (PF) from patients with severe OHSS and from controls without OHSS. SETTING University Hospitals. PATIENT(S) Eleven patients with severe OHSS, 8 patients with ascites of other origin, 9 patients with a first-trimester pregnancy, and 15 patients stimulated with gonadotropins for IVF. MAIN OUTCOME MEASURE(S) Angiotensin II immunoreactivity was measured in blood and PF and analyzed by high-performance liquid chromatography (HPLC) in ascites from OHSS. RESULT(S) Angiotensin II immunoreactivity (pg/mL; mean +/- SE) was highest in the ascites from pregnant OHSS (1,669 +/- 418), reaching levels 5 times higher than in the plasma (331 +/- 61) and 100 times higher than in control ascites (17 +/- 6.7). Angiotensin II immunoreactivity was elevated in the PF during early pregnancy (211 +/- 68) and after gonadotropin stimulation (244 +/- 41) and was higher than in the plasma in both groups. Analysis by HPLC showed that the majority of Ang II immunoreactivity in the ascites of OHSS was because of true Ang II. CONCLUSION(S) Severe forms of OHSS, especially those associated with pregnancy, are consistently characterized by huge concentrations of Ang II immunoreactivity in the ascites, proved to be true Ang II by HPLC analysis. This may be due to the synergistic effects of exogenous and endogenous hCG on the ovarian RAS.

Hemodynamic response to molsidomine in patients with ischemic cardiomyopathy tolerant to isosorbide dinitrate

Unlike nitrates, molsidomine is able to relax vascular smooth muscle without depending on the availability of sulfhydryl groups. To assess the clinical relevance of this property, the hemodynamic effects of a 24-h i.v. infusion of molsidomine were studied in 14 patients with ischemic cardiomyopathy rendered tolerant to i.v. isosorbide dinitrate.In order to determine the role of neurohormonal activation, six of these patients were studied in the presence of an angiotensin-converting enzyme (ACE) inhibitor (enalapril, 5 mg; b.i.d.) (group 2). Six patients out of eight in group 1 (without ACE inhibition) and all patients in group 2 responded to molsidomine with a marked reduction of pulmonary artery wedge pressure (PAWP) (49% ± 5 and 50% ± 4 versus baseline value, respectively). However, the reduction of PAWP in group 1 was no longer significant at 12 h, and at 24 h the loss of the peak effect reached 67% ± 7. On the contrary, PAWP remained persistently reduced in group 2 (loss of peak effect, 20% ± 3 at 24 h, p < 0.005). In addition, a significant decrease in hematocrit and increase in epinephrine occurred in group 1 but not in group 2. These results suggest that both the absence of dependence on sulfhydryl groups and the blockade of neurohormonal reactions are needed to avoid nitrate tolerance.

Effect of low doses of angiotensin II perfusion on the hypotensive action of captopril in anaesthetized normotensive and spontaneously hypertensive rats.

The effect of intravenous (i.v.) captopril on mean arterial blood pressure (MABP) of anaesthetized normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats perfused i.v. with two doses of angiotensin II (ANG II; 2.9 and 5.8 pmol/kg per min) was studied to determine the role of the suppression of plasma ANG II in the hypotensive action of captopril. The reduction of MABP by captopril was attenuated in WKY and abolished in SHR by the highest dose of ANG II; it was unchanged in WKY and attenuated in SHR by the lowest dose of ANG II. The suppression of plasma ANG II thus explains a minor part of the acute reduction of MABP by captopril in WKY and a major part of this action in SHR. Plasma ANG II contributes to the maintenance of high blood pressure in SHR.

Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs

IntroductionThe role played by several vasoactive mediators that are synthesized and released by the pulmonary vascular endothelium in the regulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear. As a potent vasoconstrictor, angiotensin II could be involved. We tested the hypothesis that angiotensin-converting enzyme inhibition by enalaprilat and type 1 angiotensin II receptor blockade by candesartan would inhibit HPV.MethodsHPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa–Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin–angiotensin system was present.ResultsAdministration of enalaprilat and candesartan did not affect the Ppa–Ppao gradient at baseline or during hypoxia. Plasma renin activity and angiotensin II immunoreactivity increased during hypoxia, and subsequent measurements were consistent with effective angiotensin-converting enzyme inhibition after administration of enalaprilat, and with angiotensin receptor blockade after administration of candesartan.ConclusionThese results suggest that, although the renin–angiotensin system was activated in hypoxia, angiotensin II is not normally involved in mediating acute HPV.

Comparison of the hemodynamic responses to molsidomine and isosorbide dinitrate in congestive heart failure

To evaluate the mechanisms involved in nitrate tolerance, we randomized 23 patients with congestive heart failure resulting from coronary artery disease to an isosorbide dinitrate or a molsidomine infusion. The drugs were titrated to decrease pulmonary capillary wedge pressure by > or = 30% or > or = 10 mm Hg. Then isosorbide dinitrate, molsidomine, or placebo was infused in a double-blind randomized manner for 24 hours. In all patients, treatment with enalapril was begun > or = 48 hours before the beginning of the protocol and was continued throughout the study to avoid renin-angiotensin activation. The pulmonary capillary wedge pressure remained significantly decreased at 24 hours during molsidomine infusion only. No significant increase in catecholamines occurred. Because molsidomine differs from organic nitrates by its property of directly stimulating guanylate cyclase without depending on thiol group availability, these results suggest that impaired biotransformation of nitrates is involved in tolerance induced by high doses of isosorbide dinitrate in congestive heart failure.

Amniotic fluid embolism: Another case with non-cardiogenic pulmonary edema

Sir: The morbidity associated with the accidental aspiration of foreign bodies is well documented [1-3]. It is classically seen in children, with 70% of cases occurring in those less than 3 years of age [41. A 43-year-old asthmatic presented at our accident and emergency department with a 10-day history of increasingly severe wheezing and dry coughing. He recalled having used his salbutamol inhaler 10 days previously, immediately after which he experienced a transient choking sensation. On that occasion, the patient had taken his inhaler, the mouthpiece of

Hormone and protein excretion responses to maximal exercise in humans

Summary The increases in plasma renin activity (PRA) and in the plasma concentration in angiotensin II (AII), aldosterone (ALDO), vasopressin (ADH) after exercise were compared to the urine protein excretion of well-hydrated healthy subjects submitted to a 2-min supramaximal bicycle exercise. Venous blood and urine samples were obtained at rest and after exercise. PRA, AII and ALDO were increased to about 4, 2 and 2-fold respectively of the resting basal values. ALDO continued to rise following exercise while PRA and AII returned to resting values ( P 2 -microglobulin (β 2 -m) increased 7, 38 and 162-fold during the first 20 min postexercise period respectively. The enhanced total protein, albumin and (β 2 -m) excretion were related to a decrease in plasma volume at 20 min postexercise. A positive relationship ( r =0.515; P 2 -m excretion following exercise. It was concluded that: 1) postexercise proteinuria was negatively correlated with the reduction in plasma volume; 2) the PRA-AII-ALDO system does not develop concomitantly with this transient kidney impairment.

Influence of bedside blood insulin measurement on acute coronary syndrome pathways.

BACKGROUND The aim of the study was to evaluate the influence of blood insulin measurements on acute coronary syndrome (ACS) pathways. METHODS All patients admitted to the emergency department within 12 months for acute, retrosternal, constrictive chest pain lasting for more than 30 minutes; cardiogenic pulmonary edema; electrocardiogram ST changes; and echographic alterations were included. The study parameters were clinical (age, sex, blood pressure, presence of pulmonary rales and gallop), including classic laboratory tests associated with troponin T, blood insulin levels, and hemoglobin A1C, and echographic values. These were taken on admission and throughout hospital stay. All patients underwent a coronary angiography for ACS diagnosis confirmation as well as treatment intention. RESULTS Sixty patients were included in the study. Abnormal blood insulin levels were present on admission in 47% of the population. Blood insulin level was significantly correlated to thrombolysis in myocardial infarction coronary perfusion score (Spearman Rank, 0.55, P < 0.0001). Abnormal insulinemia was normalized with reperfusion. Insulin was administered essentially to the 16 patients with hypoinsulinemia. Patients with hypoinsulinemia seem to have the most severe coronary lesions and highest Killip score. CONCLUSIONS In ACS, insulin levels are altered in half of the patients. After the investigators noted its tight correlation with the thrombolysis in myocardial infarction coronary flow score, its determination could be important in ACS for triggering emergency coronary angiography for percutaneous coronary intervention. This could modify the critical pathways of ACS patients in the emergency department.

Failure of indomethacin to impair the diuretic and natriuretic effects of the loop diuretic torasemide in healthy volunteers

SummaryThe effects of torasemide, a new potent loop diuretic, on renin release, water and sodium excretion were investigated in young healthy volunteers before and after 3 days of treatment with indomethacin. Torasemide 20 mg i. v. induced a rapid and biphasic increase both in plasma renin activity and plasma angiotensin II levels, which was almost completely abolished by pretreatment with indomethacin. Torasemide also increased urine volume, sodium excretion and, during the first hour after dosing, the creatinine clearance. None of the latter effects was impaired by indomethacin pretreatment. It is concluded that, like other loop diuretics, torasemide stimulates renin release by increasing renal prostaglandin production. However, at variance with what is observed with other loop diuretics, the diuretic and natriuretic effects of torasemide as well as the change in creatinine clearance do not appear to be inhibited by indomethacin.