Early onset of a decreased intracellular magnesium and phosphate concentration in smooth muscle cell of SHR.

A decrease in total magnesium content is not a direct proof of a decreased magnesium ion concentration. It could reflect a phosphate alteration or an ATP metabolism disorder. Plasma phosphate levels are lower in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto rats (WKYs), and defects in membrane regulation or mitochondrial ATP synthase occur. Only sparse data exist concerning cellular magnesium and phosphate concentrations in hypertensive cells. In aortic smooth muscle cells from 10 SHRs of the Münster strain and 10 age-matched normotensive WKY rats, the intracellular phosphate and magnesium content was measured by electron probe X-ray microanalysis (Camscan CS 24 apparatus, Cambridge, U.K.). The Mg++ content was 0.09 +/- 0.15 g/kg dry weight in SHRs versus 1.15 +/- 0.10 g/kg dry weight in WKY rats (p < 0.01). Vascular smooth muscle phosphate content was 23.6 +/- 0.79 g/kg dry weight in WKY rats versus 15.81 +/- 1.22 g/kg dry weight in SHRs (p < 0.01). In aortic smooth muscle cells of one month old SHRs intracellular magnesium was measured as 1.05 +/- 0.08 versus 1.09 +/- 0.09 g/kg dry weight in WKYs. Intracellular phosphate concentration in one month old SHRs was 18.71 +/- 2.41 versus 21.36 +/- 1.25 g/kg dry weight in WKYs (eight animals in each group). Aortic smooth muscle cells of SHRs are caracterized by markedly lowered intracellular phosphate and magnesium concentrations, resulting in an altered ATP-metabolism, as described earlier. Possibly a membrane defect or a magnesium deficiency or disturbed magnesium channels are responsible for the early onset in the pathogenesis of primary hypertension.

Use of FemoStop system for arterial puncture site closure after coronary angioplasty.

Different protocols exist concerning the method and timing of post-coronary angioplasty arterial puncture site closure. Easy handling and good effectiveness are well-documented for the Femostop femoral artery compression system; however, no hard data exist concerning the relationship between heparin anticoagulation level and femoral artery compression time (FSCT). Thus, we prospectively randomized 267 patients after elective percutaneous transluminal coronary angioplasty (PTCA) into two groups [group A (n=137) had early sheath removal 6 to 8 hours after PTCA; group B (n=130) had late sheath removal 14 to 16 hours after PTCA] and analyzed the dependence of the FSCT on the heparin anticoagulation level (aPTT) and the incidence of vagal reactions and puncture site complications. FSCT was significantly longer in group A (69+/-27 minutes versus 45+/-15 minutes; p<0.001) with high heparin anticoagulation level (aPTT, 88+/-46 seconds) in comparison to group B with low heparinization (aPTT, 59+/-34 seconds). Vagal reactions occurred more frequently in group A (15.3% versus 10.0%; p<0.01) and the incidence of minor hemorrhage at the arterial puncture site was also increased (9.5% versus 3.1%; p<0.05). In the clinical setting of intensive heparin anticoagulation and early sheath removal after PTCA (<8 hours), the FemoStop system cannot be recommended due to prolonged femoral artery compression times.

Early-onset increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in SHR versus WKY.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives, our group showed increased calcium and decreased magnesium and an increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4+/-9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron-probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick. The calcium content was 124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in NT (Means+/-SD, p < 0.01), the magnesium content was 35.5+/-3.9* in SHR versus 50.1+/-4.9 mmol/kg dry weight in NT /p < 0.01). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p < 0.01). In hypertensive one month old animals the increase in the calcium/magnesium ratio was not as pronounced as in 9 month old animals. The calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to 2.51+/-0.39 in normotensive animals (n = 8, p < 0.01). Aortic smooth muscle cells from SHR are characterized by markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. The increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic factor for the development of arteriosclerosis and hypertension.

Intrapericardial instillation of mitoxantrone in palliative therapy of malignant pericardial effusion.

BACKGROUND: Pericardial effusions occurring with pericardial or myocardial metastases often cause serious complications, necessitating temporary or emergency relief by percutaneous pericardiocentesis. However, this often results in recurrences. For long-term therapy success, the intrapericardial instillation of anti-neoplastic agents is an alternative to surgical methods, which are stressful for the patient. Following our positive experiences with mitoxantrone in the treatment of malignant pleural effusions, we applied this substance for the therapy of malignant pericardial effusions. PATIENTS AND METHODS: 16 patients with cytologically verified malignant pericardial effusions (8 with bronchial carcinoma, 7 with carcinoma of the breast, 1 with adenocarcinoma of the stomach) received an intrapericardial instillation of mitoxantrone 1-3 x10-20 mg. Responses were evaluated by echocardiography 30 days after completion of therapy. RESULTS: 12 of 16 patients showed complete remission (no recurrence of a detectable effusion). 3 patients showed a partial remission (recurrence of non-drainage-dependent effusion) (CR + PR = 94%). Within the mean follow-up period of 189 days no recurrences occurred. The rate of side effects was low. CONCLUSION: Intrapericardial instillation of mitoxantrone is a feasible and effective palliative method for the control of malignant pericardial effusions with little strain on the patients, short duration of hospital stay, cytotoxic characteristics of the substance with a correspondingly high rate of response and low side effects.

Improvement of cardiac output in patients with severe heart failure by use of ACE-inhibitors combined with the AT1-antagonist eprosartan.

BACKGROUND: The efficacy of ACE-inhibitor therapy is well documented in the treatment of chronic heart failure. As pharmacological mechanisms of ACE-inhibition and angiotensin II AT1-receptor-antagonists differ, an additional positive effect concerning left ventricular function can be expected in combining both classes of drugs. METHODS: Twenty patients (64.9+/-8.5 years) with advanced chronic heart failure (NYHA class III) receiving long-term medication with digitalis, diuretics and ACE-inhibitors were randomized to either eprosartan (540+/-96 mg/day) or placebo, according to a blinded protocol. Hemodynamic measurements by impedance cardiography were performed at baseline and after 8.85+/-1. 5 days of study medication treatment. RESULTS: Additional treatment with eprosartan resulted in a higher cardiac output than in the control group (P<0.05). While in the active treatment group cardiac output increased significantly from baseline (2.27-3.24 l/min, P=0. 039), there was no change in the control group. CONCLUSIONS: The additional treatment with the AT1-receptor antagonist eprosartan, given to severe heart failure patients, who received digitalis, diuretics and ACE-inhibitors, resulted in a beneficial effect by increasing cardiac output. This effect may be due to eprosartan's additional property of blocking the autocrine interaction of locally and not ACE-generated angiotensin II with their respective vascular and myocardial AT1-receptors as well as the influence on prejunctional AT1-receptors located on sympathetic nerve terminals.