Assessment of the role of the renin-angiotensin system in cardiac contractility utilizing the renin inhibitor remikiren

1. The role of the renin-angiotensin system in the regulation of myocardial contractility is still debated. In order to investigate whether renin inhibition affects myocardial contractility and whether this action depends on intracardiac rather than circulating angiotensin II, the regional myocardial effects of systemic (i.v.) and intracoronary (i.c.) infusions of the renin inhibitor remikiren, were compared and related to the effects on systemic haemodynamics and circulating angiotensin II in open-chest anaesthetized pigs (25-30 kg). The specificity of the remikiren-induced effects was tested (1) by studying its i.c. effects after administration of the AT1-receptor antagonist L-158,809 and (2) by measuring its effects on contractile force of porcine isolated cardiac trabeculae. 2. Consecutive 10 min i.v. infusions of remikiren were given at 2, 5, 10 and 20 mg min-1. Mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), systemic vascular resistance (SVR), myocardial oxygen consumption (MVO2) and left ventricular (LV) dP/dtmax were not affected by remikiren at 2 and 5 mg min-1, and were lowered at higher doses. At the highest dose, MAP decreased by 48%, CO by 13%, HR by 14%, SVR by 40%, MVO2 by 28% and LV dp/dtmax by 52% (mean values; P < 0.05 for difference from baseline, n = 5). The decrease in MVO2 was accompanied by a decrease in myocardial work (MAP x CO), but the larger decline in work (55% vs. 28%; P < 0.05) implies a reduced myocardial efficiency ((MAP x CO)/MVO2). 3. Consecutive 10 min i.c. infusions of remikiren were given at 0.2, 0.5, 1, 2, 5 and 10 mg min-1. MAP, CO, MVO2 and LV dP/dtmax were not affected by remikiren at 0.2, 0.5 and 1 mg min-1, and were reduced at higher doses. At the highest dose, MAP decreased by 31%, CO by 26%, MVO2 by 46% and LV dP/dtmax by 43% (mean values; P < 0.05 for difference from baseline, n = 6). HR and SVR did not change at any dose. 4. Thirty minutes after a 10 min i.v. infusion of the AT1 receptor antagonist, L-158,809 at 1 mg min-1, consecutive 10 min i.c. infusions (n = 5) of remikiren at 2, 5 and 10 mg min-1 no longer affected CO and MVO2, and decreased LV dP/dtmax by maximally 27% (P < 0.05) and MAP by 14% (P < 0.05), which was less than without AT1-receptor blockade (P < 0.05). HR and SVR remained unaffected. 5. Plasma renin activity and angiotensin I and II were reduced to levels at or below the detection limit at doses of remikiren that were not high enough to affect systemic haemodynamics or regional myocardial function, both after i.v. and i.c. infusion. 6. Remikiren (10(-10) to 10(-4) M) did not affect contractile force of porcine isolated cardiac trabeculae precontracted with noradrenaline. In trabeculae that were not precontracted no decrease in baseline contractility was observed with remikiren in concentrations up to 10(-5) M, whereas at 10(-4) M baseline contractility decreased by 19% (P < 0.05). 7. Results show that with remikiren i.v., at the doses we used, blood pressure was lowered primarily by vasodilation and with remikiren i.c. by cardiac depression. The blood levels of remikiren required for its vasodilator action are lower than the levels affecting cardiac contractile function. A decrease in circulating angiotensin II does not appear to be the sole explanation for these haemodynamic responses. Data support the contention that myocardial contractility is increased by renin-dependent angiotensin II formation in the heart.     

Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice

When administered intracerebroventricularly to mice performing various learning tasks involving either short-term or long-term memory, secreted forms of the beta-amyloid precursor protein (APPs751 and APPs695) have potent memory-enhancing effects and block learning deficits induced by scopolamine. The memory-enhancing effects of APPs were observed over a wide range of extremely low doses (0.05-5,000 pg intracerebroventricularly), blocked by anti-APPs antisera, and observed when APPs was administered either after the first training session in a visual discrimination or a lever-press learning task or before the acquisition trial in an object recognition task. APPs had no effect on motor performance or exploratory activity. APPs695 and APPs751 were equally effective in the object recognition task, suggesting that the memory-enhancing effect of APPs does not require the Kunitz protease inhibitor domain. These data suggest an important role for APPss on memory processes.     

Vom Damaststahl zum Scharsachstahl

Verbesserung der Schwertklingen durch Damaszierung. Nachweis des Übergangs auf eine andere Schmiedetechnik in der Ritterzeit (11. bis 14. Jh.) an Hand von zwölf mittelalterlichen Schwertern, die aus in der Steiermark hergestellten Stählen nach der Gärbtechnik gefertigt wurden. Kennzeichnung des sogenannten Scharsachstahles mit rd. 0,80% C und seine Verarbeitung zu Schwertklingen mit hoher Elastizität.     

V/Q mismatch without pulmonary emboli in children with histoplasmosis

In two children with histoplasmosis pulmonary perfusion and ventilation studies revealed mismatched abnormalities characterized by almost unilaterally absent perfusion but normal ventilation in the right lung. Chest roentgenograms demonstrated right hilar enlargement and pulmonary contrast angiograms revealed narrowing of the right pulmonary arteries by extrinsic fibrotic granulomata but no pulmonary emboli were present. Fibrosing mediastinitis due to histoplasmosis was found by mediastinoscopic examination in one of the patients. Non-embolic causes of V/Q mismatch lung imaging are discussed briefly, and the correlation with clinical findings is stressed for the diagnosis of pulmonary emboli.     

The development of peat-oil (POM) and peat-alcohol (PAM) slurries as alternative fuels

The preparation and evaluation of peat/No. 2 fuel oil mixtures (POM) and peat/methanol mixtures (PAM) is described. POM and PAM prepared using North Carolina peat and having varied peat loadings, peat moisture contents, and peat particle sizes have been studied by measuring slurry sedimentation ratios and drain times from sedimentation tubes. The peat moisture content was particularly crucial in forming stable slurries. The effect of a variety of additives at 0.5–1.0 wt.% on sedimentation ratios, drain times, and viscosities was studied. Calorimetric studies of several PAM and POM slurries as well as preliminary combustion tests of POM slurries in a salamander burner are also reported.