Felodipine once daily in elderly hypertensives. Binational MC Study Group (United Kingdom and Netherlands).

In this monotherapy study, 102 elderly hypertensive patients aged 65-80 years with a diastolic blood pressure (DBP) greater than or equal to 100 mmHg were randomized to double-blind treatment with felodipine 5 mg as an extended release (ER) formulation or placebo once daily. In patients with a DBP greater than 95 mmHg after two weeks the dose was doubled. Total treatment time was four weeks. Blood pressure and heart rate were measured 24 hours after dose intake. At the end of the study, supine BPs were reduced in comparison with values at randomization by 14/13 mmHg in the felodipine group and by 4/8 mmHg in the placebo group (P = 0.005/P = 0.007, felodipine vs. placebo). The proportion of responders was also significantly greater on felodipine than on placebo, 75% and 42%, respectively (response was defined as a reduction in supine DBP to less than or equal to 95 mmHg and/or a reduction by greater than or equal to 10 mmHg). A dose increase was performed in 41% of the patients on felodipine and in 50% on placebo. The proportion of patients reporting adverse events was low and of the same magnitude in both groups.

Influence of changes in ionized calcium on cardiovascular reactivity during hemodialysis.

In order to prevent hypercalcemia due to the treatment of secondary hyperparathyroidism the use of low calcium dialysate is advocated. However, as calcium ions play a pivotal role in both myocardial and vascular smooth muscle contraction, lowering the dialysate calcium concentration might result in a further impairment of the cardiovascular response during dialysis. Therefore, arterial blood pressure, forearm vascular resistance (FVR) and venous tone (VT) (straing-gauge plethysmography) as well as cardiac dimensions and output (echocardiography) were measured in 10 hemodynamically stable dialysis patients (ejection fraction > 30%) during two standardized sessions of three-hour combined ultrafiltration-hemodialysis (UF + HD) at two different dialysate calcium concentrations: 1.25 and 1.75 mmol/l. High calcium UF + HD resulted in a significant increase in plasma ionized calcium (+0.19 +/- 0.11 mmol/l; p < 0.01) while ionized calcium remained unchanged during low calcium UF + HD (-0.02 +/- 0.07 mmol/l). As a result, systolic, diastolic and mean arterial blood pressure were respectively 14 +/- 10, 5 +/- 7 and 9 +/- 9 mmHg higher during high calcium UF + HD as compared to low calcium UF +/- HD (p < 0.05). There were no significant differences in FVR and VT between the two treatments. During both treatments FVR increased while VT decreased. In addition, there were no differences in calculated systemic vascular resistance. However, with comparable end-diastolic dimensions, stroke volume (-18 +/- 13 ml) and cardiac output (-1.3 +/- 1.5 l/min) decreased significantly (p < 0.05) only during low calcium UF + HD. We conclude that even in hemodynamically stable patients changes in plasma ionized calcium are an important determinant of the blood pressure response during dialysis therapy. Whereas peripheral vascular reactivity is unaffected by changes in ionized calcium, myocardial contractility is improved with higher dialysate calcium concentrations.

The hemodynamic effect of different ultrafiltration rates in patients with cardiac failure and patients without cardiac failure: comparison between isolated ultrafiltration and ultrafiltration with dialysis.

OBJECTIVE: The increasing number of dialysis patients with cardiovascular diseases will lead to an increase in the incidence of intradialytic hypotension. Intradialytic hypotension is determined by changes in plasma volume, changes in vascular reactivity and structural cardiovascular changes. In this study the effect of two different ultrafiltration rates (UF-rate), i. e. 500 and 1000 ml/h, on plasma volume, extracellular volume and arterial blood pressure was studied during different treatments of 2 hours combined ultrafiltration + hemodialysis (UF+HD) and 2 hours isolated ultrafiltration (i-UF). PATIENTS AND METHODS: 15 Patients, 8 patients with cardiac failure, CFpts (NYHA classification III and IV) and 7 patients without cardiac failure (NCFpts) were investigated during a standardized dialysis treatment. RESULTS: The decrease in plasma volume and decrease in extracellular volume was comparable both between i-UF and UF+HD and comparable between CFpts and NCFpts and was only dependent on the UF-rate. i-UF resulted in minor blood pressure changes in both CFpts and NCFpts. In CFpts UF+HD resulted in a significant decrease in systolic blood pressure (SBP) at both UF-rates while in NCFpts SBP decreased significantly only at the higher UF-rate during UF-HD. Although there were no significant differences in hemodynamic stability during the different treatment modalities between CFpts and NCFpts, the decrease in SBP in CFpts at the higher UF-rate during UF+HD was much more pronounced. CONCLUSION: From this clinical study we conclude that differences in hemodynamic stability between i-UF and UF+HD and between CFpts and NCFpts are not related to differences in plasma volume preservation. Other factors like different changes in vascular reactivity and in CFpts structural cardiovascular changes might be responsible for the observed differences.

Angiotensin-II sensitivity and prostaglandin-synthetase inhibition in pregnancy.

Angiotensin-II sensitivity was measured with a standardized test in 8 healthy nonpregnant females and in 14 healthy primigravid women. In the primigravid women the effective pressor dose (EPD), i.e. the minimal dose of angiotensin-II (A-II) necessary for a rise in diastolic blood pressure of 20 mm Hg, was 17.1 +/- 5.7. This is significantly higher than the EPD in the control group (5.2 +/- 1.2). The pregnant patients were also tested 75 min after a 50 mg indomethacine suppository, which produced a decrease of the EPD of 9.5 +/- 3.0, a fall of 44%. None of the 7 patients tested between 28 and 32 wk of gestation developed pregnancy-induced hypertension. They all had a normal EPD. It may be concluded that (1) A-II sensitivity is decreased in pregnancy, and (2) vascular reactivity in pregnancy is at least in part mediated by prostaglandins.

Acute renal failure after cardiovascular surgery. Current concepts in pathophysiology, prevention and treatment.

Acute renal failure (ARF) is a serious complication of cardiovascular surgery and has a high mortality rate, especially with oliguria. It is usually caused by ischaemic injury of the kidney, resulting from inadequate perfusion. Certain risk factors which might lead to the development of ARF following open heart operations have been identified: age greater than 70 years; elevated pre-operative serum creatinine; low blood pressure during cardiopulmonary bypass; rate of haemolysis; a postoperative critical circulation. It is necessary to establish the diagnosis as soon as possible in order to institute corrective measures to prevent oliguric ARF. Once renal failure is established close control of hydration, solutes and potentially toxic metabolites is necessary. Early renal replacement therapy with proper nutritional support appears to improve survival.

Severe coagulopathy after a bite from a 'harmless' snake (Rhabdophis subminiatus).

European physicians may occasionally be confronted with cases of snake venom poisoning. The increasing interest in snakes as pets has unfortunately resulted in the importation of a number of venomous snakes. We here report the third known case in the medical literature of a patient who was exposed to severe coagulopathy after being bitten by a 'harmless' ringsnake (Rhabdophis subminiatus). The prolonged bleeding diathesis and the complete depletion of fibrinogen observed in our patient are consistent with the presence of a factor X activator in the venom, as has been described in a murine model. In agreement with the two previous case reports, we found no evidence of severe organ damage, despite active intravascular coagulation.

Decrease of angiotensin sensitivity after bed rest and strongly sodium-restricted diet in pregnancy.

Angiotensin II (A-II) sensitivity was determined in 23 nonmedicated nulliparas in the third trimester of pregnancy, before and after a 7- to 10-day period of bed rest and a strongly sodium-restricted diet (maximal 20 mmol Na+/24 hr). Seventeen nulliparous women had pregnancy-induced hypertension (PIH). The effective pressor dose (EPD), that is the minimal amount of A-II necessary for a 20 mm Hg elevation of the diastolic blood pressure, rose from a mean of 11.0 +/- 5.0 to 17.9 +/- 5.7 ng/kg/min. This is an increase of the mean of 63%. Six women were normotensive during the course of the pregnancy. They showed an increase of EPD from 12.6 +/- 4.9 to 28.3 +/- 10.9 ng/kg/min after sodium restriction and bed rest. This is a mean increase of 124%. It is concluded from this study that sodium not only is important in volume regulation but also seems to play a role in vessel wall reactivity. This effect of sodium on vascular reactivity could be the explanation for the favorable effect of a strongly sodium-restricted diet in lowering the incidence of eclampsia in women with PIH.

Liquid-chromatographic profiling of solutes in serum of uremic patients undergoing hemodialysis and chronic ambulatory peritoneal dialysis (CAPD); high concentrations of pseudouridine in CAPD patients.

Using "high performance" liquid chromatography, we studied non-protein-bound fractions and total concentrations of 18 solutes accumulating in sera from a group of 12 patients who were undergoing chronic ambulatory peritoneal dialysis (CAPD) and in predialysis sera from a group of 15 hemodialysis (HD) patients. We monitored longitudinal changes in solute concentrations for two patients with respect to change of therapy between HD and CAPD. The concentrations of pseudouridine (P less than 0.001), uric acid (P less than 0.001), and an unknown fluorescent solute, "UKF3" (P less than 0.01), differed in sera of HD and CAPD patients. When standardized with respect to serum creatinine concentrations, the concentration of the transfer-RNA catabolite, pseudouridine, was significantly (P less than 0.0001) higher in sera of CAPD patients than in HD patients, suggesting an increase in turnover of transfer RNA. In stepwise linear discriminant analysis, the combination of pseudouridine and the probably biochemically related fluorescent unknown, UKF3, contributed most to the differentiation between sera from CAPD and HD patients.

Acetate versus bicarbonate hemodialysis in critically ill patients.

The hemodynamic state, acid-base balance and blood gases were studied in 9 acute renal failure patients during recirculation acetate- and bicarbonate dialysis. A significant hemodynamic instability, due to a decreased cardiac performance, was observed during acetate dialysis, whereas during bicarbonate dialysis, there was a stable hemodynamic state. During acetate dialysis, pO2 dropped significantly, due to a decreasing ventilatory drive as a consequence of the significantly lower pCO2 in acetate dialysis. From these findings, we conclude that bicarbonate dialysis should be the first choice in the treatment of acute renal failure patients.