Intracellular cations and diuretic therapy following acute myocardial infarction.

In a controlled, prospective, randomized study of the effects of diuretic therapy on serum, lymphocyte, and erythrocyte potassium, magnesium, and calcium concentrations, 155 patients were followed up for six months after experiencing acute myocardial infarction. Of these, 48 patients received furosemide and potassium; 37 patients received hydrochlorothiazide and amiloride hydrochloride; and 70 patients did not require diuretics. Lymphocyte and erythrocyte cation concentrations were all statistically significantly lower in the furosemide-treated patients when compared with the patients in the nondiuretic-therapy group or the hydrochlorothiazide-amiloride-treated group, with no change in serum levels. Since the combination of low intracellular potassium and magnesium concentrations in patients with recent myocardial infarction may be of importance in the cause of arrhythmias, we suggest that potassium- (and magnesium-) sparing diuretics be used in the treatment of patients, when necessary, unless their diuretic needs cannot be met by such agents.

Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction.

Seven of 48 patients (14.6%) with acute myocardial infarction who were given 2.4 g of magnesium sulfate as a single intravenous dose had potentially lethal arrhythmias during the first 24 hours after admission, whereas 16 (34.8%) of 46 patients receiving placebo had similar arrhythmias. In addition, 14 of these 16 patients in the placebo group had their first arrhythmia (in the intensive coronary-care unit) within two hours after the start of the study, whereas in the magnesium-treated group, there were no such arrhythmias until some four hours later. The higher the lymphocyte potassium concentration, the greater the reduction in the incidence of arrhythmias. Serum magnesium levels increased by 16.5% and lymphocyte magnesium concentrations by 72% in the magnesium treated group. Intravenous magnesium reduces the incidence of serious arrhythmias after acute myocardial infarction.

Magnesium levels in patients with chronic ischemic heart disease.

Serum magnesium was measured in 89 control subjects ages 19 to 86 years and in 64 patients (ages 35 to 82 years) who had suffered from acute myocardial infarction at least 6 months previously. No differences were found in the serum magnesium levels due to age or sex nor was there any statistical difference between the mean levels in the two groups. It is concluded that the level of serum magnesium is not associated with the presence or absence of clinically evident ischemic heart disease.

Serum, lymphocyte, and erythrocyte potassium, magnesium, and calcium concentrations and their relation to tachyarrhythmias in patients with acute myocardial infarction.

Serum, lymphocyte, and erythrocyte potassium, magnesium, and calcium levels were measured in 215 patients during the five days following acute myocardial infarction. Serum potassium fell from 4.25 +/- 0.05 to 4.08 +/- 0.06 mmol/liter (p less than 0.001), magnesium from 0.93 +/- 0.01 to 0.85 +/- 0.01 mmol/liter (p less than 0.001), and calcium from 2.4 +/- 0.02 to 2.2 +/- 0.08 mmol/liter (p less than 0.001). Lymphocyte potassium increased from 18.1 +/- 1.5 to 51.6 +/- 4.3 pmol/100 cells (p less than 0.001) and magnesium from 2.0 +/- 0.1 to 8.2 +/- 0.8 pmol/100 cells (p less than 0.001), whereas calcium decreased from 2.9 +/- 0.27 to 1.4 +/- 0.25 pmol/100 cells (p less than 0.001). Erythrocyte cations remained constant. There was a larger increase in lymphocyte potassium in patients with tachyarrhythmias than in patients without (70.4 and 46.9 pmol/100 cells, respectively, p less than 0.001), whereas the presence of a high lymphocyte magnesium level was associated with a significant decrease in the development of tachyarrhythmias, despite high potassium concentrations. It is suggested that lymphocyte cation concentrations mirror myocardial interstitial concentrations and that a high interstitial magnesium level has a protective effect on the increased cell excitability due to, and despite, a high interstitial potassium level.

Effects of hydrochlorothiazide, diltiazem and enalapril on mononuclear cell sodium and magnesium levels in systemic hypertension.

Sixteen patients (mean age 68 years) with mild to moderate hypertension were treated with either diltiazem or hydrochlorothiazide for 6 weeks, followed by enalapril for a further 6 weeks. A second group of 40 patients (mean age 71 years) was treated with either hydrochlorothiazide or enalapril for 12 weeks; nonresponders received both drugs for 8 weeks. Treatment with hydrochlorothiazide or enalapril resulted in a lowering of systolic and diastolic blood pressures, but diastolic pressure was lower in patients treated with enalapril (89 +/- 2 and 82 +/- 2 mm Hg, respectively; p less than 0.05). Treatment with diltiazem resulted in a decrease in diastolic pressure only. Treatment with hydrochlorothiazide resulted in a 17% decrease in serum potassium (p less than 0.05), which returned to normal when enalapril was substituted. Hydrochlorothiazide also produced a 23% decrease in mononuclear cell sodium content at 4 weeks (p less than 0.01), with a further 15% decrease at 12 weeks (p less than 0.05). Mononuclear cell potassium and magnesium also decreased at 12 weeks by 18 and 16%, respectively (p less than 0.05). All these effects were reversed when enalapril was substituted. A similar pattern of events was seen with diltiazem, which was again reversed with enalapril. Finally, there was no relation between changes in mononuclear cell sodium or other cation content and changes in blood pressure.

The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes.

Seventy-six patients with established atherosclerotic disease were treated daily with either 250 micrograms of chromium orally as chromium chloride or a placebo for a period of 7 to 16 months (mean, 11.1 months). Serum chromium increased from 2.69 +/- 0.09 to 12.12 +/- 0.77 nmol/L (mean +/- SE, P less than .005). Serum triglycerides were lower (1.68 +/- 0.11 and 2.10 +/- 0.14 nmol/L, respectively; P less than .02) in the chromium-treated patients than in the patients who received placebo, and serum high-density lipoprotein (HDL) increased (from 0.94 +/- 0.05 to 1.14 +/- 0.07 mmol/L, P less than .005) in the patients who received chromium. There was no change in serum cholesterol or blood glucose during the study.

In vivo interaction of anticonvulsant drugs. The mathematical correlation of plasma levels of anticonvulsant drugs in epileptic patients.

The phenytoin plasma levels were measured in 45 epileptic patients whose only treatment was phenytoin. The plasma of 20 other patients receiving both phenytoin and phenobarbital was also tested for concentration of these two drugs and 18 patients treated with phenytoin, phenobarbital and primidone were investigated in the same way. The results were used to calculate the plasma levels of phenytoin in relation to dosage and to measure the effect of the simultaneous use of phenobarbital on the phenytoin plasma levels and of primidone together with phenobarbital on phenytoin concentration. The results led to the following conclusions: The population of epileptic patients can be divided into 2 groups. In the first group the patients reach equilibrium at the relatively high phenytoin plasma level for a given dose of phenytoin, and in the second group the phenytoin plasma level tends to be significantly lower for parallel dosages. Both groups, in their behavior, obey mathematically an exponential graph specific for each group. Phenobarbital tends to lower the plasma phenytoin level when the two drugs are used simultaneously. It is also possible, by the graphs produced, to calculate the expected phenytoin plasma levels when using the drugs together. Primidone and phenobarbital together decrease the phenytoin level much more than expected from the effect of phenobarbital alone.

"In vitro" studies on the fate of diphenylhydantoin in uremia.

"In vitro" studies were undertaken to evaluate the fate of DPH in blood of uremic patients. DPH incubated for 18 h at 37 degrees C disappears from plasma in the presence of erythrocytes and more when the blood underwent hemolysis. This phenomenon was more pronounced in uremic blood. These findings suggest not only that DPH is absorbed onto the erythrocyte membrane, but also that it is bound by erythrocyte contents. It could be possible that, because of a low binding capacity of the albumin carrier in uremic blood, the drug penetrates more easily the erythrocyte membrane and is bound there. An intraery throcyte enzymatic metabolism of DPH is not excluded.

The CSF lipid content in brain atrophy.

Significantly low CSF values for cholesterol and total lipids were found in a group of patients with brain atrophy in comparison with a control group. It is possible that these changes are a function of reduced brain mass or of defect in brain lipid metabolism in brain atrophy patients. Further metabolic studies are required to clarify the biochemical aspects of brain atrophy.

A routine method for the measurement of the sodium, potassium, magnesium and calcium content of human lymphocytes.

We describe a rapid, single-step procedure for the isolation of human lymphocytes from whole blood, suitable for a routine clinical laboratory. Lymphocyte content of sodium, potassium, magnesium and calcium were measured simultaneously in a group of controls and found to fall within expected ranges. Expression of results per mg protein produced less inter-individual variation than per unit cell. In order to examine another, physiologically different but normal population, women during pregnancy were also studied. The cation content of lymphocytes expressed per mg protein was significantly lower than for controls due to a 44% increase in protein content per cell.

Ossification centers as evidence of fetal lung maturity.

Fetal pulmonary maturity based on visualization of one or both fetal knee secondary centers of ossification was assessed in 84 gravidas. Amniotic fluid lecithin/sphingomyelin ration of 2:1 or greater was the criterion of fetal lung maturity. It was concluded that when antenatal radiographs reveal the presence of both centers of ossification, fetal lung maturity can be assured in 100% of the fetuses. When the distal femoral center along is seen, only 60% of the fetuses will have mature lungs.

The relationship between beta-endorphin levels and uterine muscle contractions during labor.

Plasma beta-endorphin (BE) levels (8.6 +/- 0.8 pmol/l) (mean +/- SE) were lower in the third trimester than in non-pregnant controls (14.8 +/- 1.1 pmol/l) (P less than 0.001), increased during labor, to 29.3 +/- 4.4 pmol/l (P less than 0.005) and decreased, 72 h after delivery, to 3.5 +/- 0.4 pmol/l (P less than 0.001). BE levels were found to correlate significantly with uterine muscle contraction (r = 0.966, P less than 0.05) and with cervical effacement (r = 0.974, P less than 0.05) during labor.

Differential diagnosis of chest pain. Use of isoenzyme LDH1 level as a criterion.

Changes in level of isoenzyme LDH1 seem to be a valuable criterion in differentiating acute myocardial infarction from active coronary insufficiency without infarction. LDH1 level increases noticeably within 48 hours after onset of pain from acute myocardial infarction but tends to decrease if the pain is due to active coronary insufficiency.

Serum and intracellular electrolytes in patients with and without pain.

The effect of acute stress, with and without pain, on serum and mononuclear cell cation content was studied in 205 healthy women in their last trimester of pregnancy or during normal labour, in patients with acute medical conditions in which pain was or was not present, in acute surgical conditions, and immediately prior to elective surgery. In all subjects there was a fall in serum sodium, potassium, magnesium and calcium concentrations during stress, with an apparent shift into the intracellular space. An inverse correlation was present between the severity of pain and the fall in serum cations.

Serum and mononuclear cell potassium, magnesium, sodium and calcium in pregnancy and labour and their relation to uterine muscle contraction.

Thirty women in their third trimester of pregnancy (37-42 weeks), 40 women during and 72 h after labour and 18 non-pregnant controls were studied for changes in serum and mononuclear cell cation content, and their relationship to cervical effacement and intensity of pain as measured by plasma beta endorphin concentrations during labour. Serum magnesium fell from 0.95 +/- 0.01 (mean +/- SEM) to 0.84 +/- 0.02 mmol/litre at late pregnancy and further to 0.76 +/- 0.01 during labour (P < 0.001); serum potassium fell from 4.25 +/- 0.05 to 3.79 +/- 0.06 mmol/litre (P < 0.0001) during labour; and serum calcium fell from 2.40 +/- 0.02 to 2.28 +/- 0.01 mmol/litre at late pregnancy (P < 0.001) and further to 2.25 +/- 0.02 mmol/litre during labour (P < 0.001). Mononuclear cell magnesium content rose from 4.5 +/- 0.3 to 5.6 +/- 0.04 fmol/cell (P < 0.02); potassium content rose from 37.7 +/- 2.0 to 50.9 +/- 3.0 fmol/cell (P < 0.001); and calcium content rose from 4.4 +/- 0.4 to 7.6 +/- 1.1 fmol/cell (P < 0.105). On the other hand, mononuclear cell sodium content fell from 7.2 +/- 0.5 to 3.8 +/- 0.3 fmol/cell (P < 0.001). Plasma beta endorphin concentrations increased with increasing degrees of effacement, as did intracellular Na, whereas intracellular Mg and K showed an inverse trend. A significant correlation was found between intracellular cation and beta endorphin levels (r = -0.98, Mg; -0.99, K; 0.83, Na). These changes are probably due either to intercompartmental cation shifts or possibly to endometrial ischaemia and damage during labour.