Barriers to implementation of placental transfusion of babies at birth in Zambia.

Delayed cord clamping (DCC) and umbilical cord milking (CM) have many benefits. However, a previous study done in Zambia showed that it was not a common practice among midwives. This study investigated possible barriers to DCC and CM, at the University Teaching Hospital in Lusaka. This was a qualitative study. A convenience sample was chosen, and snowball sampling was used. The midwives were interviewed using semi-structured interviews. Burnard's method of thematic content analysis was used. Through 14 interviews it became clear that the midwives were aware of DCC and used it whenever possible. The participants reported that the main barriers were the high workload and a variation in knowledge. A lack of facilities, such as heaters and resuscitation equipment in the delivery room also led to earlier cord clamping. The midwives were motivated to continue improving the routines. They expressed a need for more training as well as equipment and resources to facilitate DCC.

Comparative hemodynamic dose-response effects of five slow calcium channel-blocking agents in coronary artery disease.

A prospective, randomized study compared the hemodynamic effects of equivalent doses of five slow calcium channel blockers (verapamil, diltiazem, nicardipine, nisoldipine, and amlodipine) in 50 patients with ischemia. After a stable control period, dose-response curves were constructed for each drug with hemodynamics measured 10 minutes after intravenous boluses. Each drug reduced mean systemic arterial pressure (P less than 0.01) and systemic vascular resistance index (P less than 0.01). The heart rate increased after nicardipine, nisoldipine, and amlodipine (P less than 0.01) but was unchanged after verapamil and reduced after diltiazem (P less than 0.01). The left ventricular filling pressure increased after amlodipine (P less than 0.05) and verapamil (P less than 0.01) but was unchanged with the other compounds. Cardiac index increased substantially after the dihydropyridines (P less than 0.01), with little change after verapamil or diltiazem. Cardiac double product fell only after verapamil and diltiazem. These studies provide quantitation of the comparative actions of acute intravenous calcium channel blockade in coronary disease.

Effects of long-term verapamil therapy on serum lipids and other metabolic parameters.

Calcium antagonists have been used successfully in the management of hypertension for more than a decade, but less is known about their long-term metabolic effects. To define the impact of one calcium antagonist, verapamil, on serum lipids and other metabolic parameters, we placed 45 hypertensive patients on verapamil monotherapy and followed them for 4 to 8 years. After a mean treatment period of 5.3 years, total cholesterol and triglyceride levels were not significantly different from baseline, whereas the mean high-density lipoprotein cholesterol value increased significantly from 1.17 +/- 0.41 mmol/L at the initiation of treatment to 1.39 +/- 0.36 mmol/L at 5.3 years (p less than 0.05). Other important biochemical parameters, including serum glucose, potassium and uric acid levels were unaffected by verapamil therapy. No serious side effects or adverse cardiovascular events occurred during verapamil therapy, and there were no study dropouts. It therefore seems likely that this agent will become increasingly useful in the long-term management of essential hypertension.

Instant and sustained-release verapamil in the treatment of essential hypertension.

In a series of controlled studies for periods of 4 to 6 weeks comprising 103 patients altogether, and in 1 long-term trial for 1 year, various dosages of instant and sustained-release verapamil were administered in the treatment of mild and moderate essential hypertension. One of these trials was a double-blind comparison with nifedipine, in which the 2 calcium antagonists had an equally good effect on blood pressure. A significant blood pressure reduction was achieved with verapamil both at rest and during isometric work in most patients. About 10% of the patients were nonresponders. Pharmacokinetic studies demonstrated great interindividual variations in plasma concentrations of verapamil and its active metabolite norverapamil. Except for 1 study, no significant correlation was found between drug concentration and blood pressure reduction. All formulations of verapamil were well tolerated by the patients, and adverse effects were generally mild and often transient. No negative metabolic effects were observed during long-term treatment; serum lipids, in particular, were unaffected. PQ intervals on the electrocardiogram were significantly but moderately prolonged. QRS and QT intervals were unchanged. No increase in body weight occurred. It is concluded that verapamil is an efficacious, safe drug and a first-line treatment alternative in mild and moderate essential hypertension. The recently developed sustained formulation of the drug renders a simple dosage regimen possible.

Primary prevention potential of the calcium antagonists. Effects on blood pressure and lipid pattern.

Untreated hypertension has a variety of serious consequences, such as stroke, congestive heart failure and coronary heart disease, the incidences of which escalate sharply in the presence of other risk factors. Traditional antihypertensive therapy has been associated with reductions in the frequency of strokes, congestive heart failure and kidney failure, but a corresponding decline in myocardial infarctions has not been observed. Deleterious changes in lipid metabolism that are induced by these agents may counteract the beneficial effects of blood pressure reduction. Calcium antagonists have been used successfully in the management of hypertension for more than a decade. To define the impact of the calcium antagonist verapamil on metabolic parameters, 45 hypertensive patients were treated with verapamil monotherapy and followed up for 4 to 8 years. After a mean treatment period of 5.3 years, total cholesterol and triglycerides were unchanged, whereas mean high density lipoprotein (HDL) cholesterol increased significantly, from 1.17 +/- 0.41 to 1.39 +/- 0.36 mmol/L (p less than 0.05). Other important biochemical parameters were unaffected by verapamil therapy. The primary target organs of hypertension are the arterial system and the myocardium. Accumulating literature now suggests that the calcium antagonists may represent an effective therapeutic approach to hypertension that controls both the pressure-related and atherosclerotic complications.

Correlations of exercise test and quality of life variables with clinical improvement in effort angina.

The value of the exercise test has been challenged in connection with assessments of the effects of drugs on angina. Therefore, a series of test variables were correlated with clinical improvement in 30 patients with effort-related angina and coronary stenoses proved by angiography. The patients had two bicycle tests with an interval of 1 year. They were also clinically graded by a combined score of drug consumption and self-assessment of physical fitness on those two occasions, and classified as deteriorated or unchanged, improved, or without symptoms. Sixteen patients had an aortocoronary bypass during the time between the tests. The highest coefficient of correlation was between differences in heart rate at 1 mm ST depression and changes in clinical grading (r = 0.78, p = 0.001). Fairly good correlations were found when changes in total exercise time and changes in maximum double product were related to changes in clinical grading. Differences in maximum ST depression and in blood pressures at 1 mm ST depression did not correlate with clinical improvement; neither did changes in estimates of quality of life.

Serum N-terminal pro-atrial natriuretic factor 1-98 before and during thyroxine replacement therapy in severe hypothyroidism.

Decreased plasma concentrations of atrial natriuretic factor (ANF) and of its N-terminal prohormones have been demonstrated in severely hypothyroid patients compared with control subjects, and shown to normalize with thyroxine (T4) replacement therapy. Whether this depends on thyroid hormone deficiency exclusively or is secondary to hemodynamic changes that result from it remains a matter of debate. In a recent investigation dose-related increases in both ANF and N-terminal prohormones of ANF by T4 replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid hormones may enhance synthesis rather than release of atrial peptide hormones. The aim of the present study was to confirm this assumption in hypothyroid patients with normal cardiac performance. Serum N-terminal amino acids 1-98 (ie, pro-ANF 1-98) of pro-ANF was determined in 11 severely hypothyroid patients without pericardial effusion and with normal cardiac left ventricular function. Mean pro-ANF 1-98 concentration before T4 replacement therapy remained unchanged after 10 days on T4 (p = .12). After 2 months of therapy, mean pro-ANF 1-98 was significantly increased compared with pretreatment values (p < .003). A significant correlation to the increase in free T4 (r = 0.48, p < .01) but not to the decrease in thyrotropin (TSH) (r = -0.32, p = .09) was found. The present results indicate that thyroid hormones directly increase pro-ANF 1-98 independently of cardiac hemodynamics in the hypothyroid state.

Incidence of hypertrophic cardiomyopathy in hypothyroidism.

In 13 consecutive severely hypothyroid patients no sign of endocrine cardiomyopathy in the form of asymmetric septal hypertrophy (ASH) could be disclosed by M-mode and two-dimensional (2D) echocardiography on examination prior to thyroxine replacement therapy. In previous investigations ASH was demonstrated to be almost invariably present in untreated hypothyroidism irrespective of thyrotropin levels. Consequently application of positive inotropic and afterload reducing agents that may invoke deleterious effects in ASH has been considered hazardous in hypothyroidism even when indicated by concurrent other heart disease. Determination of exact confidence limits reveals that the proportional incidence of hypothyroid hypertrophic cardiomyopathy could not exceed 24.7% with 95% probability. We conclude that ASH is not necessarily inherent in hypothyroidism.

Silent myocardial ischemia in hypothyroidism.

In some patients with severe hypothyroidism thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even disappears. The reason for this paradox is unknown. It has been attributed either to reversible endocrine cardiomyopathy in the form of asymmetric septal hypertrophy (ASH) or reversible anatomical narrowing of the coronary arteries. The results of a recent investigation, in which myocardial performance was surveyed by radionuclide ventriculography throughout early thyroxine replacement therapy in severe hypothyroidism, were compatible with the presence of reversible coronary dysfunction rather than of ASH. The aim of the present investigation was to confirm these findings. In six severely hypothyroid patients, without echocardiographic evidence of ASH or evidence of concomitant coronary artery disease (CAD), exercise and redistribution tomographic myocardial thallium-201 imaging (SPECT) was performed before thyroxine replacement therapy and repeated after 10 days and again after 2 months during therapy. In four patients substantial regional perfusion defects were demonstrated after exercise that were normalized at rest both before, and in one subject also after 10 days, on thyroxine. With restoration of euthyroidism, exercise and redistribution SPECT were normal in every patient. Determination of exact confidence limits reveals that the proportional incidence of myocardial perfusion defects in hypothyroidism, indicating myocardial ischemia, will at least be 22% with 95% probability. Despite the relatively low specificity of SPECT it seems pertinent to conclude that impaired myocardial perfusion as assessed by SPECT probably is due to reversible coronary dysfunction inherent in the hypothyroid state, and that this is not an infrequent manifestation of severe hypothyroidism.

A haemodynamic study of the effects of combined slow-calcium channel blockade (nisoldipine) and beta-blockade (metoprolol) in coronary heart disease.

The interaction of a new slow-calcium blocker (nisoldipine) and the beta-blocker metoprolol was evaluated in 16 patients with stable angina. Haemodynamic parameters were determined in a control rest and exercise period. Patients were then randomised equally to nisoldipine (4-8 micrograms/kg) or metoprolol (10 mg) and the haemodynamics of monotherapy assessed; finally the second drug was administered and the effects of combination determined. At rest nisoldipine reduced systemic blood pressure and vascular resistance (P less than 0.01); heart rate, cardiac and stroke volume indices increased (P less than 0.01) at an unchanged pulmonary artery occluded pressure. Metoprolol alone reduced heart rate (P less than 0.05) and increased the pulmonary artery occluded pressure (P less than 0.05). Combination therapy reduced systemic blood pressure and vascular resistance (P less than 0.01); cardiac index and pulmonary artery occluded pressure increased (P less than 0.01) at an unchanged heart rate. The effect of combination was influenced by the order of administration; an improvement in cardiac performance was particularly evident when nisoldipine was added to metoprolol. The interaction during dynamic exercise was similar to that at rest. Thus these data indicated the haemodynamic safety of concurrent nisoldipine/metoprolol therapy; the addition of nisoldipine to metoprolol appeared to offset in part the cardiodepressant properties of beta-blockade.

Serum ionized calcium--a predictor of therapeutic response to slow calcium channel blockade in essential hypertension.

In 20 patients with mild to moderate essential hypertension, serum ionized calcium was determined before and after four weeks of treatment with 240 mg verapamil sustained release bid. Pretreatment systolic blood pressure was inversely correlated to serum ionized calcium (r = -0.44, p = 0.05). Mean blood pressure was significantly (p less than 0.001) reduced (from 161/100 to 145/88 mm Hg), but mean serum ionized calcium did not change during treatment (from 1.23 to 1.24 mmol/L). A significant inverse correlation (r = -0.56, p = 0.01) was found between pretreatment serum ionized calcium and reduction in systolic blood pressure during verapamil treatment. Thus serum ionized calcium in untreated essential hypertensive patients may predict the blood pressure response to the slow calcium channel blocker verapamil.

No metabolic side effects of long-term treatment with verapamil in hypertension.

In a prospective, open study 45 patients (mean age fifty-three years) with essential hypertension were treated with verapamil for four to eight years (mean 5.3 years). Blood pressure was satisfactorily controlled (from 160/104 to 145/91) and the side effects were infrequent, mild, and often transient. Verapamil did not exert any unfavorable metabolic or hematologic effects over the years. HDL-cholesterol was moderately increased (mean 24%) and the other plasma lipids were unaffected. These data suggest that the calcium channel blocker verapamil is a metabolically safe drug to use as monotherapy in essential hypertension.

Depressor effects of ionized calcium infusion in essential hypertension.

The circulatory effects of an acute increase in serum ionized calcium were assessed in 27 patients with mild to moderate hypertension. Following a control period of fifteen minutes with confirmed circulatory variables, 1,375 mg calcium gluconate was infused over three minutes. Systemic mean arterial blood pressure and heart rate were recorded before, at one-minute intervals during, and for five minutes following the infusion. There was a brief increase of serum ionized calcium concentration (from 1.28 +/- 0.06 mmol/liter to 1.42 +/- 0.07 mmol/liter; p less than 0.001) maximum by one minute after infusion with return toward control by a further four minutes. This was accompanied by a significantly decreased mean arterial blood pressure (from 117 +/- 8 mmHg to 110 +/- 9 mmHg at three minutes; p less than 0.05) and heart rate (from 70 +/- 11 min-1 to 63 +/- 10 min-1 at three minutes; p less than 0.01). There was a significant correlation between the change in ionized calcium and that of the systemic arterial blood pressure (r = 0.68; p less than 0.01). No major side effects were recorded. The blood pressure reduction may theoretically be related to increased membrane stabilization of vascular smooth muscle cells, the acute increase in extracellular ionized calcium impairing calcium ions influx.

Circulatory effects of intravenous and oral atenolol in acute myocardial infarction.

The hemodynamic dose-response effects of intravenous (0.05 and 0.10 mg/kg) and oral (50 and 100 mg) atenolol were compared in a randomized between-group study of 24 men within seventeen hours of an acute uncomplicated myocardial infarction; 6 subjects were evaluated in each of the four groups. Hemodynamic variables were determined over a one-hour control period, following which the randomized dose of atenolol was administered and measurements repeated at 15 (intravenous therapy only), 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The peak hemodynamic effect was similar and independent of either the dosage or route of administration. In all groups atenolol reduced heart rate and cardiac and stroke volume indices. The pulmonary artery occluded pressure and systemic vascular resistance index were transiently increased. Mean arterial pressure was significantly reduced only in the oral group with the highest pretreatment pressure. Maximum changes developed between fifteen and thirty minutes after intravenous dosing and between two and three hours after oral dosing. However, substantial reductions in cardiac index (-0.6 L/min/m2; p less than 0.05) were already achieved at sixty minutes following oral dosing. The duration of pharmacodynamic activity was for two to three hours following intravenous and for the study duration (four to six hours) after oral dosing. These data confirm the hemodynamic safety of atenolol after acute myocardial infarction.

Oral verapamil and calcium infusion in patients with sick sinus syndrome.

Electrophysiologic and circulatory effects of a single oral dose of verapamil (120 mg) were evaluated in 8 patients with symptomatic sick sinus syndrome. Ninety min. after verapamil, calcium gluconate (1375 mg) was infused in an attempt to reverse the depressor actions of the drug. Verapamil significantly increased sinus node recovery time (P less than 0.05) and atrioventricular conduction time (P less than 0.01), and decreased both systolic (P less than 0.01) and diastolic blood pressure (P less than 0.05) and spontaneous heart rate (P less than 0.01). Intravenous calcium significantly reversed blood pressure reduction (P less than 0.001) and further lowered heart rate (P less than 0.05) without affecting sinus node recovery time and atrioventricular conduction significantly. There was no significant correlation between plasma verapamil concentrations and any of the cardiovascular parameters. These data confirm that verapamil is principly contraindicated in patients with sinus node dysfunction and demonstrate that the actual calcium dose, although partly reversing blood pressure reduction, cannot reverse the depressant action of the drug on the sinus and atrioventricular node in such patients.

Can blood pressure reduction induced by slow calcium channel blockade (verapamil) be reversed by calcium infusion?

The pressor effects of a single infusion of calcium gluconate (1375 mg) were measured in 20 patients, aged 31-63 years, with mild and moderate essential hypertension, being on long-term treatment with the slow calcium channel blocker verapamil. The calcium load induced a significant (P less than 0.001) increase in mean serum ionized calcium (from 1.24 +/- 0.01 to 1.40 +/- 0.2 mmol/l). This did not alter mean blood pressure or mean heart rate, although the individual patients responded differently to the mild hypercalcaemia; a significant fall in blood pressure being observed in a few patients. These results demonstrate the unpredictable effects of an increase in extracellular calcium on vascular smooth muscle cells and suggest that an intravenous bolus of 1375 mg calcium gluconate is not effective in counteracting the hypotensive action of verapamil.

Amlodipine versus slow release metoprolol in the treatment of stable exertional angina pectoris (AMSA).

OBJECTIVES: To compare the effects of amlodipine and slow release metoprolol on subjective symptoms and signs of ischaemia during bicycle ergometric exercise tests in patients with stable angina pectoris. DESIGN: A randomized double-blind comparison of the two drugs in patients with documented coronary disease required to have at least three attacks of angina per week and to perform a symptom-limited exercise test with significant signs of ischaemia in the ECG. RESULTS: Out of 127 patients, 117 completed the study. Both amlodipine and metoprolol significantly increased total exercise time, total workload, time to onset of angina and time to 1 mm ST-depression with no significant differences between the drugs. Amlodipine was significantly more efficient than metoprolol in reducing ST-depression at maximum workload. Diary data revealed no differences in patients' self-rating of drug effects. CONCLUSIONS: Judged by suppression of subjective symptoms and performance on exercise tolerance tests amlodipine represents a useful alternative to metoprolol as monotherapy in stable angina pectoris.

Vectorcardiography in the diagnosis of postoperative myocardial infarction.

Fifty-three consecutive patients, mean age 63 years, undergoing either peripheral vascular reconstructive surgery (n = 40) or lobectomy for bronchial carcinoma (n = 13) were examined pre- and postoperatively with conventional electrocardiogram (ECG), vectorcardiogram (VCG) and estimation of serum levels of aspartate aminotransferase, alanine aminotransferase, total lactic dehydrogenase and the heat-stable fraction of lactic dehydrogenase for the diagnosis of per/postoperative myocardial infarction (MI). Six patients (11%) developed signs of acute MI. In 2 patients whose ECG showed only unspecific changes, the VCG was decisive for the diagnosis. The serum enzyme values alone were of limited value in the diagnosis of per/postoperative MI.

A new sustained-release formulation of verapamil in the treatment of hypertension.

The study was carried out in 24 patients with mild to moderate essential hypertension to assess the antihypertensive efficiency and tolerability of a new sustained-release formulation of verapamil (tablets containing 240 mg). The trial was conducted as a single-blind crossover study for periods of 4 weeks, preceded by a 2-week placebo period, comparing sustained-release verapamil twice daily with instant-release verapamil (conventional tablets of 80 mg) mg) 160 mg twice daily. Both regimens induced a significant reduction in blood pressure and heart rate, and this effect was (particularly for sustained-release verapamil) significant from the very first day of treatment. Both formulations were well tolerated. The pharmacokinetic data obtained and the even blood pressure reduction achieved demonstrate that this new verapamil formulation has sustained-release characteristics and is sufficient as a twice-daily medication in mild/moderate essential hypertension.