Alpha-Tricalcium phosphate-gelatin composite cements.

This study investigates gelatin influence on calcium phosphate cement (CPC) setting properties. Cements of different compositions were prepared using |Alpha -tricalcium phosphate (|Alpha -TCP) enriched with a small amount of dicalcium phosphate dihydrate (DCPD), and different gelatin amounts up to 20 wt%. The cements, prepared with a liquid/powder ratio of 0.3 ml/g, were soaked in simulated body fluid (SBF) for different times inverted exclamation markU21 days. The setting reaction of the control cement prepared without gelatin occurred in 7 days, whereas the transformation of the cements at high gelatin content into apatite was almost complete in 2-day aging in SBF. Gelatin presence reduced the total porosity of the cements, and significantly modified their microstructure. The fractured surface of the aged control cement was covered with entangled plate-like apatite crystals, whereas the gelatin cements displayed more compact surfaces, most likely due to the inhibiting effect of gelatin on apatite crystal growth. The microstructural modifications were in agreement with the mprovement of the mechanical properties in the aged cements, the compressive strength of which increased linearly as a function of gelatin content, from 2.0 inverted exclamation markA 0.8 to 14 inverted exclamation markA 1 MPa.

Comparative hemodynamic effects of intravenous digoxin and enoximone in severe chronic heart failure.

In order to compare the acute hemodynamic effects of digoxin (0.01 mg/kg) and enoximone (1 mg/kg), a phosphodiesterase inhibitor inotropic agent, in severe chronic congestive heart failure, 8 patients (male, mean age 56.7 years, sinus rhythm) were investigated with a randomized cross-over study. Peak effect of enoximone (30 min) in comparison to that of digoxin (90 min) resulted in a similar reduction of left-ventricular filling pressure (-27 vs. -28%) and mean pulmonary artery pressure (-23 vs. -24%). Pulmonary (-39 vs. -16%; p < 0.01) and systemic vascular resistance (-27 vs. -4%; p < 0.001) were significantly lowered by enoximone. Cardiac index (+30 vs. +6%; p < 0.001) and heart rate (+11 vs. -3%; p < 0.05) were increased significantly more by enoximone than by digoxin. Since enoximone resulted in an enhancement of cardiac performance greater than that produced by digoxin, enoximone could be a useful and powerful substitute for digoxin in the acute therapy of severe chronic congestive heart failure with sinus rhythm.

A double-blind comparison of bisoprolol and captopril for treatment of essential hypertension in the elderly.

The aim of the study was to compare the antihypertensive efficacy and safety of a new beta blocker with high beta 1 selectivity, bisoprolol, with captopril in 28 elderly patients, aged over 65 years, with mild-to-moderate essential hypertension (WHO classes I and II). After a placebo run-in period of 4 weeks, the patients were randomly allocated to receive bisoprolol (5 mg od) or captopril (25 mg bid) (double-dummy technique) for 6 weeks, according to a crossover double-blind design, with a 4-week washout period between the two active treatments. The doses were doubled after 2 weeks if the supine blood pressure was greater than 160/95 mmHg. In basal conditions and after 2, 4, and 6 weeks of each treatment, the blood pressure and heart rate were assessed both in the supine and erect positions. At the same time, the side effects and quality of life were investigated by a checklist and a self-assessment questionnaire. Standard laboratory tests and a resting ECG tracing were performed before and after each active treatment. The data from 24 patients (4 dropouts) showed a significant antihypertensive effect of both treatments (p less than 0.01) with a reduction of diastolic blood pressure to values less than or equal to 95 mmHg in 75% (18/24) of the patients treated with bisoprolol and in 83.3% (20/24) of those treated with captopril, without significant differences between the two drugs. Bisoprolol also produces a marked but symptom-free reduction of heart rate compared with captopril (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Combination of positive inotropic and vasodilating substances in congestive heart failure.

Therapy combining vasodilators and inotropic agents is considered to be one of the most powerful means of improving cardiac function in patients with congestive heart failure (CHF). The vasodilators enhance the effectiveness of inotropic agents by providing a reduction in preload and/or afterload. Inotropic drugs with different mechanisms of action, such as digitalis glycosides, ephedrine, dopamine, dobutamine, ibopamine, terbutaline, salbutamol, pirbuterol, prenalterol, amrinone, and milrinone, have been tested in combination with vasodilators with a predominant effect on preload (nitrates, molsidomine), with a predominant effect on afterload (hydralazine, nifedipine), or with a balanced action on both arterial and venous beds (nitroprusside, prazosin, captopril), showing positive results. The problem of the combination of digitalis glycosides and vasodilators with different sites of action has been considered by our group. In 42 patients with CHF, digoxin (DIG, 0.01 mg/kg intravenously) was tested in combination with molsidomine (MLS, 4 mg sublingually) (12 patients), a nitrate-like agent with a predominant vasodilating action on the capacitance vessels, nifedipine (NFP, 10 mg sublingually) (22 patients), a Ca2+ antagonist drug with a predominant action on the resistance vessels, and captopril (CPT, 25 mg orally) (8 patients), an ACE inhibitor with a balanced effect on both preload and afterload. The combination DIG plus MLS caused a reduction in left ventricular filling pressure (LVFP) greater than that achieved with either agent alone. The hemodynamic improvement was obtained without side effects, in spite of the striking fall in preload. We stress that this investigation was performed on patients with CHF following acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined digoxin-molsidomine therapy in congestive heart failure following acute myocardial infarction.

The acute hemodynamic effects of combining administration of digoxin (DIG)(0.01 mg/kg intravenously) with molsidomine (MLS)(4 mg sublingually) were compared with those of DIG and MLS considered alone in 12 patients with congestive heart failure following acute myocardial infarction. The patients were classified into two subgroups, A (cardiac index [CI] less than or equal to 2.2 L/min/m2 and B (CI greater than 2.2 L/min/m2), to verify differences between the responses to the three drug regimens. MLS significantly reduced systolic blood pressure from 121.2 +/- 12.3 (mean +/- SD) to 111.7 +/- 10.9 mm Hg (p less than 0.01) after 60 min, mean right atrial pressure (RAP) from 6.2 +/- 3.6 to 2.4 +/- 2.1 mm Hg (p less than 0.0001), mean pulmonary arterial pressure (PAP), left ventricular filling pressure (LVFP) from 20.6 +/- 2.1 to 12.2 +/- 2.8 mm Hg (p less than 0.0001), and pulmonary vascular resistance (PVR). Left ventricular stroke work index (LVSWI) significantly increased after 60 min. DIG induced a significant reduction in heart rate, RAP, PAP, and LVFP from 20.1 +/- 2 to 14.3 +/- 2.7 mm Hg (p less than 0.0001) after 90 min. Stroke volume index (SVI) increased from 24.7 +/- 4.2 to 27.7 +/- 3.1 ml/beat/m2 (p less than 0.001) and LVSWI from 25.9 +/- 7.2 to 31.9 +/- 5.4 g X m/m2 (p less than 0.0001). The combination of DIG and MLS produced a reduction in RAP, PAP, and LVFP greater than that achieved with either agent alone, with a further shift of the ventricular function curve to the left, thereby leading to an improvement in cardiac performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of propafenone and disopyramide for treatment of chronic ventricular arrhythmias: placebo-controlled, double-blind, randomized crossover study.

In a double blind, placebo-controlled study, the efficacy of propafenone, a new antiarrhythmic drug was compared to that of disopyramide. Sixteen patients with frequent and complex premature ventricular contractions (PVCs) were studied by serial 24-hour ambulatory monitoring, while they were receiving propafenone, 300 mg, and disopyramide, 200 mg, both every 8 hours. A reduction in the mean frequency of PVCs per hour, in comparison to the placebo period, from 574 +/- 535 to 100 +/- 130, was observed after propafenone (p less than 0.005) and from 629 +/- 455 to 231 +/- 280 after disopyramide (p less than 0.008). A greater than 70% reduction in PVCs in comparison to placebo was observed in 11 of 14 after propafenone and 9 of 15 after disopyramide (NS). A greater than or equal to 90% reduction in PVCs was observed in 9 of 16 with propafenone and in 4 of 15 with disopyramide (p less than 0.05). The suppression of complex PVCs (repetitive, polymorphic, or more than 5/min with bigeminism) was observed in 11 of 14 after propafenone and in 9 of 14 after disopyramide. The abolition of nonsustained ventricular tachycardia was observed in 6 of 6 and 3 of 5, respectively, after propafenone and disopyramide (p less than 0.05). A lower incidence of side effects, 4 of 16 vs 8 of 16, was observed during propafenone than during disopyramide treatment. We conclude that propafenone, in a dose of 900 mg daily, is more effective than disopyramide, in a dose of 600 mg daily, in the treatment of frequent and complex PVCs and nonsustained ventricular tachycardias. Propafenone also showed a lower incidence of side effects.

Hemodynamic effects of molsidomine in patients with heart failure following acute myocardial infarction.

The short-term hemodynamic effects of molsidomine (4 mg sublingually) were evaluated in 13 patients with congestive heart failure following acute myocardial infarction. Right heart catheterization was performed by means of a Swan-Ganz thermodilution catheter. Hemodynamic measurements were made 30, 60, 120, and 180 minutes after the administration of the drug. Molsidomine significantly reduced systolic blood pressure from 121.5 +/- 3.3 (mean +/- SEM) to 111.1 +/- 2.9 mm Hg (p less than 0.001) after 60 minutes, mean right atrial pressure from 6.1 +/- 1 to 2.6 +/- 0.6 mm Hg (p less than 0.0001), mean pulmonary arterial pressure from 29.8 +/- 1.9 to 20.1 +/- 1.3 mm Hg (p less than 0.0001), and left ventricular filling pressure from 20.3 +/- 0.6 to 12.2 +/- 0.7 mm Hg (p less than 0.0001). No significant change occurred in heart rate, diastolic and mean blood pressure, cardiac index, stroke volume index, left ventricular stroke work index, systemic vascular resistance, and pulmonary vascular resistance. No side effects were seen after the administration of molsidomine.

Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction.

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 +/- 5 to 107 +/- 3 mm Hg: mean +/- SEM; P less than 0.002) and diastolic blood pressure (from 85 +/- 3 to 75 +/- 2 mm Hg; P less than 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 +/- 2 to 27 +/- 2 mm Hg (P less than 0.005). The left ventricular filling pressure decreased from 24 +/- 1 to 19 +/- 1 mm Hg (P less than 0.0001). A significant increase in cardiac index (from 2.33 +/- 0.13 to 2.69 +/- 0.15 l/min per m2; P less than 0.001) and in stroke volume index (from 24 +/- 2 to 28 +/- 2 ml/beats per m2; P less than 0.005) was registered. Systemic vascular resistance fell from 1742 +/- 145 to 1308 +/- 85 dynes/sec per cm-5 (P less than 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 +/- 1.6 to 5.1 +/- 1.2 mm Hg; P less than 0.0001), in mean pulmonary arterial pressure (from 32 +/- 1 to 23 +/- 1 mm Hg; P less than 0.00001) and in left ventricular filling pressure (from 23 +/- 1 to 16 +/- 1 mm Hg; P less than 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.

[Dynamic electrocardiography evaluation of the effectiveness of prajmalium bitartrate, disopyramide and procainamide in patients with stabilized ventricular extrasystole]. / Valutazione con elettrocardiografia dinamica della efficacia di prajmalium bitartrato, disopiramide e procainamide in pazienti con extrasistolia ventricolare stabilizzata.

20 patients with chronic premature ventricular contractions (P.V.Cs) underwent several Holter ECG monitorings to assess clinical effectiveness of three antiarrhythmic drugs: Prajmalium Bitartrate (P.B.) 80 mg/daily, Disopyramide (D.) 600 mg/daily and Procainamide (P.) 2400 mg/daily, to assess the most effective antiarrhythmic medication in every patient. Clinical effectiveness was considered as 80% reduction of P.V.Cs or 50% reduction with suppression of all complex ventricular ectopy (repetitive, polymorph, bigeminy). These results were observed respectively, for 80% reduction, in 5/20 patients for P.B., in 9/20 for D., and in 3/19 for P; and for 50% reduction in 11/20 for P.B., in 18/20 for D., and in 9/19 for P. Comparison in the same patient, using Holter ECG monitoring with a computer assisted analysis, of the effects of different antiarrhythmic medications, is a rational procedure to assess clinical efficacy of new antiarrhythmic drugs and to choose the most effective in each case.