Tienilic acid: a single treatment for hyperuricaemia and hypertension?

Tienilic acid is a drug with established uricosuric and hypotensive properties. We have examined its potential role as a single treatment for hyperuricaemia and hypertension, 2 disorders which are commonly associated. In 17 subjects with gout, blood uric acid levels were reduced by approximately 50%. Eleven of these patients also had hypertension which was improved by tienilic acid. However, a statistically significant effect was observed only with standing diastolic blood pressure. Side effects included acute episodes of gout in 4 patients and transient loin pain and dysuria in 1 patient. The precipitation of gouty arthritis is an acknowledged risk of all potent hypouricaemic drugs. The hazard of urate deposition in the renal tract implicit in the history of loin pain is a more serious complication. Thus, it would appear that tienilic acid is a potentially valuable drug which may have a special role in patients with hyperuricaemia and hypertension. Further study is necessary to determine how it may be best administered without the risk of renal damage.     

Aortic valve insufficiency in arterial hypertension

An improved phonocardiographic method for adequate recording of cardiac murmurs, characterized by medium-high frequency vibrations of low amplitude, is presented. This method utilizes a special band-pass filter and an amplifying stethoscope.

The faint, early, basal diastolic murmur which is present in some patients with arterial hypertension was satisfactorily recorded in nine of ten instances by this method, whereas the murmur was not recorded by the routine phonocardiogram. We believe that this murmur suggests insufficiency of the aortic valve.

On phonocardiography, the diastolic vibrations were low in amplitude and were more readily detected when a frequency band of 150 to 200 c.p.s. was selected. These vibrations immediately followed a second heart sound of increased amplitude and duration and were best visualized at the third left parasternal area. The presence of the murmur did not seem to be related to the level of the systolic, diastolic or pulse pressures at the time of the technical procedure.     

Dose-response relation of intravenous enoximone in congestive cardiac insufficiency

Enoximone (MDL 17043) is a new generation inotropic drug which acts by inhibiting phosphodiesterase and is endowed with both inotropic and vasodilator properties. The purpose of this study, which involved 23 patients aged from 18 to 75 years in NYHA class III or IV and with evidence of severe haemodynamic disturbances (cardiac index below 2.5 1/mn/m2, pulmonary wedge pressure above 15 mmHg), was to evaluate the acute haemodynamic responses to doses of enoximone that ranged from 0.25 to 2.50 mg/kg administered by bolus intravenous injection. Heart failure was either of ischaemic origin (6 cases) or idiopathic (10 cases) or due to various causes (7 cases). Group A patients (n = 11) received the drug in low doses (less than or equal to 1 mg/kg) as opposed to group B patients (n = 12) who were given high doses (greater than 1 mg/kg). Results were evaluated from the amplitude and duration of the haemodynamic response at maximum effect time (30 min). The following parameters were measured: cardiac index, pulmonary wedge pressure, systemic vascular resistance, mean arterial pressure and heart rate. Cardiac index and pulmonary wedge pressure were significantly improved in both groups (P less than 0.005): cardiac index +39 p. 100 in group A, +55 p. 100 in group B; pulmonary wedge pressure -36 p. 100 in group A, -48 p. 100 in group B; systemic vascular resistance -46 p. 100 in group B. Heart rate and arterial pressure were not significantly altered. The duration of response was 1 to 3 hours in group A patients and 4 to 8 hours in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-digitalis inotropic agents in the treatment of congestive heart insufficiency

The action mechanisms of the inotropic agents are reviewed: adrenergic stimulants, dopaminergic agents, phosphodiesterase inhibitors direct adenylcyclase stimulants. The hemodynamic effects of these drugs are compared. According with the items proposed by Braunwald e Colucci the inotropic agents are classified. The therapeutic effect is concluded from the published randomized trials placebo. The value of these drugs on the therapy of Congestive Heart Failure is discussed.     

Treatment of hypertension in patients with congestive cardiac failure

Hypertension is a major risk factor for the development of cardiac failure. Patients with severe heart failure and left ventricular ejection fraction <40% are excluded from the majority of hypertension trials. The European Guidelines recommend treatment of hypertension in patients with heart failure and the introduction of blood pressure-lowering drugs that deal with the underlying disease. Several of the drugs may be needed in combination to achieve target blood pressure.     

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital cardiac disease

AIMS: Bosentan is efficacious in idiopathic pulmonary arterial hypertension, and the variants associated with connective tissue disease, but not currently approved for treatment of pulmonary arterial hypertension due to Eisenmenger's syndrome. We sought to evaluate its effect in adults with Eisenmenger's syndrome. METHODS: We administered bosentan on the basis of compassionate use in 23 patients with Eisenmenger's syndrome, aged 37 plus or minus 14 years. Of the patients, 17 had never received specific treatment for pulmonary arterial hypertension, five were transitioned from treprostinil, and one from beraprost to bosentan. We measured functional class, saturation of oxygen, haemoglobin levels and six-minute walk distance at baseline, one, six months and at most recent follow-up. RESULTS: Baseline functional class was IV in three, III in fifteen, and II in five patients. At follow-up, with a mean of 15 plus or minus 10 months, 13 of the 23 patients (57%) had improved by at least one functional class, from a median baseline of III to II (p equal to 0.016), mean saturation of oxygen at rest had increased from 81% to 84% (p equal to 0.001), and levels of haemoglobin had decreased from 178 plus or minus 26 grams per litre to 167 plus or minus 19 grams per litre (p equal to 0.001). Overall, the six-minute walk distance did not change from baseline of 335 metres. The distance walked by those not previously receiving specific therapy, however, improved from 318 plus or minus 129 to 345 plus or minus 123 metres (p equal to 0.03). CONCLUSION: Treatment of adults with Eisenmenger's syndrome using bosentan significantly improved functional class, saturation of oxygen at rest, and decreased levels of haemoglobin. Treatment with bosentan was associated with improvement in six-minute walk distance in those not previously receiving specific therapy. In patients already in receipt of specific therapy, transition to bosentan resulted in no clinical deterioration.     

Prazosin in the treatment of chronic cardiac insufficiency

Vasodilators may be required when signs of cardiac failure persist, despite adequate digitalo-diuretic therapy. Prazosin is a post-synaptic alpha-blocker which acts on both cardiac preload and afterload. For this reason, it has been widely used in the treatment of cardiac failure. We used prazosin in an open uncontrolled trial in 17 patients with an average of 59 years, in whom Stage III or IV cardiac failure persisted despite digitalis and diuretic therapy. Haemodynamic data obtained with a Swan Ganz catheter was used to judge the effectiveness of an initial dose of prazosin and long-term results were assessed by repeat studies after 6 and 10 weeks of continuous therapy. After the first, we observed a marked fall in pulmonary capillary (15.5% 7.4 vs 22.9% 8.8 mm Hg, p less than 0.01) and mean pulmonary artery pressures (23.8% 9.2 vs 34.2 +/- 10.6 mm Hg, p less than 0.001). Systemic vascular resistances were also significantly reduced (1 370 +/- 406 vs 1 983 +/- 464 dynes.s.cm-5, p less than 0.001). There was a moderate fall in mean systemic blood pressure (80.8% 10.6 vs 95.6 +/- 129 mm Hg, p less than 0.001). Cardiac index increased significantly (2.7 +/- 0.68 vs 2.13% 0.56 1/min/m2, p less than 0.01). The heart rate was constant. The maintenance dose was 5 mg three times daily in 9 cases, and 10 mg three times daily in the other 8 cases. The medium term results were assessed in 14 patients as 2 patients died and 1 stopped treatment for undetermined reasons. The symptomatic improvement was marked (class 2.5 +/- 0.76 vs 3.64 +/- 0.49, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Paradoxes of the treatment of cardiac insufficiency

The explosion of new techniques and concepts arising from progress in molecular and cellular biology transformed our way of thinking about cardiac failure of mechanical origin in 1990. Cardiac failure indicates the limitations and imperfections of biological adaptation to a change in conditions of cardiac loading. Understanding this process of adaptation, understanding why cardiac hypertrophy of hypertensive origin remains compensated for such a long time, is and should be the basis of treatment. Inotropic therapy is paradoxically, fundamentally deleterious for the myocardial fibres, although, when considering the heart as a whole, reduction in chamber size is beneficial. Vasodilators and diuretics are not an alternative but a complement. Careful analysis of recently published clinical trials invalidates a dogmatic attitude in the debate of inotropic versus vasodilator therapy. Future developments should be based on a rational approach. The treatment of a disease of adaptation would seem to lie in the wide and virgin field of gene therapy or therapies modifying genetic expression or "drug design" based on the know structure of the hypertrophied myocyte.     

Irbesartan in the treatment of arterial hypertension

Irbesartan (Aprovel) belongs into the new group drugs for the cardiovascular system which exert an antagonistic effect at the level of angiotensin II, but experimental pilot studies as well as clinical studies draw also attention to the possible therapeutic potential of AT1 receptor blockers in the treatment of chronic heart failure. Irbesartan has a marked antihypertensive effect as is apparent from a recent clinical study in 139 patients with mild and moderate hypertension--implemented in the Czech Republic. Twelve-week treatment with Irbesartan led to a marked drop of the systolic and diastolic blood pressure (159.2 +/- 14 vs. 137 +/- 13 mmHg/99.2 +/- 7 vs. 85.3 +/- 7 mmHg, p < 0.01). A very favourable therapeutic effect was recorded in this investigation also in 24-hour monitoring of the blood pressure. The use of irbesartan in patients with arterial hypertension has according to other studies also a favourable effect on organ complications of hypertension and diabetes (regression of left ventricular hypertrophy, reduction of albuminuria). Irbesartan may prove due to its favourable effect a suitable alternative in conditions associated with intolerance of ACE-inhibitors in patients with moderate and severe forms of arterial hypertension, in chronic heart failure and in diabetic nephropathy.