Giacomo Tamburino

Transient myocardial ischemia stimulates atrial natriuretic factor release

Atrial natriuretic factor release during transient myocardial ischemia was investigated in 29 patients with coronary artery disease and symptoms of angina (Canadian Cardiovascular Association classes II-III). Eleven patients (group I) underwent single-vessel percutaneous transluminal coronary angioplasty. Repeat determinations of mean pulmonary artery wedge pressure and blood sampling from pulmonary artery for atrial natriuretic factor measurements were performed at baseline, and at 2, 5, and 15 minutes after percutaneous transluminal coronary angioplasty was begun. Baseline atrial natriuretic factor levels (34.6 +/- 4.5 pg/ml) rose to 56.3 +/- 7.3 pg/ml (p = 0.02) and decreased at 5 minutes (43.7 +/- 5.7 pg/ml, not significant) and 15 minutes (35.3 +/- 4.4 pg/ml, not significant). Changes in atrial natriuretic factor concentrations were significantly correlated with those in mean pulmonary artery wedge pressure (2 minutes: r = 0.69, p = 0.02; 5 minutes: r = 0.90, p less than 0.001). In group II (n = 10) the increase in atrial natriuretic factor after dye load occurred later (baseline: 25.8 +/- 2.1; 60 minutes: 40.6 +/- 2.6 pg/ml; p = 0.005) than that observed in group I after percutaneous transluminal coronary angioplasty. In group III, atrial natriuretic factor during angina rose as early (baseline 11.3 +/- 1.3; 5 minutes: 20 +/- 2.3 pg/ml; p = 0.006) as after percutaneous transluminal coronary angioplasty. Results indicate that transient myocardial ischemia stimulates atrial natriuretic factor release, probably through changes in cardiac function.

Plasma endothelin-1 concentrations during cold exposure in essential acrocyanosis

To assess endothelin-1 (ET-1) response to cold stimulation in essential acrocyanosis (EA), the authors measured ET-1 plasma concentrations in 6 patients with EA (6 women, age range seventeen to thirty-seven years) and in 6 controls (5 women, 1 man, age range twenty-one to thirty-seven years) before and after cold challenge by unilateral hand immersion in water bath at 13°C for five minutes. The contralateral upper limb was considered as control. Blood samples were simultaneously drawn from an antecubital vein in the cooled side and in the contralateral upper limb at baseline, at the end of cooling, and at ten and ninety minutes after cooling was begun. Plasma ET-1 was deter mined by a radioimmunoassay system. Results are mean ±SD. Baseline ET-1 was higher in patients with EA (5.1 ±0.3 pmol/L) than in controls (1.9 ± 0.1 pmol/L, P < 0.001). After hand cooling, ET-1 in the cold-exposed upper limb rose in patients with EA to a peak value of 7.2 ±0.7 pmol/L, which was greater than that observed in healthy subjects (2.7 ±0.4 pmol/L, P < 0.001). The absolute increase in ET-1 plasma concentrations from baseline to peak value was significantly higher in patients with EA than in controls (2.1 ±0.3 vs 0.8 ± 0.2 pmol/L, respectively, P < 0.001). In patients with EA, but not in controls, the rise in ET-1 plasma concentrations was still detected ninety minutes after cooling. The same time course of the plasma ET-1 concentrations was observed in the noncooled upper limb, but the increases in ET-1 at different times after cold stimulus were smaller than in the cold-challenged upper limb in both groups (P < 0.001). In conclusion, the results demonstrate that in patients with EA, baseline plasma levels of ET-1 are enhanced and are further increased by cooling until ninety minutes after cold challenge. This rise in plasma ET-1 could contribute to potentiating and prolonging cold-induced vasoconstric tion/vasospasm and/or could be a marker for endothelial damage in EA.

Multicenter, double-blind clinical trial with different doses of pinacidil in patients with mild-to-moderate essential hypertension☆

Abstract The antihypertensive efficacy and therapeutic safety of pinacidil, 12.5 or 25 mg twice daily (BID), were assessed in a multicenter, double-blind, crossover trial. Seventy-seven patients (mean age, 47.3 years) with mild-to-moderate essential hypertension were enrolled in the study and randomly assigned to one of the following schedules: sequence A: pinacidil 12.5 mg BID for 3 weeks; 1-week washout period (two placebo capsules per day); pinacidil 25 mg BID for 3 weeks. Sequence B: pinacidil 25 mg BID for 3 weeks; 1-week washout (two placebo capsules per day); pinacidil 12.5 mg BID for 3 weeks. Both drug doses (25 or 50 mg/d) were equally effective, producing a similar and significant reduction in systolic and diastolic blood pressures in the sitting and standing positions. Systolic blood pressure was reduced by approximately 7% to 8% from baseline in both sequences A and B. Diastolic blood pressure, measured in both positions, was reduced by 8% to 9% from baseline. Heart rate did not appear to be influenced by either dose. Analysis of variance showed no significant differences between the sequences; the only highly significant difference was between the times ( P

COMPARISON OF KETANSERIN AND ENALAPRIL IN THE TREATMENT OF MILD-TO-MODERATE ESSENTIAL HYPERTENSION

SummaryIn a double-blind 3-month study in mild-to-moderate essential hypertensive patients over 50 years of age, ketanserin, a selective S2-serotoninergic antagonist with additional alpha1-adrenergic blocking properties, has been compared with enalapril, an angiotensin-converting enzyme inhibitor. Supine and upright blood pressures and heart rates were recorded for placebo and during active treatment (-4,-2, 0, 2, 4, 6, 8, 10, and 12 weeks). Metabolic profile (plasma glucose, creatinine, sodium, potassium, total and HDL-cholesterol, triglycerides, uric acid) was monitored during treatment with placebo and at the end of the study. Mean blood pressure was equally and significantly (p<0.001) lowered by both drugs from 2 weeks of treatment, whereas no changes occurred in mean heart rate or in biochemical variables. Dizziness was observed in three patients on ketanserin and in one patient on enalapril, whereas headache occurred in only one patient on enalapril. These data indicate that ketanserin is as effective and well tolerated as enalapril in hypertensive patients over 50 years of age.

Baseline and post-atrial pacing release of atrial natriuretic factor in mitral stenosis

To investigate the release of atrial natriuretic factor (ANF) in mitral stenosis and the influence of the increase on the frequency of atrial contraction or atrial distention on ANF secretion, we studied 10 patients with symptoms of congestive heart failure (New York Heart Association classes II and III) in sinus rhythm, who were undergoing cardiac catheterization as part of an evaluation workup for mitral stenosis. Echocardiographic tracings, repeat determinations of mean pulmonary artery wedge pressure (MPAWP) and mean right atrial pressure, and blood sampling from the pulmonary artery for measurements of ANF were performed at baseline, during atrial pacing (pacing rate of 125 beats/min for 5 minutes), and 5 minutes after the pacing protocol was completed. Baseline ANF levels were closely related to right atrial pressure (r = 0.89; p less than 0.001) and increased markedly after atrial pacing from 205.6 +/- 39.8 (SEM) to 343.9 +/- 57.9 (SEM) pg/ml. A similar pacing-induced increase was shown for MPAWP and left atrial size. Our data indicate that pacing-induced increases in atrial distention and intracavitary pressure further stimulate release of ANF. However, an independent effect of frequency of atrial pacing on plasma ANF in humans could not be identified.

Muzolimine in the Treatment of Arterial Hypertension in the Elderly

Thiazide diuretics are often used in the treatment of arterial hypertension, although a number of side-effects, such as hypokalaemia, hyper-glycaemia and hyperuricaemia, caused by its prolonged administration, may diminish the benefits of its hypotensive effect (1). Loop diuretics, on the other hand, have not so far been recommended in this indication because of either its sharp and short-term activity or its kaliuretic effect. Muzolimine, a new pyrazolinone derivative loop diuretic with high-ceiling activity and prolonged action (2), was shown in animal studies to cause a kaliuresis lower than that by Furosemide (2). Taking into account these features, the present open trial was designed to investigate the antihypertensive effect of a single oral dose (30 mg once a day) of Muzolimine in a group of overweight, elderly hypertensive patients who are more likely to develop metabolic side-effects on diuretic therapy.