Nitrate tolerance in patients with effort angina.

BACKGROUND: In some patients with chronic stable angina the beneficial effects of nitrates may result not only from a reduction in venous return, but also from their action on coronary circulation. In these patients, rate-pressure product at ischemia (RPPI) increases to > 2500 bpm x mmHg after sublingual nitrates (SLN). The relative susceptibility of the venous system and the coronary circulation to the development of nitrate tolerance and the effects of two different drug schedules on the development of tolerance were investigated in patients with these characteristics. METHODS: Five patients were treated with isosorbide-5-mononitrate (IS5MN) 20 bid (8.00 am and 3.00 pm) for 1 week (Group 1) and 5 patients with IS5MN 40 bid (8.00 am and 8.00 pm) for 1 week (Group 2). Tolerance was identified as the decreased effect of SLN; the effects of nitrates were evaluated in relation to: reduction in left ventricle area (delta LVA), which had been measured using equilibrium radionuclide ventriculograms in LAO 45 degrees; this area was considered as an index of the venous return effects; increase in RPPI (delta RPPI), which had been assessed by ergometric test; RPPI was considered an index of coronary flow reserve. Measurements of LVA and RPPI were made in wash-out at the start of the study (delta LVA 1 and delta RPPI 1) and after 1 week of treatment (delta LVA 2 and delta RPPI 2). The mean values of the differences were then evaluated and compared using Student's "t" test. RESULTS AND CONCLUSIONS: In Group 1 patients delta LVA 2 and delta RPPI 2 showed values which were similar to delta LVA 1 and delta RPPI 1 (mean value delta LVA 2 47 vs mean delta LVA 1 48.2 pixels, p = ns; mean value delta RPPI 2 5264 vs mean delta RPPI 1 5536 bpm x mmHg, p = ns). These results suggest that Group 1 patients did not develop tolerance either at the coronary or at the venous level. In Group 2 patients, delta LVA 2 was significantly lower than delta LVA 1 (mean delta LVA 2 18.4 vs mean delta LVA 1 54 pixels, p < 0.01). This finding indicated tolerance to nitrates at the venous level. On the other hand, in all Group 2 patients, values of delta RPPI 2, though lower than delta RPPI 1 (mean delta RPPI 2 3095 vs mean delta RPPI 1 6083 bpm x mmHg, p < 0.01) were still higher than 2500 bpm x mmHg, indicating that the effect of nitrates at the coronary level was preserved. These data suggest that in patients treated with high doses of nitrates, the effect of these drugs at the coronary level is still present when tolerance has already developed at the venous level.

[Myocardial ischemia induced by exercise. Analysis of the recovery phase. Behavior of the rate-pressure normalization product in patients with fixed ischemic threshold and patients with variable ischemic threshold]. / Studio dell'ischemia miocardia indotta dallo sforzo. Analisi della fase di recupero. Comportamento del doppio prodotto di normalizzazione nei pazienti con soglia ischemica variabile e nei pazienti con soglia ischemica fissa.

Traditionally, in patients with exercise-induced myocardial ischemia we analyze the stress-test by studying the behaviour of double product at ischemia. We recognize the presence of a functional component in the reduction of coronary-flow reserve if the double product at ischemia (DPI) varies in 3 stress-tests i.e. more than 20% or more than 3200 mmHg b m'-1. Any analysis that relies exclusively on double product at ischemia is, of necessity, limited to the beginning of the ischemic phenomenon. To better understand the development of the whole event, we also considered the double product calculated when the ischemic electrocardiographic signal regressed (double product of normalization: DPN). More specifically, we set out to determine whether or not double product at ischemia behaviour in patients with variable ischemic threshold (i.e. double product at ischemia variation greater than 3200 mmHg b m'-1) differs from that of patients with fixed ischemic threshold (i.e. double product at ischemia variation less than b m'-1). We performed four multistage bicycle ergometer tests, without drugs, on 19 patients with chronic exertional anginal and exercise-induced ST depression. Patients were tested at the same time of day, within a 10 day period. In the second, third and fourth stress test double product at ischemia was calculated. On the basis of double product at ischemia values in three stress-tests, we distinguished two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Buprenorphine and pentazocine in acute myocardial infarct. Study for a differential use]. / Buprenorfina e pentazocina nell'infarto miocardico acuto. Studio per un impiego differenziato.

Morphine is known as the best analgesic for patients with acute myocardial infarction complicated by heart failure. In patients with uncomplicated acute myocardial infarction, buprenorphine has recently been indicated as an alternative to the widely used pentazocine. In order to verify if the haemodynamic effects of the two drugs differed, a randomized double-blind controlled trial was performed on 20 patients with uncomplicated acute myocardial infarction: 10 patients were treated with i.v. pentazocine 30 mg. and 10 patients with buprenorphine 0.30 mg. (equianalgesic doses). Right atrial, ventricular and pulmonary artery and capillary pressure, cardiac index, total pulmonary and total systemic resistance were measured before testing and 15', 30', 60', 180' and 240' after drug injection. PO2 was measured before drug injection and 30' and 60' later. Data were analyzed using the Wilcoxon test. All patients in each group showed uniform results: pentazocine increased total systemic resistance (mean increase 17%) while buprenorphine lowered it (mean reduction 12%) (P less than 0.05). Pentazocine lowered cardiac index (mean reduction 5.9%) while buprenorphine increased it (mean increase 9.3%) (P less than 0.05). Maximum changes occurred within 60' after the administration of both drugs. The other parameters did not change significantly from basal values. These results suggest that in patients with acute myocardial infarction uncomplicated by heart failure pentazocine and buprenorphine may be used in different haemodynamic situations. In the cases in which a reduction in total systemic resistance is desired, buprenorphine seems most suitable. However, in the presence of vagal reaction for instance, pentazocine may be administered.

[Circadian variations of bilirubin in the blood]. / Variazioni circadiane della bilirubina nel siero

A group of 12 presumably healthy subjects was standardized for 7 days with rest time extending from 22.00 to 05.00. Meals were scheduled at 08.00-08.30, 12.00-12.30, 17.30-18.00 and the amounts consumed were standardized and measured. Each subject was sampled at 4-hour intervals throughout one 24-hour period; this involved the measurement of body temperature, radial pulse, blood pressure. In addition a sample of blood was collected at each time point and subsequently total, direct and indirect bilirubin measurement was made on each sample of serum. All data were analized by macroscopic approach (chronograms) and by mean cosinor. A circadian rhythm is detected in total, direct and indirect serum bilirubin.