Concurrent nitroglycerin administration reduces the efficacy of recombinant tissue-type plasminogen activator in patients with acute anterior wall myocardial infarction.

The aim of this study was to evaluate the impact of concurrent nitroglycerin administration on the thrombolytic efficacy of recombinant tissue-type plasminogen activator (rTPA) in patients with acute anterior myocardial infarction (AMI). Sixty patients (53 men, 7 women; mean age 54 +/- 7 years) with AMI entered the study. Thirty-three patients were randomized to receive rTPA alone (100 mg in 3 hours) (group A) and 27 to receive rTPA plus nitroglycerin (100 micrograms/min) (group B). Time from the onset of chest pain and delivery of rTPA was similar in the two groups of patients. Patients in group A had signs of reperfusion more often than the patients in group B (25 of 33 or 75.7% vs 15 of 27 or 55.5%, p < 0.05). Time to reperfusion was also shorter in group A than in group B (19.6 +/- 9.4 minutes vs 37.8 +/- 5.9 minutes, p < 0.05). Group B had a greater incidence of in-hospital adverse events (9 of 27 vs 5 of 33, p < 0.05) and a higher incidence of coronary artery reocclusion (8 of 15 or 53.3% vs 6 of 25 or 24%, p < 0.05). Peak plasma levels of rTPA antigen were higher in group A compared with group B (1427 +/- 679 vs 512 +/- 312 ng/ml, p < 0.01). In conclusion, concurrent nitroglycerin administration reduces the thrombolytic efficacy of rTPA in patients with AMI probably by lowering the plasma levels of rTPA antigen. The diminished efficacy of rTPA is associated with an adverse outcome.

Effectiveness of prolonged low dose recombinant tissue-type plasminogen activator for refractory unstable angina.

OBJECTIVES: The aim of the present study was to evaluate the effectiveness of prolonged administration of thrombolytic therapy with low doses of recombinant tissue-type plasminogen activator (rt-PA) in patients with refractory unstable angina. BACKGROUND: Intracoronary thrombosis is often the cause of instability in patients with unstable angina. Thrombolytic therapy has been tested in these patients with conflicting results. METHODS: Sixty-seven patients with unstable angina refractory to standard antianginal therapy were randomized to receive, in addition to the common antianginal therapy, either rt-PA (0.03 mg/kg body weight per h for 3 consecutive days) plus heparin (to achieve activated clotting time of 250 to 400 s) (36 patients, group A) or the same dose of heparin plus placebo (31 patients, group B). RESULTS: No major bleeding was observed in either group of patients. One patient in group A and four in group B (2.7% vs. 12.9%, p < 0.01) developed acute myocardial infarction during the hospital period. Eight patients in group B underwent emergency coronary artery surgery or angioplasty because of worsening of symptoms. Group A patients had a significant reduction in the occurrence of chest pain compared with those in group B (95% confidence interval -7.2 to -2.1 episodes/3 days, p < 0.01). Patients in group B had a greater number of episodes of transient myocardial ischemia (237 vs. 103, p < 0.01) and a longer total ischemic burden (114 +/- 23 vs. 45.6 +/- 8.9 min/day, p < 0.01) than group A patients. After a mean follow-up of 14 +/- 6 months, group A patients were more frequently angina free and had a lower incidence of readmission to the hospital than group B patients. CONCLUSIONS: The combination of heparin and protracted administration of rt-PA at low doses is effective in stabilizing and reducing in-hospital adverse events in patients with unstable angina refractory to antianginal therapy.

Isotachophoresis as a useful tool for monitoring neurological complications of acute leukaemia in children.

Cerebrospinal fluid proteins from 42 children with acute lymphoblastic leukaemia were analysed by isotachophoresis. The isotachopherograms of cerebrospinal fluid taken from patients undergoing central nervous system prophylaxis with neurological complications showed an increase of several peaks (albumin, prealbumin, and an unidentified peak), and changes in the globulin zone, compared with those from patients who had completed central nervous system prophylaxis for at least six months. The most striking finding was that these alterations were not associated with any other biochemical changes in the cerebrospinal fluid, as assayed by routine analysis. Isotachophoresis may be useful in the monitoring of therapy in children affected with acute lymphoblastic leukaemia.

Opsonized-zymosan induces a respiratory burst in human blood platelets.

Opsonized-zymosan-stimulated polymorphonuclear cells show a cyanide-insensitive oxygen consumption. We have investigated whether opsonized-zymosan could induce similar metabolic change in human blood platelets. Preparation of intact human blood platelets, obtained by separation through a Ficoll layer (23% w/v) were challenged with opsonized-zymosan. The polymorphonuclear cell contamination was less than 1/10(8) platelets. The opsonized-zymosan-stimulated platelets showed an increase of oxygen consumption. The mean of oxygen burst measured by a polarographic method with a Clark electrode was 11 nmole/10(9) platelets/min (S.E.M. 4; n = 15). The duration of the burst was 2 min. Unstimulated platelets did not show the oxygen burst. The inhibitors of respiratory chain and prostaglandin synthesis completely abolished the oxygen consumption by opsonized-zymosan-stimulated platelets. The simultaneous addition of NADH (1 mM) and opsonized-zymosan induced a burst of oxygen consumption, which occurred after a variable lag phase (10-12 min) from the stimulation, also in the presence of inhibitors. This burst, which lasted about 1 min, amounted to 10 nmole/10(9) platelets/min (S.E.M. 2; n = 15) and it was higher in the presence of NAN3, a catalase inhibitor. Zymosan treated with hydrazine or heated plasma (56 degrees C) did not cause increased oxygen consumption. Inulin or inulin-treated serum did not stimulate platelets. In these experimental conditions some NADH disappeared, as shown by isotachophoresis. The results demonstrated that an immunological stimulus may activate a membrane-linked cyanide-insensitive oxygen metabolizing system.