Treatment of reinfarction after thrombolytic therapy for acute myocardial infarction: an analysis of outcome and treatment choices in the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (gusto I) and assessment of the safety of a new thrombolytic (assent 2) studies.

BACKGROUND: Early reinfarction after thrombolytic therapy is associated with adverse outcomes and increased mortality. Among patients with reinfarction in the 1992 Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and the 1998 Assessment of the Safety of a New Thrombolytic (ASSENT 2) trials, we investigated temporal and regional differences in the use of repeat thrombolysis, revascularization (angioplasty and/or bypass surgery), or conservative measures and the outcomes of each management strategy. METHODS AND RESULTS: Data from the 4% of patients (n=2301) who experienced reinfarction after thrombolytic therapy were studied. Baseline characteristics, 30-day mortality, and incidence of total and hemorrhagic strokes were compared among the 3 treatment groups. The 30-day mortality did not differ between the repeat thrombolysis and revascularization groups (P=0.72), and it was significantly lower among patients treated by these 2 strategies than in those treated conservatively (11% and 11% versus 28%, respectively; P<0.001). Stroke rates did not differ significantly between the 3 treatment strategies (P=0.49). From 1992 to 1998, the percentage of reinfarction patients treated with repeat thrombolysis decreased from 29.3% to 18.5% in US centers and from 51.4% to 41.9% in all other centers (P<0.001). In contrast, use of revascularization procedures increased from 33.5% to 47.9% in US centers and from 8.1% to 23.0% in all other centers (P<0.001). CONCLUSIONS: Repeat thrombolysis and revascularization are associated with significantly lower mortality among reinfarction patients. Randomized trials are necessary to assess the exact risks and benefits of rethrombolysis versus interventional revascularization in this subset of high-risk patients presenting with reinfarction after thrombolytic therapy.

Aerosol deposition in equine lungs following ultrasonic nebulisation versus jet aerosol delivery system.

Therapeutic aerosols pay an increasing role in the treatment of equine respiratory disorders. This route of delivery permits concentration of significant amounts of drugs at the site of action without unwanted high systemic concentration and resultant side effects. The efficiency of such a topical therapy depends on the quantity of inhaled drugs deposited in the lungs and, for some drugs, on the proportion retained in specific parts of the lungs. The objective of this study was to define and to compare quantitative (dose deposited) and qualitative (regional distribution) deposition of an aerosol in the equine lungs, using either a ultrasonic nebuliser (UN) currently used in human medicine or a high pressure jet nebuliser (JN) especially developed for the equine species. This comparison was possible owing to gamma-scintigraphy, a noninvasive technique ideally suited to give information about both total and regional deposition of inhaled drugs in the respiratory tract. The quantitative study did not point out any difference between the 2 systems concerning the activity released from the nebuliser proportionally to the initial loaded dose (mean +/- s.d. 45.95 +/- 4.93% for the UN vs. 46.47 +/- 8.49% for the JN). By contrast, the percentage of the dose released reaching the lungs was significantly lower with the UN compared to the JN (5.09 +/- 0.66% vs. 7.35 +/- 1.96%). The qualitative analysis did not show any significant difference in size of aerosol deposition image between the 2 nebulisers. However peripheral deposition was significantly higher with JN compared to UN. In conclusion, both nebulisers may be used for aerosol therapy in the equine species. The ultrasonic and pneumatic nebulisation achieved drug deposition in the peripheral part of the lungs (i.e. small airways and lung parenchyma).

Deposition in the distal parts of the bovine respiratory tract: assessment of equipment suitable for drug inhalation.

The efficiency of equipment suitable for the inhalation of drugs by calves was assessed in six animals which inhaled radioisotopically labelled particles while suffering from reversible diffuse bronchoconstriction induced experimentally with 5-hydroxytryptamine and while they were breathing normally. Respiratory rates and data from pulmonary function tests and scintiscans were recorded during both investigations. After the first investigation, a mean (se) wash-out period of 9.8 (3.2) days was allowed. Under diffuse bronchoconstriction, the respiratory rate, the oscillatory resistance and the compliance of the respiratory system reached 282.1 (22.0), 161.1 (10.8) and 68.8 (2.7) per cent of their respective baseline values. When the calves were breathing normally these parameters did not change over time. The ratios (Cp/Ct) of the counts of gamma-disintegrations in the peripheral part (Cp) of the lungs and in the total lung area (Ct) were not significantly different when comparing the results from the two investigations. The ratios of Cp/Ct in the left lungs did not differ significantly from those in the right lungs.