Effect of 5-aminosalicylic acid on myocardial capillary permeability following ischaemia and reperfusion.

Abstract

The aim was to evaluate the effect of 5-aminosalicylic acid on myocardial capillary permeability for small hydrophilic molecules after ischaemia and reperfusion. Open chest anaesthetised dogs were subjected to a 20 min occlusion of the left anterior descending coronary artery followed by 1 h reperfusion. 5-Aminosalicylic acid (bolus injection 12 mg.kg-1, followed by 105 micrograms.kg-1.min-1) (n = 10) or saline (control, n = 12) was given intravenously for 1 h, starting 20 min before ischaemia. The myocardial plasma flow rate, myocardial capillary extraction fraction, and myocardial capillary permeability-surface area (PS) product for 99mTc-DTPA were determined before ischaemia, and 5 and 60 min after the start of reperfusion by employing the single injection residue detection method. Immediately after reperfusion, the reactive hyperaemic plasma flow was measured by the 133Xe washout method. Four dogs (two untreated and two treated with 5-aminosalicylic acid) were eliminated due to ventricular fibrillation at the time of reperfusion. In the remaining animals (10 controls and eight treated) the plasma flow rate, capillary extraction fraction and PS were similar before myocardial ischaemia. After 5 min reperfusion, the plasma flow rate and PS were significantly increased in control animals (p < 0.02 and p < 0.008, respectively), but were unchanged in dogs treated with 5-aminosalicylic acid. In addition, after 5 min reperfusion, PS was significantly higher in the control group than in treated animals (p < 0.005). Microcirculatory variables returned to preocclusive values in both groups by 60 min after reperfusion. 5-Aminosalicylic acid had no significant effect on haemodynamics or on reactive hyperaemic plasma flow. The results suggest that 5-aminosalicylic acid can attenuate the microvascular changes after reversible myocardial ischaemia. The effect is potentially beneficial, and may be mediated by well recognised anti-inflammatory actions of 5-aminosalicylic acid (ie, scavenging of oxygen free radicals and neutrophil inhibition).