Comparison of the Anti-Anaphylactic Effects of Milrinone, Sulmazole and Theophylline in the Rat

Abstract

Milrinone and sulmazole, two recently developed cardiotonic drugs, inhibit specific fractions of the phosphodiesterase (PDE) isozyme system, while theophylline inhibits the PDE complex aspecifically. Since these drugs were shown to have anti-allergic effects in isolated lungs, we wanted to study milrinone and sulmazole in comparison with theophylline in an in vivo model of anaphylaxis. For this purpose, actively sensitized rats were intravenously challenged with antigen, while tracheal pressure, oesophageal pressure, blood pressure and airflow were continuously monitored. Antigen challenge induced a transient bronchoconstriction and a persistent fall in blood pressure until death occurred. Anaphylactic shock was consistently followed by metabolic acidosis. Milrinone, 3 mg/kg, and theophylline, 40 mg/kg (but not 10 mg/kg), reduced anaphylactic bronchoconstriction. Sulmazole, 40 mg/kg, almost abolished bronchoconstriction. Although milrinone, sulmazole and theophylline, 40 mg/kg, caused a fall in blood pressure prior to antigen challenge, total fall in blood pressure (drug-induced and antigen-induced) was not affected by these drugs. Surprisingly, sulmazole reduced mortality significantly. This phenomenon is probably related to the less severe metabolic acidosis in the presence of sulmazole.

Lactic acid suppresses IgE-mediated mast cell function in vitro and in vivo

“…There are no published measures of pulmonary lactic acid concentrations in asthmatics, but patients have acidic exhaled breath condensate (EBC) and elevated serum LA/lactate levels [28,46]. Similarly, systemic anaphylaxis is linked to metabolic acidosis [47][48][49]. It has not been made clear whether LA/lactate has beneficial or pathological effects on asthma or other mast cellassociated diseases.…”

Use of enoximone in management of anaphylaxis complicated by labetalol use

“…The elevation of smooth muscle cAMP, which occurs with both glucagon and enoximone, can lead to marked vasodilation9 and worsening hypotension; we would suggest that, in the situation described above, it be used with concomitant vasopressor therapy and cardiac output monitoring. There are some limited in vitro as well as animal studies supporting both glucagon and phosphodiesterase inhibitors in the treatment of anaphylaxis, through prevention of mast cell degranulation, bronchodilation and improvement in metabolic acidosis 10 11…”

Methylxanthine Use in Anaphylaxis: What Does the Evidence Tell Us?

“…The antianaphylactic effects of milrinone and sulmazole, two other phosphodiesterase inhibitors, were tested along with theophylline in a rat model. 19 Male Wistar rats were sensitized by an intraperitoneal injection with 2-mL suspension of trinitro-phenyl-haptenized ovalbumin. All drugs were administered intravenously 10 minutes prior to antigen challenge with trinitro-phenyl-haptenized ovalbumin 0.17 mL/kg.…”