Pseudomonas aeruginosa exotoxin A enhances automaticity and potentiates hypoxic depression of isolated rat hearts.

The potent virulence factor exotoxin A, produced by Pseudomonas aeruginosa, has been reported to suppress the synthesis of the alpha-subunit of cardiac Gi protein and may have general effects upon synthesis of other myocardial proteins. To determine whether such exotoxin A actions influence specific functional properties of the intact heart, characteristics of isolated perfused hearts obtained from rats receiving injections of exotoxin A 48 hr before sacrifice were compared with those of rats receiving no exotoxin A. Exotoxin A treatment increased the spontaneous beating rates and potentiated the suppressive effects of hypoxia upon heart rate, left ventricular systolic pressure, and rates of ventricular contraction and relaxation. On the other hand, exotoxin A treatment did not influence the magnitude or rate of pressure development under control conditions, the positive chronotropic and inotropic responses to isoproterenol, or the negative chronotropic responses to adenosine. Since a specific exotoxin A-induced suppression of myocardial alpha-subunit of the Gi protein should confer hypersensitivity to isoproterenol and reduced sensitivity to adenosine, the absence of alterations in responses to these interventions suggests that exotoxin A's effect was not confined to specific suppression of this protein. However, net effects of exotoxin A exposure included a pronounced increase in excitability of the hearts and enhanced vulnerability to hypoxic insults.