Effects of beta- and alpha-adrenergic agonists, adenosine, and carbachol in heart muscle isolated from malignant hyperthermia susceptible swine.
During malignant hyperthermia crisis, cardiac arrhythmias and increased myocardial oxygen consumption are observed. It was the purpose of the present study to investigate whether or not a greater sensitivity to cardiac alpha- or beta-adrenoceptor stimulation or an impaired adenosine- or m-cholinoceptor-mediated inhibition of beta-adrenergic stimulation contributes to the cardiac symptoms of malignant hyperthermia. The effects of phenylephrine, isoproterenol, adenosine, [-]-N6-phenylisopropyladenosine (PIA), and carbachol on force of contraction were studied in electrically driven trabeculae isolated from the left ventricles of malignant hyperthermia susceptible (MHS) and healthy control pigs. The positive inotropic effects of phenylephrine and of isoproterenol were similar in MHS and control pigs. The EC50 values for the inotropic effect of phenylephrine were 4.1 (2.1-8.3) mumol.l-1 (n = 9) in MHS and 6.3 (3.4-12.9) mumol.l-1 (n = 9) in control swine. The maximal positive inotropic effects at 30 mumol.l-1 phenylephrine also did not differ in both groups (176.7 +/- 14.4% of pre-phenylephrine value in MHS swine, n = 9; 170.3 +/- 15.9% of pre-phenylephrine value in control swine, n = 9). The EC50 values for isoproterenol were 0.16 (0.06-0.39) mumol.l-1 (n = 9) and 0.19 (0.05-0.29) mumol.l-1 (n = 9) in MHS and control swine, respectively. The maximal positive inotropic effects at 1 mumol.l-1 isoproterenol were also similar (213.8 +/- 12.6% of the pre-isoproterenol value in MHS swine, n = 9; 216.4 +/- 36.0% of the pre-isoproterenol value in control swine, n = 9). Also, no difference could be detected in the antiadrenergic effects of adenosine, PIA, or carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)
D000241:Adenosine / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004198:Disease Susceptibility; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013552:Swine
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D010660:Phenylisopropyladenosine; D002217:Carbachol; D000241:Adenosine; D007545:Isoproterenol