Halothane increases epinephrine-threshold for the development of slow reaponses in isolated canine trabeculae

To clarify the mechanisms of ”sensitization” of myocardium to epinephrine, which most frequently occurs during halothane anesthesia, the effects of halothane, prazosin and/or metoprolol on epinephrine-threshold for the development of slow responses (ESTR) were studied in isolated canine trabeculae. The generation of slow responses by the stimulation (10ms, 5mA) was evaluated with extracellular electrograms displayed on oscilloscope. After the confirmation that no slow responses occurred in 26mM K^＋ (high K^＋) Tyrode's solution, the constant infusion of hight K^＋ solutions containing low doses of epinrphrine was started. If slow responses were not observed during 15min of infusion, standarized logarithmically spaced higher doses of epinephrine were infused and progressively larger doses of epinephrine were continued until ETSR was established. In the present study, ETSR was defined as the dose of epinephrine that produced nine or more slow responses within the last 3min during 15min of infusion. ESTR obtained before halothane was 0.54±0.19(×10^<-6>M, n＝7, mean±SE). 1% haolthane did not alter ESTR, while significantly greater doses of epinephrine were needed to produce solw responses at 2 and 4% halothane. Over a clinically appropriate range, β_1blockade with metoprolol significantly and dose-dependently increased ESTR (n＝7), whereas α_1blockade with prazosin had no influence on ESTR (n＝7). The effectes of metoprolol and prazosin obtained when given in combination with 2% halothane were almost the same as those obtained when given alone (n＝7). The results suggest that halothane directly desensitizes rather than sensitizes myocardium to epinephrine. Our results also suggest that postsynaptic β_1 adrenergic receptors mediate most of the sensitivity of mypcardium to epinephrine.