Hypocapnia prolongs bradycardia induced by bupivacaine or levobupivacaine in isolated rat hearts

Purpose: Systemic alkalinization is recommended for resuscitation from local anesthetic-induced cardiotoxicity. It has been suggested that inducing hypocapnic alkalosis, prior to exposure to toxic concentrations of local anesthetics, may minimize cardiotoxicity. However, it remains unclear whether inducing severe hypocapnic alkalosis after administration of local anesthetics will minimize the duration of bradycardia. We used isolated rat hearts to investigate the effects of hypocapnic alkalosis on heart rate (HR) recovery from bupivacaine or levobupivacaine-induced bradycardia. Methods: We measured the time required for the HR in 24 isolated rat hearts, respectively, to attain 90% of the baseline HR (recovery time) following bradycardia induced by 1 μg·mL^-1 and 10 μg·mL^-1 concentrations of either bupivacaine or levobupivacaine. Normal pH perfusate (bupivacaine or levobupivacaine with normal pH washout groups) or severe hypocapnic alkalosis perfusate (bupivacaine or levobupivacaine with hypocapnic alkalosis washout groups) were reperfused after exposure to the local anesthetics. Results: Severe hypocapnic alkalosis prolonged the recovery time from 273 ± 122 sec, at the 1 μg·mL^-1 bupivacaine concentration with normal pH washout, to 1203 ± 540 sec, in the bupivacaine with hypocapnic alkalosis washout (p = 0.029). Severe hypocapnic alkalosis also prolonged the recovery time from 1153 ± 644 sec, at a 10 μg·mL^-1 bupivacaine concentration in the normal pH washout group, to 2065 ± 617 sec, in the bupivacaine with hypocapnic alkalosis washout group (p = 0.032). With levobupivacaine 10 μg·mL^-1 in the normal pH washout group, HR recovery time increased from 863 ± 186 sec to 1565 ± 567 sec, compared to the hypocapnic alkalosis washout group (p = 0.045). Conclusions: Severe hypocapnic alkalosis prolonged the recovery time from bupivacaine or levobupivacaine-induced bradycardia in isolated rat hearts. When bradycardia occurs after intravascular bupivacaine or levobupivacaine administration, maintenance of normocapnia may minimize the duration of bradycardia.