Effects of insulin on the reversal of myocardial contractility after bupivacaine-induced cardiac asystole in vitro

Abstract Background: Insulin-glucose treatment effectively reverses severe bupivacaine (BPV)-induced myocardial depression or cardiovascular collapse in in vivo. However, the mechanisms for the recovery are poorly defined. Methods: Using the guinea pig myocardium, cumulative concentration-responses on contractile forces for insulin or insulin combined with 33 mM glucose (insulin/glucose) were measured. After achieving asystole by 500 µM BPV, different concentrations of insulin or insulin/glucose were applied to determine the recovery of stimulated contractile responses and contractions in either recirculating or non-recirculating (washout) condition. Because we did not observe any recovery from asystole with insulin treatment in the recirculating condition, further experiments were performed whether intermittent contractile responses (conduction block) could be reversed by insulin. In the washout condition, after achieving asystole, the muscles were washed with the Tyrode solution containing insulin or insulin/glucose for 60 minutes. After achieving asystole, BPV concentrations in the Tyrode solution in the presence or absence of insulin for 60 minutes were measured. Results: There were similar concentration-dependent decreases in contractility in both the insulin and insulin/glucose groups. Neither insulin nor insulin/glucose restored the stimulated contractile responses from conduction disturbance or asystole induced by BPV in the continued presence of BPV. In the BPV-washout condition, while superfusion with a control (plain Tyrode) solution for 60 minutes after achieving asystole by BPV restored contractility to approximately 60% of the baseline, time-dependent complete recovery was observed in the insulin- and insulin/glucose-treated groups. At each time period from asystole to 60 minutes, the BPV concentrations in the insulin-treated group were slightly lower than those in the control group. Conclusions: Neither insulin nor insulin/glucose treatment does not rescue Na+ channel function to reverse BPV-induced cardiac conduction block or asystole regardless of improved cardiac performance, possibly due to improved myocardial energetics in isolated in vitro animal myocardium model. These findings suggest that treatment with insulin or insulin/glucose is desirable for metabolic energy supply to the myocardium in cases of BPV-induced cardiac collapse. However, considering the importance of decreased BPV concentrations in cardiac tissues, insulin or insulin/glucose may not achieve satisfactory outcomes.