Effects of intravenous anesthetics on function and metabolism in the reperfused working rat heart

We investigated the comparative effects of ketamine, flunitrazepam, diazepam and midazolam on function and metabolism in reperfused rat hearts. Seventy-two hearts were rapidly excised and perfused with buffer as a Neely's working model. Whole heart ischemia was induced for 15 min followed by reperfusion for 20 min. Four intravenous anesthetics in 2 different concentrations (10 and 50 times of therapeutic concentrations) were administered during reperfusion. The data were compared to a control group in which intravenous anesthetics were not used. At the end of reperfusion, myocardial metabolites were measured by liquid chromatography. Cardiac outputs in the both groups given lower and higher doses of ketamine and flunitrazepam and in the groups given the higher dose of diazepam and midazolam were significantly lower than that in the control group [at the end of reperfusion: control: 60.4; ketamine: 48.8 (lower) and 14.6 (higher); flunitrazepam: 50.2 (lower) and 50.6 (higher); diazepam: 62.6 (lower) and 42.5 (higher); midazolam: 59.5 (lower) and 51.2 (higher), ml/min]. The levels of ATP in all higher concentration anesthetic groups were significantly lower than those in the control group (control: 23.7, ketamine: 17.8, flunitrazepam: 17.8, diazepam: 17.7, midazolam: 17.7, mumol/g). These results suggest that ketamine and flunitrazepam moderately depress cardiac function more than diazepam and midazolam when they are given during reperfusion.