['Volatile anesthetics are used to provide anesthesia to patients with heart disease under heightened adrenergic drive. The purpose of this study was to test whether volatile anesthetics can inhibit norepinephrine (NE)-induced apoptosis in cardiomyocytes.', 'Rat ventricular cardiomyocytes were exposed to NE (10 microm) alone or in the presence of increasing concentrations of isoflurane and halothane.', 'Isoflurane at 1.6 minimum alveolar concentration (MAC) (4 +/- 2% [SD]) and halothane at 1.2 MAC (3 +/- 2%) abolished the percentage of cardiomyocytes undergoing NE-induced apoptosis (34 +/- 8%), as assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) (P < 0.0001). Lower concentrations of isoflurane and halothane markedly decreased the number of TUNEL-positive cells. Similarly, isoflurane at 1.6 MAC (5 +/- 3%) and halothane at 1.2 MAC (6 +/- 3%) prevented the increase in annexinV-staining cardiomyocytes (38 +/- 7%; P < 0. 0001). These findings were corroborated with a decreased quantity of NE-induced DNA laddering by volatile anesthetics. Halothane at 1.2 MAC abolished the increase in TUNEL-positive cardiomyocytes exposed to the dihydropyridine Ca2+-channel agonist BAY K-8644 (1 microm) (BAY K-8644 + halothane: 3 +/- 2% vsBAY K-8644: 34 +/- 6%; P < 0. 0001) and the Ca2+-ionophore 4-bromo-A23187 (1 microm) (4-bromo-A23187 + halothane: 2 +/- 2% vs4-bromo-A23187: 13 +/- 4%; P = 0.03). NE treatment increased caspase-9 activity to 197 +/- 62% over control myocytes (P < 0.0001), whereas no caspase-8 activation was detectable. This increase in caspase-9 activity was blocked by isoflurane at 1.6 MAC and halothane at 1.2 MAC.'] Is norepinephrine-induced apoptosis inhibited in adult rat ventricular myocytes exposed to volatile anesthetics?