Anesthesia and analgesia
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Anesthesia and analgesia · Mar 2003
Modulation of myofilament Ca2+ densitivity by delta- and kappa-opioid agonists in intact guinea pig hearts.
We investigated whether delta- and kappa-opioid agonists alter myocardial function, intracellular Ca(2+) concentration ([Ca(2+)](i)), and myofilament Ca(2+) sensitivity in intact guinea pig beating hearts and whether these effects are mediated by an opioid receptor. Intact guinea pig hearts were perfused with modified Krebs Ringer solution containing delta- (TAN-67) and kappa- (ICI-199441) opioid agonists in the absence and presence of delta- (BNTX) and kappa- (nor-BNI) opioid antagonists, respectively, while functional variables and [Ca(2+)](i) were recorded. TAN-67 (1 microM) and ICI-199441 (1 microM) decreased heart rate (P < 0.05). TAN-67 (1 microM) and ICI-199441 (1 micro M) decreased available [Ca(2+)](i) without changing developed left ventricular pressure (LVP) (P < 0.05). TAN-67 (1 microM) and ICI-199441 (1 microM) also caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). ICI-199441 (1 microM) produced a steeper slope in the relation curve compared with baseline (P < 0.05). BNTX (1 microM) and nor-BNI (1 microM) blocked the effects of TAN-67 and ICI-199441, respectively. delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available [Ca(2+)](i) in intact isolated guinea pig hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation. ⋯ Our results indicate that delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available intracellular Ca(2+) concentrations in intact isolated guinea pig beating hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation.
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Anesthesia and analgesia · Mar 2003
Carbon monoxide production from sevoflurane breakdown: modeling of exposures under clinical conditions.
Isoflurane, enflurane, sevoflurane, and especially desflurane produce carbon monoxide (CO) during reaction with desiccated absorbents. Of these, sevoflurane is the least studied. We investigated the dependence of CO production from sevoflurane on absorbent temperature, minute ventilation (VE), and fresh gas flow rates. We measured absorbent temperature and in vitro CO concentrations when desiccated Baralyme reacted with 1 minimum alveolar anesthetic concentration of (2.1%) sevoflurane at 2.3-, 5.0-, and 10.0-L VE. Mathematical modeling of carboxyhemoglobin concentrations was performed using an existing iterative method. Rapid breakdown of sevoflurane prevented the attainment of 1 minimum alveolar anesthetic concentration with low fresh gas flow rates. CO concentrations increased with VE and with absorbent temperatures exceeding 80 degrees C, but concentrations decreased with higher fresh gas flow rates. Average CO concentrations were 150 and 600 ppm at 2.3- and 5.0-L VE; however, at 10 L, over 11,000 ppm of CO were produced followed by an explosion and fire. Methanol and formaldehyde were present and may have contributed to the flammable mixture but were not quantitated. Mathematical modeling of exposures indicates that in average cases, only patients < or =25 kg, or severely anemic patients, are at risk of carboxyhemoglobin concentrations >10% during the first 60 min of anesthesia. ⋯ Sevoflurane breakdown in desiccated absorbents is expected to result in only mild carbon monoxide (CO) exposure. Completely dry absorbent and high minute ventilation rates may degrade sevoflurane to extremely large CO concentrations. Serious CO poisoning or spontaneous ignition of flammable gases within the breathing circuit are possible in extreme circumstances.