The effects of epinephrine on the anesthetic and hemodynamic properties of ropivacaine and bupivacaine after epidural administration in the dog.

Ropivacaine is a new local anesthetic that is chemically related to mepivacaine and bupivacaine. Previous laboratory studies have demonstrated that ropivacaine possesses an anesthetic profile similar to that of bupivacaine and has less arrhythmogenic potential. The current study was initiated to compare the hemodynamic and anesthetic effects of epidurally administered 0.75% bupivacaine and 1% ropivacaine, with and without epinephrine (1:200,000), in the dog. Two groups of six dogs were randomly assigned to the ropivacaine or bupivacaine treatment groups. Administration of 0.75% bupivacaine and 1% ropivacaine with and without epinephrine was randomized. Volumes of 3 ml of each solution were injected in a blinded manner via an indwelling lumbar epidural catheter with 48 hours between injections. No statistically significant difference existed between the four treatment groups with regard to onset and duration of sensory or motor block. Hemodynamic changes were, for the most part, not different between drugs. Significant decreases were seen in mean arterial blood pressure and cardiac output in all test groups. No difference in the degree of cardiovascular depression was observed. The addition of epinephrine did not alter onset or duration of sensory or motor block in this animal model. Epinephrine reduced the average anesthetic blood concentration observed in both treatment groups at the various time intervals, but not the time to achieve the mean maximum blood level. No residual adverse effects were observed in any animal.

Lipopolysaccharide-induced myocardial depression is not mediated by cyclooxygenase products.

BACKGROUND AND METHODS: We tested the hypothesis that a sublethal dose of lipopolysaccharide in vivo induces in vitro atrial depression in rats via release of cyclooxygenase products. Male Sprague-Dawley rats (mean weight 366 +/- 9 [SE] g) were injected iv at time 0 with Escherichia coli lipopolysaccharide (1 mg/kg, n = 22) or saline (2.5 mL, n = 11). Some animals injected with lipopolysaccharide were pretreated 30 mins before with ibuprofen (15 mg/kg, n = 7). At time 2 hrs, the hearts were harvested and the atria were immersed in tissue baths and attached to force displacement transducers. Blood was collected for measurement of thromboxane B2 (TxB2) by radioimmunoassay. Force of contraction and rate in response to four different preloads were measured. Afterward, the preload was changed to 1 g, and force of contraction and rate were evaluated in response to graded doses of isoproterenol. RESULTS: Force of contraction was significantly (p less than .05) lower at all preloads in animals given lipopolysaccharide. Pretreatment with ibuprofen did not prevent the depression in force of contraction but prevented the increase in TxB2 seen after lipopolysaccharide injection (p less than .05). The force of contraction and rate response to isoproterenol were similar across groups. CONCLUSIONS: These data suggest that cyclooxygenase products do not mediate lipopolysaccharide-induced cardiac dysfunction in the rat.

Endotoxin-induced myocardial depression in rats: effect of ibuprofen and SDZ 64-688, a platelet activating factor receptor antagonist.

We tested the hypothesis that lipopolysaccharide (LPS)-induced myocardial dysfunction is mediated by cyclooxygenase-derived metabolites of arachidonic acid or platelet activating factor (PAF). Ether-anesthetized rats were injected iv with normal saline (NS; 2.5 ml/kg), ibuprofen (cyclooxygenase inhibitor; 15 mg/kg), or SDZ 64-688 (PAF receptor antagonist; 5 mg/kg). Thirty minutes later, the rats were injected iv with NS (5 ml/kg) or Escherichia coli 0111:B4 LPS (20 mg/kg). Two hours later, atria were harvested, connected to an isometric force transducer-amplifier-recorder apparatus, and maintained in vitro in oxygenated 37.5 degrees C Krebs--Henseleit buffer. Force of contraction indexed to body weight (FOCI; g/kg) was significantly (P less than 0.05) lower in the NS/LPS group (N = 7) than in the NS/NS group (N = 7). Pretreatment with ibuprofen (ibuprofen/LPS group; N = 8) did not affect the adverse effect of LPS on atrial FOCI. In contrast, pretreatment with SDZ 64-688 (64-688/LPS group; N = 8) ameliorated (P less than 0.05) the deleterious effect of LPS on contractility. The PAF antagonist did not manifest intrinsic positive inotropic activity (64-688/NS group; N = 8). These results support the notion that LPS-induced myocardial dysfunction in the rat is mediated, at least in part, by PAF.