Ben F. Rusy

Ibuprofen in the Treatment of Postoperative Pain

The site and type of operation and the age of the patient help determine the intensity of postoperative pain and the level of medication necessary for relief. Controlled clinical trials have shown that ibuprofen (Motrin) is an effective and safe analgesic for patients with mild to moderate postoperative pain. In a study of 120 patients with postoperative orthopedic pain, ibuprofen was more effective than acetaminophen-codeine and had a longer duration of action.

Negative inotropic effects of isoflurane and halothane in rabbit papillary muscles

The possibility that the negative inotropic effect of isoflurane is primarily due to a competitive inhibition of the influx of extracellular Ca2+ with little effect on the availability of Ca2+ stored intracellularly in the sarcoplasmic reticulum was examined in rabbit papillary muscle. The negative inotropic effect of isoflurane (1.4%) on steady state contractions (primarily dependent on the influx of extracellular Ca2+) was significantly greater than that on potentiated-state contractions (primarily dependent on Ca2+ released from the sarcoplasmic reticulum). In previous work from this laboratory we found that halothane has an opposite effect in this regard. Increasing stimulation frequency in the presence of isoproterenol (0.1, 1 μM) completely reversed the negative inotropic effect of isoflurane (1.4%) but not that of halothane (0.6%). These results suggest that isoflurane inhibits Ca2+ influx with little effect on the availability of activator Ca2+ stored in and released from the sarcoplasmic reticulum, and that the effect of isoflurane but not that of halothane can be effectively counteracted by conditions that are known to increase Ca2+ influx in the absence of an anesthetic. These properties of isoflurane may in part account for the minimal myocardial depressant effect of the anesthetic on the intact heart in the presence of a functional autonomic system.

Effects of Bupivacaine and Lidocaine on Av Conduction in the Isolated Rat Heart: Modification by Hyperkalemia

The intrinsic cardiotoxicities of bupivacaine and lidocaine were examined in the isolated, perfused rat heart. The perfusates contained no protein and were equilibrated with a gas mixture of 95 per cent O2 and 5 per cent CO2. Autonomic activity, competitive binding, and postseizure hypoxia and acidosis were absent in this experimental model. The effects of the two local anesthetics were evaluated at normokalemia (5.9 mEq/l) and hyperkalemia (9.0 mEq/l). For normokalemia, the ratio of the potency of bupivacaine to that of lidocaine was 14 for slowing ventricular rate to 50 per cent of control, 6 for slowing atrial rate to 50 per cent of control, and 17 for doubling of the PR interval. The action of bupivacaine to slow ventricular rate was due to an inhibitory effect on both AV conduction and atrial rate. For lidocaine, ventricular slowing was mediated mainly by an inhibition of atrial rate with decreased AV conduction playing a minor role. Hyperkalemia of 9.0 mEq/l had little effect on heart rate or AV conduction in the absence of bupivacaine or lidocaine. It did, however, greatly potentiate the effect of both local anesthetics to slow ventricular rate. For bupivacaine, ventricular slowing to 50 per cent of control during hyperkalemia was accomplished almost entirely via an inhibition of AV conduction, while for lidocaine it occurred because of inhibition of both AV conduction and atrial rate. Regardless of the mechanism, hyperkalemia of this degree increased the ventricular slowing effect of both bupivacaine and lidocaine.

Recovery of function and adenosine triphosphate metabolism following myocardial ischemia induced in the presence of volatile anesthetics

Using a normothermic isolated working rabbit heart model, experiments were performed to determine whether exposure to halothane or isoflurane prior to ischemia improved postischemic recovery of myocardial function and the preservation of myocardial high energy phosphates. After 30 min of Langendorff perfusion, hearts were perfused for 30 min in the working mode. Three groups were studied: 1) the blank undergoing no pretreatment during an additional 15 min of working mode; 2) hearts exposed to 1.5% halothane; and 3) hearts exposed to 2.3% isoflurane during the additional 15 min of working mode. Subsequently, all hearts underwent 15 min of global normothermic ischemia, followed by 5 min of Langendorff reperfusion and 15 min of working heart mode using a perfusate devoid of volatile anesthetic. Adenosine triphosphate (ATP) and catabolites were determined after 15 min exposure to volatile anesthetics or blank, after 15 min global ischemia and at the end of the recovery phase. Myocardial function was determined after 30 min of working mode, after exposure to volatile anesthetics, and at the end of the recovery phase. In nonischemic hearts, 15-min treatment with 1.5% halothane or 2.3% isoflurane resulted in a significant decrease in positive LVdP/dt, from 1858 ± 286 to 1316 ± 180 mm Hg·s−1and from 1888 ± 304 to 1541 ± 226 mm Hg·s−1, respectively. Coronary flow was increased significantly after isoflurane but not after halothane. After 15 min of global ischemia followed by 5 min of Langendorff reperfusion and 15 min of working mode, left ventricular contractility assessed by positive LVdP/dt was depressed significantly (P < 0.05, paired t-test) in all three groups. Recovery, expressed as a percentage of control value at 30 min working heart, was not significantly higher in both groups pretreated with anesthetics compared to the blank group (P > 0.05 two-way ANOVA for repeated measures): recovery was 80 ± 6% in the blank group, 88 ± 9% in the halothane 1.5% group, and 86 ± 7% in the isoflurane 2.3% group. The myocardial content of ATP and catabolites remained unchanged during the exposure to volatile anesthetics under normoxic preischemic conditions. The catabolism of ATP to ADP and AMP induced by 15 min of global ischemia was similar in the three groups. During reperfusion, there was a fast resynthesis of ATP such that ATP levels were not different from control values. Again, there was no significant difference in high energy phosphate content between the blank and the pretreated hearts. We conclude that depressed cardiac function during exposure to halothane and isoflurane is not related to any change in myocardial ATP content, and that ATP catabolism during ischemia is not influenced by halothane and isoflurane. Further, treatment with halothane or isoflurane preceding ischemia has no effect on functional indices of recovery after myocardial stunning, which is in concert with unaltered myocardial tissue content of high energy phosphates.

Negative inotropic effect of ketamine in rabbit ventricular muscle.

The effect of ketamine on myocardial contractile force was examined in rabbit papillay muscles in order to determine the underlying mechanism of action of the anesthetic. Ketamine HCl (20 and 40 mg/L) inhibited rested-state contractions that are dependent on the transsarcolemmal influx of Ca2+ for activation and reduced the upstroke velocity of the slow action potential, which reflects Ca2+ influx through the slow Ca2+ channel. On the other hand, ketamine had a relatively small effect on potentiated-state contractions and no effect on rapid cooling induced contractures, both of which are activated by the release of Ca2+ stored in the sarcoplasmic reticulum. These results suggest that ketamine inhibition of transsarcolemmal Ca2+ influx plays a major role in the negative inotropic action of the anesthetic.

The Influence of Serum Potassium on the Cerebral and Cardiac Toxicity of Bupivacaine and Lidocaine

: The influence of hyperkalemia on the central nervous system and cardiac toxicity of bupivacaine and lidocaine was studied in open-chested mechanically ventilated dogs. The seizure and cardiotoxic doses of intravenously administered lidocaine and bupivacaine were determined in two separate groups of normokalemic (2.7 +/- 0.05 SEM mEq/1) dogs. In the case of both anesthetics, the cardiotoxic dose was found to be approximately four times the seizure dose. Under conditions of hyperkalemia (5.4 +/- 0.08 SEM mEq/1), however, the cardiotoxic doses of both anesthetics were decreased significantly to approximately two times the seizure dose. Hyperkalemia did not change the seizure dose for either anesthetic. The cardiac to seizure dose ratio was decreased significantly for bupivacaine but not for lidocaine. The results of this study suggest that hyperkalemia enhances the cardiotoxic effects of both lidocaine and bupivacaine, with this enhancement being more pronounced in the case of bupivacaine.

Volatile anesthetics selectively alter [3H]ryanodine binding to skeletal and cardiac ryanodine receptors

The effect of clinical concentrations of volatile anesthetics on ryanodine receptors of cardiac and skeletal muscle sarcoplasmic reticulum was evaluated using [3H]ryanodine binding. At 2 volume percent, halothane and enflurane stimulated binding to cardiac SR by 238% and 204%, respectively, while isoflurane had no effect. In contrast, halothane and enflurane had no effect on [3H]ryanodine binding to skeletal ryanodine receptors, while isoflurane produced a significant stimulation. These results suggest that volatile anesthetics interact in a site-specific manner with ryanodine receptors of cardiac or skeletal muscle to effect Ca2+ release-channel gating.

Direct effect of halothane and isoflurane on the function of the sarcoplasmic reticulum in intact rabbit atria.

The negative inotropic effect of halothane and isoflurane on potentiated-state contractions of isolated rabbit atria in a normal Ca2+ (2.5 mM) medium was compared with the force depression in low Ca2+ media without an anesthetic. When this comparison was made in the presence of 1 microM ryanodine so that the force of contraction was dependent only upon transsarcolemmal Ca2+ influx with no Ca2+ contribution from the sarcoplasmic reticulum (SR), the force of contraction was depressed equally by 0.6% halothane in a normal Ca2+ medium and by a 1.5 mM Ca2+ medium without the anesthetic. Similarly, 1.0% halothane or 1.5% isoflurane and a 1.0 mM Ca2+ medium were equally depressant as were 2.4% isoflurane and a 0.5 mM Ca2+ medium. In the absence of ryanodine, where the atrial contractile activity is largely dependent on Ca2+ released from the SR, 0.6% halothane in the normal Ca2+ medium depressed contractile force by 32%, whereas the force was depressed by only 16% in the 1.5 mM Ca2+ medium without the anesthetic. Similar results were obtained when the effects of 1.0% halothane and of 1.0 mM Ca2+ were compared. In contrast, the force of contraction measured in the absence of ryanodine was not at all inhibited by 1.5% isoflurane and minimally (11%) inhibited by 2.4% isoflurane. Consequently, the force depression by isoflurane was less than that found in the low Ca2+ media.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in the myocardial depressant action of thiopental and halothane.

The negative inotropic effects of thiopental (10–30 mg/L) and halothane (0.5–1.5%) were compared in rabbit papillary muscles under various stimulation conditions to gain insight into the action of these anesthetics on the availability of Ca2+ for the activation of myocardial contractile activity. The negative inotropic effect of thiopental was more pronounced at short (0.5 sec) than at long (1 sec) beat-to-beat intervals under steady-state conditions, and thiopentals effect on potentiated state contractions was less than that on steady-state contractions. For all variables studied, the effect of halothane was opposite that of thiopental. These results suggest that thiopental reduces the influx of extracellular Ca2+ and the amount of Ca2+ in sarcolemmal sites and slows the transport of intracellular Ca2+ within the sar-coplasmic reticulum from sites of uptake to sites of release without markedly diminishing the amount of intracellular Ca2+ Halothane does not appreciably affect the transport but does diminish the amount of Ca2+ within the sarco-plasmic reticulum that is available for the activation of myocardial contractile activity.

Effect of thiopental on Ca2+ release from sarcoplasmic reticulum in intact myocardium.

BackgroundWhile thiopental is known to inhibit the myocardial transsarcolemmal influx of Ca2+, the effect of thiopental on sarcoplasmic reticular Ca2+ release has not been characterized. MethodsIsolated papillary muscles of rabbits were used. We measured postrest contractions to assess the Ca2+ release by sarcoplasmic reticulum in response to electrical stimulation. Contractures induced by rapid cooling were used as an index of Ca2+ content of sarcoplasmic reticulum. The effect of thiopental on the availability of extracellulariy derived Ca2+ was evaluated from measurements of contractions at 0.1 Hz in the presence of 1 μM ryanodine. ResultsThiopental sodium (10, 20, and 30 mg/1; 38,76, and 113 μM) inhibited the postrest contraction but not the contracture induced by rapid cooling. In the presence ryanodine, thiopental inhibited the postrest contraction elicited after 10 s of rest after 2-Hz stimulation much less than the steady-state contraction at 0.1 Hz (beat interval 10 s). Thiopental inhibited the postrest contraction (no ryanodine present) more strongly than did Ni2+ (an inhibitor of the transsarcolemmal Ca2+ influx) when the contraction at 0.1 Hz in the presence of ryanodine was inhibited to the same extent. ConclusionsThese results suggest that thiopental decreases sarcoplasmic reticulum Ca2+ release induced by electrical stimulation and inhibits the ryanodine-induced efflux of sarcoplasmic reticuium Ca2+.