The effects of extracellular pH with and without bicarbonate on intracellular procaine concentrations and anesthetic effects in crayfish giant axons.

BACKGROUND: The potentiating effect of sodium bicarbonate on local anesthetic action is attributed to two mechanisms: (1) an increase in the un-ionized local anesthetic due to extracellular alkalinization, and (2) an accelerated conversion of local anesthetic from un-ionized to ionized form with intracellular acidification caused by bicarbonate. To evaluate these hypotheses, the intracellular pH, intracellular ionized procaine concentration, and evoked action potentials were measured in crayfish giant axons. METHODS: In all measurements, axon preparations from crayfish were perfused extracellularly for 15 min with either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH was measured using a pH-sensitive microelectrode. Intracellular anesthetic concentration was measured using a specially designed procaine-sensitive microelectrode with each of three solutions containing 1 mM procaine hydrochloride. Membrane potential was measured and, as an index of anesthetic action, the dV/dt of evoked action potential was calculated during perfusion with procaine. RESULTS: Mean intracellular pH was significantly lower in the bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08 mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6 (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately coincident with the mean intracellular procaine concentration in each solution. CONCLUSION: The presence of bicarbonate or extracellular alkalinization increased the intracellular concentration of ionized procaine and the anesthetic effect.

Monocarboxylic acids enhance the anesthetic action of procaine by decreasing intracellular pH.

Sodium monocarboxylates are known to enhance the anesthetic action of procaine, and also decrease intracellular pH (pHi). We studied the effect of 30 mM Na monocarboxylates (formate, acetate, propionate, butyrate, and salicylate) on the pHi and on the anesthetic action of procaine HCl using giant axons of crayfish (Procambarus clarkii). The pHi was measured using pH sensitive microelectrode method and the anesthetic action was evaluated by the change in the action potential (AP) amplitude. The tested acids except for formate showed apparent decrease in pHi and enhancement of the action of 2 mM procaine. Other organic acids (maleate and benzensulfonate) did not affect pHi and anesthetic action of procaine. In the bicarbonate free solution, pHi increased and the anesthetic action was weakened. The EC25 values (the concentration of procaine which depresses the AP amplitude by 25%) of acetate, propionate, and bicarbonate free solution were coincided with the predicted EC25 values from the simple simulation on intracellular procaine increase according to the pHi change. But the EC25 value of salicylate group was less than half of the predicted. These results suggested that the enhancing action of straight chain monocarboxylic acids is due to pHi decrease, and salicylate has other additional mechanisms.

Intravenous trimethaphan during epidural plus general anesthesia decreases the direct radial artery pressure lower than the brachial artery pressure.

STUDY OBJECTIVE: To determine whether vasodilators such as sodium nitroprusside (SNP) and trimethaphan (TMP) produce a pressure difference between the radial artery and the brachial artery during epidural plus general anesthesia or simple general anesthesia. DESIGN: Randomized study and prospective study. SETTING: Operating rooms of two hospitals. PATIENTS: 36 and 6 adult patients in the first and second studies, respectively, who received spherical acetabular osteotomy with induced hypotensive anesthesia. INTERVENTIONS: In the first study, 18 patients received epidural plus general anesthesia (epidural group) and 18 patients received general anesthesia alone (general group). All patients received the hypotensive drugs for more than 50 minutes each. In the second study, 6 patients received TMP-induced hypotension for 20 minutes under epidural plus general anesthesia. MEASUREMENTS AND MAIN RESULTS: In the first study, radial intra-arterial blood pressure (RIBP) and tonometric blood pressure (TBP) calibrated with oscillometric blood pressure of the arm were compared. In the second study, RIBP and the brachial intra-arterial blood pressure (BIBP) were compared. In the first study, the bias between RIBP and TBP for systolic, mean and diastolic blood pressure were significantly less during TMP-induced hypotension in the epidural group (-11.5 +/- 2.5 (mean +/- SD), -6.0 +/- 3.1, and -2.8 +/- 3.7 mmHg, respectively] than during SNP-induced hypotension in the epidural group and SNP- and TMP-induced hypotension in the general group (p < 0.01). The precision of systolic and mean pressures were significantly greater during TMP-induced hypotension in the epidural group (11.8 +/- 2.3 and 7.1 +/- 1.9 mmHg, respectively) than the other three hypotension groups (p < 0.01). In the second study, the bias between RIBP and BIBP for systolic, mean, and diastolic pressures were significantly less (p < 0.01), and precision was significantly greater during hypotension than during normotension (p < 0.01). CONCLUSIONS: Our results demonstrate that TMP decreases the direct radial artery systolic and mean pressures to levels below the brachial artery systolic and mean pressures in patients who received epidural plus general anesthesia.