Differences In Dose Requirements Research Articles

A Method for Testing for Epinephrine-Induced Arrhythmias in Rats

Evaluation of a new inhaled anesthetic requires determination of the anesthetic's potential to predispose to ventricular (and other) arrhythmias in an animal model. This need poses logistic and economic burdens if the effects of large numbers of new anesthetics are to be surveyed. We have devised a technique for determining the potential of a new anesthetic to produce arrhythmias using a smaller animal (the rat) than previous methods. Our technique requires preliminary selection of male rats sensitive to the arrhythmias produced by the intravenous injection of epinephrine. Rats are tested after demonstrating the desired sensitivity. Using this model, rats given 1.4% halothane developed premature ventricular extrasystoles at a dose of 2.4 +/- 1.0 micrograms/kg epinephrine, and those receiving 1.6%-2.2% isoflurane at a dose of 28 +/- 24 micrograms/kg. This difference in dose requirements is about two to three times that in humans.

Resetting of baroreflex sensitivity after induced hypotension.

The effect of sodium nitroprusside (SNP)-induced hypotension on the sensitivity of the baroreflex was studied in 11 informed patients anesthetized with morphine (M) or halothane (H). PaCO2 was controlled at 28 to 32 mmHg with a respirator. Baroreflex sensitivity was assessed with a depressor test using a small dose of SNP (4–6 μg/kg, iv) to decrease the systolic pressure (SP) rapidly by about 30 mmHg. The slope of the regression line (in ms/mmHg) relating SP and the succeeding pulse interval (PI, R-R interval) was used as an index for the sensitivity of baroreflex control of heart rate. In control measurements, SP-PI slopes were 6.4 ms/mmHg for the morphine group and 3.2 ms/mmHg for the halothane group, indicating that baroreflex sensitivity is greater during morphine than during halothane anesthesia. This difference in baroreflex sensitivity might explain the differences in dose requirements for SNP in patients anesthetized with either morphine or halothane. Following a control test, SNP was infused at a rate adjusted to maintain the mean arterial pressure between 55 and 60 mmHg. The duration of hypotension was in accordance with surgical needs. SNP infusion was then discontinued and SP was allowed to recover spontaneously. When SP recovered to its control level, PI was significantly prolonged by 18 per cent in patients anesthetized with morphine and by 13 per cent in those anesthetized with halothane over the respective control values. Immediately after the recovery of SP following the discontinuation of SNP infusion, another baroreflex sensitivity test was made; the SP-PI slopes increased markedly by 105 per cent in patients anesthetized with morphine and by 179 per cent in those with halothane over the respective control values, indicating a resetting of the baroreflex. These changes may have significant implications in hemodynamic adjustments following induced hypotension in patients during general anesthesia.

Triethylene Melamine in the Treatment of Neoplastic Disease

Triethylene Melamine in the Treatment of Neoplastic Disease