John A. Reitan

Decrease in vascular resistance in the isolated canine hindlimb after graded doses of alfentanil, fentanyl, and sufentanil

Under halothane anesthesia five dogs were prepared with both hindlimbs isolated from the systemic circulation to allow intermittent placement on extracorporeal perfusion at constant flow. One limb of each dog was surgically denervated. In this relatively anesthetic-free preparation, graded equivalent doses of alfentanil, fentanyl, and sufentanil were infused over 30 s, and vascular resistance was measured. Increasing opioid administration caused a progressive diminution in peripheral resistance. By the high dose level, alfentanil (500 μg/kg), fentanyl (50 μg/kg), and sufentanil (6 μg/kg) caused equal and significant decreases of 48%, 48%, and 44% in resistance, respectively. There was no difference among the opioids in effects on resistance at equivalent dosages. Neither pretreatment with naloxone nor denervation changed the response to the narcotics. We conclude that the three synthetic opioids produce vasodilation by direct action on the peripheral vascular smooth muscle.

Hyperbaric oxygen increases survival following carotid ligation in gerbils.

We studied the effects of graded exposure to hyperbaric (1,875 mm Hg) oxygen therapy in an acute stroke model prepared by unilateral carotid artery interruption in gerbils. Pentobarbital alone, superoxide dismutase alone, two periods of hyperbaric oxygen alone, and each agent combined with hyperbaric oxygen were administered to investigate possible mechanisms of protection from cerebral ischemia. Survival rates and neurologic deficit scores over 5 days in all treated groups were compared with those in a control group. Survival rates in the groups subjected to 2 (63.9 +/- 4.0%) and 4 hours (70.1 +/- 5.2%) of hyperbaric oxygen alone were significantly higher than in the control group (53.6 +/- 4.2%). The group treated with pentobarbital alone also demonstrated increased survival (69.8 +/- 7.0%), but the combination of therapeutic regimens offered no apparent additive protection. By 5 days there were no differences in the neurologic deficit scores of the survivors in the groups. The toxic pulmonary effects of hyperbaric oxygen were assessed in a pilot LD50 study. The pressure used caused no mortality during 4 hours of exposure, and the calculated LD50 was 7.26 hours. This investigation demonstrates that graded doses of hyperbaric oxygen given after the insult increase survival in a gerbil model of stroke.

Use of propranolol to control rate-pressure product during cardiac anesthesia.

The use of propranolol to control heart rate (HR), systolic pressure, and rate-pressure product (RPP) during laryngoscopy and sternotomy was studied in 21 patients, New York Heart Association functional Classes 1 and 2, scheduled for coronary artery bypass graft surgery. All patients were anesthetized in an identical fashion, but the treatment group (N = 13) received propranolol, 0.5 to 1 mg IV, 4 minutes before laryngoscopy and again, in most cases, before skin incision. Patients not given propranolol (N = 8) showed a clinically and statistically significant increase in HR and RPP, whereas HR and RPP remained essentially unchanged from the preanesthetic period in patients given propranolol.

Myocardial Performance and N2O Analgesia in Coronary-artery Disease

Inhalation of 40 per cent N2O by nine patients who had occlusive disease in two or more coronary arteries with elevation of left ventricular end-diastolic pressures (LVEDP) significantly decreased arterial pressure (average 5 per cent) and myocardial contractility as measured by dP/dt/CPIP (average 14 per cent), and increased LVEDP (average 21 per cent). N2O had no significant effect in four patients who had angina without angiographically demonstrable coronary arterial disease. It is concluded that N2O depresses myocardial function in patients who have occlusion of the coronary arteries and impaired left ventricular function.

Comparison of psychomotor skills and amnesia after induction of anesthesia with midazolam or thiopental.

In two groups of 31 healthy patients undergoing minor elective surgery, anesthesia was induced intravenously with either midazolam maleate, 0.2 mg/kg, or thiopental, 3.5 nig/kg. All subjects received 2 μg/kg fentanyl 5 min before the induction agents. Induction time with midazolam was significantly longer than with thiopental (97.1 ± 20.9 sec vs 59.4 ± 5.0 sec) and time to orientation postoperatively was significantly longer after midazolam (31.7 ± 4.2 min vs 11.0 ± 1.1 min). Continued recovery after orientation, measured by a series of psychomotor tests, was also significantly longer with midazolam than with thiopental. Anterograde amnesia was evident in 84.8% of the midazolam treated patients and in only 31.4% of the thiopental group. This degree of absence of recall was acknowledged positively by the affected patients. The protracted recovery period may limit the use of midazolam in short surgical procedures.

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.

Comparison of halothane and isoflurane for rapid anesthetic induction

To study the hypothesis that isoflurane will induce anesthesia faster than halothane when given by a single vital capacity breath technique, we studied 20 ASA I and II adults who breathed approximately 4.5 MAC equivalents of either vapor. The patients, randomly assigned to receive either agent, were fully preoxygenated and monitored for cardiovascular, respiratory, and EEG parameters. All subjects were premedicated with 5 μg/kg fentanyl IV 5 min before induction. Time to loss of consciousness was significantly longer with halothane than with isoflurane (86 ± 4 vs 38 ± 2 sec, respectively) although there were no clinically remarkable differences in cardiovascular or respiratory variables. Patients given halothane had a greater excitatory phase on EEG, whereas those given isoflurane had low frequency predominance. Overall rapid inhalation induction was well-received by all patients and was significantly faster with isoflurane.

Hypothermia minimally decreases nitrous oxide anesthetic requirements.

Over the 38-28 degrees C range, changes in minimum alveolar anesthetic concentration (MAC) parallel changes in lipid solubility of the anesthetics studied. We hypothesized that there would be minimal change in N2OMAC, since N2O lipid solubility is relatively unaltered by temperature changes. We determined N2OMAC in rats using a hyperbaric chamber. In Group N (normothermia, n = 10) rectal temperature was maintained at 37.5 +/- 1 degrees C (mean +/- SD). In Group H (hypothermia, n = 9) temperature was maintained at 29.7 +/- 1.8 degrees C. The hyperbaric chamber was pressurized with N2O and oxygen partial pressure was 0.4 +/- 0.1 atm. Chamber pressure was adjusted approximately 15% up or down, stabilized for approximately 15 min, and the noxious stimulus (electrical current) was applied. This process was continued until two N2O partial pressures were determined which just prevented and just permitted gross, purposeful movement. Nitrous oxide MAC for Group N and Group H were 1.9 +/- 0.2 atm and 1.6 +/- 0.2 atm, respectively, P < 0.01. Temperature and MAC correlated: r = 0.59, P < 0.01. We conclude that hypothermia minimally decreases N2OMAC, which is consistent with the effects of hypothermia on N2O solubility in lipid membranes.

Videodensitometric estimation of the protective effect of hyperbaric oxygen in the ischemic gerbil brain

To verify its protective effect on the ischemic mammalian brain, hyperbaric oxygen was administered to six groups of carotid-ligated gerbils. The outcome was evaluated clinically and by a colorimetric videodensitometry technique by comparing differences in the interhemispheric color density through the translucent intact cranium. It was found that there was a graded decrease in interhemispheric differences with increasing exposure to hyperbaric oxygen (the appearance of the ischemic hemisphere increasingly approached that of normal brain). This correlated with the incidence of ischemia in each group.

The cardiac pre-ejection period: a correlate of peak ascending aortic blood-flow acceleration.

The relationship between peak ascending aortic blood-flow acceleration and the cardiac pre-ejection period (PEP) was studied in five chronically prepared dogs. Acceleration was measured as the first derivative of the signal from a flow probe placed around the aortic root. PEP was derived indirectly by subtracting left ventricular ejection time (obtained from a central arterial pressure signal) from the total active electromechanical time (the Q-S2 interval measured from the ECG and heart sounds). Resulting values of PEP were inverted and squared so that they shared a common time unit with acceleration-time−2. Comparison of 1/PEP2 and peak acceleration produced correlation coefficients from 0.74 to 0.96. A linear relationship between these two measurements was maintained over a sixfold change in the inotropic state of the heart. The quotient 1/PEP2 appears to be an easily obtainable, potentially noninvasive expression of the myocardial contractile state.