Richard A. Jaffe

The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer’s type

Objective: To evaluate the production rate of CSF in patients with differing disease states. Methods: The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 ± 4 years, mean ± SD), nine with PD over age 60 (aged 69 ± 6 years, mean ± SD), and seven with dementia of the Alzheimer’s type (AD) (aged 72 ± 9 years, mean ± SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL. Results: These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 ± 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 ± 0.12 mL/minute, and in patients with AD the mean rate was 0.20 ± 0.06 mL/minute. Conclusion: These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.

Intrathecal sufentanil for labor analgesia--sensory changes, side effects, and fetal heart rate changes.

This study was designed to evaluate intrathecal (IT) sufentanil for labor analgesia with respect to sensory changes, side effects, and fetal heart rate (FHR) changes. In Phase I of the study, data regarding duration of analgesia and hemodynamic changes were obtained retrospectively from the labor and anesthetic records of 90 patients who had received IT sufentanil, 10 micrograms in 1 mL of saline, during active labor. In Phase II, an additional 18 parturients who received similar treatment were studied prospectively to document sensory, motor, and hemodynamic changes, as well as the incidence of side effects. In Phase I, analgesia occurred rapidly and lasted 124 +/- 68 min (SD); 19% of patients required no further analgesia before delivery. In Phase II, median time to onset of analgesia was 3 min (range 1-6 min) and mean duration of analgesia was 96 +/- 36 min. Decreased sensation to pinprick and cold occurred within 6 min extending from T4 to L4 (upper and lower median levels) in the majority of patients. All subjects requested additional analgesia within approximately 30 min of recession of sensory changes. Motor strength remained normal throughout. Hypotension (systolic blood pressure [BP] < or = 90 mm Hg or > 20% decrease in systolic BP) occurred in 14% and 11% of patients in Phase I and II, respectively. Perineal itching preceded analgesia in 95% of patients and all subjects experienced mild sedation. FHR changes occurred in 15% of cases but were not associated with adverse neonatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the local anesthetic effects of meperidine, fentanyl, and sufentanil on dorsal root axons

The local anesthetic effects of opioids have been demonstrated in both clinical and laboratory studies.Clinically, both meperidine and sufentanil can produce segmental sensory anesthesia. However, previous studies of the effects of opioids on nerve conduction have all made use of peripheral nerve preparations and yielded conflicting results. In the present study we describe the local anesthetic effects of phenylpiperidine opioids on individual dorsal root axons, the probable target for intrathecal local anesthetics. Dorsal roots were removed from anesthetized adult male rats and maintained in vitro. Standard single fiber recording techniques were used to isolate activity in the individual axons. Drug exposure was accomplished by perfusing the isolated dorsal root with an artificial cerebrospinal fluid containing the study drug at a clinically relevant concentration. Steady-state drug effects were measured after 15-30 min of exposure and compared to control measurements in the same preparation. Meperidine (705 micro Meter) blocked conduction in 61.5% of 39 myelinated and unmyelinated axons, and significantly reduced conduction velocity in the remaining unblocked axons. These effects were not naloxone reversible. Fentanyl (0.6 micro Meter and 3 micro Meter) and sufentanil (1.04 micro Meter) failed to affect the nerve conduction in any dorsal root axon. The discrepancy between laboratory and clinical observations is discussed. We suggest that the site of conduction block may occur at the proximal end of the dorsal root as it passes through the dorsal root entry zone, an anatomically unique segment of the primary sensory pathway with decreased conduction safety for action potential propagation. (Anesth Analg 1996;83:776-81)

Subanesthetic concentrations of lidocaine selectively inhibit a nociceptive response in the isolated rat spinal cord

&NA; Systemically administered local anesthetics are known to provide analgesia in a variety of pain states; however, the site of action and the mechanism by which these effects are produced remain in question. In the present study, the effects of low (subblocking for nerve conduction) concentrations of lidocaine on a spinal cord nociceptive potential were studied. Spinal cords were removed from neonatal rats and maintained in vitro. Lumbar dorsal and ipsilateral ventral roots were attached to suction electrodes for stimulation and recording, respectively. Following a stabilization period (60–120 min) with control measurements, each preparation was exposed to a single concentration of lidocaine (30–60 min) then returned to control perfusate for recovery (60–120 min). Data were digitized and integrals computed for both monosynaptic and slow ventral root potentials (VRP). Low concentrations of lidocaine produced a selective reduction in the magnitude of the slow‐VRP. At lidocaine concentrations of 1–10 &mgr;g/ml (3.6–36 &mgr;M), the slow‐VRP was reduced from 79% to 36% of control. Recovery to pre‐exposure control levels was slow and sometimes not complete after 60–120 min in drug‐free perfusate. The monosynaptic component of the VRP was unaffected by lidocaine at any concentration, suggesting that the depression of the slow‐VRP cannot be attributed to simple conduction block. The addition of naloxone 0.1 &mgr;M to the perfusate had minimal effect on lidocaine‐induced depression. Although resembling the selective effects of morphine, the antinociceptive effects of lidocaine do not appear to be primarily mediated through opiate receptors. Subblocking concentrations of tetrodotoxin, a selective sodium‐channel blocker, did not mimic the effects of lidocaine. However, a subblocking concentration of benzonatate, an orally effective local anesthetic, did produce lidocaine‐like selective effects on the slow‐VRP. This study demonstrated that lidocaine at clinically relevant concentrations can selectively depress a well‐characterized nociceptive response in the isolated rat spinal cord. We propose that the site of action for systemic lidocaine analgesia is, at least in part, at the level of the spinal cord.

An in vitro study of femoral intramedullary pressures during hip replacement using modern cement technique.

Five femora (four cadaveric and one plastic) were used to measure the intramedullary pressures simultaneously at two different locations along the proximal femur during the insertion of bone cement and the femoral component using modern cement technique. The pressures were monitored by transducers located at the midpoint of each femoral stem (P1), and just beyond the tip of the femoral stem proximal to a cement plug (P2). Transient increases in intramedullary pressure were noted during the initial compaction of the bone cement using a conventional device. However, during insertion of the femoral component, the pressures at P1 and P2 increased dramatically to peak pressures exceeding 2385 mm Hg at P1 and 3710 mm Hg at P2 respectively. These pressure elevations were not sustained; eight to 10 minutes after prosthesis insertion, the pressures decreased to below baseline levels in all five femora. This probably resulted from contraction of the cement during the curing phase. Transient elevations of intramedullary pressure to levels greater than 100 times capillary pressure are produced during hip replacement using modern cement technique. The highest pressures are generated during insertion of the femoral component rather than during the cement compaction step. These findings suggest that the use of a cement compactor to improve intrusion of the cement into bone is probably unnecessary.

Aspects of mechanical ventilation affecting interatrial shunt flow during general anesthesia.

Intraoperative transesophageal echocardiography was used to study the incidence of flow-patent foramen ovale in 33 normal, healthy patients (ASA physical status I) undergoing general anesthesia in the supine position for nonthoracic surgical procedures. Echocardiographic contrast was injected intravenously during mechanical ventilation in the presence of 0, 5, 10, 15, or 19 cm H20 positive end-expiratory pressure (PEEP). A final test was performed during the release of 19 cm H20 PEEP. The presence of a flow-patent foramen ovale was detected when the injected echo targets were observed crossing the interatrial septum from right to left. Most interesting, 3 of 33 patients developed a right-to-left shunt that was first detected with the steady application of 10 (1 patient) or 15 cm H20 PEEP (2 patients). In all three cases, the shunt flow was accentuated on the release of PEEP; however, no additional cases were detected using this respiratory maneuver. These cases represent the first demonstration of right-to-left interatrial shunting evoked as the result of the sustained application of PEEP. This study also revealed a lower than expected incidence of flow-patent foramen ovale (9%) when measured during general anesthesia and positive pressure ventilation with or without PEEP.

Excitatory effects of 5-hydroxytryptamine, veratridine and phenyl diguanide on sensory ganglion cells of the nodose ganglion of the cat☆

Abstract 5-hydroxytryptamine (5-HT), phenyl diguanide (PDG) and veratridine, injected into the common carotid artery in doses of 5–10 μg, caused action potentials to be generated in small bundles dissected from the infranodose vagus nerve of cat. These excitatory effects persisted following transection of the supranodose vagus nerve. 5-HT and PDG also produced action potentials in fibers dissected from the supranodose vagus, before and after transection of the cervical vagus nerve; veratridine was not tested on these fibers. Not all infranodose or supranodose fibers were excited by these drugs in the doses used. Susceptibility of the fibers to 5-HT, PDG or veratridine did not appear to be related to the type of sensory modality transmitted by the fibers, as fibers subserving different modalities were excited. Pentobarbital, 1–4 mg/kg injected intravenously, depressed responses to 5-HT (responses that the reflexes produced by 5-HT, PDG and veratridine through an action on the nodose ganglion probably result from direct excitatory effects of these drugs on sensory ganglion cells.

Differential nerve block. Direct measurements on individual myelinated and unmyelinated dorsal root axons.

Background Clinically, differential block is manifested by the loss of small fiber mediated sensation (e.g., temperature) two or more dermatomes beyond the sensory limit for large fiber mediated sensations. These observations support the belief that sensitivity to local anesthetics is inversely proportional to axon diameter. This study reports the first measurements of differential sensitivity to lidocaine in individual myelinated and unmyelinated mammalian dorsal root axons. Methods Lumbar dorsal roots and vagus nerves were isolated from anesthetized adult rats and maintained in vitro in a perfusion/recording chamber at 37+/‐0.3 degree C. Using single fiber techniques, evoked action potentials in individual myelinated and unmyelinated axons were digitized and recorded for subsequent analysis. Axons were exposed to lidocaine at 150, 260, or 520 micro Meter. Sensitivity to local anesthetic was assessed by measuring the incidence of conduction block and the magnitude of conduction velocity slowing under steady‐state conditions. Results Data were obtained from 77 dorsal root axons and 41 vagal axons. The estimated steady‐state EC50 lidocaine concentration for myelinated dorsal root axons (232 micro Meter) was comparable to that for unmyelinated axons (228 micro Meter). Similarly, the incidence of conduction block was not significantly different among dorsal root axon groups. However, unmyelinated dorsal root axons were significantly less sensitive to the conduction velocity slowing effect of lidocaine than their myelinated counterparts (P < 0.01). The incidence of conduction block in short (mean length 13.5 mm) dorsal root axons was not significantly different from that in long (mean length 22.4 mm) axons. Compared with dorsal root axons, the estimated EC50 s for vagal myelinated and unmyelinated axons (345 and 285 micro Meter, respectively), while lower were not significantly different. However, the incidence of conduction block at 260 micro Meter lidocaine was significantly lower (16.7% vs. 56.7%; P < 0.05) in vagal myelinated axons. Conclusions Although no difference in sensitivity to the conduction blocking effects of lidocaine could be demonstrated among dorsal root axons, myelinated axons were more sensitive to the conduction velocity slowing effects of lidocaine. This differential effect cannot explain clinical observations of differential nerve block. Differential sensory block with lidocaine may depend on factors (e.g., physiologic function) related only indirectly to individual axon conduction velocity (diameter).

Influence of centrifugal sinus nerve activity on carotid body catecholamines: Microphotometric analysis of formaldehyde-induced fluorescence

The effects of centrifugal activity in the carotid sinus nerve (CSN) on the intensity of formaldehyde-induced fluorescence of carotid body were examined in cat. Measurements of intensity were obtained from 21 to 56 sections of each carotid body with a microscope photometer attached to a fluorescence microscope. Comparisons were made between the two carotid bodies removed from each cat. In one series of experiments, one carotid body (CSN intact) served as control, while the experimental carotid body was on the side on which centrifugal activity was increased by electrical stimulation of the peripheral end of the cut CSN. In a second series, centrifugal CSN activity was increased by hypoxemia; one CSN was transected (control) and the other was left intact (experimental). In untreated cats, fluorescence intensity was significantly higher on the side with increased centrifugal CSN activity. In cats treated with either MK486, which inhibits conversion of L-DOPA to dopamine, or reserpine, increased centrifugal CSN activity caused a significant decrease in intensity of type I cells. These findings indicate that centrifugal discharges regulate, in part, the synthesis and release of catecholamines by type I cells of the carotid body.

Dosimetry and cardiopulmonary function in rats chronically exposed to cigarette smoke

Abstract Groups of 80 female F-344 rats were exposed, in Maddox-ORNL smoking machines, to smoke from three types of research cigarettes: high tar, low nicotine (HT-LN, code 13 as provided by the National Cancer Institute); low tar, high nicotine (LT-HN, code 27); and high tar, high nicotine (HT-HN, code 32). Rats were exposed to approximately 10 puffs of cigarette smoke during each of eight daily exposure sessions, 7 days/week for 24 months. Additional groups were sham-exposed on the same schedule, or served as untreated “shelf” controls. Heart rate and breathing pattern (tidal volume, respiration rate, and minute volume) were measured both during exposure and while the animals were not exposed to smoke. During exposure, smoke-exposed rats inhaled 75% less air and had 40% lower heart rates than sham-exposed rats. Results were similar for all smoke-exposed groups, and differences between sham- and smoke-exposed groups persisted throughout the 24-month exposure. When not being exposed, heart rate and breathing pattern were also different between smoke- and sham-exposed groups; tidal volumes were higher and respiration and heart rates were lower in smoke-exposed than in sham-exposed animals. In general, these differences between smoke- and sham-exposed groups developed during the first 12 months of exposure and diminished thereafter. Of the smoke-exposed groups, rats exposed to LT-HN cigarettes showed the greatest changes, and rats exposed to HT-LN cigarettes showed the least changes, in heart rate and breathing patterns. Arterial blood pressure was consistently higher in smoke-exposed than in sham-exposed animals following 18 and 24 months of exposure. This study showed that cardiopulmonary function in rats was significantly affected by chronic cigarette-smoke exposure.