Epidural air injection assessed by transesophageal echocardiography.

BACKGROUND AND OBJECTIVES: The object of this study, using transesophageal echocardiography (TEE) in anesthetized patients, was to investigate the occurrence of venous air embolism (VAE) when air is injected into the epidural space. METHODS: Six patients between the ages of 18 and 50 years (ASA I-II) undergoing general anesthesia in a supine position for nonthoracic surgical procedures were studied. Prior to general anesthesia, an epidural catheter was placed into the epidural space using a Tuohy needle and a standard saline loss-of-resistance technique. Following verification of proper catheter placement, general anesthesia was induced and the trachea intubated. Thereafter, a TEE probe was inserted into the esophagus. After a 10-minute control period, and during continuous TEE videotape recording, 5 mL of air was rapidly injected into the epidural space through the epidural catheter. This was followed 10 minutes later by the epidural injection of 5 mL of room-temperature preservative-free saline. Microbubble echo targets were quantified in a range from 0 to 4+. RESULTS: Venous air microbubble emboli appeared in the circulation within 15 seconds after injecting either air or saline into the epidural space. CONCLUSIONS: No evidence of clinically significant VAE was seen in any patient. The results suggest that drugs injected into the epidural space may have unexpectedly easy access to the venous circulation with a potential to produce unwanted systemic effects. Clinicians should be alert to the possibility that local anesthetics, or any other drug placed epidurally, may rapidly enter the systemic circulation even without the intravenous placement of an epidural catheter.

Segmental wall motion abnormalities in patients undergoing total hip replacement: correlations with intraoperative events.

We examined the effect of methylmethacrylate cement on venous embolization and cardiac function in 20 patients having total hip arthroplasty under general anesthesia. Segmental wall motion abnormalities and intracardiac targets (presumably emboli) were investigated by making videotaped recordings of the transgastric short axis and longitudinal 4-chamber views of the heart with transesophageal echocardiography at different points during surgery. The incidence of segmental wall motion abnormalities was the most frequent during insertion of cemented femoral prostheses (8 of 14 patients had wall motion abnormalities). This was significantly different from baseline measurements taken at the beginning of surgery (P < 0.05). In addition, there were also significantly more segmental wall motion abnormalities in patients having a cemented femoral component compared to those having an uncemented femoral prosthesis (P < 0.05). The incidence of wall motion abnormalities during acetabular and femoral reaming and during wound closure was not significantly different from baseline. Intracardiac targets (emboli) were seen in all 20 patients during surgery. The largest number of emboli occurred during reaming of the femur and during insertion of the femoral prosthesis. Significantly more emboli were seen with cemented components (P < 0.02). Most emboli were small (< 2 mm) and appeared similar to the microbubbles produced by agitating saline with a small amount of air. Six patients also had larger (> 5 mm) emboli that appeared to be solid material. One patent foramen ovale was detected (5% incidence). There were no adverse cardiac or neurologic events, and heart rate and arterial blood pressure remained within normal limits throughout surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations between active zone ultrastructure and synaptic function studied with freeze-fracture of physiologically identified neuromuscular junctions.

The active zone is a unique presynaptic membrane specialization that is believed to be the site of neurotransmitter release. To examine directly the relationship between active zone ultrastructure and synaptic efficacy, frog neuromuscular junctions were studied with a new technique combining electrophysiology, light microscopy, and freeze-fracture of identified single muscle fibers. This technique allows correlations to be made between quantal content (measured in low Ca2+ and high Mg2+ Ringer solution), endplate size, and active zone structure at the same neuromuscular junctions. By measuring physiological and morphological variables at the same junctions, the validity of structure-function correlations is significantly improved. Synaptic quantal content in 91 physiologically identified muscle fibers varied considerably and was only poorly correlated with endplate size, as shown in previous studies. To measure the total length of endplate branches, either a modified cholinesterase stain or rhodamine-labeled peanut agglutinin stain was used. When the same identified muscle fibers were freeze-fractured, active zones were exposed in 17 junctions. In a replica that contained a large part of one nerve terminal, there was no detectable gradient in active zone structure along the length of 3 different nerve terminal branches identifiable with both light and electron microscopy. The results from these 17 identified junctions indicate that quantal content per unit terminal length is positively correlated with the amount of active zone per unit terminal length. The estimated total active zone length and total number of active zone particles per junction are also positively correlated with the quantal content in these identified junctions. This study suggests that active zone size and spacing are better indicators of transmitter release than is endplate size and that the active zone may play an important role in regulating synaptic efficacy at the neuromuscular junction.

A comparison of active zone structure in frog neuromuscular junctions from two fast muscles with different synaptic efficacy.

To search for ultrastructural correlates of differences in synaptic safety factor and neurotransmitter release, neuromuscular junctions from the cutaneous pectoris and cutaneous dorsi muscles of the grass frog Rana pipiens were freeze fractured. Synaptic efficacy in these muscles was determined by the extent to which isometric twitch tension could be blocked by lowering [Ca2+] in the bathing solution. We found that junctions in the cutaneous pectoris were significantly more effective than those of the cutaneous dorsi. Morphometric analysis of 16 junctions from each type of muscle showed significant differences in some aspects of active zone structure. Cutaneous pectoris terminals had longer active zone segments and active zones spaced more closely together. This resulted in 20% more active zone length per unit terminal length in the cutaneous pectoris. Cutaneous dorsi terminals had active zones that were more often segmented into two or more sections at a single junctional fold. Mean active zone length per junctional fold and the number of active zone particles per micrometre of active zone length were not significantly different. As a result of the somewhat larger terminal width in the cutaneous dorsi, the percentage of terminal width occupied by active zone was greater in the cutaneous pectoris. As an attempt to indirectly estimate active zone spacing with the light microscope, we applied rhodamine-conjugated alpha bungarotoxin to neuromuscular junctions from the cutaneous pectoris and cutaneous dorsi. No significant difference in the spacing of fluorescently labelled acetylcholine receptor bands was found between the two types of junctions. Our results indicated that the greater active zone length per unit terminal length in the cutaneous pectoris was associated with its increased synaptic efficacy. In addition the continuity and particle organization of active zones may have contributed to the observed differences in synaptic safety factor at frog neuromuscular junctions.

Absence of sterol-specific complexes at active zones of degenerating and regenerating frog neuromuscular junctions.

Freeze-fracture combined with filipin treatment has been used as a cytochemical probe for membrane cholesterol. As previously shown at the frog neuromuscular junction, distinctive sterol-specific complexes were formed on the presynaptic membrane after filipin treatment, except at active zones. The absence of sterol-specific complexes from active zones was confirmed using two other cytochemical agents--digitonin and saponin. We also studied the maintenance and differentiation of the presynaptic membrane heterogeneity revealed by membrane cholesterol probes at degenerating and regenerating neuromuscular junctions. During degeneration, active zones in frog nerve terminals were disorganized, but still lacked sterol-specific complexes. After engulfing the degenerating nerve terminals, Schwann cells occupied the synaptic gutters and displayed a uniform distribution of sterol-specific complexes. Schwann cell ridges opposite the postjunctional folds also had prominent sterol-specific complexes in regions formerly occupied by active zones. By 2 weeks after nerve crush, nerve terminals reinvaded the endplate region and active zones began to regenerate. While the intramembrane particles of the early regenerating active zones were not arranged in the normal double-rowed organization, filipin-sterol complexes were nevertheless excluded from these primitive active zones. Areas of nerve terminal membrane opposite to junctional folds but lacking active zones were covered with filipin-sterol complexes. These results show that the normal double-rowed organization is not required for the expression of the membrane heterogeneity associated with the active zone. In addition, the absence of sterol-specific complexes is closely associated with the active zone particles and not simply the membrane regions opposite to the postjunctional folds. The membrane heterogeneity does not seem to be directly linked with the functional state of the active zone since it is still associated with degenerating active zones after transmission failure has occurred.