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Biomedical subjects

B M Carlson

Publications and source records attributed to B M Carlson.

At least 91 records · Page 5Linked to original sources

Myotoxicity of single and repeated injections of mepivacaine (Carbocaine) in the rat.

Young rats received single or repeated injections of 2% mepivacaine (Carbocaine) into the tibialis anterior or extensor digitorum longus muscles. Repeated injections consisted of six injections of the anesthetic (100 microliter per injection into the tibialis anterior) on three different schedules, at intervals of 2 1/2 hours, 24 hours, or 4 days. The muscles that had been given injections were examined histologically for evidence of myotoxicity at 0 to 7 and 20 days after the last injection. Single injection studies showed that mepivacaine is a myotoxic drug, producing a lesion which ultimately results in the degeneration and subsequent regeneration of large amounts of muscle. A similar picture was seen with repeated injections except that greater tissue destruction was noted. Long-term studies following a single injection of mepivacaine showed restoration of the original muscle structure whereas after repeated injections some muscles showed persisting foci of increased intersitial connective tissue. This study shows that in rats 2% mepivacaine is a myotoxic drug, but that the damage it produces is to a large extent restored by the regeneration of new muscle fibers.

Animals↗

Myotoxicity of local anesthetics and regeneration of the damaged muscle fibers.

In view of the documented myotoxic effects of the local anesthetic, bupivacaine, a survey of myotoxic effects of seven local anesthetics was conducted. In 70 rats, 200 microliters of an anesthetic solution was injected into one tibialis anterior muscle and a control solution was injected into the contralateral muscle. The anesthetics fell into two groups in their effects upon muscle. One group, including 1% procaine, 0.2% tetracaine, 0.5% lidocaine, and 0.75% bupivacaine, produced effects that were confined principally to the muscle fiber. The other group (2% chloroprocaine, 0.25% dibucaine, 0.5% lidocaine with 1:200,000 epinephrine and 2% piperocaine) produced toxic effects on other tissue components of the muscles in addition to affecting muscle fibers. With all anesthetics, the initial damage to and breakdown on muscle fibers was restored by regeneration and 30-day muscles showed relatively few long-term effects of the damage.

Anesthetics, Local↗

Cellular responses to free grafting of the extensor digitorum longus muscle of the rat.

The cellular and subcellular responses related to the survival or destruction and subsequent regeneration of muscle fibers within the freely grafted extensor digitorum longus muscle of the rat were examined by light and electron microscopy. A small number of fibers at the periphery of the grafts survived the initial ischemia but underwent denervation changes and accumulated lipid deposits. The majority of fibers in the grafts, however, became ischemic and underwent an intrinsic degeneration within 4 hours. Cell-mediated destruction of the degenerating fibers occurred as the grafts became revascularized. The basal laminae and some of the satellite cells were the only elements of the original fibers that persisted. Regeneration began at the periphery of the graft within three days after grafting and reached the center about three days later. After phagocytosis of the original fibers, presumptive myoblasts within the grafts differentiated into myoblasts and myotubes. The formation of myotubes followed a biphasic pattern of development comparable to that of normal fetal muscle. Although most of the myotubes were formed within the basal lamina remaining from the original fiber, there was also evidence for regeneration outside the basal lamina. Myotubes matured into muscle fibers which were essentially normal in apperance when examined up to 180 days after grafting. Some fibers, however, were atrophic, presumably due to a failure to become innervated, and some fibers were joined by myo-myous junctions. Pre-denervated grafts and Marcaine-treated grafts were also examined. There were more surviving fibers in pre-denervated grafts, and cell-mediated destruction of degenerating fibers proceeded more rapidly than in normal grafts. No surviving fibers were found in Marcaine-treated grafts. The changes in these grafts were otherwise similar to normal grafts. A schematic model of the spatial and temporal sequence of degeneration and regeneration within a free muscle graft is presented.

Animals↗

The formation of muscles in regenerating limbs of the newt after denervation of the blastema.

The purpose of this experiment was to examine the relationship, if any, between nerve fibers and the formation of muscle pattern in the regenerating amphibian limb. During embryogenesis, nerve fibers grow into the limb bud at the time when the common muscle blastemas subdivide into individual muscle primordia, whereas in regeneration nerve fibers are always present. In order to learn whether or not the muscle pattern could be laid down in the absence of nerves we amputated 58 limbs of newts (Notophthalmus viridescens) at the mid humeral level and allowed them to regenerate to the medium-bud or late-bud stage. The limbs were then denervated. The majority of limbs denervated at the medium-bud stage either regressed or failed to regenerate further. Regeneration after denervation failed in 9 of 25 limbs denervated at the late-bud stages. In those limbs that continued to regenerate after denervation, the formation of individual muscle primordia did occur, following the same sequence with respect to the gross stage of regeneration as innervated regenerates. In comparing these results with our previous results on the development of muscular pattern in aneurogenic limbs of the axolotl, we conclude that in neither the embryonic nor the regenerating amphibian limb are nerve fibers directly involved in the subdivision of common muscle blastemas into the primordia of individual muscles.

Animals↗

Regeneration of skeletal muscle after grafting in monkeys.

Twenty-five palmaris longus muscles were transplanted into the forearm (orthotopic autografts) or into the face (heterotopic autografts) in 15 Rhesus monkeys. These muscles were transplanted with or without anastomosis to a motor nerve. No significant difference was observed long-term between the grafts done with or without prior denervation of the muscle. The forearm muscle grafts without neurorrhaphies formed a static, fibrous sling which did not contract. The forearm autografts with neurorrhaphy and the grafts to the face, with or without neurorrhaphy, all developed regenerating skeletal muscle fibers and showed contractile activity.

Animals↗

A review of muscle transplantation in mammals.

Recent research in the field of mammalian muscle transplantation is reviewed with respect to the typical postoperative course of a free muscle graft. Several questions of clinical relevance are discussed, such as 1) whether or not predenervation of a muscle graft is necessary, 2) the issue of survival vs. regeneration of muscle fibres within the graft, and 3) whether or not a muscle must be grafted as an intact anatomical unit. In addition problems of neuromuscular relations are discussed.

Animals↗

The free autografting of entire limb muscles in the cat: morphology.

Normal or pre-denervated extensor digitorum longus (EDL) muscles were sucessfully grafted in place of the contralateral EDL muscles in cats. Histological preparations of 57 grafts were examined at intervals from 4 to 170 days after transplantation. The morphological sequence of events in a cat muscle graft is similar to that in the rat except that the time course of regeneration is considerably slower. Surviving original muscle fibers form a thin rim at the periphery of the graft. Beneath this rim, the original muscle fibers undergo fragmentation, starting near the periphery and progressing toward the center. Regenerating muscle fibers take the place of the degenerated muscle fibers. In pre-denervated grafts, the last of the original muscle fibers in the center of the graft have broken down by 41 days whereas in normal muscle grafts the original muscle fibers in the central region persist until 50 days. The main difference between grafts of normal and pre-denervated muscles is the rate of breakdown of the original muscle fibers. Long term grafts of both groups are morphologically very similar.

Animals↗

A scanning electron microscopic comparison of the development of embryonic and regenerating limbs in the axolotl.

A comparison between the surface features of embryonic limb development and limb regeneration was made in the axolotl. Scanning electron microscopy revealed an overall similarity between embryonic and regenerating limbs. A notable feature was the lack of a morphologically discrete apical epidermal specialization on the surface of any of the limbs. Histological preparations revealed no thickening of the apical epidermis in embryonic limbs. There is a definite thickening of the apical epidermis in regenerating limbs during the stages of dedifferentiation and the early blastemal phases, but the thickening projects into the underlying tissues rather than altering the smooth surface contours of the blastema. Minor differences in epidermal specializations (ciliated cells scattered over the entire body and very irregularly shaped cells with knob-like projections at the tips of digits in embryos) may be attributable to differences in overall activity of the animals at various stages in their life history.

Ambystoma↗

Inhibition and axial deviation of limb regeneration in the newt by means of a digit implanted into the amputated limb.

This research was designed to follow up the observation of Thornton and Kraemer ('51) that regressed, denervated limbs of Ambystoma larvae will not regenerate upon reinnervation if all digits on the limbs were not completely resorbed. The object of this experiment was to determine whether the presence of an apical structure, protruding past the amputation surface, would affect the regenerative process. Both forearms of adult newts were amputated midway between the elbow and the wrist. One limb served as a normal regeneration control, and in the other limb the third digit from the removed hand was implanted in place of the removed radius, so that the three distal phalangeal segments protruded past the plane of amputation. Blastema formation in the experimental limbs was delayed by several weeks as compared with control limbs. Approximately one third of the experimental limbs did not regenerate. The regenerates that did form were strongly deviated (45-90 degrees) radially from the longitudinal axis of the limb. Experimental analysis showed that the delay in regeneration is due largely to the projecting part of the digit. The radial deviation of the regenerates is not due to the digital implant, but rather to the removal of the radius. Trauma alone does not account for this phenomenon.

Ambystoma↗

Developmental patterns of glycolytic enzymes in regenerating skeletal muscle after autogenous free grafting.

Extensor digitorum longus muscles of rats were removed and injected with a solution of Marcaine plus hyaluronidase. After incubation in Marcaine solution for 10 min, the muscles were grafted into their original beds. The grafts and the contralateral control muscles were removed from the rats at 0, 1-5, 7, 11, 36, and 69 days postoperatively. The muscles were then frozen in dry ice and isopentane and subsequently homogenized and centrifuged. The supernatant was analyzed for a number of enzymes, the regenerative patterns of which can be classified into 3 groups: (1) early increase in activity: hexokinase, glucose-6-phosphate dehydrogenase; (2) early decrease in activity with failure to recover to control levels: phosphorylase, phosphofructokinase, alpha-glycerophosphate dehydrogenase; and (3) early decrease followed by return to control levels: lactate dehydrogenase, pyruvate kinase, creatine phosphokinase, adenylate kinase. These patterns are not identical to those reported for embryogenesis of muscle. The data are discussed with regard to correlative histological studies of muscle regeneration.

Adenylate Kinase↗

A staging system for forelimb regeneration in the axolotl, Ambystoma mexicanum.

A staging system has been devised for normal regeneration from the upper arm in the mature axolotl. It consists of seven externally definable stages: (1) Wound healing (WH): (2) Dedifferentiation (DD); (3) Early bud (EB); (4) Medium bud (MB); (5) Late bud (LB); (6) Palette (Pal), and (7) Digital outgrowth (DO). Serial histological sections of 38 regenerating limbs were used to correlate gross stages with microscopic events in the regenerative process.

Ambystoma↗