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Cervical epidural steroid injection with intrinsic spinal cord damage. Two case reports.

STUDY DESIGN: Intrinsic cervical spinal cord damage represents the serious and permanent complications that can occur if cervical epidural steroid injections are administered while the patient is sedated. Two case reports are presented. OBJECTIVES: To draw attention to the dangerous consequences that can arise from sedating a patient before administering a cervical epidural steroid injection. SUMMARY OF BACKGROUND DATA: Reported complications of cervical epidural steroid injections have been minor and infrequent. No reports of intrinsic cervical cord damage could be found in a comprehensive English language literature search. METHODS: Two case reports of permanent intrinsic cervical cord damage in patients who had been administered cervical epidural steroid injections while under intravenous sedation are presented. Magnetic resonance imaging was performed before and after the administration of cervical epidural steroid injections. Each patient had herniated nucleus pulposus before they received cervical epidural steroid injections and intrinsic cord damage on postinjection magnetic resonance images. RESULTS: Both patients developed increased pain and neurologic symptoms within 24 hours of injection. To date, these symptoms appear to be permanent. However, Patient 1 had pain relief in her right arm and shoulder after undergoing a microdiscectomy, but pain was still persistent in her left leg, and she has developed a positive Lhermitte's sign. CONCLUSION: These case reports indicate fluoroscopic guidance will not insure or prevent intrathecal perforation or spinal cord penetration during the administration of cervical epidural steroid injections. In addition, although intravenous sedations during cervical epidural steroid injections have been used numerous times without reported complications, it appears intravenous sedation in these two cases resulted in the inability of the patient to experience the expected pain and paresthesias at the time of spinal cord irritation. Therefore, the authors conclude that the patient should be fully awake during the administration of cervical epidural steroid injections, with only local anesthetic in the skin used for analgesia.

Adult↗

Induction of specific unresponsiveness (tolerance) to skin allografts by intrathymic donor-specific splenocyte injection in antilymphocyte serum-treated mice.

Although chronic immunosuppression has been extremely successful in clinical organ transplantation, it is associated with severe complications such as opportunistic infections, spontaneous neoplasms, drug toxicities, metabolic complications, and the inability to control rejection. We therefore have investigated the ability of allogeneic donor lymphoid cells to produce specific tolerance following intrathymic (IT) injection into allograft recipients. Groups of B6AF1 mice received ALS on days -1 and +2 relative to C3H/He skin grafts on day 0; experimental groups received 1, 5, or 10 x 10(7) syngeneic (B6AF1) or allogeneic (C3H) spleen cells (SPCs) by IT injection on day +7. IT injection of C3H splenocytes significantly prolonged allograft survival at all cell doses tested when compared with ALS controls. The best survival was obtained following IT injection of 5 x 10(7) C3H cells (median survival time [MST] = 132 days; ALS controls = 21.5 days), with 8 of 13 skin grafts surviving longer than 100 days. IT injection of syngeneic splenocytes or third-party DBA/2 splenocytes did not prolong allograft survival beyond that observed in ALS controls. C3H spleen cells injected IT into ALS treated mice on day 0 relative to grafting of C3H skin also produced significant allograft survival (1, 5, or 10 x 10(7) SPCs = MSTs of 75, 47, and 35, respectively) but the results were inferior to those obtained by 5 x 10(7) SPCs IT on day +7. Spleen cells (1 or 5 x 10(7)) injected intraperitoneally or intravenously prolonged allograft survival beyond that seen in ALS controls but were inferior to IT injection at all doses and times studied. Bone marrow, thymocytes, or lymph node cells (5 x 10(7) cells) were substituted for SPCs for IT injection. IT injection of BM, LN or thymocytes all significantly prolonged graft survival over ALS controls. However none of these cell types was as effective as IT splenocytes. Eight B6Af1 recipients of IT splenocytes bearing C3H skin grafts for > 100 days received a second C3H skin graft as well as a simultaneous third-party B10.AKM skin graft. All rejected third-party grafts in normal first-set fashion. Three tolerated both 1st and 2nd C3H grafts without any sign of rejection; 1 rejected the 2nd C3H graft while tolerating the 1st graft; and 4 rejected the 2nd C3H graft in an attenuated fashion but also rejected the 1st graft at the same pace.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cervical epidural steroid injections for symptomatic disc herniations.

OBJECTIVES: Cervical disc herniations are a common cause of radicular pain from nerve root impingement and may necessitate surgical decompression to alleviate symptoms. The use of cervical epidural injections has not been studied in detail. The objective of this retrospective study was to examine the efficacy of cervical epidural steroid injections for the treatment of symptomatic herniated cervical discs. METHODS: Patients with herniated cervical discs without myelopathy that had failed conservative management and were otherwise surgical candidates were offered a trial of cervical epidural injections. The results and benefits of the injections were examined as well as the incidence of proceeding to surgical intervention. RESULTS: Of the 70 treated patients, 44 (63%) had significant relief of their symptoms and did not wish to proceed with surgical treatment. Of the 26 patients who underwent surgical decompression, 92% had successful resolution of their symptoms. The nonsurgical and surgical groups were similar in terms of gender, preinjection symptoms, or number of injections. However, significant differences between the two groups were found with regard to age (P<0.05) and time from initial consultation to initial injection (P<0.05). With an average of 13-month follow-up, 45 (65.3%) patients reported a good/excellent result per Odom criteria. In addition, 53 (75%) would attempt cervical epidural steroid injections again in the future. No complications were noted in our series. CONCLUSIONS: Cervical epidural injections are a reasonable part of the nonoperative treatment of patients with symptomatic cervical disc herniations. The success rates appear to be very similar to prior studies of lumbar epidural injections for symptomatic lumbar disc herniations. It appears that a large percentage of the patients may obtain relief from radicular symptoms and avoid surgery for the follow-up period up to 1 year. In addition, patients older than 50 years and those who received the injections earlier, less than 100 days from diagnosis, seemed to have a more favorable outcome.

Adult↗

Accumulation in tumor tissue of adoptively transferred T cells: A comparison between intravenous and intraperitoneal injection.

Accumulation of T cells at the tumor is essential in cancer immunotherapy based on adoptive transfer of tumor-specific T cells. To gain further insight into the accumulation process and to evaluate the effect of using different routes of cell transfer, we investigated the accumulation of ovalbumin-specific CD8+ T cells (OT-I) injected either intravenously (IV) or intraperitoneally (IP) into mice carrying a subcutaneous tumor of the ovalbumin-expressing melanoma cell line B16-OVA. Maximal accumulation of the adoptively transferred cells in tumor tissue was observed 5 days after injection, irrespective of the injection route. The route of injection affected neither the total number of adoptively transferred cells found in tumor tissue nor the kinetics of this accumulation. In the spleen, however, the accumulation of adoptively transferred cells was clearly dependent on the injection route. IP injections resulted in a large number of adoptively transferred cells in the spleen on all days analyzed. In comparison, IV injection resulted in significantly fewer adoptively transferred cells in the spleen, and this number decreased over time. The route of injection affected neither the activation status of the adoptively transferred T cells that accumulated at the tumor site, nor the ability of these cells to control tumor growth. Two cell populations, SIINFEKL-tetramer(Low)(Tet(Low))CD69+ CD25+ and Tet(high)CD69- CD25-, were present in tumor samples, whereas only Tet(High)CD69- CD25- cells accumulated in the spleen. In tumors, IV injection resulted in a higher fraction of adoptively transferred cells with an activated phenotype (Tet(Low)CD69+ CD25+) compared with IP injection.

Adoptive Transfer↗

Intratympanic injections of dexamethasone for long-term control of vertigo.

OBJECTIVE: To examine whether intratympanic injection of dexamethasone is effective in long-term control of vertigo for patients with Ménière disease whose dietary and diuretic therapy has proved unsuccessful. STUDY DESIGN: Retrospective chart review performed at Carolina Ear and Hearing Clinic, Raleigh, North Carolina. METHODS: Thirty-four patients with intractable Meniere disease were given intratympanic injections of corticosteroids using dexamethasone 10 mg/mL for 4 weeks. The control of vertigo was documented in the 2-year period after completion of the course of injections. All patients were continued on a diet and a diuretic during the study period. RESULTS: Only 24% (8 of 34) of patients had control of vertigo with a single course of injections. Three patients had control of vertigo for 12 months and responded to a repeat series of injections with good control. Five patients who had recurrent vertigo at 6 months or earlier responded to repeat injections, for a total of 16 patients (47%) whose vertigo was controlled with a single course or multiple courses of intratympanic injections of corticosteroids. CONCLUSIONS: Approximately one-half of patients (47%) with intractable Ménière disease achieved control of vertigo with one or more courses of intratympanic injections of corticosteroids. A single course of treatment alone can be expected to produce long-term control of vertigo in only one-fourth (24%) of patients. This study indicates that intratympanic injections of corticosteroids should not be expected to give long-term control of vertigo in patients with Ménière disease. Multiple courses of intratympanic injections of corticosteroids, in conjunction with other treatments, are necessary in most patients with Ménière disease who have intractable vertigo.

Dexamethasone↗

Office steroid injections of the larynx.

OBJECTIVE: Steroid injection into the larynx has been sporadically reported as helpful in benign lesions of the larynx. Its role in laryngology remains unclear. This study reviews the indications and results of 47 steroid injections in 34 patients in an office setting. METHODS: The authors conducted a retrospective review of 47 injections in 34 patients. Methylprednisolone acetate suspension, USP (40 mg/mL), was injected by indirect laryngoscopy under local anesthesia. Results were evaluated by stroboscopy and by perceptual evaluation of the GRABS scale before and after injection. Pre- versus postinjection ratings were compared by paired t test. RESULTS: Indications for injection were: 1) postoperative scar with local stiffness (12 patients), 2) vocal nodules and polyp (18 patients), and 3) sarcoidosis/granuloma (4 patients). Steroid injections were done in professional singers instead of repeated oral administration of steroids and/or to avoid surgery in patients with polyps and cysts. Improvement was noted in 28 of 34 (82%). Eleven of the 18 patients with polyps and nodules had significant improvement and avoided surgery. Vocal fold scars improved after injection with an improved voice grade (P < .01), an improved amplitude (P < .05), and improved mucosal wave (P < .05). There were no complications. Only two patients could not tolerate office injection. CONCLUSION: Office steroid injections are a valuable adjunct in management of vocal fold scars, polyps, nodules, and granulomas.

Anti-Inflammatory Agents↗

Power injection of microcatheters: an in vitro comparison.

PURPOSE: To determine the tolerance of 0.021-inch and 0.027-inch microcatheters to power injection in an in vitro flow model. MATERIALS AND METHODS: Twenty-four microcatheters (0.021-inch, n = 13; 0.027-inch, n = 11) were injected with iothalamate meglumine through a flow model with use of a power injector and high-pressure tubing. Catheters used included Rebar (0.021-inch, n = 4; 0.027-inch, n = 4), Transit (0.021-inch, n = 3; 0.027-inch, n = 3), Renegade (0.021-inch, n = 4; 0.027-inch, n = 4), and Renegade STC-18 (0.021-inch, n = 2) models. Through the 0.021-inch microcatheters, 5-second injections were performed at an initial rate of 0.7 mL/sec. Injection rates were increased by 0.5 mL/sec and the process was repeated until the pressure approached 1,000 psi or catheter breakage occurred. A similar process was repeated for the 0.027-inch catheters starting at a rate of 3.4 mL/sec. RESULTS: The 0.021-inch catheters were injected 303 times and the 0.027-inch catheters were injected 210 times. Three catheter failures occurred, with all breaks occurring at pressures greater than manufacturer recommendations. The 0.027-inch catheters as a group tolerated significantly higher injection rates than the 0.021-inch catheters. Of the 0.021-inch catheters, the STC-18 also provided superior maximum flow and volume compared with the Renegade catheter. The Rebar catheter tolerated significantly lower maximum injection rates and volumes than the other 0.027-inch catheters. CONCLUSIONS: The majority of microcatheters can be power-injected in vitro at pressures far greater than manufacturer recommendations. When fractures occur, they are near the hub of the catheter. Significantly greater rates of injection are possible through 0.027-inch catheters.

Catheterization↗

Intraoperative subareolar radioisotope injection for immediate sentinel lymph node biopsy.

OBJECTIVE: To determine the identification of sentinel lymph node biopsy (SLNB) in breast cancer patients after intraoperative injection of unfiltered technetium-99m sulfur colloid (Tc-99) and blue dye. BACKGROUND: SLNB guided by a combination of radioisotope and blue dye injection yields the best identification rates in breast cancer patients. Radioisotope is given preoperatively, without local anesthesia, whereas blue dye is given intraoperatively. We hypothesized that, because of the rapid drainage noted with the subareolar injection technique of radioisotope, intraoperative injection would be feasible and less painful for SLN localization in breast cancer patients. METHODS: Intraoperative injection of Tc-99 and confirmation blue dye was performed using the subareolar technique for SLNB in patients with operable breast cancer. The time lapse between injection and axillary incision, the background count, the preincision and ex vivo counts of the hot nodes, and the axillary bed counts were documented. The identification rate was recorded. RESULTS: Ninety-six SLNB procedures were done in 88 patients with breast cancer employing intraoperative subareolar injection technique for both radioisotope (all 96 procedures) and blue dye (93 procedures) injections. Ninety-three (97%) procedures had successful identification; all SLNs were hot; 91 (of 93 procedures with blue dye) were blue and hot. The mean time from radioisotope injection to incision was 19.9 minutes (SD 8.5 minutes). The mean highest 10 second count was 88,544 (SD 55,954). Three of 96 (3%) patients with failure of localization had previous excisional biopsies: 1 circumareolar and 2 upper outer quadrant incisions that may have disrupted the lymphatic flow. CONCLUSION: Intraoperative subareolar injection of radioisotope rapidly drains to the SLNs and allows immediate staging of the axilla, avoiding the need to coordinate diagnostic services and a painful preoperative procedure.

Aged↗

Effect of injection site on the pharmacokinetics and pharmacodynamics of subcutaneously administered luteinizing hormone releasing hormone.

Serum concentrations of LHRH and the subsequent LH responses were compared following s.c. injections of 20 micrograms LHRH into the upper arm and the lower abdominal wall, in 9 hypogonadal women responsive to pulsatile LHRH therapy. Tests were carried out at the two sites in random order. Peak LHRH concentrations were reached by 5 min after upper arm and by 20 min after lower abdominal wall injections, the maximum concentrations being significantly greater following injections into the former. There was no increase in LH until 10 min and then maximum concentrations were reached at 30 min following injection into both sites. There was no significant correlation between the LHRH increments and the LH response but there was a negative correlation between the Ponderal Index of the patients and the LHRH increments following injections into the lower abdominal wall only. There was no significant overall difference between the LH increments related to the site of injection, but the order of injections affected the responses. When upper arm injections were given first the LH responses were significantly greater, but when lower abdominal wall was injected first the subsequent responses to upper arm injections were impaired. A possible reason for this is that the absorption from the lower abdominal wall was delayed so prolonging the exposure of the pituitary gonadotrophs to LHRH, resulting in pituitary desensitization at the time of the second test.

Abdominal Muscles↗

Reducing injection pain in children and adolescents with diabetes: a review of indwelling catheters.

Most children and adolescents find the pain when injecting insulin quite minimal but still significantly more painful than a placebo injection. However, injection pain and needle phobia are major problems for a small number of patients, even after many years of diabetes. Needle diameter is of less importance for the experienced pain. The use of indwelling catheters (Insuflon, Unomedical, Lynge, Denmark) for introducing insulin injections at the onset of diabetes results in an evident relief of preinjection anxiety, injection problems, and the procedural pain of repeated injections. The average indwelling time is 3-5 d. Fixation problems and local redness at the insertion site are the most frequent side effects. However, the frequency is low and they can be dealt with effectively. Needles of 8-10 mm should be used for injecting to avoid penetration of the tubing of the catheter. Using indwelling catheters for up to 4-5 d does not affect the absorption of insulin, when the catheter is inserted in an area free from lipohypertrophies. The long-term (measured by hemoglobin A1c) and short-term metabolic control (measured by blood glucose profiles and serum-free insulin) is not altered. Using this type of injection aid may decrease the risk of future injection problems, such as needle phobia, in very select patients. In conclusion, indwelling catheters can safely be used from the onset of diabetes to lessen injection pain in children and adolescents, and may facilitate the use of intensive insulin therapy in this age group.

Adolescent↗

Injectable polydimethylsiloxane for treating incontinence in children with the exstrophy-epispadias complex: long-term results.

OBJECTIVE: To present our experience with the use of injectable polydimethylsiloxane (Macroplastique, Uroplasty, Minneapolis, MI, USA) for treating incontinence in children with the exstrophy-epispadias complex (EEC), as incontinence continues to be a challenging problem in such children, and although the primary management of EEC has developed over the last few decades, with early closure and reconstruction of the penis, achieving satisfactory continence status remains elusive. PATIENTS AND METHODS: We retrospectively reviewed the hospital records of 52 patients (41 boys and 11 girls, mean age at first injection 6.6 years, range 3.6-16.7) with EEC who had injections with Macroplastique between January 1991 and February 2004; 34 had bladder exstrophy and 18 primary epispadias. For this study we defined success as complete dryness with no use of pads or nappies. Improvement was defined as being occasionally wet but with dry intervals lasting >or= 4 h. RESULTS: The mean (range) follow-up was 4.6 (0.5-9) years. Twenty patients had one injection, 10 had two, 13 had three, six had four, two had six and one had seven injections. In most patients a maximum of three injections predicted the outcome. The injection of Macroplastique was successful in nine patients (17%; with an annual follow-up, two at 1-2 years, three at 2-5 years and four at >5 years), whilst 17 (33%) improved significantly (one at <1 year, two at 1-2 years, eight at 2-5 years and six at >5 years). Those patients comprised five of 18 (27%) with epispadias and four of 34 (12%) with exstrophy. A history of previous surgery and gender had no significant effect on the outcome. Overall half the patients benefited from the procedure. CONCLUSIONS: This series confirms that injection with Macroplastique is minimally invasive, durable in significantly many patients and has a reasonable success rate. A history of previous surgery and gender had no significant effect on the outcome. Patients with epispadias are more likely to benefit from an injection with Macroplastique than those with bladder exstrophy. A maximum of three injections is predictive with reasonable certainty of any benefit from the procedure.

Adolescent↗

Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin.

The absorption of isophane(NPH) insulin (Human Insulatard) from palpably abnormal thigh insulin injection sites was determined in 10 C-peptide negative diabetic patients. Absorption was compared with a control day study when the insulin was injected into normal thigh. Standard meals were given 30 and 240 min after the injection. Within 2 weeks the tissue morphology and adipose tissue depths at both injection sites were assessed by ultrasound scanning. Absorption of isophane(NPH) insulin was markedly defective from the abnormal compared with the normal injection sites (area under the free insulin curve to 10 h 115 +/- 15 vs 188 +/- 21 mU l-1 h; p less than 0.01). The area under the blood glucose curve from 270 min to the end of the study at 600 min was significantly greater after injection into the palpably abnormal injection site compared with normal thigh (80.4 +/- 5.2 vs 61.2 +/- 7.0 mmol l-1 h; p less than 0.05) representing a 22% improvement in blood glucose control on the normal injection site afternoon. The depth of abnormal injection site tissue was significantly greater than the depth of adipose tissue at the control site (17 +/- 6 vs 5 +/- 4 mm; p less than 0.001) and considerable disruption of the normal anatomy observed. These results demonstrate defective absorption of isophane(NPH) insulin from palpably abnormal injection sites and describe the morphology of the abnormal tissue.

Absorption↗

Electrocerebral recovery during the intracarotid amobarbital procedure: influence of interval between injections.

PURPOSE AND METHODS: During the intracarotid amobarbital procedure (IAP) at the University of Michigan, continuous scalp EEG monitoring guides the timing for presentation of memory items and postinjection testing. Most of our patients have undergone bilateral injections. The interval between injections varied from 22 to 60 min, depending on the test and recovery time, as well as the time to catheterize the second side. After noting a trend toward prolonged electrographic recovery following the second injection, we tested our clinical impression that recovery of the second hemisphere may be influenced by (a) the time between injections and (b) which hemisphere is injected first (epileptogenic or nonepileptogenic). To study these questions, we analyzed EEG recovery data from 48 consecutive IAPs. Approximately half the patients had the epileptogenic side injected first. RESULTS: We found that (a) electrographic recovery after the second injection is prolonged if the interval between bilateral injections is less than 40 minutes and (b) electrographic recovery is more rapid after injection of the epileptogenic hemisphere. CONCLUSIONS: We now recommend waiting at least 45 min between injections. The pathophysiology of more prolonged amobarbital effect on the nonepileptogenic hemisphere than on the epileptogenic hemisphere remains unclear.

Amobarbital↗

A randomised study of two training programmes for general practitioners in the techniques of shoulder injection.

OBJECTIVES: To evaluate the impact of two different modes of shoulder injection training on the level of confidence and number of injections performed by general practitioners (GPs) METHODS: Demographic details, and information on referrals for shoulder problems, shoulder joint injection activity, and confidence in the six months before training were obtained for 40 GP principals at baseline. Standardised training in the techniques of shoulder joint injection using rubber mannequins was given to all GPs. Twenty of these GPs were randomly allocated to receive additional training on patients in hospital joint injection clinics. Six months after both forms of training the shoulder injection and referral activities of all GPs were reassessed. RESULTS: Both training groups had comparable demographic characteristics and baseline clinical activity. GPs who had additional training with patients reported a marked increase in their level of confidence in performing shoulder injections and the number performed. The number of shoulder referrals did not differ between the groups CONCLUSION: Training on patients in addition to conventional training on mannequins increased GPs' shoulder injection activity and their level of confidence. Hospital injection clinics may provide a suitable setting in which to train GPs interested in developing their shoulder joint injection skills.

Clinical Competence↗

Intraocular pressure after intravitreal injection of triamcinolone acetonide.

AIM: To investigate the intraocular pressure (IOP) response after intravitreal injections of triamcinolone acetonide as treatment of intraocular neovascular or oedematous diseases. METHODS: The prospective consecutive non-comparative interventional case series study included 71 patients (75 eyes) with progressive exudative age related macular degeneration (n = 64 eyes) or diffuse diabetic macular oedema (n = 11 eyes), who received an intravitreal injection of 25 mg triamcinolone acetonide. Mean follow up time was 6.86 (SD 2.52) months (range 3.1-14.47 months). RESULTS: IOP increased significantly (p<0.001) from 15.43 (3.26) mm Hg preoperatively to a mean maximum of 23.38 (8.37) mm Hg (range 13-64 mm Hg) postoperatively. An IOP rise to values higher than 21 mm Hg was observed in 39 (52%) eyes. Elevation of IOP occurred about 2 months after the injection. Preoperative predictive factor for the rise in IOP was younger age (p=0.013). It was statistically independent of refractive error, presence of diabetes mellitus, and indication for the injection. In all but one eye, IOP could be lowered to the normal range with topical medication, without development of glaucomatous optic nerve head changes. In the eyes with an elevation of IOP, IOP normalised about 6 months after the injection, without further medication. Eyes undergoing repeatedly intravitreal injections of triamcinolone acetonide showed only an elevation of IOP, if after the first injection a rise of IOP had occurred. CONCLUSIONS: After intravitreal injections of 25 mg of triamcinolone acetonide, an IOP elevation can develop in about 50% of eyes, starting about 1-2 months after the injection. In the vast majority, IOP can be normalised by topical medication, and returns to normal values without further medication about 6 months after the injection.

Aged↗

Effects of injecting electronic transponders into the auricle of pigs.

Electronic transponders (3 x 18 mm) were injected into the base of the auricle of 69 10-day-old pigs, 111 four-week-old pigs and 24 six-month-old pigs, to examine the procedure of injection in the auricle, the tissue reaction and the ease of removal from the carcase. The injection was difficult in the 10-day-old pigs, but was easier at four weeks. One of the 204 transponders were lost and five of them appeared to be broken. Only one gilt showed some exudate around the transponder. The transponders could easily be removed when the pigs were slaughtered by cutting off the ear. The position of the transponder was significantly (P < 0.05) more ventral in the animals injected at 10 days old than in those injected at four weeks. The mean thickness of the connective tissue capsule around the transponders increased at first (P < 0.1) and then decreased when they were injected into 10-day-old pigs but decreased (P < 0.1) from shortly after injection in the pigs injected at four weeks old. After five months, the capsule in the animals injected at 10 days old was on average significantly (P < 0.01) thinner than in those injected at four weeks.

Animal Identification Systems↗

Systemic site of action for pressor effect of angiotensin II injected into the fourth cerebral ventricle of rats?

Angiotensin II (ANG II) causes a systemic pressor effect when injected into the cerebral ventricles. In the rat fourth ventricle, the effective doses for the ANG II pressor effect are over 100 times larger than in the systemic circulation. Considering the discrepancy of doses, the possibility that ANG II may reach the systemic circulation and promote pressor effects, following injection into the fourth ventricle, was investigated. The effects on blood pressure of different vasoactive peptides that produce pressor responses when injected into the central nervous system were compared. Dose-response curves were obtained for intravenous or fourth cerebroventricular injections of ANG II, lysyl-vasopressin (LVP), bradykinin (BK), or endothelin-1 (ET-1). The ED50 ratios for intracerebroventricular/intraveneous injections were 110 for ANG II, 109 for LVP, 0.01 for BK, and approximately 0.4 for ET-1. In cross-circulation preparations, pressor responses occurred in the donor rat following injection into the fourth cerebral ventricle of the recipient animal, showing that effective doses of ANG II, administered to the fourth cerebral, reach the systemic circulation. The same results were obtained for the microinjection of 4 nmol of LVP into the fourth cerebral ventricle of recipient animals. High-performance reverse-phase liquid chromatography analyses of arterial blood showed that approximately 1% of the [125I]ANG II injected into the fourth cerebral ventricle may be recovered from the systemic circulation a few seconds after the microinjection. The systemic administration of the ANG II receptor antagonist losartan blocked the response to ANG II injected into the fourth ventricle whereas antagonist administration in the same ventricle did not. Angiotensin injections into the lateral ventricle produced pressor responses that were reduced by antagonist administration to the same ventricle but not by systemic administration of the antagonist. The data suggest that the pressor effect resulting from ANG II or LVP injections into the fourth cerebral ventricle may be due to the action of this peptide in the systemic circulation. On the other hand, the pressor effect due to ANG II microinjection into the lateral ventricle apparently results from the direct stimulation of central periventricular structures.

Angiotensin II↗

Changes in serum enzyme activities after injection of bupivacaine into rat tibialis anterior.

This study investigated the time course of changes in serum creatine kinase (CK), aspartate aminotransferase (AST), and alanine amino-transferase (ALT) activities after intramuscular injection of bupivacaine into the tibialis anterior (TA) of rats. Morphological changes in muscle cells, relationships between the amount of increase in the enzyme activities and the muscle mass damaged, and responses of serum enzymes to additional injections of bupivacaine hydrochloride (BPVC) were also examined. Adult male Wistar rats (24 wk) were placed into one of four groups. Group A (n = 7) was a control, and no injection was applied. Saline solution (0.5 ml of 0.9%) was injected into the right TA for group B (n = 5). BPVC (0.5 ml of 0.5%) was injected into the right TA for group C (n = 9) and into both the right and left TA for group D (n = 9). No increases in CK, AST, and ALT were observed for groups A and B. After BPVC injection, groups C and D showed significant (P < 0.01) increases in serum enzyme activities. CK peaked 4 h after BPVC injection, and AST and ALT peaked 12 h postinjection, then returned to the baseline by the time infiltration of mononuclear cells into the damaged muscle cells progressed. The amount of enzyme increase was significantly larger (P < 0.01) for group D compared with group C. Injection of BPVC into the right then into the left TA 4 h later displayed a bipolar response, and the second injection into the TA 12 wk after the first injection resulted in smaller increase in serum enzyme activities. It appeared that increases in serum enzyme activities reflected muscle damage; however, changes in enzymes occurred in the early stage of myonecrosis.

Alanine Transaminase↗