Vertebral Route Research Articles

Intervertebral administration of 153Samarium with kyphoplasty for vertebral metastases

13136 Background: Kyphoplasty is an effective procedure to alleviate pain in metastatic vertebrae. 153Samarium-EDTMP (153Sm) is used for palliative treatment of multiple bone metastases. The hematological toxicity is the main limiting factor. Objectives: Study the feasibility of intervertebral administration of 153 SM with Kyphoplasty. Assess procedure related morbidities specifically haematological since a direct vertebral route is planned though to a much smaller dose. Methods: IRB approval for an off label use of 153Sm-EDTMP was obtained. Six patients with documented vertebral bone metastasis and pathological compression fractures were studied (Thoracic in 2 and lumbar in 4). Primary cancer was lung in 2, prostate (1), maxillary sinus (1), myeloma (1) and colon (1). Serial dilution of 153 SM was performed to obtain 2 mci/1ml. Kyphoplasty procedure was carried out using the known protocol. 2 mCi of 153Sm was admixed with the bone cement and administered under tight radiation safety measures. Serial nuclear body scans were obtained. Pain assessment was evaluated using analog pain score at 1, 7 and 30 days. Serial blood counts are followed. Results: All patients tolerated procedure well. No immediate procedure(s) related morbidities were noted. One case was not technically satisfactory and no significant uptake was detected in the injected vertebra. Nuclear scan done on 0 revealed excellent radiotracer uptake in the other 5 vertebrae injected. The absorbed radiotracer was seen to target other skeletal metastatic lesions in 2 patients. There was no significant change in WBC, HCT or Platelets seen in blood counts obtained over one month post-procedure. Except for the first patient, no appreciable radiation leakage was encountered. Pain score was reduced from a mean of 8.5 to 3.2 during the first week and was maintained below score of 4 at one month assessment. Conclusions: The combination of intervertebral administration of 153SM and Kyphoplasty seems to be well tolerated. No haematological side effects were encountered; probably due to the use of only 2 mci compared to over 70 mci in intravenous administration. Pain control seems to be satisfactory at areas treated. Analysis of procedure related radiological changes is underway. No significant financial relationships to disclose.

Enkephalins, substance P, bradykinin and angiotensin II: Differential sites of action on the hypothalamo-neurohypophysial system

To test the hypothesis that enkephalins, substance P, bradykinin and angiotensin II could act as neurohumoral modulators of hypothalamic function, these peptides (0.01-20 microgram) were injected into the general circulation of anesthetized rats, and changes in hypothalamo-neurohypophysial activity were determined by continuously monitoring the amplitude of antidromic compound action potentials (CAP) in the hypothalamo-hypophysial tract. A decrease of CAP amplitude was taken to indicate an increase of orthodromic impulse traffic. All peptides elicited a CAP decrease. On a molar basis when injected i.v., the enkephalin analog FK 33-824 was the most effective substance, followed by substance P, Leu-enkephalin and angiotensin II. Enkephalins and substance P injected through the internal carotid artery, were 2-5 times more effective than when injected i.v., whereas bradykinin was most effective when it reached the brain through a vertebral route. Angiotensin II produced the same CAP decrease irrespective of the route of administration and, in contradistinction to the other peptides, its effect was not abolished by stalk section. Tachyphylaxis and reversibility with naloxone was observed only for the enkephalins. The data suggest that sites of action are the hypothalamus for enkephalins and substance P, the neurohypophysis for angiotensin II, and the hindbrain for bradykinin.

Studies on the cardiovascular depressor actions of St 91 — an analogue of clonidine

St 91 is an analogue of the α-adrenoceptor agonist and antihypertensive agent clonidine. I.v. infusion of St 91 (8 μg/kg/min, 2 min) produces an immediate but transient pressor response and a prolonged bradycardia but, unlike clonidine, it produces no hypotension, allegedly because this drug does not penetrate the C.N.S. It was found that, after pretreatment with phenoxybenzamine (1.5 mg/kg, i.v.) an infusion of St 91 (8 μg/kg/min, 2 min) produced a much diminished pressor response and a later small hypotension, while still causing the same degree of bradycardia. Infusion of St 91 (4–16 μg/kg over 2 min) into the vertebral artery (i.a. vert.) produced dose-dependent hypotension and bradycardia only, which were reversed by piperoxan (300 μg/kg, intracisternal). There was no significant difference in the potency of St 91 when given i.a. vert. or i.c.m. (5–20 μg/kg) and the dose-response curves for hypotension and bradycardia were parallel, although the onset of effects was more rapid via the vertebral route. It is suggested that St 91 can cross the blood-brain barrier although why no hypotension is observed after i.v. administration still remains obscure.