Use Of ACTH Research Articles

EFFECT OF ACTG(4-7)-PRO-GLY-PRO AND ACTG(6-9)-PRO-GLY-PRO ON THE INTENSITY OF REDOX PROCESSES AND BEHAVIOURAL STATUS OF RATS UNDER THYROID HYPERFUNCTION CONDITIONS

The aim of the work is to study the effect of melanocortins on the intensity of redox processes in the prefrontal region of the brain and the behavioral status of rats against the background of thyroid hyperfunction. Material and methods. In the experiment, the test animals were divided into the following groups (n = 10): intact rats (control); animals treated with sodium salt pentahydrate L-thyroxine (hyperthyroidism); rats receiving ACTH (4-7)-Pro-Gly-Pro and individuals receiving ACTH (6-9)-Pro-Gly-Pro, re-spectively, intraperitoneally daily for 21 days, starting from day 22 of administration of sodium salt pentahydrate L-thyroxine. Hyperthyroidism was simulated in animals by intragastric administration of L-thyroxine sodium salt pentahydrate for 42 days. The intensity of lipoperoxidation processes was studied by the content of diene and triene conjugates in the prefrontal zone tissue, the initial level of TBА-reactive products, and the rates of spon-taneous and ascorbic peroxidation of lipids. The level of protein peroxidation products was determined by the reaction of oxidized amino acid residues of proteins with 2,4-dinitrophenyl hydrazone. Evaluation of the enzymatic unit of the antioxidant system of the prefrontal region was carried out by de-termining the activity of superoxide dismutase and catalase. The behavioral status of laboratory rodents was studied using the «Hole board» test. Results. The use of ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro compounds under experimental hyperthyroidism led to a decrease in the intensity of the processes of peroxidation of lipids, proteins and the restoration of levels of activity of antioxidant enzymes – superoxide dismutase and catalase in the tissue of the prefrontal region of the brain of animals, as well as correction behavioral indicators in the «Hole board» test. Conclusion. The obtained experimental data indicate that ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro show antiperoxy and antioxidant activity against lipoperoxidation parameters and oxidative modification of proteins and enzymatic protection systems in the prefrontal brain zone tissue, as well as exert psychocorregating action on behavioral responses of white rats against the background of thyroid hyperfunction.

Adrenocorticotropic hormone: an effective "natural" biologic therapy for acute gout?

Treatment of acute gout consists of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids. However, the typical patient with gout has multiple comorbidities such as cardiovascular disease, hypertension, renal dysfunction or diabetes/metabolic syndrome that represent contraindications to these therapeutic options. The aim of this study is to review the available evidence regarding the use of ACTH as an alternative therapeutic option for acute gout and explore potential mechanisms of action. We performed an electronic search (MEDLINE, Scopus and Web of Science) using the keywords ACTH or adrenocorticotropic hormone combined with gout or crystal-induced arthritis. ACTH appears suitable for patients with many comorbidities due to its good safety profile. Clinical evidence shows that ACTH is at least as effective as classic agents. The mechanism of action of ACTH in gout is not entirely known. Robust experimental evidence points to the direction that ACTH does not act solely by triggering the release of endogenous steroids but also appears to downregulate inflammatory responses by activating melanocortin receptors on innate immune cells, such as macrophages. Moreover, indirect evidence indicates that ACTH may have an IL-1 antagonistic effect. We propose that ACTH may be an alternative therapeutic option for gout in patients with multiple comorbidities. Large-scale studies assessing the efficacy and safety of ACTH compared to classic therapeutic options are needed.

Prognostic usefulness of ACTH in the postoperative period of Cushing's disease.

ObjectivesTo analyze the usefulness of plasma ACTH in predicting CD remission after surgery and to evaluate the prognostic usefulness of ACTH measurement after the cortisol and ACTH nadir (48 h prior to discharge).DesignA prospective study was made of 65 patients with CD operated upon between 2005 and 2016.MethodsPostsurgery plasma ACTH and cortisol were measured every 6 h, in the absence of corticosteroid coverage. Hydrocortisone was started in the presence of adrenal insufficiency or cortisol <55.2 nmol/L. Plasma ACTH was again determined before discharge.Main outcome measureUsefulness of plasma ACTH in predicting CD remission.ResultsRemission at 3 months of CD was achieved in 56 of 65 cases, with late recurrence in 18 of 58 cases. Following resection, the ACTH nadir was significantly lower referred to late remission (2.8 vs 6.5 pmol/L; P = 0.031) and higher for recurrence (2.1 vs 4.8 pmol/L; P < 0.001), and identical results were obtained for the ACTH values before discharge. In the analysis of the ROC curves, nadir and before discharge ACTH values <1.9 pmol/L and <2.6 pmol/L were respectively indicative of early remission (AUC 0.827; P < 0.001); <6.2 pmol/L of remission at 3 months (AUC 0.847; P = 0.001) and >3.2 pmol/L of recurrence (AUC 0.810; P < 0.001) in both ACTH values. A time to ACTH nadir <46 h was indicative of early remission (AUC 0.751; P = 0.001), while a time >39 h was indicative of recurrence (AUC 0.773; P = 0.001).ConclusionsWe propose an ACTH value <3.3 pmol/L as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate.

Recombinant Factor XIIIA and ACTH(1‐24) as Adjuncts During Prolonged Hypotensive Resuscitation in swine (Sus scrofa domesticus): Optimizing Outcomes for the Prolonged Field Care Environment

BackgroundTraumatic injuries with hemorrhage are the leading cause of potentially survivable death in trauma. A permissive hypotension strategy (Goal resuscitation systolic blood pressure (SBP) of 80–90 mmHg) plus early blood product administration over a short transport interval has been linked to improved survival. If blood products are unavailable during this pre‐hospital time, crystalloids and colloids such as hydroxy ethyl starch (Hextend®) remain the standard fielded resuscitative fluid. However, studies have demonstrated the correlation of kidney injury and failure, increased risk of coagulopathy, and higher mortality risk with this treatment. To improve outcomes in this prolonged field care (PFC) setting, in the absence of blood products, we investigated the survival and therapeutic benefits of ACTH(1‐24) and rFXIIIA treatment as an adjunct to Hextend® in a permissively hypotensive PFC model of hemorrhagic shock in swine.MethodsAnesthetized male swine (n = 16) underwent pressure‐targeted, decompensated hemorrhagic shock (MAP = 30–35 mmHg) for 45 minutes followed by permissively hypotensive (SBP = 80–90) resuscitation with Hextend® for 8 hours (with or without adjuncts such as ACTH(1‐24)), simulating a PFC environment. At the end of PFC, animals were fully resuscitated (return of shed blood plus normal saline). Animals were then monitored for 24 hours and assessed for neurocognitive function via latency to food reward. Sham animals (n = 5) received only anesthesia for the same time period. Tissues and serum were isolated at euthanasia for histopathological and biomarker analysis. Results reported as mean ± SD, Statistics: two‐way ANOVA with P &lt; 0.05 significance.ResultsInitial results from this experiment indicate successful use of 500 mL (n = 5) versus 1L (n = 5) of Hextend® to model a survivable permissively hypotensive state (SBP 80–90) for up to 8 hours in swine. Hextend® treatment amount shows no significant deleterious cardiovascular (HR, BP; p &gt; 0.05) or metabolic effects (lactate, BD; p &gt; 0.05) following initial shock treatment. ROTEM analysis indicated ACTH treatment (n = 1) decreased the latency for clot formation time in the later stages of PFC compared to the Hextend® + vehicle control. Additionally, there were no significant neurological detriments induced by the prolonged permissive hypotensive state, which makes this model ideal for PFC studies of shock (p &gt; 0.05).ConclusionThis swine model of prolonged permissively hypotensive resuscitation was designed to align with pre‐hospital hemorrhage control. The use of ACTH as an adjunct to standard treatments may improve outcomes, specifically with regard to bleeding. These results extend beyond military application to the rural civilian environment, where extended pre‐hospital times are commonplace. Further investigation is underway to elucidate whether rFXIIIA + ACTH, as a combination treatment, could improve PFC outcomes.Support or Funding InformationThis work was supported by the Defense Medical Research and Development Program, Joint Program Committee 6/Combat Casualty Care Research Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Adrenocorticotropic Hormone for Steroid-Resistant and Oral Steroid-Intolerant Children With Minimal Change Nephrotic Syndrome

Background: The most frequent cause of nephrotic syndrome (NS) in childhood, minimal change disease, is generally steroid-responsive. Children who are intolerant of oral steroids or steroid-resistant still present a significant therapeutic challenge. Additionally, adverse effects of long-term corticosteroid administration warrant the search for an alternative safe and effective treatment. Here we report the use of adrenocorticotropic hormone (ACTH; H.P. Acthar® Gel), an agent originally introduced in the 1950s, for the treatment of these patients. Methods: We report 3 children with NS who were not able to attain remission with standard steroid therapy due to oral steroid intolerance or steroid resistance. Results: Two of the patients attained remission with a long-acting formulation of ACTH. Conclusions: ACTH is an option for the treatment of pediatric patients with NS who are oral steroid-intolerant. This approach may also be useful for the treatment of other steroid-responsive conditions in patients with limiting gastrointestinal toxicity to oral preparations. The use of ACTH for the treatment of steroid-resistant NS requires further investigation.

Síndromes espleno-hepáticos

Tratándose de un esfuerzo de síntesis y no da investigación, debo decir, en resumen, que la frecuencia de estos síndromes esplenohepáticos es mayor en nuestro medio; que, seguramente, exámenes más precisos permitirán encuadrarlos dentro de capítulos nosológicos precisados, hasta llegar a la desaparición del sí ndrome en sí. Es factible, se trate de cuadros clínicos. con síntomas comunes (hemorragias, esplenomegalia, hemocitopenia) con una base anatómica precisa, iniciada por trastornos neurovasculares con alteración primaria del sistema portal y de reactividad especial de su sistema retículo endotelial. No se puede hablar de precisión de lesiones esplénicas y hepáticas, ya que ambos órganos, por su especial constitución histopatológica, enferman juntos. No se conoce de manera precisa, cuáles son las formas en que el bazo actúa sobre la médula ósea, para determinar los trastornos considerados como hiperesplenismo. Las hemorragias son frecuentas desde el inicio de la enfermedad y casi siempre son gastrorragias, por los fenómenos ya señalados. En el momento actual, y por lo menos en las etapas iniciales de la enfermedad, disponemos de dos armas que, al inhibir la alteración esplénica, permiten, si no la desaparición, por lo menos la mejoría de la enfermedad. y ellas son la esplenectomía y el uso de ACTH y cortizona. Quién sabe por estos hechos, sea posible, en lo futuro, considerar el mecanismo íntimo de estas afecciones, semejante al que determina las enfermedades de adaptación.

Adrenal vein sampling in primary aldosteronism: towards a standardised protocol

Primary aldosteronism comprises subtypes that need different therapeutic strategies. Adrenal vein sampling is recognised by Endocrine Society guidelines as the only reliable way to correctly diagnose the subtype of primary aldosteronism. Unfortunately, despite being the gold-standard procedure, no standardised procedure exists either in terms of performance or interpretation criteria. In this Personal View, we address several questions that clinicians are presented with when considering adrenal vein sampling. For each of these questions we provide responses based on the available evidence, and opinions based on our experience. In particular, we discuss the most appropriate way to prepare the patient, whether adrenal vein sampling can be avoided for some subgroups of patients, the use of ACTH (1-24) during the procedure, the most appropriate criteria for interpretation of adrenal vein cannulation and lateralisation, the use of contralateral suppression, and strategies to improve success rates of adrenal vein sampling in centres with little experience.

Use of Cosyntropin for Treatment of Refractory Post Dural Puncture Headache (PDPH): Case Report and a Suggested Algorithm

Postdural Puncture Headache (PDPH) is a frequent complication of neuraxial blockade. Use of ACTH or its synthetic analogs for the treatment of PDPH has been reported in the literature since 1994. We describe a case of refractory PDPH in a 36 year old female despite two epidural blood patches (EBPs). Evidence-based algorithmic management of PDPH has never been reported in Anesthesiology literature. Based on the available evidence we developed an opinion-based algorithm for management of PDPH. The associated case report highlights the role of ACTH and the importance of algorithmic management of PDPH.

P5-18-08: A Comparative Effectiveness Analysis of Trastuzumab Persistence between Two Adjuvant Breast Cancer Treatment Regimens among US Health Plan Enrollees.

Abstract Background Approved US indications for trastuzumab include adjuvant treatment of HER2−overexpressing breast cancer in anthracycline-based (ACTH) or non-anthracycline-based (TCH) regimens. The objective of this study was to compare trastuzumab persistence across adjuvant breast cancer treatment regimens for US health plan enrollees. Materials and Methods: This retrospective cohort study using the IMS LifeLink™ Health Plan Claims Database included adjuvant breast cancer patients, defined as those with a mastectomy or lumpectomy and a primary breast cancer diagnosis (index diagnosis) from 1/1/2006 to 12/31/2008. Additional inclusion criteria were: aged ≥18 years; a second primary breast cancer diagnosis ≤90 days of the first; no other primary or secondary neoplasms ≤180 days before or ≤90 days after the index diagnosis; a first trastuzumab claim (index claim) and ≥1 carboplatin, cyclophosphamide, taxane, or anthracycline claim ≤210 days of the index diagnosis; and no trastuzumab claim before the index diagnosis. Regimens were classified as ACTH (doxorubicin, cyclophosphamide, a taxane, trastuzumab) or TCH (docetaxel, carboplatin, trastuzumab) from therapies observed after the index claim. Trastuzumab persistence (days from the index claim to earliest of trastuzumab discontinuation, a new malignant neoplasm, end of plan enrollment, 360 days after the index claim, or end of available data) was reported for patients with ≥2 trastuzumab claims and compared across regimens using the Kaplan-Meier estimator and Cox proportional hazards models. Results: 550 breast cancer patients met all study criteria (291 ACTH, 259 TCH, 46 unassigned); patients receiving TCH were older (median 52 vs. 50 years; P=0.018). For years 2006–2008, the annual share of the cohort initiating ACTH decreased from 69.3% to 35.2%; patients initiating TCH increased from 26.7% to 56.5%. Patients receiving ACTH were treated with trastuzumab for fewer days (mean=256, median=334) versus patients on TCH (mean=282, median 344, P=0.018). Fewer patients on ACTH remained on trastuzumab at day 90 (83% vs. 91%), day 180 (71% vs. 79%), day 270 (61% vs. 72%), and day 360 (20% vs. 26%). Compared to patients on TCH, patients on ACTH continued to be treated with trastuzumab for a shorter duration post-index after adjusting for age, region, plan type, prescriber specialty, and comorbidities (HR=0.77, 95% CI [0.63, 0.95]; P=0.016). Discussion: The share of adjuvant breast cancer patients initiating TCH increased from 2006 to 2008, while use of ACTH decreased over the same time period, and patients treated with TCH remained on trastuzumab for a longer period of time. From a clinical standpoint, patients derive maximum benefit from their medications when they are persistent long-term, which can lead to economic benefits with regards to lower overall healthcare costs. Further analyses will evaluate whether adjuvant breast cancer regimens differ in weight-adjusted cumulative trastuzumab doses received during therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-08.

Effect of Price on Use of ACTH for Infantile Spasms

The effect of the 14-fold price increase on Aug 27, 2007 of ACTH treatment of infantile spasms in the US was evaluated at University of Colorado, Denver, in 97 patients treated 2007-2009.

Galectin-3 Expression in Functioning and Silent ACTH-Producing Adenomas

Galectin-3 (Gal-3), a beta galactoside-binding protein, has been implicated in a variety of biological functions including cell growth, differentiation, tumor cell adhesion, angiogenesis, tumor progression, and metastasis. We recently reported that Gal-3 was expressed in a subset of normal pituitary cells and tumors including PRL, ACTH, and in folliculo-stellate (FS) cells and tumors and that Gal-3 had an important regulatory role in pituitary cell proliferation. We further investigated the expression of Gal-3 protein in ACTH- and PRL-producing tumors and the expression of various galectin mRNAs by RT-PCR in pituitary adenomas and normal pituitary. Most silent ACTH subtypes 1 and 2 adenomas were negative or only focally positive for Gal-3 expression compared to functioning ACTH tumors from patients with Cushing's disease and Nelson's syndrome. In the normal pituitary, Gal-3 was expressed in less than 1% of the basophil-invading cells (ACTH cells present in the posterior pituitary) and in a subset of the anterior lobe ACTH-positive cells. RT-PCR analyses showed that many members of the galectin family including galectins 1, 2, 3, 4, 5, 6, 7, 8, and 9 were expressed in normal pituitary and in functioning ACTH- and PRL-producing tumors. These results indicate that Gal-3 is associated with functioning ACTH and PRL tumors and is expressed infrequently in silent ACTH adenomas, suggesting that Gal-3 protein and/or gene is altered in non-functioning ACTH tumors. The use of ACTH and Gal-3 immunostaining should help in the diagnosis of silent ACTH adenomas.

Effect of whole-body vibration in the vertical axis on cortisol and adrenocorticotropic hormone levels in piglets.

Vibration, being a consequence of motion during transport, may impair the welfare of pigs. Therefore, the primary objectives of this study were 1) to evaluate during transport simulation the use of ACTH and cortisol plasma levels, which are part of a basic adaptation mechanism of pigs and 2) to define comfort conditions for pigs related to the frequency and acceleration of vibration. Pigs with a body weight between 20 and 25 kg were vibrated in the vertical direction for 2 h at 2, 4, 8, and 18 Hz, in combination with root mean square acceleration magnitudes of 1 or 3 m/s2. Blood was sampled at regular intervals before, during, and after vibration as the pig's behaviors were recorded. Data on ACTH, cortisol, and behavior could be collected from 104 vibrated pigs and 21 controls. In addition, eight animals (3 controls, 5 vibrated) were treated with 0.1 mg of dexamethasone/kg BW, eight animals (3 controls, 8 vibrated) with 0.1 mg naloxone/kg BW, and six (2 controls, 4 vibrated) with a physiological salt solution. Blood samples were taken and products were administrated via an intravenous catheter. The pigs spent less time lying during both hours of vibration treatment than during control conditions. Compared with 2 and 4 Hz, time spent lying was 10 times shorter at 8 Hz and 18 times shorter at 18 Hz. At 1030, ACTH levels were significantly higher than basal levels in animals vibrated at 2 (P < 0.0001), 4 (P < 0.002), and 18 Hz (P < 0.0006). After 1 h, levels returned to basal values. Cortisol levels increased very rapidly after the beginning of vibration (P < 0.0001) and remained higher until 1 h after cessation of vibration (P < 0.003). An inferrence of the lines of equal responses for ACTH and cortisol indicated that, in the beginning of vibration exposure, pigs were extremely susceptible to vibrations at lower frequencies (2 and 4 Hz), whereas at the end of vibration exposure the responses were higher at 18 Hz. The application of dexamethasone and naloxone underpinned the emotional component of the response strategy of pigs to vibration. Hence, vibration during transport should be minimized in order to enhance the adaptive capacities of pigs.

The ACTH test in the diagnosis of hirsutism.

The ACTH test has been used to confirm the diagnosis of adrenal insufficiency and the classic and the non-classic adrenal hyperplasia due to the 3-HSD, 21 OH e 110H deficiencies. This article reviews the historical aspects of the use of ACTH in the diagnosis of hirsutism and points out its mains indications. In spite of new biological molecular advances in the diagnosis of adrenal enzymatic deficiencies, the use of the ACTH test can help the physician to predict both genothipus and fenothipus in populations with hyperandrogenic manifestations due to non-classical or late-onset congenital adrenal hyperplasia.

Neonatal ACTH administration elicits long-term changes in forebrain monoamine innervation. Subsequent disruptions in hypothalamic-pituitary-adrenal and gonadal function.

The findings from this study demonstrated that the manipulation of the HPA system resulting from ACTH administration during neonatal development produces long-term, differential effects, not only on adrenocortical activity, but also on the activity and integrity of the forebrain monoamine systems. Increased concentrations of the monoamines within the forebrain regions studied at days 7 and 15, suggest a hastened maturation of these neural systems in animals neonatally treated with ACTH. The observed neurochemical alterations in these animals at one year are suggestive of an accelerated aging in the monoamine systems. A further consequence of these disturbances during development is an altered functioning of the HPG axis, as demonstrated by a delayed onset of puberty as previously reported, as well as significantly decreased proestrus plasma estradiol. Although deficits in sexual behavior also existed, it seems probable that these behavioral changes are a manifestation of altered neural systems regulating the ability to cope with a novel stimulus or situation, rather than a disruption of the "feminization" of the brain during sexual differentiation. This is in contrast to the male rat which exhibits permanent deficits in male typical sexual behavior following developmental ACTH treatment. The clinical relevance of these findings may be extensive. Perinatal exposure to events or agents that markedly increase ACTH and the corticosteroids may cause significant immediate and long-term changes in central monoamine functioning. These changes may constitute some of the most deleterious effects of stress exposure in infants and children. The alterations may be especially devastating in individuals with predispositions to stress-sensitive disorders such as anxiety, depression, and Tourette's syndrome. Finally, the use of ACTH in the treatment of infantile spasms may need to be reassessed in light of the possible long-term effects of ACTH on central monoamine functioning.

Endocrine responses during acute nicotine withdrawal

Acute administration of nicotine increases cortisol and prolactin but the endocrine effects of tobacco withdrawal are unknown. In a residential, double-blind, placebo-controlled, crossover study, volunteers smoked ad lib for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, patches delivering 0, 10, 20, or 30 mg nicotine were applied for 16 h. Daily plasma samples were analyzed for ACTH, cortisol, and prolactin. During nicotine abstinence (0 mg patch), circulating levels of ACTH, cortisol, and prolactin did not significantly change from ad lib smoking levels. Over all the patch conditions there was a significant effect of day, with modest but significant elevations of cortisol and ACTH levels on the second no-smoking day (Wed, 37 h abstinent). Prolactin levels increased during nicotine abstinence, but this effect was not significant. The observed endocrine changes did not correlate with physiologic, performance, or subjective measures of tobacco withdrawal. Our data indicate endocrine changes during acute tobacco withdrawal are transient and small. Thus, the present results do not support the use of ACTH as a treatment for tobacco cessation.

Effect of cisplatin and ACTH 4–9 on neural transport in cisplatin induced neurotoxicity

Cisplatin causes a dose limiting peripheral neuropathy, however, the biological mechanism by which this occurs is unknown. Murine N1E.115 neuroblastoma cells and neural crest derived pigment cells have similar transport mechanisms to human neural cells and were used to study the effect of cisplatin on cellular transport. Cisplatin reduced both the number and velocity of organelles moving in the anterograde and retrograde direction, compared to control cells. Cisplatin induced inhibition of transport was prevented by the simultaneous administration of ACTH 4–9. This analog alone had no effect on N1E.115 organelle, or erythrophore granule, movement. In both N1E.115 and pigment cells cisplatin inhibited transport within 1 h of exposure to the drug. The degree of inhibition did not increase significantly if pigment cells were incubated in cisplatin for 48 h compared to acute exposure. Microtubules in both pigment cells and N1E.115 neurites retained their structural integrity suggesting that factors other than changes in gross microtubule morphology are responsible for cisplatin neurotoxicity. Cisplatin reduces N1E.115 neurite growth after 48 h incubation but this can be prevented by simultaneous use of ACTH 4–9. This study demonstrates for the first time that cisplatin and ACTH 4–9 affect fast axonal transport by specific mechanisms which appear related to their observed neurotoxic and neuroprotective roles, respectively.

Comparison of the effects of ACTH-(1–24), methylprednisolone, aprotinin, and norepinephrine in a model of hemorrhagic shock in rats

Rats bled to a severe condition of volume-controlled hemorrhagic shock were randomly assigned to one of the following treatments: (1) saline, 1 ml/kg i.v.; (2) saline, 0.2 ml/kg per min i.v. for 10 min; (3) ACTH-(1-24), 160 micrograms/kg i.v.; 4) methylprednisolone, 40 mg/kg i.v.; (5) methylprednisolone, 80 mg/kg i.v.; (6) aprotinin, 10,000 KIU/kg i.v.; (7) norepinephrine, 5 micrograms/kg per min i.v. for 10 min; (8) norepinephrine, 10 micrograms/kg per min i.v. for 10 min. All rats treated with saline or with either of the two doses of methylprednisolone, and half of the rats treated with aprotinin, died within the subsequent 2 h. On the other hand, rats treated with norepinephrine, at either dose, or with ACTH-(1-24) were all still alive 2 h later, a similar improvement in cardiovascular and respiratory parameters being obtained with the two treatments. The effect of ACTH on mean arterial pressure was however more sustained throughout the observation period. These results further support the potential usefulness of ACTH-(1-24) as first-aid treatment in cases of severe blood losses.

Haemorrhagic shock in cardiac surgery. Pharmacological treatment with ACTH (1–24)

Spontaneous rupture of one or more cardiac chambers following open heart surgery is not common. A case is reported of a 45 year-old woman who sustained a spontaneous rupture of the right atrium in the intensive care unit after mitral valve replacement. Exsanguination of the patient was very rapid. On the basis of clinical and experimental convincing studies in this case a high dose of ACTH was used to prevent the damaging effect of haemorrhagic shock. During the reopening manoeuvre and initial conventional management, 10 mg ACTH (1–24) was injected into a peripheral vein. Although the blood lost was 93% of her circulating blood volume and a lot of fluid transfused via the central venous catheter was lost into the pericardium and hemithorax, the patient's condition improved rapidly after the occlusion of the atrial tear with initial small volume of transfusion. Based on the review of recent investigations the use of ACTH is emphasized.

Preliminary data on the use of ACTH-(1-24) in human shock conditions

Recent experimental data indicate that endogenous opioid system activation plays a key role in the course of shock and that, conversely, melanocortins (endogenous physiological opioid antagonists) can reverse hypovolemic shock [1,2]. Since ACTH-(l-241 is known to be practically devoid of acute toxicity and it is reported to be well tolerated by humans up to 100 mg i.v. [3], it has been administered to patients with shock.

Cardiac hypertrophy secondary to ACTH treatment in children.

The usefulness of ACTH in the treatment of childhood epilepsy is assessed by improvement in the EEG and in the clinical condition. However, pronounced side effects, even serious ones, must be encountered. The most common complications are Cushing syndrome, infections, and arterial hypertension. We report on seven patients with infantile myoclonic seizures, who exhibited myocardial hypertrophy with increased left ventricular function during ACTH treatment. These changes were detected and followed by serial echocardiographic investigations. Within a period of 5 months after the termination of ACTH therapy the abnormal echocardiographic findings disappeared. We believe that the cardiac hypertrophy is ACTH-induced. Based on the various biological effects of ACTH different explanations are proposed: oedema or deposition of glycogen in the myocardial tissue, hyperinsulinism, arterial hypertension and increased inotropic stimulus. Because of our observations, we suggest careful monitoring of children treated with ACTH by performing serial echocardiographic investigations.