GABAA Receptors in the Mongolian Gerbil: a PET Study Using [18F]Flumazenil to Determine Receptor Binding in Young and Old Animals.

PURPOSE: Plastic changes in the central auditory system involving the GABAergic system accompany age-related hearing loss. Such processes can be investigated with positron emission tomography (PET) imaging using [18F]flumazenil ([18F]FMZ). Here, [18F]FMZ PET-based modeling approaches allow a simple and reliable quantification of GABAA receptor binding capacity revealing regional differences and age-related changes. PROCEDURES: Sixty-minute list-mode PET acquisitions were performed in 9 young (range 5-6 months) and 11 old (range 39-42 months) gerbils, starting simultaneously with the injection of [18F]FMZ via femoral vein. Non-displaceable binding potentials (BPnd) with pons as reference region were calculated for auditory cortex (AC), inferior colliculus (IC), medial geniculate body (MGB), somatosensory cortex (SC), and cerebellum (CB) using (i) a two-tissue compartment model (2TCM), (ii) the Logan plot with image-derived blood-input (Logan (BI)), (iii) a simplified reference tissue model (SRTM), and (iv) the Logan reference model (Logan (RT)). Statistical parametric mapping analysis (SPM) comparing young and old gerbils was performed using 3D parametric images for BPnd based on SRTM. Results were verified with in vitro autoradiography from five additional young gerbils. Model assessment included the Akaike information criterion (AIC). Hearing was evaluated using auditory brainstem responses. RESULTS: BPnd differed significantly between models (p < 0.0005), showing the smallest mean difference between 2TCM as reference and SRTM as simplified procedure. SRTM revealed the lowest AIC values. Both volume of distribution (r2 = 0.8793, p = 0.018) and BPnd (r2 = 0.8216, p = 0.034) correlated with in vitro autoradiography data. A significant age-related decrease of receptor binding was observed in auditory (AC, IC, MGB) and other brain regions (SC and CB) (p < 0.0001, unpaired t test) being confirmed by SPM using pons as reference (p < 0.0001, uncorrected). CONCLUSION: Imaging of GABAA receptor binding capacity in gerbils using [18F]FMZ PET revealed SRTM as a simple and robust quantification method of GABAA receptors. Comparison of BPnd in young and old gerbils demonstrated an age-related decrease of GABAA receptor binding.

[Is morphine still the analgesic of choice in acute myocardial infarction?]. / Sigue siendo la morfina el analgésico de elección en el infarto agudo de miocardio?

Chest pain is the most common symptom of patients who present with ischemic heart disease. Morphine has traditionally been the drug of choice for managing chest pain in acute coronary syndrome (ACS) due to its high analgesic potency, though its physiological effects are poorly understood. Routinely used for managing chest pain, morphine is recommended in the 2002 guidelines of the American College of Cardiology/American Heart Association. This recommendation, however, is not based on a high level of scientific evidence but on expert opinion. Studies have found both for and against the use of morphine in ACS, suggesting that its benefits are perhaps not altogether clear. This review examines the pathophysiological effects of morphine and their cardiac implications, with special attention to a possible negative effect on ACS. We reviewed articles in the MEDLINE database from 1982 to 2006.

¿Sigue siendo la morfina el analgésico de elección en el infarto agudo de miocardio? / Is morphine still the analgesic of choice in acute myocardial infarction?

El dolor torácico es el síntoma más frecuente de presentación en pacientes con cardiopatía isquémica. Tradicionalmente la morfina ha sido el fármaco de elección para el control del dolor torácico en el síndrome coronario agudo (SCA) ya que su potencia analgésica es muy elevada, sin embargo sus efectos fisiológicos no están del todo claros. Su uso como terapéutica para el control del dolor torácico es de rutina, e incluso está incluida como recomendación en las guías de la ACC/AHA (American College of Cardiology/American Heart Association) delaño 2002, aunque esta recomendación no está basada enestudios científicos sólidos, sino en la opinión de expertos de la práctica clínica. La presencia de estudios a favor y en contra del uso de la morfina en el SCA, hacen ver que tal vez su beneficio no esté del todo claro. El objetivo de este trabajo es revisar los efectos fisiopatológicos de la morfina y sus implicaciones a nivel cardiaco, alertando de un posible efecto deletéreo en el SCA. Revisamos artículos desde el año 1982 al 2006 incluidos en la base de datos MEDLINE

Chest pain is the most common symptom of patientswho present with ischemic heart disease. Morphine hastraditionally been the drug of choice for managing chestpain in acute coronary syndrome (ACS) due to its highanalgesic potency, though its physiological effects arepoorly understood. Routinely used for managing chestpain, morphine is recommended in the 2002 guidelinesof the American College of Cardiology/American HeartAssociation. This recommendation, however, is not basedon a high level of scientific evidence but on expertopinion. Studies have found both for and against the useof morphine in ACS, suggesting that its benefits are perhaps not altogether clear. This review examines the pathophysiological effects of morphine and their cardiacimplications, with special attention to a possible negative effect on ACS. We reviewed articles in the MEDLINE database from 1982 to 2006