Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism.

AIMS: The pulmonary vasodilation induced by adrenomedullin may be beneficial in the acute pulmonary embolism (APE) setting. This study examined effects of adrenomedullin in sheep with microsphere-induced APE. MAIN METHODS: Twenty four anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups (n=8 per group): animals not subjected to any intervention (Sham), animals with APE induced by microspheres (500 mg, intravenously) treated 30 min later by intravenous physiological saline (Emb group) or intravenous adrenomedullin (50 ng/kg/min) during 30 min (Emb+Adm group). Plasma concentrations of cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) were determined by enzyme immunoassay. KEY FINDINGS: Variables did not change over time in sham animals. In both embolized groups, microsphere injection significantly (P<0.05) increased pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (MPAP) from baseline by 181% and 111-142%, respectively (% change in mean values). Adrenomedullin significantly decreased PVRI (18%-25%) and significantly increased cardiac index (22%-25%) from values recorded 30 min after APE (E30), without modifying MPAP. Adrenomedullin decreased mean arterial pressure (18%-24%) and systemic vascular resistance index (32%-40%). Embolization significantly increased arterial-to-end tidal CO2 gradient, alveolar-to-arterial O2 gradient, and pulmonary shunt fraction from baseline, but these variables were unaffected by adrenomedullin. While adrenomedullin significantly increased plasma cAMP, cGMP levels were unaltered. SIGNIFICANCE: Adrenomedullin induces systemic and pulmonary vasodilation, possibly via a cAMP mediated mechanism, without modifying the gas exchange impairment associated with APE. The pulmonary anti-hypertensive effect of adrenomedullin may be offset by increases in cardiac index.

Analgesic comparison of systemic lidocaine, morphine or lidocaine plus morphine infusion in dogs undergoing fracture repair

To compare the postoperative analgesic effects of lidocaine, morphine and lidocaine plus morphine administered by constant rate infusion (CRI) and analyzing their effects on opioid requirements after orthopedic surgery in dogs. Twenty-four dogs underwent fracture repairs were premedicated with IM acepromazine (0.05 mg/kg) combined with morphine (0.3mg/kg). Anesthesia was induced with IV propofol (4 to 5 mg/ kg) and maintained with isoflurane. The dogs were randomly assigned to 3 groups and administered a CRI IV of lidocaine (T-L), morphine (T-M) or lidocaine plus morphine (T-LM) at the same doses. Postoperative analgesia was assessed for 24 hours using a Visual Analog Scale (VAS) and the Glasgow Composite Pain Scale (GCPS). Rescue analgesia was performed if the evaluation score exceeded 50% of the VAS and/or 33% of the GCPS. The pain score and postoperative opioid requirements did not differ among the treatments. Rescue analgesia was administered to 1/8 dogs in the T-M and T-LM, and to 3/8 dogs in the T-L. Lidocaine, morphine or lidocaine/morphine CRI may be efficacious techniques for pain management in the first 24 hours post-surgery. However, the two drugs administered together did not reduce the postoperative opioid requirement in dogs undergoing fracture repair. Key words: Anesthesia. Analgesics. Analgesics, Opioid. Lidocaine. Morphine. Dogs.