Blood pressure levels and haematoma growth in patients with Intracerebral Haemorrhage (ICH) A retrospective observational study

Intracerebral haemorrhage (ICH) is a spontaneous extravasation of blood into brain parenchyma. Although ICH represents approximately only 15% of all strokes, it is one of the major causes of stroke-related death and disability. One of the causes of poor outcome is the haematoma growth. The association between elevated blood pressure (BP) and haematoma enlargement in acute ICH has not been clarified. Our objective is to try to identify this relationship that may suggest an immediate target for intervention to possibly improve outcomes in patients with spontaneous ICH and might settle the controversy surrounding the optimal management of blood pressure.We propose a retrospective revision using a sample present in our database of approximately 250 patients with primary ICH and less than 12h from symptoms onset. Systolic blood pressure levels (SBP) are assessed at baseline, at 6h, at 12h, at 24h and at 72h, being these last four the average levels of the different recordings during those time intervals. Haematoma growth will be defined as an increase in the volume of intraparenchymal haemorrhage of >33% as measured by image analysis on the 24-hour CT or 72-hour CT compared with the baseline CT scan. A qualified neuroradiologist not informed of the aim of the study, will review the CT images. The secondary objective will be to correlate the BP levels in the acute phase of ICH with clinical outcome. We will evaluate early neurologic deterioration at 72h by using the National Institutes of Health Stroke Scale (NIHSS); outcome at 90 days by using the modified Rankin scale and mortality at 72h and 90 days. The statistical analysis will be adjusted by possibly confounding variables

Inhibition of nociceptive responses after systemic administration of amidated kyotorphin

BACKGROUND AND PURPOSE Kyotorphin (KTP; L-Tyr-L-Arg), an endogenous neuropeptide, is potently analgesic when delivered directly to the central nervous system. Its weak analgesic effects after systemic administration have been explained by inability to cross the blood-brain barrier (BBB) and detract from the possible clinical use of KTP as an analgesic. In this study, we aimed to increase the lipophilicity of KTP by amidation and to evaluate the analgesic efficacy of a new KTP derivative (KTP-amide - KTP-NH 2). EXPERIMENTAL APPROACH We synthesized KTP-NH 2. This peptide was given systemically to assess its ability to cross the BBB. A wide range of pain models, including acute, sustained and chronic inflammatory and neuropathic pain, were used to characterize analgesic efficacies of KTP-NH 2. Binding to opioid receptors and toxicity were also measured. KEY RESULTS KTP-NH 2, unlike its precursor KTP, was lipophilic and highly analgesic following systemic administration in several acute and chronic pain models, without inducing toxic effects or affecting motor responses and blood pressure. Binding to opioid receptors was minimal. KTP-NH 2 inhibited nociceptive responses of spinal neurons. Its analgesic effects were prevented by intrathecal or i.p. administration of naloxone. CONCLUSIONS AND IMPLICATIONS Amidation allowed KTP to show good analgesic ability after systemic delivery in acute and chronic pain models. The indirect opioid-mediated actions of KTP-NH 2 may explain why this compound retained its analgesic effects although the usual side effects of opioids were absent, which is a desired feature in next-generation pain medications