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Early treatment of ischemic-stroke
Pharmacological Research, Vol. 25, Supplement 2, 1992
203
EARLY TREATMENT OF ISCHEMIC•S TROKE Malferrari G ., Borioni D ., Negri E ., Bondi M . i° Divisione Medicina Generale (Primario Prof . Ospedale Civile Modena
Melini
L .)
It is well know that Calcium is a universal second messenger responsable for regulating all forms of cellular activity . Calcium functions as part of a signal pathway which begins external signals are detected at the cell surface were by specific receptors . These receptors are connected to various tranduction mechanisms wich bring about an increase in the intracellular level of Calcium . Then the Calcium combines with an internal receptor (i .e . calmodulin) to activate a great variety of cellular processes . A very wide and interesting field of application of Ca antagonists in neurology is obviously by brain hypoxia/ischemia as well as by seizures . Ischemia is known to induce a complex series of modifications in the intra/extracellular content of Calcium, variously modulated by peculiar types of receptors, such as the NMDA receptors, which are known to activate a great Ca influx . The pathological increase in cytosolic Calcium due to ischemia exaggerates the physiological phenomena mediated by Calcium such as lypolisis with accumulation of FFA, disaggregation of microtuboli, proteolysis and protein phosphorilation . In ischemia these events lead to inhibition of axonal transport, membrane damage and receptor dysfunction with enhanced catabolism and possibly cell death . Calcium antagonists can provide cerbral protection through various mechanisms and at different stages of hypoxic : ischemic damage . METHODS We performed a feasibility and safety study of nimodipina, a Calcium antagonist, in 86 patients . The objectives of the study were to begin therapy as early as possible 5 hours) after the onset of ischemic stroke . To determine whether treatment with a Calcium-channel blocker would improve survival and neurologic outcome in acute ischemic stroke, we enrolled 86 patients in a prospective, double-blind, randomized, other drugs - controlled trial of nimodipine (30 mg every six hours, for three weeks) begun within 5 hours of the onset of symptoms of an acute ischemic stroke . A significantly better neurologic outcome, as assessed by the canadian scale of neurologic deficit, was also observed in the minodipine group . The improvement in neurologic status was greatest in patients with a moderate to severe deficit at base line . Our data suggest that patients with acute ischemic stroke may benefit from earlytreatment with nimodipine .
1043-6618/92/25110203-01/$03 .00/0
© 1992 The Italian Pharmacological Society
203
EARLY TREATMENT OF ISCHEMIC•S TROKE Malferrari G ., Borioni D ., Negri E ., Bondi M . i° Divisione Medicina Generale (Primario Prof . Ospedale Civile Modena
Melini
L .)
It is well know that Calcium is a universal second messenger responsable for regulating all forms of cellular activity . Calcium functions as part of a signal pathway which begins external signals are detected at the cell surface were by specific receptors . These receptors are connected to various tranduction mechanisms wich bring about an increase in the intracellular level of Calcium . Then the Calcium combines with an internal receptor (i .e . calmodulin) to activate a great variety of cellular processes . A very wide and interesting field of application of Ca antagonists in neurology is obviously by brain hypoxia/ischemia as well as by seizures . Ischemia is known to induce a complex series of modifications in the intra/extracellular content of Calcium, variously modulated by peculiar types of receptors, such as the NMDA receptors, which are known to activate a great Ca influx . The pathological increase in cytosolic Calcium due to ischemia exaggerates the physiological phenomena mediated by Calcium such as lypolisis with accumulation of FFA, disaggregation of microtuboli, proteolysis and protein phosphorilation . In ischemia these events lead to inhibition of axonal transport, membrane damage and receptor dysfunction with enhanced catabolism and possibly cell death . Calcium antagonists can provide cerbral protection through various mechanisms and at different stages of hypoxic : ischemic damage . METHODS We performed a feasibility and safety study of nimodipina, a Calcium antagonist, in 86 patients . The objectives of the study were to begin therapy as early as possible 5 hours) after the onset of ischemic stroke . To determine whether treatment with a Calcium-channel blocker would improve survival and neurologic outcome in acute ischemic stroke, we enrolled 86 patients in a prospective, double-blind, randomized, other drugs - controlled trial of nimodipine (30 mg every six hours, for three weeks) begun within 5 hours of the onset of symptoms of an acute ischemic stroke . A significantly better neurologic outcome, as assessed by the canadian scale of neurologic deficit, was also observed in the minodipine group . The improvement in neurologic status was greatest in patients with a moderate to severe deficit at base line . Our data suggest that patients with acute ischemic stroke may benefit from earlytreatment with nimodipine .
1043-6618/92/25110203-01/$03 .00/0
© 1992 The Italian Pharmacological Society