Key result
rt-PA worsens post-stroke neurological outcomes in hyperglycemic mice but causes no harm under normoglycemia.
Why the study?
Patients with a recent stroke are typically not treated with rt-PA due to contraindications, but whether rt-PA after recent stroke with or without hyperglycemia increases hemorrhagic transformation or worsens outcome remains unclear.
Does rt-PA treatment after recent ischemic stroke increase the risk for hemorrhagic transformation and worsen functional outcome in mice with or without hyperglycemia?
Does rt-PA treatment after recent ischemic stroke increase the risk for hemorrhagic transformation and worsen functional outcome in mice with or without hyperglycemia?
Thrombolysis after recent ischemic stroke does not worsen outcomes in healthy mice, but the addition of hyperglycemia leads to neurological deterioration and increased hemorrhagic transformation.
Answers are grounded in this paper and cite their sources.
Suggests hyperglycemia may worsen rt-PA risks in stroke models; hypothesis-generating and should not change clinical practice.
(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.
No takes yet. Share an insight, caveat, or question.
Gelhard et al. (2022) studied Experimental ischemic stroke (transient middle cerebral artery occlusion) with or without streptozotocin-induced hyperglycemia (n=72). Recombinant tissue plasminogen activator (rt-PA, Actilyse) vs. Saline (250 µL intravenously) was evaluated on Neurological deficit score (experimental Stroke Scale, eSS, 0-42 points) 24 hours after treatment in the 24-hour substudy (hyperglycemia + rt-PA vs. saline control) (p=0.02). Recombinant tissue plasminogen activator did not worsen neurological outcome or hemorrhagic transformation after recent stroke in normoglycemic mice, but worsened outcomes in hyperglycemic mice.
Synapse has enriched 10 related papers. Consider them for comparative context: