Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas

Abstract

Objective Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NCCa-ATP channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT. Methods We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls). Results During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), while no patient in the SU group experienced sHT (P=0.016). No patient in the SU group died, compared to 18 (10%) in the control group (P=0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons. Interpretation We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs.

Explicit Consideration of Baseline Factors to Assess Recombinant Tissue-Type Plasminogen Activator Response With Respect to Race and Sex

“…18,20,21 A matching method based on weighted Euclidean distances was adapted to obtain a pair of subjects considered to be the nearest neighbors in an 3D space of NIHSS, age, and glucose. 18,23,24 Because there were fewer blacks relative to whites available to match, we were able to find a suitable white subject for each black subject.…”

“…19 pPAIRS can be applied to smaller populations, as long as there is sufficient overlap of subject characteristics for matching. 18,20,21 Despite being completed nearly 2 decades ago, the NINDS rtPA dataset remains one of the best characterized datasets, and the only randomized controlled clinical trial of rtPA with a reasonably proportionate enrollment of blacks. Therefore, we used this dataset to investigate potential race, sex, and race-plus-sex outcome differences after rigorous consideration of baseline variables.…”

Hyperbaric Oxygen Preconditioning Attenuates Hemorrhagic Transformation Through Reactive Oxygen Species/Thioredoxin-Interacting Protein/Nod-Like Receptor Protein 3 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats

“…Hyperbaric oxygen preconditioning attenuated hemorrhagic transformation through reactive oxygen species/thioredoxin-interacting protein/Nod-like receptor protein 3 pathway. (Crit Care Med 2016; 44:e403-e411) H emorrhagic transformation is the secondary cause of petechial or confluent hemorrhage in the affected area of a stroke, which contributes to high mortality and poor functional recovery in stroke patients (1,2). Currently, diabetes is one of the main risk factors of hemorrhagic transformation (3,4), and therefore, in animal models, hyperglycemia is used to induce hemorrhagic transformation after cerebral ischemia (5).…”

Sulfonylurea Receptor 1 in Humans with Post-Traumatic Brain Contusions

“…19 Expression of SUR1 has been investigated in many experimental models, 4,10,16,[19][20][21][22][23] but only four studies have been published for humans thus far, all of which were conducted with postmortem specimens and none with PTBCs. [24][25][26] Our aim in this study was to investigate the expression of SUR1 in human contusion specimens obtained at surgery from a cohort of TBI patients whose lesions were surgically evacuated. The main objectives were to investigate the expression of SUR1 in different cell types (neurons, astrocytes, ECs, microglia, macrophages, and neutrophils) and determine whether the abundance of SUR1 is related to the time that elapsed between the injury and the time of surgery.…”