Blood Pressure Lowering Decreases Intracerebral Hemorrhage Volume and Improves Behavioral Outcomes in Experimental Animals.
Ontology highlight
ABSTRACT:
SUBMITTER: Bohmann FO
PROVIDER: S-EPMC7568971 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Blood Pressure Lowering Decreases Intracerebral Hemorrhage Volume and Improves Behavioral Outcomes in Experimental Animals.
Bohmann Ferdinand O FO Seiler Alexander A Gelhard Sarah S Stolz Leonie L Brill Boris B Brunkhorst Robert R Steinmetz Helmuth H Harter Patrick N PN Mittelbronn Michel M Foerch Christian C
Journal of stroke 20200929 3
Similar Datasets
Project description: Not available
| S-EPMC4006299 | biostudies-literature
Project description:BackgroundIt is unknown if race/ethnicity modifies the response to blood pressure (BP) lowering treatment after intracerebral hemorrhage (ICH). We aimed to examine the race/ethnicity differences in the response to BP lowering treatment after ICH.MethodsThis is a post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The primary outcome is good outcome, defined as 90-day modified Rankin Scale 0-3. The primary predictor is race/ethnicity for which we included non-Hispanic categories of White, Black, Asian, and the category of Hispanic. We fit adjusted logistic regression models with the predictor of race/ethnicity and models with the interaction term of treatment*race/ethnicity.ResultsWe included a total of 953 patients in our analysis (White = 213, Black = 112, Asian = 554, and Hispanic = 74). In the models with the interaction between race/ethnicity and treatment, we found that White patients assigned to the intensive treatment arm had lower predicted probability of good outcome than those assigned to the standard treatment arm (Model 1: 56.2% vs. 68.1%, p = .027; Model 2: 53.4% vs. 68.3%, p = .009). When divided into White and non-White groups, intensive treatment was associated with higher odds of serious adverse events in White group but not in the non-White group. In addition, there was an association between intensive treatment and higher risk of hematoma expansion in White patients and lower risk of hematoma expansion in non-White patients.ConclusionsIn the ATACH-2, there was an interaction between race/ethnicity and response to BP lowering treatment after ICH, with White patients having an association between intensive blood pressure reduction and worse outcome.
| S-EPMC8948521 | biostudies-literature
Project description:While oral anticoagulants are associated with greater hematoma expansion and higher mortality rates in patients with intracerebral hemorrhage (ICH), there is ongoing discussion whether pretreatment with antiplatelet drugs also worsens prognosis. Using an experimental model of ICH, we investigated the effects of antiplatelet pretreatment on hematoma volume and functional outcome. CD-1 mice were treated with acetyl-salicylic acid (ASA, 60 mg/kg per 24 hours), clopidogrel (22.5 mg/kg per 24 hours), or both (ASA+clopidogrel) through drinking water for 3 days (n=20 per group). Thereafter, platelet aggregation was found to be significantly reduced. Untreated mice and mice pretreated with warfarin served as controls. A stereotactic injection of collagenase into the right striatum was used to induce ICH. Twenty-four hours after ICH induction, hematoma volume was measured to be 15.0 ± 4.4 μL in controls, 14.1 ± 5.3 μL in ASA mice, 16.8 ± 5.1 μL in clopidogrel mice, and 16.4 ± 5.1 μL in ASA+clopidogrel animals. These differences were not statistically significant. However, mice pretreated with warfarin revealed largely increased hematoma volumes (25.0 ± 7.4 μL versus controls, P=0.001). Neurologic outcome was not different between antiplatelet-pretreated animals and untreated controls. Our results suggest that plasmatic coagulation rather than platelet function is the most critical element for preventing hematoma expansion in acute ICH. Future therapeutic strategies may take these findings into account.
| S-EPMC3170939 | biostudies-literature
Project description:Hyperlipidemia is common in patients with intracerebral hemorrhage (ICH). Accumulating evidence indicates that patients with ICH are at risk for future hemorrhage recurrence, cardiovascular disease, and ischemic stroke and highlights the importance of secondary prevention of vascular events after ICH. Although the benefits of intensive treatment of hyperlipidemia for reducing ischemic cardiac and vascular events in patients with ischemic stroke are well established, the benefit versus harm in patients with ICH are less clear. Epidemiological studies suggest that hyperlipidemia is protective against ICH and that intensive lowering of lipids is associated with increased risk for ICH. Similarly, although currently available lipid-lowering treatments have been thoroughly studied in patients with ischemic cardiac and vascular disease, only few randomized trials of these therapies included a very small number of patients with history of ICH. Thus, limiting any definitive conclusions regarding the safety and net benefit of these treatments in ICH populations. Currently, there is no consensus regarding the optimal strategy for management of hyperlipidemia after ICH. In this article, we review relevant literature to outline the competing risks and benefits of lipid-lowering treatments in this vulnerable patient population. We suggest a treatment paradigm based on available data but note that data from dedicated randomized trials are needed to build the necessary evidence to guide optimal lipid-lowering strategy in patients with a history of ICH.
| S-EPMC9248990 | biostudies-literature
Project description:Intraventricular hemorrhage (IVH) extension is common following acute intracerebral hemorrhage (ICH) and is associated with poor prognosis.To determine whether intensive blood pressure (BP)-lowering therapy reduces IVH growth.Pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and INTERACT2) computed tomography (CT) substudies; multicenter, open, controlled, randomized trials of patients with acute spontaneous ICH and elevated systolic BP, randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) BP management. Participants had blinded central analyses of baseline and 24-hour CT. Association of BP lowering to IVH growth was assessed in analysis of covariance.There was no significant difference in adjusted mean IVH growth following intensive (n = 228) compared to guideline-recommended (n = 228) BP treatment (1.6 versus 2.2 ml, respectively; p = 0.56). Adjusted mean IVH growth was nonsignificantly greater in patients with a mean achieved systolic BP ?160 mm Hg over 24 h (3.94 ml; p trend = 0.26).Early intensive BP-lowering treatment had no clear effect on IVH in acute ICH.
| S-EPMC5040888 | biostudies-literature
Project description:Background and purposeEvidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)-lowering therapy.MethodsEligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110-139 mm Hg) or standard (140-179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored.ResultsIn total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02-1.37, P=0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74-1.13) in women versus 1.13 (95% CI, 0.92-1.39) in men (P for interaction=0.11), with inconclusive Gail-Simmon test (P=0.16).ConclusionsWomen had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565.
| S-EPMC9371624 | biostudies-literature
Project description:ObjectiveThe aim was to investigate whether intensive blood pressure treatment is associated with less hematoma growth and better outcome in intracerebral hemorrhage (ICH) patients who received intravenous nicardipine treatment ≤2 hours after onset of symptoms.MethodsA post-hoc exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial was performed. This was a multicenter, international, open-label, randomized clinical trial, in which patients with primary ICH were allocated to intensive versus standard blood pressure treatment with nicardipine ≤4.5 hours after onset of symptoms. We have included 913 patients with complete imaging and follow-up data in the present analysis.ResultsAmong the 913 included patients, 354 (38.7%) had intravenous nicardipine treatment initiated within 2 hours. In this subgroup of patients treated within 2 hours, the frequency of ICH expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group (p = 0.02). Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma growth (odds ratio, 0.56; 95% confidence interval [CI], 0.34-0.92; p = 0.02), higher rate of functional independence (odds ratio, 2.17; 95% CI, 1.28-3.68; p = 0.004), and good outcome (odds ratio, 1.68; 95% CI, 1.01-2.83; p = 0.048) at 90 days. Ultra-early intensive blood pressure reduction was associated with a favorable shift in modified Rankin Scale score distribution at 3 months (p = 0.04).InterpretationIn a subgroup of ICH patients with elevated blood pressure given intravenous nicardipine ≤2 hours after onset of symptoms, intensive blood pressure reduction was associated with reduced hematoma growth and improved functional outcome. ANN NEUROL 2020;88:388-395.
| S-EPMC8697414 | biostudies-literature
Project description:To identify the potential lncRNA and mRNA post intracerebral hemorrhage (ICH), we have employed lncRNA microarray expression profiling. 570 mRNAs and 313 lncRNAs were identified in the ICH vs sham group .Expression of six mRNA (Saa3, Col10a1, Mmp13, Oxt, Pcdhb6 and Resp18) and lncRNA (ENSMUT00000141700, AK143011, ENSMUT00000128306, AK030988, ENSMUST00000187076 and ENSMUST00000134129) from this signature was quantified by qPCR.
2023-05-17 | GSE227683 | GEO
Project description:Background and Purpose- Mechanisms contributing to acute hematoma growth in intracerebral hemorrhage are not well understood. Neuropathological studies suggest that the initial hematoma may create mass effect that can tear vessels in the vicinity by shearing, causing further bleeding and hematoma growth. Methods- To test this in mice, we simulated initial intracerebral hemorrhage by intrastriatal injection of a liquid polymer that coagulates upon contact with tissue and measured the presence and volume of bleeding secondary to the mass effect using Hemoglobin ELISA 15 minutes after injection. Results- Secondary hemorrhage occurred in a volume-dependent (4, 7.5, or 15 μL of polymer) and rate-dependent (0.05, 0.5, or 5 μL/s) manner. Anticoagulation (warfarin or dabigatran) exacerbated the secondary hemorrhage volume. In a second model of hematoma expansion, we confirmed that intrastriatal whole blood injection (15 μL, 0.5 μL/s) also caused secondary bleeding, using acute Evans blue extravasation as a surrogate. Anticoagulation once again exacerbated secondary hemorrhage after intrastriatal whole blood injection. Secondary hemorrhage directly and significantly correlated with arterial blood pressures in both nonanticoagulated and anticoagulated mice, when modulated by phenylephrine or labetalol. Conclusions- Our study provides the first proof of concept for secondary vessel rupture and bleeding as a potential mechanism for intracerebral hematoma growth.
| S-EPMC6478448 | biostudies-literature
Project description:Background and objectiveThe clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH.MethodsWe conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis.ResultsAmong the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m2; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively. Compared with normal eGFR (≥90 mL/min/1.73 m2), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m2 (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m2 (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively (p for interaction = 0.02).DiscussionDecreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment.Trial registration informationClinicaltrials.gov identifier: NCT01176565.Classification of evidenceThis study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control.
| S-EPMC8408509 | biostudies-literature