Evaluating Neuroprotective Agents for Clinical Anti-Ischemic Benefit Using Neurological and Neuropsychological Changes After Cardiac Surgery Under Cardiopulmonary Bypass

Grieco, Giacinto; d’Hollosy, Marilyn; Culliford, Alfred T.; Jonas, Saran

doi:10.1161/01.str.27.5.858

Cited by 51 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This method of handling the data is, however, considered to be insensitive, because it applies a conventional but arbitrary cut-off and ignores any improvements in performance. 8,13 We have argued elsewhere 13 that studies of interventions in cardiac surgery designed to improve outcome that include 2 or more patient groups should use all the data by comparing the change in performance between the 2 groups. This not only enables an examination to be made of each of the tests, as some may be more sensitive to change than others, but, crucially, also allows the potential effects of learning to be considered.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroprotection of the Brain During Cardiopulmonary Bypass

Arrowsmith

Harrison

Newman

et al. 1998

Stroke

136

View full text Add to dashboard Cite

Background and Purpose-Neuropsychological impairment may follow coronary artery bypass surgery as a result of peroperative cerebral microembolism. The hypothesis that remacemide, an NMDA receptor antagonist, would provide protection against such ischemic damage has been tested in a randomized trial. Methods-One hundred seventy-one patients undergoing coronary artery bypass surgery by a single cardiothoracic surgical team were randomized to receive remacemide (up to 150 mg every 6 hours) or placebo from 4 days before to 5 days after their bypass procedure. Peroperative monitoring included an estimate of the number of microembolic events detected by transcranial Doppler ultrasonography of the middle cerebral artery. A battery of 9 neuropsychological tests was administered before and 8 weeks after surgery. Results-The proportion of patients showing a decline in performance of 1 SD or more in 2 or more tests was reduced in the treated group (9% versus 12%), but this was not statistically significant. On the other hand, overall postoperative change (reflecting learning ability in addition to reduced deficits) was more favorable in the remacemide group, which demonstrated significantly greater improvement in a global z score (Pϭ0.028) and changes in 3 individual tests (PϽ0.05). The 2 patient groups were well matched, including for the burden of microembolic events. Conclusions-This is the first study to show statistically significant drug-based neuroprotection during cardiac surgery. In addition to offering improvement in cerebral outcome for such at-risk patients, it supports the hypothesis that drugs acting on the excitotoxic mechanism of ischemic cerebral damage can be effective in humans. (Stroke. 1998;29:2357-2362.)

show abstract

Section: Discussionmentioning

confidence: 99%

“…Grieco et al 8 recently reported a pilot study using GM1 ganglioside in 18 patients undergoing bypass surgery, with 11 patients on placebo. No statistically significant differences were detectable, and a sample size of 150 was estimated to be needed to confirm or reject a nonstatistically significant treatment benefit.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection of the Brain During Cardiopulmonary Bypass

Arrowsmith

Harrison

Newman

et al. 1998

Stroke

136

View full text Add to dashboard Cite

show abstract

“…In the context of cardiac surgery and studies that attempt to protect the brain, preservation learning as indicated by an improvement in the neuropsychological test performance may be considered to reflect the protection of the brain during surgery (see Arrowsmith and colleagues7). The use of score change takes account of both potential preserved learning ability and potential deterioration on the tests providing a sensitive tool for the assessment of interventions in cardiac surgery (see also Grieco and colleagues8). …”

Section: Discussionmentioning

confidence: 99%

Changes in cognition following cardiac surgery

Newman

Stygall

1999

Heart

View full text Add to dashboard Cite

“…1-7 Because it leads to brain changes, cardiac surgery has been proposed as a model to screen potential neuroprotective agents, particularly when DWI is used to identify incident lesions. 2, 8 …”

Section: Introductionmentioning

confidence: 99%

Blood-Brain Barrier Disruption after Cardiac Surgery

Merino

Latour

Tso

et al. 2012

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

Background and purpose CNS complications are often seen after heart surgery, and post-surgical disruption of the blood-brain barrier (BBB) may play an etiologic role. The objective of this study was to determine the prevalence of MRI-detected BBB disruption (Hyperintense Acute Reperfusion Marker: HARM) and DWI lesions after cardiac surgery. Materials & methods All patients had an MRI after cardiac surgery. In half the patients (group 1), we administered gadolinium 24 hours after surgery and obtained high-resolution DWI and FLAIR images 24-48 hours later. In the other half (group 2), we administered gadolinium at the time of the post-operative scan (2-4 days after surgery). Two stroke neurologists evaluated the images. Results We studied 19 patients. None of the patients had clinical evidence of a stroke or delirium at the time of the gadolinium administration or the scan, but 9 patients (47%) had HARM (67% in group 1 and 30% in group 2, p=0.18) and 14 patients (74%) had DWI lesions (70% in group 1 and 78% in group 2, p=1.0). Not all patients with DWI lesions had HARM, and not all patients with HARM had DWI lesions (p=0.56). Conclusions Almost half the patients undergoing cardiac surgery have evidence of HARM and three quarters have acute lesions on DWI after surgery. BBB disruption is more prevalent in the first 24 hours after surgery. These findings suggest that MRI can be used as an imaging biomarker to assess therapies that may protect the BBB in patients undergoing heart surgery.

show abstract

Evaluating Neuroprotective Agents for Clinical Anti-Ischemic Benefit Using Neurological and Neuropsychological Changes After Cardiac Surgery Under Cardiopulmonary Bypass

Cited by 51 publications

References 31 publications

Neuroprotection of the Brain During Cardiopulmonary Bypass

Neuroprotection of the Brain During Cardiopulmonary Bypass

Changes in cognition following cardiac surgery

Blood-Brain Barrier Disruption after Cardiac Surgery

Contact Info

Product

Resources

About