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George W Weyer

Publications and source records attributed to George W Weyer.

2 recordsLinked to original sources

Evidence-based cerebral vasospasm management.

Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness. The purpose of this work was to perform a systematic review of the literature on the treatment of cerebral vasospasm. A literature search for randomized controlled trials of therapies used for prevention or treatment of cerebral vasospasm and/or delayed cerebral ischemia was conducted, and 41 articles meeting the review criteria were found. Study characteristics and primary results of these articles are reviewed. Key indicators of quality were poor when averaged across all studies, but have improved greatly over time. The only proven therapy for vasospasm is nimodipine. Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium, statin medications, endothelin antagonists, steroid drugs, anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have yielded inconclusive results. The following conclusions were made: nimodipine is indicated after SAH and tirilazad is not effective. More study of hemodynamic maneuvers, the effectiveness of other calcium channel antagonists such as nicardipine delivered by other routes (for example intrathecally), magnesium, statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is warranted. There is less enthusiasm for the study of steroid drugs and anticoagulant/antiplatelet agents because they entail more risks and investigations so far have shown little evidence of efficacy. The study of rescue therapy such as balloon angioplasty and intraarterial vasodilating agents will be difficult. The quality of clinical trials should be improved.

Evidence-Based Medicine↗

Expression and function of inwardly rectifying potassium channels after experimental subarachnoid hemorrhage.

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is because of smooth muscle contraction, although the mechanism of this contraction remains unresolved. Membrane potential controls the contractile state of arterial myocytes by gating voltage-sensitive calcium channels and is in turn primarily controlled by K(+) ion conductance through several classes of K(+) channels. We characterized the role of inwardly rectifying K(+) (K(IR)) channels in vasospasm. Vasospasm was created in dogs using the double-hemorrhage model of SAH. Electrophysiological, real-time quantitative reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemistry, and isometric tension techniques were used to characterize the expression and function of K(IR) channels in normal and vasospastic basilar artery 7 days after SAH. Subarachnoid hemorrhage resulted in severe vasospasm of the basilar artery (mean of 61% +/- 5% reduction in diameter). Membrane potential of pressurized vasospastic basilar arteries was significantly depolarized compared with control arteries (-46 +/- 1.4 mV versus -29.8 +/- 1.8 mV, respectively, P < 0.01). In whole-cell patch clamp of enzymatically isolated basilar artery myocytes, average K(IR) conductance was 1.6 +/- 0.5 pS/pF in control cells and 9.2 +/- 2.2 pS/pF in SAH cells (P = 0.007). Blocking K(IR) channels with BaCl(2) (0.1 mmol/L) resulted in significantly greater membrane depolarization in vasospastic compared with normal myocytes. Expression of K(IR) 2.1 messenger ribonucleic acid (mRNA) was increased after SAH. Western blotting and immunohistochemistry also showed increased expression of K(IR) protein in vasospastic smooth muscle. Blockage of K(IR) channels in arteries under isometric tension produced a greater contraction in SAH than in control arteries. These results document increased expression of K(IR) 2.1 mRNA and protein during vasospasm after experimental SAH and suggest that this increase is a functionally significant adaptive response acting to reduce vasospasm.

Animals↗