Cavitation fatigue - the weakening of cavitation resistance of xylem and its reversibility

Journal ArticleXylem function is essential for the growth and survival of higher land plants. Xylem must not only be efficient under favorable conditions to facilitate high rates of stomatal conductance and carbon uptake, but it should also remain functional under drought conditions, when water potential (Ψ) drops to low values. Since water in the xylem is lifted up to the leaves by negative pressure (Steudle, 2001; Zimmermann, 1983), it is intrinsically vulnerable to cavitation

Hydraulic consequences of vessel evolution in angiosperms

Journal ArticleWe tested two hypotheses for how vessel evolution in angiosperms influenced xylem function. First, the transition to vessels decreased resistance to flow--often considered the driving force for their evolution. Second, the transition to vessels compromised safety from cavitation--a constraint emerging from the "pit area hypothesis" for vulnerability to cavitation. Data were obtained from branch wood of 17 basal taxa with vessels and two eudicots possessing "primitive" perforation plates. Results were compared with previous data from vesselless angiosperms and eudicots with simple perforation plates. Contrary to the first hypothesis, basal taxa did not have significantly lower sapwood-specific resistivity than vesselless angiosperms, despite vessels being wider than tracheids

Analysis of circular bordered pit function II. Gymnosperm tracheids with torus-margo pit membranes

Journal ArticleA model of xylem conduit function was applied to gymnosperm tracheids with torus-margo pit membranes for comparison with angiosperm vessels. Tracheids from 17 gymnosperm tree species with circular bordered pits and air-seed pressures from 0.8 to 11.8 MPa were analyzed. Tracheids were more reinforced against implosion than vessels, consistent with their double function in transport and support

Water transport in vesselless angiosperms: conducting efficiency and cavitation safety

Journal ArticleTwo structure-function hypotheses were tested for vesselless angiosperm wood. First, vesselless angiosperm wood should have much higher flow resistance than conifer wood because angiosperm tracheids lack low-resistance torus-margo pits. Second, vesselless wood ought to be exceptionally safe from cavitation if the small cumulative area of pits between tracheids confers safety (the pit area hypothesis). Data were obtained from branch wood of 19 vesselless angiosperms: Amborella trichopoda, Trochodendron aralioides, Tetracentron sinense, and 16 Winteraceae from Tasmannia, Zygogynum, Bubbia, Pseudowintera, and Drimys

Analysis of circular bordered pit function I. Angiosperm vessels with homogenous pit membranes

Journal ArticleA model predicted pit and vessel conductivity, the air-seed pressure for cavitation, and the implosion pressure causing vessel collapse. Predictions were based on measurements from 27 angiosperm species with circular bordered pits and air-seed pressures of 0.2-11.3 MPa. Vessel implosion pressure exceeded air-seed pressure by a safety factor of 1.8 achieved by the increase in vessel wall thickness per vessel diameter with air-seed pressure

Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials

Background—Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity. Methods—Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Results—Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13–91; P=0.004). Conclusions—Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that treatment is initiated, the greater the benefit

The Virtual International Stroke Trials Archive

BACKGROUND AND PURPOSE: Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. METHODS: Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. RESULTS: Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on \u3e15,000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69+/-12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. CONCLUSIONS: This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning

The Desmoteplase In Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase

Background and Purpose: Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Methods: DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 μg&#8260;kg, 90 μg&#8260;kg, and 125 μg&#8260;kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days. Results: Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 μg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 μg&#8260;kg; P=0.757) and 60.0% (125 μg&#8260;kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion. Conclusions: Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 μg&#8260;kg.</p

Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P&#8804;0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P&#60;0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration &#8805;1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.&lt;/p&gt