Hyperthermic Fibrinolysis with rt-PA: In Vitro Results

Schwarzenberg, H.; Müller‐Hülsbeck, Stefan; Brossman, Joachim; Glüer, Claus C.; Bruhn, H.; Heller, Martin

doi:10.1007/s002709900231

Cited by 23 publications

(25 citation statements)

References 18 publications

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“…After addition of tPA, concentration of D-dimer was approximately tripled and time to complete clot lysis was approximately halved from 30°C to 40°C. 16 Our present results also show an increase in fibrinolytic activity of tPA at higher temperatures as indicated by significant decrease in clot size at higher temperatures. These results thus suggest that the increased fibrinolytic activity of tPA during hyperthermia is offset by its deleterious actions and a net Effects of hyperthermia on perfusion deficit after focal cerebral ischemia.…”

Section: Discussionsupporting

confidence: 83%

Hyperthermia Masks the Neuroprotective Effects of Tissue Plaminogen Activator

Noor

Wang

Shuaib

2005

Stroke

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Background and Purpose-Previously, we have shown that hyperthermia significantly increased neuronal damage after ischemic injury in a focal embolic model of stroke in rats. In the present study, we examined the effects of hyperthermia on the efficacy of thrombolytic therapy in this stroke model. Methods-In part A, efficacy of tissue plaminogen activator (tPA) treatment was examined in normothermic and hyperthermic rats after embolization of preformed clots into middle cerebral artery (MCA). In part B, brain perfusion deficits were assessed in rats after MCA occlusion. In part C, blood-brain barrier (BBB) permeability was examined in rats after MCA occlusion. In part D, we examined the influence of hyperthermia on fibrinolytic activity of tPA in vitro. Results-Results showed that treatment with tPA significantly reduced infarct volume in normothermic and 38°C hyperthermic rats. When compared with normothermic rats, perfusion deficits in hyperthermic rats were significantly increased at both 3 hours and 6 hours after ischemic injury. Compared with normothermic sham-operated rats, Evans blue dye extravasation was increased in the injured rats with 39°C hyperthermia. In vitro study showed that hyperthermia increased the fibrinolytic activity of tPA. Conclusions-The present study shows that hyperthermia masks the neuroprotective effects of tPA treatment after ischemic injury and that this may be caused by increased BBB permeability, increased edema, and early progression of ischemic penumbral region to irreversibly damaged tissue as shown by progressively increasing perfusion deficits in hyperthermic rats.

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Section: Discussionsupporting

confidence: 83%

Hyperthermia Masks the Neuroprotective Effects of Tissue Plaminogen Activator

Noor

Wang

Shuaib

2005

Stroke

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“…In vitro studies showed an increase in fibrinolytic activity at high temperatures [35], and in a recent study in 111 patients treated with tPA, high temperatures at admission were associated with a better outcome [36]. These results have not been validated by other studies [12], [36], [37], but have shown results similar to ours [38].…”

Section: Discussionmentioning

confidence: 50%

Neuroprotection or Increased Brain Damage Mediated by Temperature in Stroke Is Time Dependent

et al. 2012

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The control of temperature during the acute phase of stroke may be a new therapeutic target that can be applied in all stroke patients, however therapeutic window or timecourse of the temperature effect is not well established. Our aim is to study the association between changes in body temperature in the first 72 hours and outcome in patients with ischemic (IS) and hemorrhagic (ICH) stroke. We prospectively studied 2931 consecutive patients (2468 with IS and 463 with ICH). Temperature was obtained at admission, and at 24, 48 and 72 hours after admission. Temperature was categorized as low (<36°C), normal (36–37°C) and high (>37°C). As the main variable, we studied functional outcome at 3 months determined by modified Rankin Scale.Temperature in stroke patients is higher than in controls, and increases gradually in the first 72 hours after stroke. A positive correlation between temperature and stroke severity determined by NIHSS was found at 24 and 48 hours, but not at admission or 72 hours. In a logistic regression model, high temperature was associated with poor outcome at 24 hours (OR 2.05, 95% CI 1.59–2.64, p<0.0001) and 48 hours (OR 1.93, 95% CI 1.08–2.34, p = 0.007), but not at admission or 72 hours.Temperature increases in patients with stroke in the first 72 hours, with the harmful effect of high temperature occurring in the first 48 hours. The neuroprotective effect of low temperature occurs within the first 24 hours from stroke onset.

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“…There is evidence from previous studies that hyperthermia facilitates the process of tPA-induced thrombolysis. 27,28 In our study where all the patients underwent tPA thrombolysis, the absence of any relationship between hyperthermia before thrombolysis and poor outcome could be explained by this process.…”

Section: Discussionmentioning

confidence: 75%