Direct action on the molecule is one of several mechanisms by which ultrasound enhances the fibrinolytic effects of reteplase.
Enhanced fibrinolytic reperfusion therapy may improve the outcome in embolic stroke, where ultrasound exposure has been shown to be one option. We recently verified that the fibrinolytic properties of streptokinase were modulated following ultrasound exposure of the molecule. We have now explored this possibility following ultrasound exposure of the reteplase molecule. The effects on clot lysis of reteplase and ultrasound both separately and in combination were studied by evaluating cumulated release of haemoglobin from whole blood clots following 1 h of exposure. Specifically, we investigated how clot lysis was modulated following pulsed 1 MHz ultrasound pre-exposure of the reteplase solution at intensities ranging between 0.125 and 4 W/cm2 spatial-average temporal-average intensity (SATA) and the effects of reteplase following 1 h of pre-exposure of clots to ultrasound at high intensity (4 W/cm2SATA). Significant enhancement of clot lysis during concomitant reteplase and pulsed ultrasound exposure were observed in two intensity ranges: 0.125-0.25 and 2-4 W/cm2SATA. Pre-exposing reteplase solution to ultrasound significantly increased clot lysis only in the lower intensity range. At high ranges, pre-exposure of clots to ultrasound was followed by an increased fibrinolytic action of reteplase. Pre-exposing reteplase solution to low-intensity ultrasound induced changes in the reteplase molecule that enhanced its fibrinolytic effects. Although this effect disappeared at moderately higher ultrasound intensity, the pre-exposure of clots to ultrasound of higher intensity induced increased fibrinolytic effects of reteplase solution.
Department of Clinical Sciences, Lund, Cardiology, Lund University, Lund, Sweden. Bjarne.Madsen-Hardig@med.lu.se
Bjarne Madsen
BM
Härdig
Hans W
HW
Persson
S Bertil
SB
Olsson
D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015424:Reperfusion / Q000379:methods; D020521:Stroke / Q000628:therapy; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use; D014464:Ultrasonic Therapy / Q000379:methods
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator