Hougaard KD, Niels H, Dora Z, Leif S, Anne N, Troels MH, et al. Remote ischaemic perconditioning as an adjunct therapy to thrombolysis in patients
with acute ischaemic stroke a randomised trial. Stroke 2014:159-67.
Preconditioning is a procedure by which a noxious stimulus near to but below the threshold
of damage is applied to the tissue through which the organ (and therefore the organism)
develops resistance to, or tolerance of, the same, similar or even different noxious
stimuli given beyond the threshold of damage thereby conferring protection. Ulrich
Dirnagl et al.,
[1] in their review article published in Lancet Neurology dwells on the mechanisms of
ischaemic preconditioning and its possible clinical uses. Basically sub-threshold
ischaemia protects through four ways which are increased substrate delivery (via angiogenesis),
metabolic downregulation through gene modulation, antagonism of damaging pathways
(downregulation of NMDA and AMPA receptors) and improved recovery by stimulating progenitor
cells in the subventricular zone of the lateral ventricles and the subgranular zone
in the hippocampal dentate gyrus.
The current study by Hougaard et al., is an open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered
remote ischaemic preconditioning through (rPerC) intermittent upper arm ischaemia
in patients with suspected acute stroke. Post-neurological examination and MRI, patients
with verified stroke receiving alteplase treatment were included and had MRI at 24
hours and 1 month and clinical re-examination after 3 months. The primary end point
was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not
progressing to infarction after 1 month. Four hundred and forty-three patients were
enrolled out of which 247 received rPerC while 196 had standard treatment. Transient
ischaemic attack was more frequent (P = 0.006), and NIHSS on admission was lower (P = 0.016) in the intervention group compared with controls. Although penumbral salvage,
infarct growth and size at 1 month, and clinical outcome after 3 months did not differ
among groups but the authors concluded that prehospital rPerC may have immediate neuroprotective
effects.
Hahn et al.,
[2] carried out the first study showing the effectiveness of preconditioning as a neuroprotective
strategy. Thirty nine male P60 Sprague-Dawley rats were randomly allocated to three
groups: a control group, which received no intervention, a preconditioning group through
transient limb ischaemia 40 minutes before surgery and a per-conditioning group where
it was initiated 40 minutes before reperfusion. Focal cerebral ischaemia was achieved
using transient right middle cerebral artery occlusion, performed surgically under
isoflurane anaesthesia. The resulting infarct size at 24 hours was quantified using
computerised image analysis of 2–3-5-triphenyl tetrazolium chloride-stained brain
sections. It was observed that compared with control, preconditioning significantly
reduced brain infarct size with the more clinically relevant per-conditioning stimulus
being superior to preconditioning. The authors concluded that remote per-conditioning
by transient limb ischaemia provides potent neuroprotection in a model of regional
brain ischaemia–reperfusion injury.
In 2012 Meng et al.,
[3] studied the protective effectiveness of brief repetitive bilateral arm ischaemic
preconditioning (BAIPC) on stroke recurrence in patients with symptomatic atherosclerotic
intracranial arterial stenosis (IAS). Sixty-eight patients were enrolled with symptomatic
IAS, diagnosed by imaging in this prospective and randomised study. All patients received
standard medical management. Patients in the BAIPC group (n = 38) underwent five brief cycles consisting of bilateral upper limb ischaemia followed
by reperfusion. The BAIPC procedure was performed twice daily over 300 consecutive
days. Incidence of recurrent stroke and cerebral perfusion status in BAIPC-treated
patients were compared with the untreated control group (n = 30). In the control group, incidence of recurrent stroke at 90 and 300 days were
23.3% and 26.7%, respectively. In the BAIPC group, incidence of recurrent stroke was
reduced to 5% and 7.9% at 90 and 300 days (P < 0.01), respectively. The average time to recovery (modified Rankin Scale score
0-1) was also shortened by BAIPC. Cerebral perfusion status, measured by SPECT and
transcranial Doppler sonography, improved remarkably in BAIPC-treated brain than in
control (P < 0.01). It was concluded that BAIPC may be an effective way to improve cerebral
perfusion and reduce recurrent strokes in patients with IAS.
A Cochrane database review[4] in 2011 on remote ischaemic preconditioning versus no remote ischaemic preconditioning
for vascular and endovascular surgical procedures conclude insufficient data at present
to say whether remote ischaemic preconditioning has any beneficial or harmful effects.
There is a need for further randomised trials on this technique to give shape to definite
therapeutic guidelines.
