Page 128 - Read Online

Page 4 of 20 Akinci et al. Vessel Plus 2021;5:56 https://dx.doi.org/10.20517/2574-1209.2021.20

In addition to aggravating primary brain injury by causing increased hematoma, elevated BP also influences
secondary brain injury through affecting brain swelling, inflammation, apoptosis and necrosis. RAS
inhibition has been reported to reduce inflammation, oxidative stress, and infarct volume, modulate nitric
[12]
oxide synthase isoenzymes in animal stroke models, and improve functional outcome in stroke patients .
Stimulation of brain and cerebrovascular Ang II systems in rats has been shown to increase micro vessel
[26]
permeability, and expression of proinflammatory factors and contribute to vasoconstriction . Angiotensin
II type 1 receptors (Ang II AT1) in neurons, astrocytes, microglia, and brain microvascular endothelial cells
are likely to play a role in inflammatory response modulation in hypertensive state [27-29] . Long-term brain
Ang II AT1 receptor blockade protects the brain from the pathological effects of stress and from ischemia,
[30]
partly through peripheral anti-inflammatory effects . Evidence suggests that elevated systemic BP can
increase norepinephrine concentration in the subfornix . Norepinephrine acts at beta-adrenoreceptors and
[31]
selective beta-adrenoreceptor 1 antagonists have been shown to provide neuroprotective effects in ischemic
stroke models [32,33] .

RECONSIDERING THE DEFINITION OF ACUTE HYPERTENSIVE RESPONSE
In a rat model of collagenase-induced ICH study, an ultra-acute elevation in SBP following induction of
ICH has been observed in both normotensive rats and rats with renovascular hypertension (RVHT) [mean
arterial pressure (MAP) in RVHT rats increased from 131.9 ± 12.6 mmHg to 138.9 mmHg; in normotensive
rats increased from 85.7 ± 11.5 mmHg to 89.5 mmHg at 30 min after ICH] and elevated SBP increased
hematoma volume, brain edema, and perihematomal apoptosis . However, the hematoma volume was
[12]
60% greater in RVHT rats and correlated with more severe neurological deficits at three weeks.
Additionally, the increase in heart rate observed during the hyperacute phase in normotensive rats was not
observed in RVHT rats, probably due to an altered cardiovascular response.

In another experimental study with rodents, researchers compared the amount of bleeding that chronic
hypertensive and normotensive rats experienced after brain surgery while the BP values of the subjects are
kept at the presurgical levels . Comparison of normotensive, acutely hypertensive, spontaneously
[34]
hypertensive (antihypertensive treatment given and not given) rats showed that only the hematoma volume
of acutely hypertensive rats was larger. These findings were thought to provide evidence that the brains of
spontaneously hypertensive rats are presumably protected against excessive bleeding due to increased
resistance in large cerebral arteries resulting in reduced cerebral intravascular pressure.

Acute hypertensive response is defined as “SBP ≥ 140 mmHg” consistent with the 2003 World Health
Organization/International Society of Hypertension statement but, is it appropriate to use this definition in
both patients with and without chronic hypertension ? Should the diagnosis and treatment criteria for
[35]
acute hypertensive response be the same in two patients with ICH of the same size and location, one with
chronic hypertension and the other without, represented by the same arterial BP value or the same amount
of increase in pre-morbid BP values? From the animal experiments mentioned above, we can easily deduce
that the outcome of these two patients will be different even with the same treatment. However, it seems
quite difficult to classify patients in this way in randomized studies. Since hypertension can be
asymptomatic for years, it is nearly impossible to predict whether the hypertension detected in an ICH
patient at the time of presentation without a history of chronic hypertension is the cause, the result or a
contributing factor, except for a few clues (patients over 45 years of age; the observation of left ventricular
hypertrophy by electrocardiogram, and cardiomegaly by chest radiography; retinal changes; the observation
of homogeneous, oval or round smooth-looking hematomas, surrounded by a thin rim of edema that can
expand for a few days, with periventricular white matter and the protuberance involvement in
neuroimaging suggest that the ICH is secondary to hypertension-related angiopathy) [16,36] . However,