Intracerebral Hemorrhage Induces Cardiac Dysfunction in Mice Without Primary Cardiac Disease

Abstract

Background: Intracerebral hemorrhage (ICH) is a life threatening stroke subtype and a worldwide health problem. In this study, we investigate brain-heart interaction after ICH in mice and test whether ICH induces cardiac dysfunction in the absence of primary cardiac disease. We also investigate underlying mechanisms such as oxidative stress and inflammatory responses in mediating cardiac dysfunction post-ICH in mice.Methods: Male, adult (3–4 m) C57BL/6J mice were subjected to sham surgery or ICH using an autologous blood injection model (n = 16/group). Cardiac function was evaluated at 7 and 28 days after ICH using echocardiography (n = 8/group per time point). Western blot and immunostaining analysis were employed to assess oxidative stress and inflammatory responses in the heart.Results: Mice subjected to ICH exhibited significantly decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 7 and 28 days after ICH compared to sham-control mice (p < 0.05). ICH induced cardiac dysfunction was significantly worse at 28 days than at 7 days after ICH (p < 0.05). ICH in mice significantly increased cardiomyocyte apoptosis, inflammatory factor expression and inflammatory cell infiltration in heart tissue, and induced cardiac oxidative stress at 7 days post-ICH compared to sham-control mice. Compared to sham-control mice, ICH-mice also exhibited significantly increased (p < 0.05) cardiomyocyte hypertrophy and cardiac fibrosis at 28 days after ICH.Conclusions: ICH induces significant and progressive cardiac dysfunction in mice. ICH increases cardiac oxidative stress and inflammatory factor expression in heart tissue which may play key roles in ICH-induced cardiac dysfunction.

Novel targets, treatments, and advanced models for intracerebral haemorrhage

“…Cardiac complications are common after ICH and higher heart rate variability in the acute phase is associated with poorer 3-month outcomes. 62 Preclinical studies using autologous blood or collagenase-induced ICH in mice have replicated cardiac complications 59,63 and metoprolol reduced cardiac damage by abrogating sympathetic overactivation in addition to its immunosuppressive effects. 59 Furthermore, splenectomy reduced cardiac dysfunction along with improving neurological outcome after autologous blood-induced ICH in mice.…”

Brain–Heart Axis and Biomarkers of Cardiac Damage and Dysfunction after Stroke: A Systematic Review and Meta-Analysis

“…Intracerebral hemorrhages are the most common stroke subtype, accounting for 10%-15% of all strokes, with an estimated annual global incidence of 16 per 100,000 people [44][45][46]. About 4% of patients with an intracerebral hemorrhage experience a series of cardiac complications, such as acute myocardial infarction, ventricular fibrillation, acute heart failure, and cardiac death within two days, of which acute heart failure is the most common serious in-hospital cardiac event [47,48]. SAHs are mainly caused by ruptured aneurysms, with a worldwide incidence of approximately nine per 100,000 people and a mortality rate of about 60% at six months [49,50].…”

“…A retrospective study of 617 consecutive patients with SAH also showed increased mortality in patients with high cTnI levels [53]. Therefore, serum cTn levels can be used as indicators to predict hospital mortality and poor prognosis and are available for risk stratification during intracerebral hemorrhage hospitalization [47].…”

Distant Organ Damage in Acute Brain Injury

“…Neurogenic heart dysfunction has been recorded in multiple acute neurological conditions, such as subarachnoid haemorrhage (SAH) intracerebral haemorrhage, traumatic brain injury (TBI) and acute ischemic stroke (AIS). Among those, SAH seems to be of greater risk value [ 54 , 59 , 60 , 61 , 62 , 63 , 64 ]. It seems that the degree of neurological injury may be related to the severity of cardiac dysfunction.…”