Abstract
Damage to the insular cortex (IC) results in serious cardiovascular consequences and
evidence indicates that the characteristics are lateralized. However, a study comparing
the effects of focal experimental hemorrhage between IC sides was never performed.
We compared the cardiovascular, autonomic and cardiac changes produced by focal experimental
hemorrhage (ICH) into the left (L) or right (R) IC. Wistar rats were submitted to
microinjection of autologous blood (ICH) or saline (n = 6 each side/group) into the
R or L IC. Blood pressure (BP), heart rate (HR) and renal sympathetic activity (RSNA)
were recorded. Measurements of calcium transient and sarcoplasmic Ca2+ ATPase expression in cardiomyocytes were performed. ICH increased baseline HR (Δ:L-ICH
452 ± 13 vs saline 407 ± 11 bpm; R-ICH 450 ± 7 vs saline 406 ± 8 bpm, P < 0.05) without changing BP. HR was restored to baseline levels after i.v. atenolol.
Strikingly, ICH rats presented a reduced baseline RSNA (Δ:L-ICH 122 ± 4 vs saline
148 ± 11 spikes/s; R-ICH 112 ± 5 vs saline 148 ± 7 spikes/s, P < 0.05). After 24 h of ICH we observed a marked increase in cardiac ectopies and
this number was greater after ICH R-IC. Heart weight, calcium amplitude and SERCA
expression were reduced only in ICH R-IC. Focal stroke into IC can alter the cardiac
and renal autonomic control. Damage to the R-IC produces a greater number of arrhythmias
and changes in calcium dynamics in cardiac cells indicating that the cardiovascular
consequences are hemisphere-dependent. These findings confirm asymmetry for cardiac
autonomic control at the IC and help to understand the cardiac and renal implications
observed after specific side cortical damage.
Graphical abstract

Graphical Abstract
Keywords
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References
- Insular involvement in brain infarction increases risk for cardiac arrhythmia and death.Ann. Neurol. 2006; 59: 691-699
- Functional cross-talk between aldosterone and angiotensin-(1–7) in ventricular myocytes.Hypertension. 2013; 61: 425-430
- Pre-excitation syndrome.in: Sports Cardiology. Springer, 2012: 179-183
- Cardiac autonomic derangement and arrhythmias in right-sided stroke with insular involvement.Stroke. 2004; 35: 2094-2098
- Asymmetric sympathetic output: the dorsomedial hypothalamus as a potential link between emotional stress and cardiac arrhythmias.Auton. Neurosci. 2017; 207: 22-27
- Animal models of stroke: do they have value for discovering neuroprotective agents?.Trends Pharmacol. Sci. 2003; 24: 402-408
- Molecular identification of a TTX-sensitive Ca2+ current.Am. J. Phys. Cell Phys. 2001; 280: C1327-C1339
- Relation between myocardial function and expression of sarcoplasmic reticulum Ca2+-ATPase in failing and nonfailing human myocardium.Circ. Res. 1994; 75: 434-442
- Brain injury after intracerebral hemorrhage: the role of thrombin and iron.Stroke. 2007; 38: 759-762
- Left insular stroke is associated with adverse cardiac outcome.Neurology. 2006; 66: 477-483
- Sex-based cardiac physiology.Annu. Rev. Physiol. 2009; 71: 1-18
- Functional topography of cardiovascular regulation along the rostrocaudal axis of the rat posterior insular cortex.Clin. Exp. Pharmacol. Physiol. 2016; 43: 484-493
- Atrial fibrillation after acute intracerebral hemorrhage: how would the insular cortex damage interact?.Eur. J. Neurol. 2018; 25: e58
- Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage.Stroke. 2008; 39: 463-469
- The insular cortex and the regulation of cardiac function.Compr. Physiol. 2011; 6: 1081-1133
- The Rat Brain in Stereotaxic Coordinates.Academic Press Australia, 1986
- Rate dependence of [Na+]i and contractility in nonfailing and failing human myocardium.Circulation. 2002; 106: 447-453
- Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: an in vivo microdialysis study.Crit. Care Med. 2003; 31: 1482-1489
- Cardiovascular responses evoked by activation or blockade of GABAA receptors in the hypothalamic PVN are attenuated in transgenic rats with low brain angiotensinogen.Brain Res. 2012; 1448: 101-110
- Adrenergic regulation of cardiac myocyte apoptosis.J. Cell. Physiol. 2001; 189: 257-265
- Cardiac arrhythmia associated with reversible damage to insula in a patients with subarachnoid hemorrhage.Stroke. 1994; 25: 1053-1055
- Repetitive asystole in right insular hemorrhage.J. Neurol. Neurosurg. Psychiatry. 2007; : 1282-1283https://doi.org/10.1136/jnnp.2007.121319
- Modeling intracerebal hemorrhage: glutamate, nuclear factor-κB signaling and cytokines.Stroke. 2007; 38: 753-758
- Stroke: understanding the differences between males and females.Pflügers Arch.-Eur. J. Physiol. 2013; 465: 595-600
- Asymmetry in the control of cardiac performance by dorsomedial hypothalamus.Am. J. Phys. Regul. Integr. Comp. Phys. 2013; 304: R664-R674
- Chronic kidney disease and clinical outcome in patients with acute stroke.Stroke. 2009; 40: 1296-1303
Article info
Publication history
Published online: June 24, 2020
Accepted:
June 21,
2020
Received in revised form:
June 20,
2020
Received:
April 14,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.