Increased Susceptibility of Spontaneously Hypertensive Rats to Ventricular Tachyarrhythmias during the Early Stages of Hypertension
| Autor: | James N. Weiss, Ali A. Sovari, Christopher Y. Ko, Hrayr S. Karagueuzian, Michael C. Fishbein, Shankar S. Iyer, Hong Cao, Aneesh Bapat, Nooshin Vahdani, Arash Pezhouman, Mostafa Ghanim, Thao P. Nguyen |
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| Rok vydání: | 2016 |
| Předmět: |
Fibrillation
medicine.medical_specialty business.industry Biophysics medicine.disease Ventricular tachycardia Muscle hypertrophy Sudden cardiac death Afterdepolarization Ventricular hypertrophy Heart failure Internal medicine cardiovascular system Cardiology medicine Left Ventricular Epicardium cardiovascular diseases medicine.symptom business |
| Zdroj: | Biophysical Journal. 110(3) |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2015.11.228 |
| Popis: | Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that during the early stages of uncontrolled hypertension, the susceptibility to otherwise benign stress promotes VT/VF. To test this hypothesis we compared the susceptibility of 5-6-month-old male spontaneously hypertensive rats (SHR) and age/gender-matched normotensive rats (NR) to VT/VF during challenge with mild oxidative stress (H2O2, 0.15 mmol/L). H2O2 initiated spontaneous VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage-Ca optical mapping of Langendorff-perfused SHR hearts revealed that H2O2-induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)-mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch-clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except that SHR myocytes had a relatively larger EAD amplitude. Histopathological and echocardiographic studies showed that compared to NR, SHR hearts exhibited increased left ventricular fibrosis and mild hypertrophy. We conclude that during the early stages of hypertension (i.e., prior to the development of overt heart failure) SHR hearts manifest increased susceptibility to VT/VF when challenged with mild oxidative stress that appears to be related to tissue remodeling (i.e., hypertrophy, fibrosis) moreso than cellular electrophysiological remodeling. Our findings highlight the need for aggressive treatment during the stages of early hypertension to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias. |
| Databáze: | OpenAIRE |
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