Hemodynamic Disturbances and Activation of Lipid Peroxidation in the Pathogenesis of Acute Myocardial Injury Induced by Propranolol in Toxic Doses

Yatsinyuk, Boris Borisovich

doi:10.1007/s10517-011-1316-x

Cited by 1 publication

(3 citation statements)

References 5 publications

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“…Both propranolol and metoprolol pretreatment groups were injected intraperitoneally with a single dose of propranolol (10 mg/kg) or metoprolol (10 mg/kg) 30 minutes prior to subcutaneous administration of ISO 100 mg/kg. Doses of beta‐blocker were based on previous studies assessing the safety and heart rate‐reducing properties of the drugs . Twenty‐four hours after ISO administration, animals underwent surgical procedure for hemodynamic recording and thereafter hearts were excised, stained with 1% 2,3,5‐triphenyl tetrazolium chloride (TTC) and stored for hematoxylin and eosin (H&E) and picrosirius red (PSR) staining.…”

Section: Methodsmentioning

confidence: 99%

“…Doses of beta-blocker were based on previous studies assessing the safety and heart rate-reducing properties of the drugs. 1,2 Twenty-four hours after ISO administration, animals underwent surgical procedure for hemodynamic recording and thereafter hearts were excised, stained with 1% 2,3,5-triphenyl tetrazolium chloride (TTC) and stored for hematoxylin and eosin (H&E) and picrosirius red (PSR) staining.…”

Section: Protocolmentioning

confidence: 99%

“…However, there is a lack of substantial evidence that proves their beneficial effect on either structure-function defect or survival at the acute phase. Therefore, the purpose of this study was (1) to better delineate the time course of changes in this model by echocardiography at both the apex and base of the heart; (2) to determine the structural and ultrastructural changes; (3) to determine whether histological abnormalities resolved at the same time as functional abnormalities; and (4) to determine whether pretreatment with beta blockers would prevent the structural and functional abnormalities.…”

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Functional and Histological Assessment of an Experimental Model of Takotsubo's Cardiomyopathy

Sachdeva

Dai

Kloner

2014

JAHA

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BackgroundOur objectives were to characterize functional and structural features of an experimental model of Takotsubo cardiomyopathy, and its response to beta‐blockers.Methods and ResultsIn protocol 1, a dose‐finding study: 69 rats received various doses of isoproterenol (ISO) and echocardiographic and histologic parameters were measured on days 2 to 3 or day 8. There were no dose‐dependent effects and, out of 69 ISO‐treated rats, 40 (58.0%) survived and 29 (42.0%) died within 24 hours. Of survivors, 30 had apical akinesis averaging 12.1±1.6% of the long axis LV circumference. Out of the 40 survivors, 32.5% showed apical akinesis ≥10%, 42.5% showed akinesis<10% and 25% showed no apical akinesis. The basal portion of the LV was always preserved. At 24 hours, histology and ultrastructure showed necrosis, vacuolization, lipid droplets, mononuclear cell infiltration, damaged mitochondria, and edema. On day 8, apical akinesis fully resolved but histologic abnormalities were still present. In protocol 2, rats were randomized to Control; ISO100 mg/kg; propranolol+ISO; and metoprolol+ISO groups. Pretreatment with propranolol and metoprolol improved survival to 90% and 100% respectively, compared with 60% in the ISO group, but did not reduce the incidence and extent of akinesis or the structural damage.ConclusionTC can be mimicked in a rat model of ISO exposure that demonstrates apical akinesis on days 2 to 3 with full recovery of systolic regional wall motion abnormality despite the presence of persistent foci of necrosis and fibrosis on day 8. Pretreatment with beta‐blockers improved survival but did not affect structural and functional alterations.

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Section: Methodsmentioning

confidence: 99%

Section: Protocolmentioning

confidence: 99%

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