Functional and histological assessment of an experimental model of Takotsubo's cardiomyopathy.

BACKGROUND: Our objectives were to characterize functional and structural features of an experimental model of Takotsubo cardiomyopathy, and its response to beta-blockers. METHODS AND RESULTS: In 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. CONCLUSION: TC 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.

Real-time assessment of flow reversal in an eccentric arterial stenotic model.

Plaque rupture is the leading cause of acute coronary syndromes and stroke. Plaque formation, otherwise known as stenosis, preferentially occurs in the regions of arterial bifurcation or curvatures. To date, real-time assessment of stenosis-induced flow reversal remains a clinical challenge. By interfacing microelectromechanical system (MEMS) thermal sensors with the high frequency pulsed wave (PW) Doppler ultrasound, we proposed to assess flow reversal in the presence of an eccentric stenosis. We developed a 3-D stenotic model (inner diameter of 6mm, an eccentric stenosis with a height of 2.75 mm, and width of 21 mm) simulating a superficial arterial vessel. We demonstrated that heat transfer from the sensing element (2 x 80 µm²) to the flow field peaked as a function of flow rates at the throat of the stenosis along the center/midline of arterial model, and dropped downstream from the stenosis, where flow reversal was detected by the high frequency ultrasound device at 45 MHz. Computational fluid dynamics (CFD) codes are in agreement with the ultrasound-acquired flow profiles upstream, downstream, and at the throat of the stenosis. Hence, we characterized regions of eccentric stenosis in terms of changes in heat transfer along the midline of vessel and identified points of flow reversal with high spatial and temporal resolution.

Mesenchymal stem cell administration at coronary artery reperfusion in the rat by two delivery routes: a quantitative assessment.

AIMS: Ideally, mesenchymal stem cells (MSC) home to and/or remain at the site of damaged myocardium when administered after myocardial infarction. However, MSC may not remain in the heart, but instead relocate to other areas. We investigated quantitatively the distribution of labeled rat MSC, given by two routes after coronary artery occlusion/reperfusion in rats. MAIN METHODS: Rats were subjected to 45 min of coronary artery occlusion and 7 days of reperfusion. Before reperfusion rats received 2 x 10(6) MSC, labeled with europium, injected directly into the ischemic region of the heart (n = 9) or intravenously (n = 8). After 1 week tissues were analyzed for label content together with a standard curve of known quantities of labeled MSC. KEY FINDINGS: In rats receiving cells injected directly into the myocardium, 15% of labeled cells were retained in the heart. When the cells were administered intravenously, no MSC were detected in the heart. The route of administration did not affect distribution to other organs, as the number of MSC in liver, spleen and lung was similar with both routes of delivery. SIGNIFICANCE: Even with direct intramyocardial injection, only a small proportion of the cells are retained in the heart, instead traveling to other organs. With intravenous injection there was no evidence that cells "homed" to the damaged heart. Although cell delivery to the heart was significantly affected by the route of administration, the distribution of cells to other organs was similar with both routes of administration.