The role of cytoprotective cytokines in cardiac ischemia/reperfusion injury.

The mechanism(s) underlying the beneficial effects of adult mesenchymal stem cells (MSCs) after myocardial infarction (MI) is poorly understood. One possible explanation is the ability of MSCs to secrete cytokines, which modulate cardiomyocyte survival and function. MSCs express at least two cytoprotective cytokines, hepatocyte growth factor (HGF) and stromal cell-derived factor-1 alpha (CXCL12). The aim of our study was to compare the effects of these two cytokines administered acutely post-MI. We subjected adult male Lewis rats to myocardial ischemia/reperfusion injury. Immediately upon reperfusion, polymers saturated with HGF or CXCL12 were placed onto the infarcted anterior wall and the rats were allowed to recover. Echocardiographic analysis at 4 wk post-MI to assess left ventricular (LV) function revealed that LV ejection fraction was increased in the HGF treated group compared with the phosphate-buffered saline (PBS) control group. Likewise, LV end diastolic dimension was reduced in the HGF treated group compared with the PBS control group. Similarly, invasive hemodynamics at 12 wk showed improved contractility and relaxation in the HGF treated group compared with the PBS control group. In contrast, no significant effect on LV function was seen in the CXCL12 treated group. To determine the potential mechanism for this effect, infarct size (IFS) at 72 h was determined. IFS was decreased 4.2-fold in the HGF treated group compared with the PBS control group. Thus, HGF acutely post-MI using polymer delivery reduces IFS, leading to beneficial effects on post-MI LV remodeling.

Comparing isoflurane with tribromoethanol anesthesia for echocardiographic phenotyping of transgenic mice.

Cardiac phenotyping of transgenic mice typically requires anesthesia. Chemical-grade tribromoethanol (TBE) is commonly used for this purpose due to its relatively short duration of action, modest cardiodepressive effects, and its noncontrolled status. In the present study, we used both genders of C57BL/6;C3H-Tg(Slc8a1)hKdp transgenic (TG) mice and C57BL/6;C3H wild-type (WT) mice to evaluate isoflurane (ISF) as a pharmaceutical-grade alternative to TBE for echocardiography and electrocardiography. Baseline target physiologic heart rates (beats per minute) were established by use of telemetry as 544 +/- 10 in WT mice and 580 +/- 21 in TG mice. TG and WT animals were anesthetized with either 0.8% to 1% inhalational ISF or 250 mg/kg intraperitoneal TBE. The following parameters were measured or calculated according to the previously defined physiologic heart rates: end diastolic and systolic dimensions; posterior wall and ventricular septal thicknesses; left ventricular mass, aortic ejection times; left ventricular fractional shortening; velocity of circumferential fiber shortening; and left ventricular ejection fraction. No significant difference between anesthetics was found for any measured cardiac parameters. However, the time required for data acquisition was significantly shorter for ISF (10 min) than for TBE (14 min). This study demonstrates that comparable echocardiographic results can be obtained at higher throughput by use of pharmaceuticalgrade ISF than with chemical-grade TBE.