Background-Hypothermia during ischemia has been shown to reduce myocardial reperfusion injury. We sought to establish the cardioprotective effect of very mild total-body hypothermia (≤ 2.5°C) and to determine whether the application of hypothermia at different points during the ischemia-reperfusion period influenced the degree of myocardial salvage.

Background-Glucagon-like peptide-1 (GLP-1) has insulinomimetic, insulinotropic and antiapoptotic properties that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI); however, GLP-1 has a short plasma half-life. Fusion of GLP-1 to human transferrin (GLP-1-Tf) significantly prolongs drug half-life.

Background Opening of the mitochondrial permeability transition pore (MPTP) has been shown to contribute to myocardial ischemia/reperfusion injury. We sought to demonstrate that the myocardial protective effect of inhibiting MPTP opening with cyclosporine A (CsA) results in stabilization of mitochondrial morphology and is independent of CsA-induced calcineurin inhibition. Methods Thirty-seven rabbits were divided into three groups: control (n = 15), CsA (MPTP and calcineurin inhibitor, n = 12), or FK506 (calcineurin inhibitor, n = 10). Each group received a 1-hour infusion of either a saline vehicle, 25 mg/kg CsA or 1 mg/kg FK506. All animals underwent 30 minutes of regional ischemia and 3 hours of reperfusion. Myocardial infarct size was determined using Evans blue dye and triphenyltetrazolium chloride. In situ oligo ligation was used to assess apoptotic cell death. Transmission electron microscopy was used to quantitatively evaluate morphologic differences in the mitochondria between groups. Results Infarct size in the CsA group (39% ± 3%) was significantly reduced compared with the control group (60% ± 2%, p < 0.001) and FK506 group (55% ± 3%, p = 0.001). Apoptotic cell death was also attenuated in the CsA group (1.2% ± 0.5%) compared with the control group (4.3% ± 0.8%, p = 0.01) and FK506 group (4.1% ± 0.9%, p = 0.05). Transmission electron microscopy revealed a preservation of normal mitochondrial morphology and a reduction in the percentage of disrupted mitochondria in the CsA group (20% ± 7%) compared with the control group (53% ± 12%) and FK506 group (47% ± 9%). Conclusions Cyclosporine A–induced MPTP inhibition preserves mitochondrial morphology after myocardial ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are independent of calcineurin inhibition.

Chance, "Fluorescence spectroscopy and imaging of myocardial apoptosis", . December 2006. Fluorescence spectroscopy and imaging of myocardial apoptosis AbstractFluorometry is used to detect intrinsic flavoprotein (FP) and nicotinamide adenine dinucleotide NADH signals in an open-chest rabbit model of myocardial ischemia-reperfusion injury. Myocyte apoptosis has been shown clinically to contribute to infarct size following reperfusion of ischemic myocardium. A noninvasive means of assessing apoptosis in this setting would aid in the treatment of subsequent ventricular remodeling. We show that in vivo fluorometry can be useful in apoptosis detection in open-chest surgeries. Specific changes in myocardial redox states have been shown to indicate the presence of apoptosis. Two main mitochondrial intrinsic fluorophores, NADH and FP signals, were measured during normoxia, ischemia, and reperfusion experimental protocol. Ischemia was induced by occlusion of the largest branch of the circumflex coronary artery and fluorescence signals are collected by applying two different fluorescence techniques: in vivo fluorometry and postmortem cryoimaging. The first technique was employed to detect FP and NADH signals in vivo and the latter technique uses freeze trapping and lowtemperature fluorescence imaging. The heart is snap frozen while still in the chest cavity to make a "snapshot" of the metabolic state of the tissue. After freezing, the ischemic area and its surrounding border zone were excised and the sample was embedded in a frozen buffer for cryoscanning. These two data sets, in vivo fluorometry and low temperature redox scanning, show consistent extreme oxidation of the mitochondrial redox states (higher redox ratio) suggesting the initiation of apoptosis following reperfusion. This represents the first attempt to assess myocyte apoptosis in the beating heart. The heart is snap frozen while still in the chest cavity to make a "snapshot" of the metabolic state of the tissue. After freezing, the ischemic area and its surroundings border zone were excised and the sample was embedded in a frozen buffer for cryo-scanning. These two data sets, in vivo fluorometry and low temperature redox scanning, show consistent extreme oxidation of the mitochondrial redox states (higher 2 redox ratio) suggesting the initiation of apoptosis following reperfusion. This represents the first attempt to assess myocyte apoptosis in the beating heart.

Interventricular septal hematoma (IVSH) is extremely rare, and most cases are reported to occur in pediatric patients as a complication after the repair of a ventricular septal defect (VSD). We present a case of a giant IVSH after patch closure of a perimembranous VSD and review of the relevant literature. CLINICAL SUMMARYA 3-month-old boy was admitted to the University of Tsukuba hospital with a diagnosis of VSD and severe pulmonary hypertension. The patient weighed 5.3 kg. Echocardiography revealed a large (6 mm) perimembranous trabecular VSD, which was surgically closed using cardiopulmonary bypass (CPB) and antegrade cardioplegia. A standard closure using a Dacron patch and a continuous suture technique along the edge starting with a pledgeted horizontal mattress suture placed near the base of the medial papillary muscle was performed. FIGURE 1. TEE showing changes in the interventricular septum hematoma over time. Longitudinal (top) and short-axis (bottom) views on postoperative day 1, month 1, and month 2. Arrows indicate hematoma. POD, Postoperative day; IVSH, interventricular septal hematoma; LV, left ventricle; Ao, aorta.