Calcium paradox in an in vivo model of multidose cardioplegia and moderate hypothermia. Prevention with diltiazem or trace calcium levels

The production and prevention of calcium paradox injury in myocardium was studied in a canine model of cardiopulmonary bypass with multidose, moderately hypothermic, crystalloid cardioplegic solution. During 4 1/2 hours of global ischemia, three groups of six dogs each received one of three histidine-buffered cardioplegic solutions (500 ml initially and 250 ml every 30 minutes) at 27 degrees C. Group 1 cardioplegic solution was calcium free, group 2 solution contained a trace amount of calcium chloride (70 mumols /L), and group 3 cardioplegic solution was calcium free but contained diltiazem (150 micrograms/kg body weight). Left ventricular function measured as percent control of developed pressure revealed significantly greater (p less than 0.05) recovery in groups 2 and 3. Triphenyltetrazolium chloride staining showed 35% +/- 9% (mean +/- standard error) of heart mass necrosis in group 1 versus 0% and 0.5% +/- 0.4% in groups 2 and 3, respectively (p less than 0.001). Electron microscopy revealed ultrastructural changes characteristic of calcium paradox injury in group 1 myocardium. Calcium paradox injury was produced in an in vivo model of global myocardial ischemia and multidose cardioplegia despite moderate hypothermia and non-coronary collateral flow. The addition of either trace levels of calcium or diltiazem to the cardioplegic solution was effective in preventing this injury.     

Cell transplantation to improve ventricular function in the failing heart

Current therapies for congestive heart failure are limited in efficacy or in applicability. Cardiac cell transplantation offers a novel therapeutic approach to improve heart function. Although significant progress has been made over the past decade in the development of cell transplantation, only recently have investigators studied the changes in ventricular function following cell transplantation. This review article describes the latest research developments, evaluates recent studies of ventricular function after cell transplantation, and discusses the future directions of cell transplantation as a new therapy to ‘repair broken hearts’.     

Percutaneous transcatheter occlusion of coronary artery fistulas using detachable balloons

Three pediatric patients underwent successful transcatheter coronary artery fistula occlusion using the Debrun system. This latex balloon system offers several advantages over other occlusion systems. First, the balloon delivery and release is controlled. Second, “test occlusions” can be performed that allow simultaneous balloon inflation, coronary cineangiography, and electrocardiographic monitoring. Third, because the balloons are flow-directed, they are easily positioned in properly chosen locations. Finally, the balloons can be constructed to suit the size of the fistula. In this study, two patients received only one balloon; in the other patient two balloons were placed in the same fistula. All fistulas drained into either the right atrium or ventricle and were successfully occluded. After a follow-up period of up to 3 years, no local or systemic reactions to the balloons were recognized. We conclude that detachable balloon occlusion of coronary artery fistulas is a safe, effective alternative to surgical ligation in selected pediatric patients.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.