Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: a study with pomegranate seed oil.

Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by micro-computed tomography and histology. Enzyme-linked immunosorbent assay was performed to analyze the levels of serum insulin-like growth factor type 1 (IGF-1). Western blotting from bone and liver tissues was done. Chromatin immunoprecipitation assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, bone mineral density and bone microarchitecture along with enhancing muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone.

Conscious cardiac surgery with cardiopulmonary bypass using thoracic epidural anesthesia without endotracheal general anesthesia.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of thoracic epidural anesthesia as an alternative technique to general anesthesia in patients undergoing cardiac surgery under cardiopulmonary bypass. DESIGN: A prospective study. SETTING: Tertiary referral heart hospital. PARTICIPANTS: Eleven patients underwent cardiac surgical procedures requiring cardiopulmonary bypass under thoracic epidural anesthesia from February to April 2004. INTERVENTIONS: An epidural catheter was inserted at C7 to T2 intervertebral space on the day before the operation. Subsequently, cardiac surgery was performed using cardiopulmonary bypass. MEASUREMENTS AND RESULTS: The midsternotomy approach was used in all the patients. Anticoagulation was achieved with 300 units/kg of heparin. Under normothermic cardiopulmonary bypass, 6 patients underwent closure of atrial septal defect, 3 underwent valve replacements, and 2 underwent coronary artery bypass surgery combined with valve replacements. Soon after establishing cardiopulmonary bypass, all but 1 patient developed apnea, which was reversed after termination of cardiopulmonary bypass. The mean cardiopulmonary bypass time was 102 +/- 28 minutes, the aortic cross-clamp time was 58 +/- 28 minutes, and the total duration of surgery was 229 +/- 64 minutes. There was no mortality or morbidity in this series. CONCLUSION: Cardiac surgical procedures requiring cardiopulmonary bypass may be performed under thoracic epidural anesthesia, without endotracheal general anesthesia.

Cardiopulmonary bypass in conscious patients undergoing cardiac surgery.

This study was undertaken to evaluate the feasibility of thoracic epidural anesthesia as an alternative technique to general anesthesia in patients undergoing cardiac surgery under cardiopulmonary bypass. This prospective study was conducted in a tertiary referral hospital. Seventeen patients underwent cardiac surgical procedures requiring cardiopulmonary bypass without general anesthesia under thoracic epidural anesthesia from February to May 2004. An epidural catheter was inserted at any of intervertebral spaces from C7 to T2 on the day before surgery. Subsequently, cardiac surgery was performed under normothermic cardiopulmonary bypass, during which the patients remained conscious. The types of surgery included closure of atrial septal defects, valve replacements, and combined bypass surgery and valve replacements. Approach to the heart was obtained through midsternotomy. Anticoagulation was achieved with 300 units/kg of heparin. Normothermic cardiopulmonary bypass was initiated slowly during the course of 10 to 15 min. Nonpulsatile flow was administered using centrifugal pump and mean perfusion pressure was maintained in the range of 70-80 mmHg. The planned surgical procedure could be performed in all the patients. Soon after establishing cardiopulmonary bypass, the patients developed apnea, which reverted to normalcy a few minutes after disconnection of cardiopulmonary bypass. The mean time for cardiopulmonary bypass was 102 +/- 28 min, aortic cross clamp time was 58 +/- 28 min, and the total duration of surgery was 229 +/- 64 min. None of the patients required conversion to general anesthesia. There was no mortality or morbidity in this series and to our knowledge our series is the first such. Cardiac surgical procedures requiring cardiopulmonary bypass may be conducted under thoracic epidural anesthesia, without endotracheal general anesthesia.

Conscious off-pump coronary artery bypass surgery.

BACKGROUND: Cardiothoracic surgery has been previously performed successfully under thoracic epidural anesthesia alone. Between October 2001 and December 2003, we performed 123 conscious off-pump coronary artery bypass surgeries using epidural anesthesia as the sole anesthetic. This technique is an alternative to cardiothoracic surgery performed under general anesthesia. Certain modifications in the technique facilitate the process. METHODS AND RESULTS: There were 24 female patients and 99 male patients with mean age of 58.6 +/- 6.2 years; 12 patients underwent repeat coronary artery bypass surgery. All the patients underwent epidural catheterization on the evening before surgery. Out of the 123 patients scheduled for coronary artery bypass graft surgery, 120 underwent off-pump coronary artery bypass graft surgery successfully; 4 patients underwent off-pump surgery via left thoracotomy and the rest through mid sternotomy. These patients received 295 grafts in all (single graft in 26 patients, double in 42 patients, triple in 35 patients, and quadruple in 20 patients). Three patients required conversion to general anesthesia and one to cardiopulmonary bypass. There was no mortality in the group. CONCLUSIONS: Our experience suggests that by modifying the surgical techniques, we can accomplish conscious coronary artery bypass surgery.