Sun Zongquan

Semi-skeletonized Internal Mammary Grafts and Phrenic Nerve Injury： Cause-and-effect analysis

SummaryPhrenic nerve injury after cardiac surgery increases postoperative pulmonary complications. The purpose of this study was to analyze the causes and effects of phrenic nerve injury after cardiac surgery. Prospectively collected data on 2084 consecutive patients who underwent cardiac surgery from Jan. 1995 to Feb. 2002 were analyzed. Twenty-eight preoperative and operation related variables were subjected to logistic analysis with the end point being phrenic nerve injury. Then phrenic nerve injury and 6 perioperative morbidities were included in the analysis as variables to determine their independent predictive value for perioperative pulmonary morbidity. An identical approach was used to identify the independent risk factors for perioperative mortality. There were 53 phrenic nerve injuries (2.5 %). There was no phrenic nerve injury in non-coronary surgery or coronary surgery using conduits other than the internal mammary artery. The independent risk factors for phrenic nerve injury were the use of internal mammary artery (Odds ratio (OR)=14.5) and the presence of chronic obstructive pulmonary disease (OR=2.9). Phrenic nerve injury was an independent risk factor (OR=8.1) for perioperative pulmonary morbidities but not for perioperative mortality. Use of semi-skeletonized internal mammary artery harvesting technique and drawing attention to possible vascular or mechanical causes of phrenic nerve injury may reduce its occurrence. Unilateral phrenic nerve injury, although rarely life-threatening, is an independent risk factor for postoperative respiratory complications. When harvesting internal mammary arteries, it should be kept in mind avoiding stretching, compromising, or inadvertently dissecting phrenic nerve is as important as avoiding damage of internal mammary artery itself.

Chemical preconditioning by 3-nitropropionic acid reduces ischemia-reperfusion injury in rat heart

SummaryThis study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly divided into two groups, a treatment group and a control group. The rats of the treatment group were treated intraperitoneally with 3-nitropropionic acid (3-NPA, 4 mg/kg) and the rats of the control group were treated with saline. 24 h after the treatment, the isolated hearts were mounted on a Langendorff apparatus. After 30 min, the hearts were subjected to 30-min ischemia and 60-min reperfusion. The HR, LVDP and ±dp/dtmax were measured at pre-ischemia and 30 min, 60 min after the reperfusion. Coronary effluent was collected 15 min after the reperfusion for the determination of CK and LDH. At the end of the 60-min reperfusion the heart was removed for the determination of myocardial SOD and MDA. Our results showed that in the 3-NPA group LVDP and ±dp/dtmax recovered significantly better, myocardial MDA, CK and LDH were significantly lower and the myocardial SOD was significantly higher than in the control group. It is concluded that chemical preconditioning by 3-nitropropionate has cardioprotective effects against ischemia-reperfusion injury.

Effect of L-carnitine on cardiomyocyte apoptosis and cardiac function in patients undergoing heart valve replacement operation.

SummaryThe effects of L-carnitine, as an ingredient of cardioplegia solution, on cardiac function and cardiomyocyte apoptosis in patients undergoing heart valve replacement operation were investigated. Twenty-three cases undergoing heart valve replacement with cardiopulmonary bypass (CPB) were randomly allocated into two groups: L-carnitine group (n=12, 12 g/L L-carnitine was put in the ST. Thomas cardioplegia) and control group (n=11, identical to the L-carnitine group except that normal saline was administered instead of L-carnitine). Serum cardial troponin I (cTnI) levels, the left ventricular ejection fraction (LVEF), and cardiac index (CI) were measured perioperatively. A bit of myocardial tissue obtained from right atria was taken before CPB and by the end of intracardiac procedure to undergo electron microscopy examination and estimate apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). From the end of CPB to 3 days after operation, the serum levels of cTnI in the L-carnitine group was significantly lower than that in the control group (P<0.05). Heart color ultrasonogram showed that the CI index and LVEF at 7th day postoperatively in the L-carnitine group were significantly higher than in the control group (P<0.05). Compared to the control group, L-carnitine significantly alleviated the morphologic changes of cardiac muscle cells (electron microscopy examination) and decreased the amounts of apoptotic cardiac muscle cells (TUNEL). Furthermore, the dosage of vasoactive drugs used after operation was significantly less in the L-carnitine group (P<0.01). It was concluded that L-carnitine cardioplegia solution could improve cardiac function in patients undergoing heart valve replacement operation and alleviate CPB-mediated apoptosis of cardiac muscle cells.

Study on the relationship between heat shock protein 70 and toll-like receptor-4 of monocytes

SummaryTo explore the relation between human heat shock protein 70 (hsp70) and TLR4 in human monocytesin vitro, human monocytes were stimulated with various concentrations of HSP70, and TNF-α production in supernatants was measured by ELISA. Pre-incubated with or without anti-TLR4 mAb, and stimulated with hsp70 (5.0 μg/ml), NF-κB p65 of human monocytes in different time points were detected by immunohistochemistry and monocyte surface expression of TLR4 was measured by flow cytometry. After the human monocytes were pre-incubated with various concentrations of anti-TLR4 and stimulated with hsp70 (5.0 μg/ml), TNF-α production in supernatants was measured. The results showed that hsp70 enhanced NF-κB activation, which was clearly inhibited by anti-TLR4, with the positive cell ratios being 67.44%, 39.17%, 31.56% and 28.05%, respectively. TLR4 was rapidly down-regulated in the presence of hsp70. MFI of TLR4 on monocytes in different time points were 87.77±5.38, 78.16±6.01 and 45.17±4.97 (P<0.05), 26.98±5.83 (P<0.01), respectively. Moreover, hsp70-induced TNF-α production by human monocytes was inhibited by anti-TLR4. It is suggested that TLR4 is involved in the hsp70-mediated activation of innate immunity.

Protective effect of heparin-coated circuits on the platelets during cardiopulmonary bypass

SummaryTo observe the protective effect of heparin-coated circuits (HCC) on the platelet function during cardiopulmonary bypass (CPB). 23 patients with heart valve replacement were studied. The system heparin dose was 3 mg/kg in the control group (n=15) and heparin-coated circuits in the HCC group (n=8). Platelet count, α-granule membrane protein-140 (GMP-140) concentrations were determined before CPB, at 60 min of CPB, 30 and 60 min after protamine administration, first 12 h after CPB, respectively. At end of CPB the arterial filters in the circuits were observed by electron microscopy. The amount of first 12-h postoperative blood loss was measured. There was significant reduction in platelet loss during and after CPB in the HCC group in contrast to the control group during CPB (P<0.05). During the first 12 h, postoperative blood loss was reduced in the HCC group as compared with that in the control group (218±61 ml, vs. 332±118 ml,P<0.05). Electron microscopy showed that in the HCC group the filter meshes and their fringes were clear and fragments of floccules were occasionally seen, without adherent cells or only few adherent cells on their surfaces, whereas several cellular and fibrous components were found to adhere to the surfaces of the filter meshes in the control group. This study indicates that heparin-coated circuits might reduce the platelet loss and activation during CPB and improve hemocompatibility of cardiopulmonary bypass equipment.

Effect of Troglitazone on expression of adhesion molecules and eNOS in human saphenous vein gaft

SummaryTo investigate whether peroxisome proliferators-activated receptor-γ (PPARγ) ligand Troglitazone can reduce endothelial injury and activation during storage of harvested saphenous vein grafts. Segments of human saphenous vein graft were collected from 9 patients undergoing coronary bypass surgery and then divided into two equal parts of control and test specimens, were stored in either heparinized blood (control group) or heparinized blood containing 20 μmol/L troglitazone (test group) for 1 h at room temperature. Tissue distribution and protein expression of VCAM-1, ICAM-1, and endothelial nitric oxide synthase (eNOS) were compared using immunohistochemistry and Western blot analysis. Myeloperoxidase (MPO) activity, a marker of neutrophil sequestration in human saphenous vein grafts, was also measured in each group. The expression of ICAM-1 (753±132 versus 7201±934; P<0.01), VCAM-1 (3731±294 versus 8292±793; P<0.01), and MPO activity (1.52±0.42 U/g, 5.04±1.26 U/g P<0.01) were significantly lower in test group. In contract, eNOS expression (7983±834 versus 3989±1008; P<0.01) was significantly higher in test group. PPARγ ligand troglitazone might reduce endothelial injury during the storage period of human saphenous vein grafts.To investigate whether peroxisome proliferators-activated receptor-γ (PPARγ) ligand Troglitazone can reduce endothelial injury and activation during storage of harvested saphenous vein grafts. Segments of human saphenous vein graft were collected from 9 patients undergoing coronary bypass surgery and then divided into two equal parts of control and test specimens, were stored in either heparinized blood (control group) or heparinized blood containing 20 μmol/L troglitazone (test group) for 1 h at room temperature. Tissue distribution and protein expression of VCAM-1, ICAM-1, and endothelial nitric oxide synthase (eNOS) were compared using immunohistochemistry and Western blot analysis. Myeloperoxidase (MPO) activity, a marker of neutrophil sequestration in human saphenous vein grafts, was also measured in each group. The expression of ICAM-1 (753±132 versus 7201±934; P<0.01), VCAM-1 (3731±294 versus 8292±793; P<0.01), and MPO activity (1.52±0.42 U/g, 5.04±1.26 U/g P<0.01) were significantly lower in test group. In contract, eNOS expression (7983±834 versus 3989±1008; P<0.01) was significantly higher in test group. PPARγ ligand troglitazone might reduce endothelial injury during the storage period of human saphenous vein grafts.

Total Arterial Revascularization with Internal Mammary Artery or Radial Artery π Graft Configuration

SummaryTo investigate the clinical use of π graft in total arterial revascularization and its outcomes, a retrospective analysis of 23 patients out of 1000 patients undergoing total arterial coronary bypass surgery with a π graft between September 1994 and December 2004 was performed. In the selected patients for the management of triple vessel disease with middle diagonal/intermediate ramus disease such that a skip with the left internal mammary artery (LIMA) or radial artery (RA), the main stem of π graft, to the left anterior descending coronary artery (LAD) will not work and the right internal mammary artery (RIMA) or right gastroepiploic artery (RGEA) cannot pick up the diagonal/intermediate ramus, hence the LAD and diagonal/intermediate ramus were grafted with a mini Y graft using the distal segment of LIMA, RIMA, RA or RGEA, together with the bilateral internal mammary artery (BIMA) or LIMA-RA T graft to compose π graft. Twenty-three patients (18 males, 5 females) underwent the π graft procedure. There were no deaths or episodes of myocardial infarction, stroke, and deep sternal wound infection. One patient required reopening for controlling bleeding. Until the end of 2004, during a mean follow-up of 81.0±28.4 months, no angina needing re-intervention or operative therapy or coronary related death occurred. In conclusion, in patients with specific coronary artery anatomy/stenosis, the BIMA (sometimes LIMA with RA or RGEA) π graft can be successfully performed for total arterial revascularization with good midterm outcomes.

Regulatory effect of bcl-2 family proteins in CPB-induced cardiomyocyte apoptosis in dog hearts.

SummaryWhether conventional hypothermic CPB induces myocyte apoptosis in dog hearts and modulation of bcl-2, bcl-xl, bax, bad, and caspase-3 pathways in this setting was investigated. Ten healthy adult dogs were randomized into sham-operated and CPB groups. Samples of left ventricle were obtained before, during and 3 h after CPB. In situ TUNEL was used to detect apoptotic myocytes. Immunohistochemistry and flow cytometry were employed for detection of expressions of bcl-2, bcl-xl, bax and bad proteins. Z-DEVD-AMC substrate cleavage and TBARS methods were used to measure the activity of caspase-3 and the content of lipid peroxide in LV myocardium, respectively. After CPB, the number of apoptotic myocytes in CPB group was significantly increased. The results of immunohistichemistry demonstrated that bcl-2, bcl-xl, bax and bad proteins were constitutionally present on the sarcolemma of the LV myocytes. FACS results showed that, after CPB, expressions of bax and bad in CPB group were significantly upregulated, while the expressions of bcl-2 and bcl-xl were not significantly changed in both groups. The activity of caspase-3 and the content of lipid peroxide in LV myocardium in CPB group were also significantly increased after CPB. The present study shows that there exists myocardiocyte apoptosis in dog hearts undergoing conventional hypothermic CPB and the myocyte apoptosis is initiated by ischemia and performed during reperfusion. Moreover, the CPB-induced myocyte apoptosis was associated with upregulation of expressions of bax and bad proteins, activation of caspase-3 and increase of oxidative stress.