Exon 47 skipping of fibrillin-1 leads preferentially to cardiovascular defects in patients with thoracic aortic aneurysms and dissections.

Excessive activation of the transforming growth factor beta signaling pathway and disorganized cellular skeleton caused by genetic mutations are known to be responsible for the inherited thoracic aortic aneurysms and dissections (TAAD), a life-threatening vascular disease. To investigate the genotype-phenotype correlation, we screened genetic mutations of fibrillin-1 (FBN1), transforming growth factor-ß receptor-1 (TGFBR1) and transforming growth factor-ß receptor-2 (TGFBR2) for TAAD in 7 affected families and 22 sporadic patients. Of 19 potential mutations identified in FBN1, 11 appeared novel while the others were recurrent. Two mutations were detected in TGFBR2. Eight patients carried no mutation in either of these genes. Characterization of FBN1 c.5917+6T>C in transfected HEK293 cells demonstrated that it caused skipping of exon 47, leading to the loss of the 33th calcium binding epidermal growth factor-like domain associated with Marfan syndrome. Compared with exon 46, skipping of 47 did not cause patients ectopia lentis in all carriers. To correlate genotypes with phenotypes in different human ancestries, we reviewed the published mutational studies on FBN1 and found that the probability of cardiovascular defects were significantly increased in Chinese patients with premature termination codon or splicing mutations than those with missense mutations (91.7 % vs 54.2 %, P = 0.0307) or with noncysteine-involved point mutations than those with cysteine-involved mutations (88.9 % vs 33.3 %, P = 0.0131). Thus, we conclude that exon 47 skipping of FBN1 leads preferentially to cardiovascular defects and human ancestries influence genotype-phenotype correlation in TAAD.

[Risk factors of cognitive impairment after off-pump coronary artery bypass grafting].

OBJECTIVE: To analyze the risk factors of cognitive impairment after off-pump coronary artery bypass grafting (OPCABG). METHODS: A total of 102 patients [male: 82, age: (65.7 ± 7.1) years] undergoing OPCABG in our hospital between January 2009 and December 2010 were divided into postoperative cognitive dysfunction (POCD) group and non-POCD group by the MMSE questionnaire survey conducted at 7 days pre- and post-operation respectively. RESULTS: The incidence of POCD was 48.0% (49/102). Multivariate logistic stepwise regression analysis showed: advanced age (OR = 1.32, 95%CI: 1.10 - 1.46, P = 0.002), smoking (OR = 1.26, 95%CI: 1.18 - 1.32, P = 0.001), hypertension (OR = 1.66, 95%CI: 1.36 - 1.78, P = 0.023), diabetes (OR = 1.62, 95%CI: 1.02 - 2.84, P = 0.032), stroke (OR = 3.32, 95%CI: 1.68 - 6.49, P < 0.001), mitral regurgitation (OR = 1.48, 95%CI: 1.26 - 1.89, P < 0.001), and time of wall clamp (OR = 4.84, 95%CI: 1.08 - 7.28, P < 0.001) were independent risk factors of POCD. CONCLUSION: Advanced age, smoking, hypertension, diabetes, stroke, mitral regurgitation, and prolonged time of wall clamp are major risk factors for POCD in patients undergoing OPCABG.

[Effect of L-arginine on rabbit sinoatrial node functions and atrioventricular nodal effective refractory period during ischemia-reperfusion of the right coronary artery].

OBJECTIVE: To study the effect of L-arginine (L-Arg) on sinoatrial conduction time (SACT) and sinus node recovery time (SNRT) and atrioventricular nodal effective refractory period (AVERP) in the course of ischemia- reperfusion (IR) of the right coronary artery in rabbits. METHODS: Thirty-two rabbit models of ischemia-reperfusion of the right coronary artery were randomly divided into control group, IR+saline group, IR+L-Arg group and IR+ L-arginine-methyl ester (IR+L-NAME group, 8 rabits in each group. At different time points after ligation or loosening of the artery, SACT, SNRT and AVERP were measured respectively by fast pacing of the right atrium and programmed electrical stimulations. RESULTS: Compared with the control group, SACT, SNRT and AVERP of the other groups were all prolonged significantly P<0.01 . In comparison with IR+NS group, at each time point, SACT, SNRT and AVERP of IR+L-Arg group were decreased during ischemia and in the early phases of reperfusion, followed by elevation during the latter stages of the reperfusion, as were contrary to the changes in IR+L-NAME group. CONCLUSIONS: The longer duration of ischemia persists, the severer are the functional damages of the sinoatrial node. Adequate supply of L-Arg to the tissues during ischemia and the early stages of the reperfusion may alleviate the damages, but its administration in the latter stages of reperfusion might contribute to the contrary result.

[Effects of open heart surgery under normothermic and hypothermic cardiopulmonary bypass on cytokines and complements].

OBJECTIVE: To explore the detrimental influence of normothermic and hypothermic cardiopulmonary bypass during open heart surgery on cytokines and complements. METHOD: Forty patients with congenital or rheumatic heart disease were randomized into 2 groups to receive normothermic cardiopulmonary bypass (CPB, study group, n=20) or hypothermic CPB (control group, n=20). Venous blood samples were respectively collected at scheduled time points preoperatively, at the end of CPB, and 1,4,7,14 d postoperatively to examine the level of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, C3, and C4. RESULTS: IL-2 in both groups decreased significantly at the end of CPB, postoperative day 1 and 4, but recovered the normal level at day 7 postoperatively. IL-2 in control group was significantly lower than that in the study group at each time points at the end of CPB and day 1 and 4 postoperatively. TNF-alpha in two groups was both elevated at the time points cited above, and in the study group, recovery of normal TNF-alpha level occurred at day 7 postoperatively, whereas in the control group, the recovery was not achieved until postoperative day 14. C3 in the study group was significantly lower at the time points of the end of CPB, day 1, 7 postoperatively than that in control group, but both elevated above normal at the end of CPB, day 1, and 4 postoperatively; in the study group, C3 became normal at day 7 postoperatively, which occurred in the control group only till day 14 postoperatively. At the end of CPB and day 1 postoperatively, C4 was significantly lower in the study group than in the control group, both below the level measured preoperatively at the time points of the end of CPB, day 1 and 4 postoperatively. CONCLUSION: Open-heart surgery under normothermic CPB has less detrimental influence on cytokines and complements than the operation under hypothermic CPB for better recovery of the patient.

[Effects of hypothermia on cerebral oxygen metabolism in patients with mitral valve replacement].

OBJECTIVE: To observe the effects of mild to moderate hypothermia on cerebral oxygen metabolism in patients with mitral valve replacement. METHODS: Twenty patients undergoing mitral valve replacement were randomly divided in mild (30 ) and moderate (26 degrees Celsius) hypothermia groups. Under alpha stat, the oxygen content and the concentration of lactic acid in the radial artery and jugular venous bulb were monitored in patients undergoing mitral valve replacement at mild and moderate hypothermia respectively. The arterial-venous difference of oxygen content, oxygen uptake rate, and blood lactic acid levels in the cerebrum and total body were calculated. The effect of cardiopulmonary bypass (CPB) under the two hypothermia strategies on cerebral oxygen metabolism was analyzed. RESULTS: In the two groups, arterial-venous differences and oxygen uptake rates were both decreased after the commencement of cardiopulmonary bypass, and were rapidly elevated during rewarming. In mild hypothermia group, the arterial-jugular venous difference and oxygen uptake were higher than those in moderate hypothermia group (P<0.05) during CPB when the lowest temperature was reached. The concentration of lactic acid in the plasma was progressively increased in both groups during CPB. Arterial-venous difference in the oxygen content in both groups was still lower during CPB than before CPB(P<0.01). CONCLUSION: Mild and moderate hypothermia during CPB is sufficient to retain the balance of cerebral oxygen metabolism, and more intensive hypothermia may not ensure better cerebral protective effect. Cerebral oxygenation progressively increases after CPB under hypothermia, but whether imbalance of cerebral oxygen metabolism occurs needs further investigation.