Comparison of the use of minimized cardiopulmonary bypass with conventional techniques on the incidence of retinal microemboli during aortic valve replacement surgery.

OBJECTIVES: Minimized cardiopulmonary bypass (MCPB) circuits have been shown to reduce cerebral and retinal microembolisation during coronary artery bypass graft (CABG) surgery compared to conventional CPB (CCPB) circuits. Our aim was to evaluate whether the reduction of microembolisation is sustained in aortic valve surgery, as well as to evaluate the effects of MCPB on inflammatory, endothelial, and platelet activation markers. MATERIAL AND METHODS: Patients were randomized to undergo aortic valve replacement (AVR), with or without CABG, with MPCB (n=20) or CCPB (n=20). After anaesthesia induction and termination of CPB, standardized digital retinal fluorescein angiography images were obtained on both eyes and analyzed in a blinded fashion. Blood samples were collected at eight time points until the third postoperative day. RESULTS: Fewer patients in the MCPB group showed evidence of microembolic perfusion defects on postperfusion retinal fluorescein angiographs compared to the CCPB group (37% vs. 63%, absolute difference 26%, 95% CI -5% -51%, P = 0.194). Polymorphonuclear leukocyte (PMN) elastase and von Willebrand factor release were statistically significantly reduced in the MCPB group, but there were no significant differences in other markers of inflammation, coagulation or endothelial activation. A significantly higher three-fold increase in the amount of shed blood was collected to the cell saver with a higher rate of intraoperative platelet transfusion in the MCPB group compared to CCPB. CONCLUSIONS: The use of MCPB was associated statistically insignificantly with less retinal microemboli compared to CCPB. MCPB was complicated by excess bleeding and need for transfusion. The feasibility of MCPB techniques in valve surgery requires further studies.

Risk of retinal microembolism after off-pump and on-pump coronary artery bypass surgery.

AIM: In order to investigate the neuroprotective efficacy of off-pump coronary artery bypass surgery (OPCAB) over conventional on-pump coronary artery bypass surgery (CCAB), we have performed a prospective randomized study evaluating retinal circulation changes after OPCAB and CCAB. METHODS: Twenty patients were randomized to OPCAB or CCAB. Retinal fluorescein angiography and 60 degrees black-and-white as well as color fundus photographs of both eyes of each patient were taken 1 to 24 h before and 5 to 6 days after the operation. RESULTS: Patients undergoing OPCAB had more severely stenosed carotid arteries (P=0.075), higher incidence of slightly diseased ascending aorta (P=0.087) and higher Northern New England Cardiovascular Study Group stroke risk score (P=0.075). Neither stroke nor transient ischemic attack occurred postoperatively in these patients. Inferotemporal retinal arterial embolization and microinfarction was detected in one patient after CCAB, but in none of the OPCAB group. CONCLUSION: The risk of retinal embolism can be minimized by the use of OPCAB and, most likely, by adequate epiaortic ultrasound scanning of the ascending aorta and avoiding clamping in case of severely diseased aorta.

GATA4 mediates activation of the B-type natriuretic peptide gene expression in response to hemodynamic stress.

To identify the mechanisms that couple hemodynamic stress to alterations in cardiac gene expression, DNA constructs containing the rat B-type natriuretic peptide (BNP) promoter were injected into the myocardium of rats, which underwent bilateral nephrectomy or were sham-operated. Ventricular BNP mRNA levels were induced about 4-fold; and the BNP reporter construct containing the proximal 2200 bp, 5-fold, in response to 1-d nephrectomy. Deletion of sequences between bp -2200 and -114 did not affect basal or inducible activity of the BNP promoter. An activator protein-1-like site and two tandem GATA elements are located within this 114-bp sequence. Both deletion and mutation of the AP-1-like motif decreased basal activity but did not abolish the response to nephrectomy. In contrast, mutation or deletion of -90 bp GATA-sites abrogated the response to hemodynamic stress. The importance of these GATA elements to BNP promoter activation was further confirmed by the corresponding 38-bp oligonucleotide conferring hemodynamic stress responsiveness to a minimal BNP promoter. In gel mobility shift assays, nephrectomy increased left ventricular BNP GATA4 binding activity significantly. In conclusion, GATA elements are necessary and sufficient to confer transcriptional activation of BNP gene in response to hemodynamic stress.

Mechanical load-induced alterations in B-type natriuretic peptide gene expression.

Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide are the known members of the mammalian natriuretic peptide system. Like ANP, BNP is a natriuretic and diuretic hormone that also causes peripheral vasodilation and inhibition of the sympathetic and renin-angiotensin systems. Although originally isolated from porcine brain, the BNP gene is expressed in a specific manner in cardiac myocytes in both the atria and the ventricles, but it is mainly released from the ventricles. The major determinant of BNP secretion is wall stretch, and the levels of BNP mRNA increase substantially in response to cardiac overload. In the clinical setting, BNP appears to be the most powerful neurohumoral predictor of left-ventricular function and prognosis. An acute increase in BNP gene expression occurs within 1 h and mimics the rapid induction of proto-oncogenes in response to hemodynamic stress. BNP can be used as a myocyte-specific marker to identify mechanisms that couple acute mechanical overload to alterations in cardiac gene expression. This paper is focused on the mechanisms that regulate BNP gene expression in cardiac overload. Particularly, autocrine-paracrine factors as well as cytoplasmic signaling pathways and transcription factors involved in mechanical stretch-induced BNP gene expression are discussed.

Pressure overload increases GATA4 binding activity via endothelin-1.

BACKGROUND: The signaling cascades responsible for the activation of transcription factors in the hypertrophic growth of cardiac myocytes during hemodynamic overload are largely unknown. Several of the genes upregulated in the hypertrophied heart, including B-type natriuretic peptide (BNP) gene, are controlled by the cardiac-restricted zinc finger transcription factor GATA4. METHODS AND RESULTS: An in vivo model of intravenous administration of arginine(8)-vasopressin (AVP) for up to 4 hours in conscious normotensive rats was used to study the signaling mechanisms for GATA activation in response to pressure overload. Gel mobility shift assays were used to analyze the trans-acting factors that interact with the GATA motifs of the BNP promoter. AVP-induced increase in mean arterial pressure was followed by a significant increase in the BNP and c-fos mRNA levels in both the endocardial and epicardial layers of the left ventricle, whereas GATA4 and GATA6 mRNA levels remained unchanged. Pressure overload within 15 to 60 minutes produced an increase in left ventricular BNP GATA4 but not GATA5 and GATA6 binding activity, and at 30 minutes a 2.2-fold increase (P:<0.001) in GATA4 binding was noted. The mixed endothelin-1 ET(A)/ET(B) receptor antagonist bosentan but not the angiotensin II type 1 receptor antagonist losartan completely inhibited the pressure overload-induced increase in left ventricular BNP GATA4 binding activity. Bosentan alone had no statistically significant effect on GATA4 binding activity of the left ventricle in conscious animals. CONCLUSIONS: ET-1 is a signaling molecule that rapidly upregulates GATA4 DNA binding activity in response to pressure overload in vivo.