Embolic cerebral insults after transapical aortic valve implantation detected by magnetic resonance imaging.

OBJECTIVES: This study assessed the rate of periprocedural embolic ischemic brain injury during transapical aortic valve replacement in 25 consecutive patients. BACKGROUND: Transcatheter aortic valve implantation is rapidly being established as a new therapeutic approach for aortic valve stenosis. Although initial clinical results are promising, it is unknown whether mobilization and embolization of calcified particles may lead to cerebral ischemia. METHODS: Twenty-five consecutive patients (10 men, 15 women, mean age: 81 ± 5 years, mean log EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 32 ± 10%) scheduled for transapical aortic valve implantation were included. All patients received a baseline cerebral magnetic resonance imaging scan. The scan was repeated approximately 6 days after valve implantation. The magnetic resonance imaging studies included axial diffusion-weighted, T(2)-weighted, fluid attenuated inversion recovery-weighted, and T(2) gradient echo sequences. Standardized assessment of the neurologic status was performed before aortic valve replacement and post-operatively. RESULTS: Transapical aortic valve implantation was successfully performed in all patients. In 17 patients (68%), new cerebral lesions could be detected, whereas 8 patients showed no new cerebral insults. The pattern of distribution and morphology were typical of embolic origin. Despite the high incidence of morphologically detectable lesions, only 5 patients showed clinical neurologic alterations. Out of these patients, only 1 suffered from a permanent stroke. CONCLUSIONS: New embolic ischemic cerebral insults are detected in 68% of patients after transapical valve implantation. Clinical symptoms are rare and usually transitory. Larger trials will need to establish the clinical significance of asymptomatic ischemic lesions as well as the rate of ischemic events in patients undergoing transfemoral valve replacement.

Low-flow perfusion via the innominate artery during aortic arch operations provides only limited somatic circulatory support.

BACKGROUND: Aortic arch operations in pediatric patients using low-flow perfusion techniques have been standardized to a certain degree, but some of the often-stated beneficial effects have never been proven. Especially, the existence or efficacy of any subdiaphragmal perfusion still remains unclear. METHODS: Twenty-six newborn male piglets (10-15 kg) underwent aortic arch surgery under general anesthesia using either low-flow perfusion via the innominate artery (LF, 30 ml/(kg min), 25 degrees C, n=12) or conventional deep hypothermic circulatory arrest (DHCA, 20 degrees C, n=14). Cortical somatosensory-evoked potentials (SSEPs), carotid, and subdiaphragmal blood flows were measured. The animals of both groups have been randomized to either pH-stat or alpha-stat management on cardiopulmonary bypass (CPB). RESULTS: During low-flow perfusion via the innominate artery only negligible flows of maximum 1-3 ml/min in the femoral arteries were detected, whereas the right carotid artery flow doubled. During reperfusion, serum-lactate and aspartate amino-transferase (AST) levels were significantly higher compared to the circulatory arrest group, whereas alanine amino-transferase (ALT), gamma-glutamyl transpeptidase (gamma-GT), AP, and creatinine did not show any significant differences. Cortical SSEP returned to preoperative values in all but two low-flow animals. There was no return of SSEP in all piglets operated under deep hypothermic circulatory arrest (p<0.01). CONCLUSION: Compared to DHCA, low-flow perfusion via the innominate artery provides superior neuroprotection despite higher tissue temperatures. Although collateral blood flow via the subclavian artery and the circulus arteriosus willisii has often been presumed, only 'trickle-flow' with some protective potential was detectable in the femoral arteries during low-flow perfusion. Origin of elevated lactate and AST levels seems to be the lower limbs.

ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression.

OBJECTIVE: Angiotensin converting enzyme (ACE) inhibitors significantly improve survival in patients with atherosclerosis. Although ACE inhibitors reduce local angiotensin II (AngII) formation, serine proteases form AngII to an enormous amount independently from ACE. Therefore, our study concentrates on the effect of the ACE-inhibitor ramiprilat on chemokine release, AngII receptor (ATR) expression, and NF-kappaB activity in monocytes stimulated with AngII. METHODS AND RESULTS: AngII-induced upregulation of IL-8 and MCP-1 protein and RNA in monocytes was inhibited by the AT1R-blocker losartan, but not by the AT2R-blocker PD 123.319. Ramiprilat dose-dependently suppressed AngII-induced upregulation of IL-8 and MCP-1. The suppressive effect of ramiprilat on AngII-induced chemokine production and release was in part caused by downregulation of NF-kappaB, but more by a selective and highly significant reduced expression of AT1 receptors as shown in monocytes and endothelial cells. CONCLUSION: In our study we demonstrated for the first time that ramiprilat reduced expression of AT1R in monocytes and endothelial cells. In addition, ramiprilat downregulated NF-kappaB activity and thereby reduced the AngII-induced release of IL-8 and MCP-1 in monocytes. This antiinflammatory effect, at least in part, may contribute to the clinical benefit of the ACE inhibitor in the treatment of coronary artery disease.