[Transcatheter aortic valve implantation : what do anesthetists need to know?]. / Kathetergestützte Aortenklappenimplantation : Was müssen Anästhesisten wissen?

Surgical replacement of aortic valves is the gold standard for therapy of high grade aortic valve stenosis. However, the changes in demography confront the responsible medical discipline with an increasingly higher risk profile of patients which necessitates the development of new less invasive alternative forms of treatment for the surgical therapy of aortic valve stenosis. This developmental process has progressed from mini-thoracotomy to transcatheter aortic valve implantation (TAVI). The TAVI procedure is a new therapeutic option for treatment of patients with high grade aortic valve stenosis and high perioperative morbidity and mortality risks with conventional aortic valve replacement. Because TAVI can be carried out while the heart is still beating and without a sternotomy or heart-lung maschine, this procedure is particularly suitable for elderly multimorbid patients and/or patients with previous cardiac surgery. The initial results of large prospective multicenter studies underline the value of TAVI in the modern treatment of high risk patients with symptomatic aortic valve stenosis. In addition to an understanding of the surgical procedure, anesthetists must have precise knowledge of the perioperative anesthesia management and possible complications of the procedure.

Role of RAS inhibition in the regulation of Cu/Zn-SOD in the cardiac and peripheral arterial beds in humans.

Inhibition of the renin-angiotensin system (RAS) improves hemodynamics and may ameliorate oxidative stress in heart failure (HF). Through activation of nicotinamide adenine dinucleotide phosphate oxidase, angiotensin II induces superoxide, which is primarily cleared by cytosolic copper-zinc superoxide dismutase (Cu/Zn-SOD). We examined the interdependency of hemodynamics and levels of Cu/Zn-SOD and oxidized low-density lipoprotein (oxLDL) in HF patients, using a randomized, double-blinded, crossover design to compare (i) the outcomes of single-agent therapy with either benazepril or valsartan alone vs. the combination thereof and (ii) the outcome of single-agent treatment with benazepril vs. single-agent treatment with valsartan. After each treatment, arterial (ART) and coronary sinus (CS) blood samples were collected. Cu/Zn-SOD and oxLDL levels were higher in CS samples than in ART samples. Furthermore, patients under combined treatment exhibited the highest CS levels of Cu/Zn-SOD, whereas there was no significant difference between the groups on either benazepril or valsartan alone. This finding suggests an augmentation of the cardiac antioxidative potential under more complete RAS inhibition. Cu/Zn-SOD and oxLDL levels correlated with measures of afterload rather than preload, which in turn suggests a beneficial effect of afterload reduction on oxidative stress in HF.

Translocation of S100A1(1) calcium binding protein during heart surgery.

Myocardial ischemia during cardiopulmonary bypass terminated by reperfusion generally leads to different degrees of damage of the cardiomyocytes induced by transient cytosolic Ca(2+) overload. Recently, much attention has been paid to the role of heart-specific Ca(2+)-binding proteins in the pathogenesis of myocardial ischemia-reperfusion injury. S100A1 is a heart-specific EF-hand Ca(2+)-binding protein that is directly involved in a variety of Ca(2+)-mediated functions in myocytes. The aim of our study was to investigate the localization and translocation of S100A1 in the human heart under normal (baseline) conditions and after prolonged ischemia and reperfusion of the myocardium. Our data suggest that S100A1 is directly involved in the transient perioperative myocardial damage caused by ischemia during open heart surgery in humans. Given its role in the contractile function of muscle cells, this S100 protein could be an important "intracellular link" in ischemia-reperfusion injury of the heart.

Altered levels of mRNA of apoptosis-mediating genes after mid-term mechanical ventricular support in dilative cardiomyopathy--first results of the Halle Assist Induced Recovery Study (HAIR).

BACKGROUND: Ventricular assist devices (VADs) lead to an immediate unloading of the failing heart. Although VADs are used as a bridge to transplant, in some cases patients suffering from dilated cardiomyopathy have been weaned from the VAD without transplantation after a recovery process initiated by the cardiac support. Myocardial apoptosis is associated with inadequate myocardium and might be reverted during VAD support of the failing heart. Therefore we measured transcription of apoptosis-associated genes FasExo6 Del, Fas-receptor, and Bcl-xL as markers of a putative recovery. METHODS: Fas-receptor, its soluble isoform FasExo6Del, and Bcl-xL mRNA were quantified by standard calibrated competitive reverse-transcription polymerase chain reaction (PCR) in 6 patients suffering from dilated cardiomyopathy. RNA standards were prepared by introducing 100 bp deletions into the native cDNA, resulting in truncated PCR products with identical primer-binding sites. Standards were transcribed in vitro and the resulting RNA was quantified. RESULTS: Transcription of apoptosis-inhibiting genes FasExo6 Del and Bcl-xL were upregulated in patients supported for more than 6 weeks. Fas receptor mRNA remained unaffected by VAD support. CONCLUSIONS: Transcriptional upregulation of apoptosis-inhibiting genes might be caused by a desensitization to apoptotic stimuli and might indicate a relaxation of the diseased status of the myocardium. These data outline the first biochemical evidence of a remodelling process occurring in supported ventricular myocardium.

Cardiac muscarinic receptors decrease with age. In vitro and in vivo studies.

The M1 muscarinic receptor antagonist pirenzepine in low doses decreases resting heart rate; this effect declines with age (Poller, U., G. Nedelka, J. Radke, K. Pönicke, and O.-E. Brodde. 1997. J. Am. Coll. Cardiol. 29:187-193). To study possible mechanisms underlying this effect, we assessed (a) in six young (26 yr old) and six older volunteers (61 yr old), pirenzepine effects (0.32 and 0.64 mg intravenous [i.v.] bolus) on isoprenaline-induced heart rate increases; (b) in five heart transplant recipients, pirenzepine effects (0.05-10 mg i.v. bolus) on resting heart rate in the recipient's native and transplanted sinus nodes; and (c) in right atria from 39 patients of different ages (5 d-76 yr) undergoing open heart surgery, M2 muscarinic receptor density (by [3H]N-methyl-scopolamine binding) and adenylyl cyclase activity. (a) Pirenzepine at both doses decreased heart rate in young volunteers significantly more than in older volunteers; (b) pirenzepine (< 1 mg) decreased resting heart rate in the recipient's native but not transplanted sinus node; and (c) M2 receptor density and carbachol-induced inhibition of forskolin-stimulated adenylyl cyclase activity decreased significantly with the age of the patients. We conclude that pirenzepine decreases heart rate via inhibition of presynaptic M1 autoreceptors, thereby releasing endogenous acetylcholine, and that the heart rate-decreasing effect of acetylcholine declines with age because right atrial M2 receptor density and function decrease.