Pressure overload-induced heart failure is characterized by a substantial defect in cardiac oxidative capacity, at least in part due to a mitochondrial defect downstream of substrate-specific pathways. Numerous changes in mitochondrial protein levels have been detected, and the contribution of these to oxidative defects and impaired cardiac energetics in failing hearts is discussed.

Pressure overload-induced impairment in fatty acid oxidation precedes the onset of congestive heart failure but mitochondrial respiratory capacity is maintained until the EF decreases in vivo. These temporal relations suggest a tight link between impaired substrate oxidation capacity in the development of heart failure and contractile dysfunction and may imply therapeutic and prognostic value.

Surgery for CP is associated with a significant risk based on the poor preoperative patient status. Whenever justified, partial over radical pericardiectomy should be preferred and TVR should be indicated liberally. Reduced LVEF and right ventricular dilatation were independent predictors for early mortality, whereas CAD, chronic obstructive pulmonary disease and renal insufficiency were risk factors for late mortality. Thus, an optimal timing for surgery on CP remains crucial to avoid secondary morbidity with an even worse natural prognosis.

Heated debates revolve around the hemodynamic performance of stented aortic tissue valves. Because the opening area strongly influences the generation of a pressure gradient over the prosthesis, and the outer diameter determines which valve actually fits into the aortic root, it would seem logical that the valve with the greatest opening area in relation to its outer diameter should allow the best hemodynamic performance. Interestingly, neither of these 2 parameters is reflected by the manufacturing companies' size labels or suggested sizing strategies. In addition, it is known that valves with the same size label from different companies may differ significantly in their actual dimension (outer diameter). Finally, the manufacturer-suggested sizing strategies differ so much that expected differences from valve design may get lost because of differences in sizing. These size and sizing differences and the lack of information on the geometric opening area complicate true hemodynamic comparisons significantly. Furthermore, some fluid dynamic considerations regarding the determination of opening area by echocardiography (the effective orifice area) introduce additional obscuring factors in the attempt to compare hemodynamic performance data of different stented tissue valves. We analyzed the true dimensions of different tissue prostheses and the manufacturer-suggested sizing strategies in relation to published effective orifice areas. We have demonstrated how sizing and implantation strategy have much greater impact on postoperative valve hemodynamics than valve brand or type. In addition, our findings may explain the different opinions regarding valve hemodynamics of different tissue valves.

Key pointsr Pressure overload induces cardiac hypertrophy developing into heart failure. r During pressure overload-induced heart failure development in the rat, mitochondrial capacity to produce reactive oxygen species (ROS) increased significantly with the onset of diastolic functional changes.r Treatment to reduce ROS production was able to diminish mitochondrial ROS production but was not able to prevent or delay heart failure development.r The results question a primary role of ROS in the mechanism causing contractile dysfunction under pressure overload. AbstractWe investigated the impact of cardiac reactive oxygen species (ROS) during the development of pressure overload-induced heart failure. We used our previously described rat model where transverse aortic constriction (TAC) induces compensated hypertrophy after 2 weeks, heart failure with preserved ejection fraction at 6 and 10 weeks, and heart failure with systolic dysfunction after 20 weeks. We measured mitochondrial ROS production rates, ROS damage and assessed the therapeutic potential of in vivo antioxidant therapies. In compensated hypertrophy (2 weeks of TAC) ROS production rates were normal at both mitochondrial ROS production sites (complexes I and III). Complex I ROS production rates increased with the appearance of diastolic dysfunction (6 weeks of TAC) and remained high thereafter. Surprisingly, maximal ROS production at complex III peaked at 6 weeks of pressure overload. Mitochondrial respiratory capacity (state 3 respiration) was elevated 2 and 6 weeks after TAC, decreased after this point and was significantly impaired at 20 weeks, when contractile function was also impaired and ROS damage was found with increased hydroxynonenal. Treatment with the ROS scavenger α-phenyl-N-tert-butyl nitrone or the uncoupling agent dinitrophenol significantly reduced ROS production rates at 6 weeks. Despite the decline in ROS production capacity, no differences in contractile function between treated and untreated animals were observed. Increased ROS production occurs early in the development of heart failure with a peak at the onset of diastolic dysfunction. However, ROS production may not be related to the onset of contractile dysfunction.M. Schwarzer, M. Osterholt and A. Lunkenbein contributed equally to this work.

Schwarzer M, Schrepper A, Amorim P, Osterholt M, Doenst T. Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria. Years ago a debate arose as to whether two functionally different mitochondrial subpopulations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), exist in heart muscle. Nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function, whereas IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction for 20 wk or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analyzed by electron microscopy. Mitochondria were isolated by differential centrifugation, and respiratory capacity was analyzed using a Clark electrode. Pressure overload induced left ventricular hypertrophy with increased posterior wall diameter and impaired contractile function. Mitochondrial state 3 respiration in control was 50% higher in IFM than in SSM. Pressure overload significantly impaired respiratory rates in both IFM and SSM, but in SSM to a lower extent. As a result, there were no differences between SSM and IFM after 20 wk of pressure overload. Pressure overload reduced total citrate synthase activity, suggesting reduced total mitochondrial content. Electron microscopy revealed normal morphology of mitochondria but reduced total mitochondrial volume density. In conclusion, IFM show greater respiratory capacity in the healthy rat heart and a greater depression of respiratory capacity by pressure overload than SSM. The differences in respiratory capacity of cardiac IFM and SSM in healthy hearts are eliminated with pressure overload-induced heart failure. The strong effect of pressure overload on IFM together with the simultaneous appearance of mitochondrial and contractile dysfunction may support the notion of IFM primarily producing ATP for contractile function. heart failure; mitochondrial population; mitochondrial respiration; pressure overload MITOCHONDRIA SERVE AS the primary site for substrate oxidation and ATP generation and are essential for cell and contractile function. Based on location, two distinct populations of cardiac mitochondria have been distinguished: interfibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM) (34). It has been a matter of debate whether these populations are also functionally different. The Hoppel group described differences in their biochemical and respiratory properties (34) and ultrastructure (37). In contrast, McKean (30) suggested that cardiac

Percutaneous groin cannulation using ACDs for establishing cardiopulmonary bypass in minimally invasive valve surgery significantly reduces groin complications, operation time and hospital stay. However, the remaining complications are mainly of vascular nature versus wound infection and lymph fistulae with cutdown.

Objective: Myocardial infarction leads to contractile dysfunction. In patients with diabetes, impaired contractility has been associated with the loss of insulin effects and mitochondrial dysfunction. We assessed cardiac insulin sensitivity and mitochondrial and contractile function in rats after ligation of the left coronary artery. Methods: At 2 weeks after left coronary artery ligation, we performed echocardiography in vivo and assessed the substrate use and insulin response in the isolated working heart and the regulation of insulin (Akt, glucose transporter type 4) and mitochondrial signaling (p38 mitogen-activated protein kinase, peroxisome proliferatoractivated receptor-g coactivator 1a, mitochondrial transcription factor A) using polymerase chain reaction and Western blotting. Results: The infarcted hearts were dilated and had a reduced ejection fraction (ejection fraction < 50%). The basal glucose oxidation was preserved, but the fatty acid oxidation was significantly reduced. Insulin's effect on substrate oxidation was significantly impaired for both the decrease in fatty acid oxidation and the increase in glucose oxidation. However, insulin-stimulated glucose uptake was normal in the infarcted hearts, consistent with normal insulin-induced phosphorylation of Akt and unchanged mRNA expression of glucose transporter type 4. The impaired oxidative response to insulin was associated with reduced mRNA expression of the genes regulating fatty acid oxidation (long-chain-acyl-coenzyme A dehydrogenase, carnitine palmitoyltransferase 1, peroxisome proliferator-activated receptor-a) and mitochondrial biogenesis (mitochondrial transcription factor A). Although mRNA expression of the mitochondrial master regulator peroxisome proliferator-activated receptor-g coactivator 1a was normal in the infarcted hearts, the protein expression of its post-transcriptional activator, p38 mitogen-activated protein kinase, was significantly reduced. Conclusions: Myocardial infarction in rats caused partial insulin resistance at the level of substrate oxidation, which was associated with mitochondrial and cardiac contractile dysfunction. Mitochondrial dysfunction was characterized by a reduced capacity to oxidize fatty acids and might have resulted from impaired mitochondrial biogenesis through the lack of p38 mitogen-activated protein kinase.