Origin and appearance of HITS induced by prosthetic heart valves: an in vitro study.

Patients with mechanical heart valve prostheses show significantly enhanced numbers of HITS detected by transcranial Doppler ultrasound. In order to assess the origin of HITS formation, an in vitro study was set out to quantify valve induced microemboli for mechanical and bioprosthetic valves under various circulatory conditions by means of Ultrasound-Doppler-Sonography. At the same time the influence of CO2 partial pressure on HITS rate vas investigated. It can be summarised that for mechanical heart valve prostheses a strong correlation exists between left ventricular dp/dtmax and the detected HITS rates. It was also demonstrated that a bioprosthesis generates significantly less HITS than a mechanical valve. The origin of HITS is gaseous since the tests were carried out using a cell-free filtered water-glycerol test fluid. The HITS rate could be increased by increasing the amount of dissolved gas within the test fluid. The results support the hypothesis that cavitation is the key factor in the appearance of gaseous microemboli at heart valve prostheses.

Durability/wear testing of heart valve substitutes.

BACKGROUND AND AIMS OF THE STUDY: The current standards for accelerated heart valve testing have considerable differences in test conditions. Another problem arises from the fact that such test systems are not standardized at all. It was shown earlier that different test systems generate totally different valve loading, even if operating at standard conditions. The present study aimed to improve this unsatisfactory situation and to develop a new concept where actual loading of valves is measured either in vitro or in vivo under physiologic conditions and subsequently to reproduce these conditions during accelerated testing. METHODS: Integral loading forces at valve closure were measured for several valve types using a piezoelectric force ring within a real-time circulatory mock loop under physiologic conditions. This facilitated definition of a physiologic loading range. Physiologic loading was subsequently reproduced in a single-chamber accelerated test system. Working conditions obtained in terms of stroke, bypass flow and compliance served as design criteria for a new test chamber and a complete 12-chamber accelerated testing system. RESULTS: The integral loading obtained using the force ring showed a correlation with previous in vitro and in vivo results of strain-gauged valves. Loading forces for mechanical valves are about one order of magnitude higher than for bioprosthetic valves and are strongly related to cardiac output for both valve types. At physiologic loading, however, the differential pressures across the valves are considerably below those given in FDA guidelines. CONCLUSIONS: This pilot study demonstrates that physiologic valve loading is reproducible over a wide range under appropriate testing conditions. It also showed that, at the back-pressures of the current standards, the loading forces during accelerated testing exceed the real-time loading forces by far and, thus, may provide unrealistically high valve loads. These initial findings indicate that amendments of the currently valid standards may be need to be accorded.

Disturbed intracoronary hemodynamics in myocardial bridging: early normalization by intracoronary stent placement.

BACKGROUND: The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS: In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS: Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.

In vitro testing of heart valve wear outside of the manufacturers laboratory--requirements and controversies.

BACKGROUND AND AIM OF THE STUDY: Currently, various national and international Standards regulate in vitro and in vivo testing as well as the clinical evaluation of heart valve prostheses. This study concentrates on a single aspect of these protocols: accelerated wear and fatigue testing. METHODS: The differences in the above Standards were appraised and an experimental study was designed to assess the validity of Standard testing conditions with respect to in vivo relevance. An instrumented BSCC tilting disc valve was tested in two different types of fatigue testers and in a separate study in a sheep model. RESULTS: By comparing the obtained results it could be clearly demonstrated that under the current Standard conditions (ISO, CEN, FDA) actual in vivo impact loading cannot be reproduced. Also, the two compared test devices, though operating under the same Standard conditions, generated totally different loading conditions on the test valve. CONCLUSIONS: Based on these findings it is suggested that the actual loading conditions of each valve type should be measured either in vivo in animal models or within a circulatory mock loop which provides physiologic loading conditions, and the test conditions for accelerated wear and fatigue testing should be modified accordingly. Cavitation effects which can be assumed to be associated with high frequency wear testing is another important issue which has to be addressed in future amendments to the Test Standards.

[Influence of water activity on the enzymatic changes in freeze-dehydrated muscle. IV. Change in the activity of glycolytic enzymes during storage (author's transl)]. / Einfluss der Wasseraktivität auf enzymatische Veränderungen in gefriergetrocknetem Muskelfleisch. IV. Anderung der Aktivität glykolytischer Enzyme während der Lagerung.

The influence of water activity (25-65% r.h.) on the changes in activity of glycolytic enzymes during storage (up to 120 days) of freeze-dehydrated bovine muscle was investigated. For this purpose, at different times of storage the decrease of glycogen and the increase in lactate in the rehydrated samples were determined. At 25% r.h. no loss in activity was observed. However, during storage at 40% r.h. and higher the glycolytic activity decreased; this effect increased with rising water activity. The denaturation of the enzyme proteins might be due to Maillard reactions, particularly to the reaction of proteins with the highly reactive glycolytic metabolites glyceraldehyde phosphate and dihydroxyacetone phosphate.

[Influence of water activity on the enzymatic changes in freeze-dehydrated muscle III. The breakdown of muscle lipids (author's transl)]. / Einfluss der Wasseraktivität auf enzymatische Veränderungen in gefriergetrocknetem Muskelfleisch. III. Abbau von Muskellipiden.

During storage of freeze-dehydrated bovine muscle triglycerides and cholesterolesters are slowly hydrolyzed even at 25% relative humidity (r.h.). The extent of lipid hydrolysis in the tissue increases with rising water activity, the final degree of hydrolysis being dependent on water activity. It has been demonstrated that these changes are due to the effect of muscle enzymes. Phospholipids are not hydrolyzed even at 65% r.h. This might be due to an association of the phospholipids with membranes or to a lack of phospholipase activity in the freeze-dehydrated tissue. The fact that lipids in muscle tissue are hydrolyzed at water activities at which water soluble substrates are not split by hydrolyses agrees well with general ideas about the influence of water activity on the enzymatic breakdown of lipids. Freeze-dehydrated beef should not contain more than 3% moisture in order to prevent undesirable flavour changes caused by lipid changes during storage.

[Influence of water activity on the enzymatic changes in freeze-dehydrated muscle. II. Reactions of carbohydrates (author's transl)]. / Einfluss der Wasserktivität auf enzymatische Veränderungen in gefriergetrocknetem Muskeltleisch II. Reaktionen der Kohlenhydrate

During storage of prerigor freeze-dried beef, glycogen is not broken down even at 97.5% r.h. (moisture content of the meat about 30%). However, the metabolites of glycogen -- glucose, fructose, and their phosphoric acid esters -- are changed during storage at r.h. greater than 25%, mainly by the effect of glycolytic enzymes. Also nonenzymic reactions of the Maillard type seem to occur. An accelerated breakdown of these carbohydrates with increasing water activity was found. Even though the sugar monophosphates are broken down, no increase in C3 metabolites was found. The reason for this could be that the energy-rich compounds glyceraldehyde phosphate and dihydroxyacetone phosphate form complexes with some proteins. It is suggested that also pyruvate reacts with free amino groups of proteins. The breakdown of carbohydrates increases in uncooked freeze-dried samples above 60% r.h. whereas nonenzymatic reactions of the Maillard type reach a maximum rate at nonenzymatic reactions of the Maillard type reach a maximum rate at 60% r.h. This also shows that the disappearance of carbohydrates during storage of freeze-dried prerigor beef is mainly due to enzymatic processes.