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Biomedical subjects

H Schwalb

Publications and source records attributed to H Schwalb.

At least 19 recordsLinked to original sources

Optimal level of hypothermia for prolonged myocardial protection assessed by 31P nuclear magnetic resonance.

The optimal level of hypothermia during myocardial preservation for cardiac transplantation is not known. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess the effect of different preservation temperatures (15 degrees C in group 1, 4 degrees C in group 2) on the myocardial high-energy phosphate profiles during prolonged global ischemia and subsequent reperfusion of isolated rat hearts. Adenosine triphosphate depletion during ischemia was more gradual in group 2, leading to significant differences in myocardial adenosine triphosphate concentrations between the two groups after 3 hours of ischemia. The fall in intracellular pH during ischemia was significantly less pronounced in hearts preserved at 4 degrees C as compared with those at 15 degrees C. The postischemic recovery of both the left ventricular peak systolic pressure and the maximum rate of increase of left ventricular pressure was enhanced in group 2, although the ischemic period was 3 hours longer than in group 1. Hypothermia at 4 degrees C as compared with 15 degrees C appears to prolong myocardial protection with respect to adenosine triphosphate preservation, prevention of the fall in intracellular pH, and the enhancement of postischemic hemodynamic recovery.

Adenosine Triphosphate

Prolonged myocardial protection with St. Thomas' Hospital solution and University of Wisconsin solution. The importance of preservation techniques.

The effectiveness of University of Wisconsin solution (UWS) and oxygenated St. Thomas' Hospital solution (STS) for prolonged myocardial protection was evaluated in isolated working rat hearts preserved for 12 h at 4 degrees C using three different preservation techniques: induction of cardiac arrest and subsequent hypothermic storage with STS (group 1, n = 9) or UWS (group 4, n = 9), intermittent coronary flush (every 90 min) with STS (group 2, n = 9) or UWS (group 5, n = 9), or continuous coronary perfusion with STS (group 2, n = 7) or UWS (group 6, n = 7) before 60 min of reperfusion. In the UWS preserved hearts, recovery of aortic flow was greater when the simple storage technique was employed compared to intermittent or continuous coronary perfusion (groups 5 and 6). In the STS preserved hearts, aortic flow recovery was superior when the intermittent perfusion technique was applied. The same pattern was observed with regard to recovery of left ventricular pressure. Lactate dehydrogenase release during reperfusion was significantly less pronounced in group 4 (UWS, single flush, simple storage) as compared to group 1 (STS, single flush and simple storage), whereas best preservation of myocardial high energy phosphates was observed when hearts were preserved with multiple dose cardioplegia using STS. Simple hypothermic storage with UWS affords the best functional recovery after prolonged myocardial ischemia in all groups. Repetitive or continuous application of this solution is detrimental, possibly due to potassium overloading. In STS treated groups, multiple dose application of oxygenated STS enhances functional and metabolic recovery compared to its single dose application.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

The effectiveness of University of Wisconsin solution on prolonged myocardial protection as assessed by phosphorus 31-nuclear magnetic resonance spectroscopy and functional recovery.

The effectiveness of the University of Wisconsin solution on extended myocardial preservation was examined in this study using phosphorus 31-nuclear magnetic resonance spectroscopy. Isolated perfused rat hearts were arrested and stored in four preservation solutions: group 1, modified Krebs-Henseleit solution; group 2, modified St. Thomas' Hospital solution; group 3, oxygenated modified St. Thomas' Hospital solution containing 11 mmol/L glucose; and group 4, University of Wisconsin solution. The changes in myocardial high energy phosphate profiles and the intracellular pH values were measured during 12 hours of cold (4 degrees C) global ischemia and 90 minutes of normothermic reperfusion. Following ischemia, the hearts were assessed for hemodynamic recovery and myocardial water content. During ischemia, adenosine triphosphate depletion was observed in all groups; however, after 5 hours of ischemia, the adenosine triphosphate levels were significantly higher in group 3 compared with the other groups (adenosine triphosphate levels at 6 hours in mumol/gm dry weight: group 3, 7.6; group 4, 3.2; group 2, < 1; p < 0.025). The tissue water content at the end of ischemia was lower with the University of Wisconsin solution compared with the modified St. Thomas' Hospital solution or the oxygenated modified St. Thomas' Hospital solution (in ml/gm dry weight: group 4, 3.0; group 2, 4.4; group 3, 3.9; p < 0.05). The adenosine triphosphate repletion during reperfusion was greater with the University of Wisconsin solution compared with the modified St. Thomas' Hospital solution or the oxygenated modified St. Thomas' Hospital solution (12 mumol/gm dry weight in group 4; 8.1 in group 2; 9.0 in group 3; p < 0.05). Similar findings were obtained for the recovery of left ventricular pressure (in percent of preischemic control: group 4, 70%; group 2, 42%; group 3, 52%; p < 0.01) and coronary flow (group 4, 61%; group 2, 49%; group 3, 49%; p < 0.05). These data suggest that preservation with the University of Wisconsin solution affords improved hemodynamic recovery, enhanced adenosine triphosphate repletion, and reduced tissue edema upon reperfusion; however, oxygenated St. Thomas' Hospital solution with glucose is associated with the preservation of higher myocardial adenosine triphosphate levels during prolonged cold global ischemia. In conclusion, these data indicate that the University of Wisconsin solution might improve graft tolerance of ischemia in clinical heart transplantation.

Adenosine

An improved method for endothelial cell seeding on polytetrafluoroethylene small caliber vascular grafts.

The creation of nonthrombogenic synthetic surfaces is a major challenge in biomedical research. The feature that clearly distinguishes natural blood vessels from their artificial counterparts is the presence of endothelial cell lining that besides being nonthrombogenic is capable of repair and renewal. This study describes a method of coating vascular grafts with a uniform, naturally produced subendothelial extracellular matrix before implantation. This substrate provides a most suitable bilayer for endothelial cell adhesion, growth, and differentiation, as compared with grafts coated with fibronectin or basement membrane extracts. It contains both adhesive glycoproteins (fibronectin, laminin, collagen) and proteoglycans (heparan sulfate) as well as endothelial cell growth factors (basic fibroblast growth factor) that support adhesion and normal growth of suboptimal concentrations of endothelial cells. We suggest that the presence in extracellular matrix of both adhesive macromolecules and potent endothelial cell-growth promoting factors will make the extracellular matrix a promising substrate for vascular grafts.

Animals

[31-phosphor-NMR spectroscopy for determining optical preservation temperature during long-term myocardial ischemia].

The ideal level of hypothermia during myocardial preservation for cardiac transplantation remains unknown. Therefore 31P-NMR spectroscopy was applied to assess the effect of different preservation temperatures (15 degrees C in group 1, 4 degrees C in group 2) on time dependent changes of myocardial high energy phosphorous compounds during prolonged global ischemia (5 hours in group 1, 8 hours in group 2) and subsequent reperfusion of isolated rat hearts preserved with modified St. Thomas Hospital solution. ATP-depletion during ischemia was slower in group 2 leading to a significant difference in myocardial ATP-concentrations between both groups after 3 hours of ischemia. The drop of intracellular pH during ischemia was significantly less pronounced in hearts preserved at 4 degrees C compared to 15 degrees C. Postischemic recovery of both left ventricular (LV) peak systolic pressure and its +dP/dt max. was superior in group 2, although the ischemic time was 3 hours longer than in group 1. Hypothermia at 4 degrees C appears favourable for prolonged myocardial protection compared to 15 degrees C with regard to preservation of ATP, prevention of intracellular acidosis and postischemic hemodynamic recovery.

Adenosine Triphosphate

An apparatus for applying a mechanical massage to rat hearts inside a wide-bore NMR spectrometer.

A device for applying mechanical massage to the isolated perfused rat heart inside a wide-bore NMR spectrometer was developed. This device exerts a squeezing pressure on a fibrillating heart placed inside a NMR spectrometer without interfering with the NMR measurements. It appears that the apparatus is important for obtaining reliable results in the postischemic reperfusion period.

Animals

Effect of anesthesia on cardiac function and response in the perfused rat heart.

In the present study we have examined the effect of the general anesthetic agent sodium pentobarbital (given i.p. to the intact animal) on the hemodynamic function of the isolated perfused heart and its response to treatments which affect calcium transsarcolemmal influx: extracellular calcium concentration and thyroid hormone. Perfused hearts (modified Langendorff system) isolated from anesthetized rats were found to respond differently to the two aforementioned effectors than hearts excised from non-anesthetized animals. Hearts of the two groups demonstrated a gradual increase in inotropic activity in response to step-wise increase in calcium concentration in the perfusion medium. However, cardiac contractility and the pattern of the response to the gradual increase in calcium concentration were different. At the lower Ca2+ concentrations of 0.5 and 1.0 mM, inotropic activity (left ventricular systolic pressure (LVP) and +dP/dt values) of hearts from anesthetized animals was significantly greater (P less than 0.05) than that of hearts from non-anesthetized animals: LVP values (mmHg, mean +/- S.E.M.) in hearts from anesthetized an non-anesthetized rats were: at 0.5 mM Ca2+, 19 +/- 3 and 9 +/- 2; and at 1.0 mM, 103 +/- 12 and 76 +/- 6, respectively. At the higher Ca2+ concentrations, hearts from anesthetized animals demonstrated maximal LVP at 1.75 mM calcium (139 +/- 9 mmHg), whereas the LVP values in hearts from non-anesthetized animals continued to increase throughout all the Ca2+ concentrations employed. A similar pattern of response was observed for +dP/dt values.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

Volume regulation of nerve terminals.

Pinched-off presynaptic nerve terminals (synaptosomes) possess significant regulatory volume increase (RVI) and regulatory volume decrease (RVD) capabilities. Following a swelling induced by a hypotonic challenge, the synaptosomes regulate their volume and adjust it, in 2 min, to within 5% of its initial value (RVD) at an initial rate of -0.77 +/- 0.10%/s (mean +/- SEM). Following a shrinking induced by a hypertonic challenge, the synaptosomes also regulate their volume at an initial rate of 0.18 +/- 0.02%/s (RVI), resulting in a new steady state, reached within 5-10 min, with a synaptosomal volume below the original volume. The omission of Na+ or K+ ions from the extrasynaptosomal medium reduces the initial rate of RVI by 72.5 and 66.5%, respectively. The "loop diuretics" bumetanide and furosemide significantly inhibited the RVI of the synaptosomes. In contrast, ouabain, amiloride, or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid did not have any significant effect on RVI parameters. Furthermore, bumetanide-sensitive 86Rb uptake by rat brain synaptosomes was stimulated threefold by a hypertonic perturbation of 30%. Thus we conclude that the RVI of synaptosomes is mainly due to a stimulation of the Na+, K+, Cl- co-transport system induced by the synaptosomal shrinking following the hypertonic challenge.

Animals

The effect of swimming exercise on spontaneous ventricular defibrillation and ventricular fibrillation threshold in the isolated perfused rat heart.

Effects of swimming exercise training on left ventricular contraction and relaxation, the incidence of spontaneous defibrillation and the ventricular fibrillation threshold were studied in the isolated, perfused rat heart. The heart/body weight ratio was 4.8 +/- 0.4 x 10(-3) in swimmers compared with 3.9 +/- 0.6 x 10(-3) in sedentary controls (p less than 0.0005). The spontaneous heart rate was lower in isolated hearts of trained animals (222 +/- 18 bpm compared with 244 +/- 28, p less than 0.05). Left ventricular systolic pressure was higher in trained hearts and the rate of ventricular relaxation enhanced (p less than 0.05). The ventricular fibrillation threshold was 7.2 +/- 5.2 and 10.8 +/- 6.1 mamp in hearts of swimmers and controls, respectively, the difference not being significant. The incidence of spontaneous defibrillation was not significantly different between the two groups. It is concluded that, while swimming induces cardiac hypertrophy and hemodynamic changes, it neither protects against the induction of ventricular fibrillation nor facilitates spontaneous defibrillation in the isolated, non-ischemic rat heart.

Animals

[Risk of cardiovascular mortality of hospitalized psychiatric patients].

In a long-term study involving 783 psychic patients (361 men and 422 women) ranging in age between 40 and 70 years and hospitalised for extended periods of time, who had been examined for the incidence of cardiovascular diseases and risk factors, the cardiovascular mortality was registered for a period of 10 years. Using a multiple logistic model, an attempt was made at assessing the mortality risk in dependence on 14 parameters. The most conclusive predictor proved to be the pathological ECG which was seen to reflect seven times a higher risk. In addition to age and sex - the cardiovascular mortality of men was twice and a half that of women - hypertension and increased serum cholesterol levels among the known risk factors revealed a significant influence with little less than a doubling of the risk. On the other hand, a correlation to cardiovascular mortality was neither established for the kind of psychic disease nor for the kind of psychopharmacotherapy.

Adult

The effect of amino acids on the ischemic heart. Improvement of oxygenated crystalloid cardioplegic solution by an enriched branched chain amino acid formulation.

This study was designed to test the effect of glucose and a formulation enriched with branched chain amino acids as additives to oxygenated crystalloid cardioplegic solution in the ischemic heart. Energy-depleted isolated working rat hearts were subjected to 68 minutes of normothermic global ischemia during which oxygenated cardioplegic solution was used to protect them. The hearts were then reperfused in the nonworking mode for 10 minutes and for a further 30 minutes in the working mode. The hearts were randomly divided into three groups, in which various oxygenated cardioplegic solutions were perfused. Group 1 (control) was subjected to modified St. Thomas' Hospital cardioplegic solution and groups 2 and 3 to the same solution with the addition of glucose (11.1 mmol/L) and glucose (11.1 mmol/L) and branched chain amino acids, respectively. Recovery of aortic flow, coronary flow, cardiac output, aortic pressure, adenosine triphosphate, creatine phosphate, and oxygen consumption was significantly better in group 2 than in group 1. In addition, recovery of aortic flow, coronary flow, cardiac output, aortic pressure, stroke volume, minute work, adenosine triphosphate, and creatine phosphate was found to be significantly enhanced in group 3. Release of adenine catabolites and lactic dehydrogenase from these hearts during postischemic reperfusion was significantly decreased. Thus, during global ischemia in the energy-depleted heart, the presence of glucose and branched chain amino acids in oxygenated crystalloid cardioplegic solution enhanced myocardial protection.

Amino Acids, Branched-Chain

Protective effect of branched chain-enriched amino acid formulation in myocardial ischemia.

The protective effect of a branched chain amino acid (BCAA) formulation on the ischemic myocardium was determined in four groups of passively perfused normothermic (37 C) isolated rat hearts perfused with Krebs-Henseleit (KH) or KH + BCAA. Time to ischemic contracture was significantly increased by the infusion of BCAA compared with KH (19.4 +/- 2.3 vs. 15.9 +/- 1.7 min). In a second set of experiments, rat hearts were perfused with KH or KH + BCAA solution followed by 2 min of glucose-free KH buffer. After 17 min of ischemia, both groups were reperfused for another 15 min. Percent of pressure recovery was significantly better with KH + BCAA (90.1 +/- 8.4) than with KH (56.4 +/- 40.0). Percent +dP/dt (time derivative of pressure at contraction) recovery was also significantly improved with KH + BCAA (96.5 +/- 26.9 vs. 58.1 +/- 44.0). Furthermore, arrhythmias were minimized by BCAA. There was no difference in change of coronary flow between these two groups. Thus, BCAAs appear to protect the heart against myocardial ischemic injury and to delay the time to ischemic contracture, particularly in the depleted ischemic heart. BCAAs enhance postischemic pressure recovery and improve postischemic systolic and diastolic myocardial function.

Amino Acids, Branched-Chain

The protective effect of enriched branched chain amino acid formulation in the ischemic heart: a phosphorous-31 nuclear magnetic resonance study.

Branched chain amino acids (BCAA) have been found to have a protective effect on the ischemic myocardium. Isolated rat hearts were perfused with phosphate-free Krebs-Henseleit (KH) solution with or without BCAA. A Latex balloon-tipped catheter was inserted into the left ventricle to measure intracavitary pressures. Hearts were subjected to 18 minutes of 'no flow' global ischemia and then reperfused for 30 mins at 37 degrees C. Metabolism of high energy phosphates during ischemia and recovery was studied by P-31 NMR. Intracellular pH was calculated from the chemical shift of Pi. Pressure recovery was better with KH + BCAA (89 +/- 16%) than with KH (41 +/- 26%) (P = 0.0001); dP/dt recovery was also improved with BCAA (84 +/- 19% vs 27 +/- 27% for KH) (P = 0.0003). After 18 mins of ischemia, ATP levels in the BCAA group were higher than in the KH perfused hearts (33 +/- 20 vs 17 +/- 10% of pre-ischemic value) (P = 0.02). No significant difference was found in the intracellular pH at the end of the ischemic period. Following reperfusion the recovery of pH was better in the BCAA group (7.09 +/- 0.06 vs 7.04 +/- 0.06) (P = 0.03). These results show that BCAA protect the heart from myocardial ischemic injury, decrease depletion of ATP during ischemia, and enhance post-ischemic hemodynamic function.

Adenosine Triphosphate

[Mortality of hospitalized psychiatric patients--results of a 10-year study].

The mortality rate of 1239 psychiatric patients--609 men and 639 women, aged between 40 and 70 years, permanently hospitalized in 6 different German clinics--was registered, ten years after they had been examined for the incidence of cardiac risk factors in 1971 and 1972. The death rate figures were compared with the corresponding figures of the total population of the Federal Republic of Germany. In all age-groups mortality among psychiatric patients, both male and female, was higher than the average rate at Federal level. The gap narrowed with increasing age. With male patients the most frequent cause of death were cardiovascular diseases, followed by respiratory diseases and malignant growths, whereas with women respiratory diseases were the primary cause of death. In comparison to the population of the Federal Republic of Germany considerably more patients died of respiratory diseases--according to age and sex the death rate was up to ten times higher. This was due to the high percentage of lethal pneumonia. The number of deaths in which the cause was unknown was also higher than the national average. A remarkably high percentage of the patients (27%) died suddenly and unexpectedly. In some age-groups fewer patients died of malignant growths than at Federal level. Death caused by cardiovascular diseases was only more frequent among younger patients. Among men acute ischaemic heart diseases were the most frequent cause of cardiac failure. Death due to cerebral sclerotic diseases was remarkably reduced among older patients, probably as a result of a less high incidence of hypertension.

Adult

Purification and characterization of pentobarbital-induced cytochrome P-450BM-1 from Bacillus megaterium ATCC 14581.

When Bacillus megaterium ATCC 14581 is grown in the presence of barbiturates, a cytochrome P-450-dependent fatty acid monooxygenase (Mr 120000) is induced (Kim, B.-H. and Fulco, A.J. (1983) Biochem. Biophys. Res. Commun. 116, 843-850). Gel filtration chromatography of a crude monooxygenase preparation from pentobarbital-induced B. megaterium indicated that not all of the induced cytochrome P-450 present in the extract was accounted for by this high-molecular-weight component. Further purification revealed the presence of two additional but smaller cytochrome P-450 species. The minor component, designated cytochrome P-450BM-2, had a molecular mass of about 46 kDa, but has not yet been completely purified or further characterized. The major component, designated cytochrome P-450BM-1, was obtained in pure form, exhibited fatty acid monooxygenase activity in the presence of iodosylbenzenediacetate, and has been extensively characterized. Its Mr of 38000 makes it the smallest cytochrome P-450 yet purified to homogeneity. Although it is a soluble protein, a complete amino acid analysis indicated that it contains 42% hydrophobic residues. By the dansyl chloride procedure the NH2-terminal amino acid is proline; the penultimate NH2-terminal residue is alanine. The absolute absorption spectra of cytochrome P-450BM-1 show maxima in the same general regions as do P-450 cytochromes from mammalian or other bacterial sources, but they differ in detail. The oxidized form of P-450BM-1 has absorption maxima at 414, 533 and 567 nm, while the reduced form has peaks at 410 and 540 nm. The absorption maxima for the CO-reduced form of P-450BM-1 are found at 415, 448 and 550 nm. Antisera from rabbits immunized with pure P-450BM-1 strongly reacted with and precipitated this P-450, but showed no detectable affinity for either the 46 kDa P-450 or the 120 kDa fatty acid monooxygenase.

Amino Acids

[Effectiveness of a preventive mass examination for cardiac risk factors (author's transl)].

18 months after a mass examination for coronary heart disease risk factors in employees of a large industrial firm, 75% of the subjects examined at that time were re-interviewed and measurements of blood pressure and weight repeated. Despite an altogether inadequate longterm control of the risk factors detected, a part of the subjects examined had drawn consequences regarding their way of life by reducing weight, changing smoking habits and increasing physical activity, thus proving the effectiveness of information and advice received in a screening investigation. In about 40% of the overweight subjects a reduction in weight and in half of the hypertensives a lowering of blood pressure to values below 160/95 mmHg was noted.

Adult