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At least 19 recordsLinked to original sources

Myocardial protection during aortic valve replacement. Physiological and metabolic effects of selective coronary perfusion on the fibrillating heart.

The physiological effects and certain aspects of cardiac metabolism were studied in 14 patients undergoing primary aortic valve replacement. The operations were performed under moderate hypothermia (30 degrees +/- 2 degrees C) and blood for coronary perfusion was taken from a sidebranch of the arterial line. The majority of the hearts went spontaneously into ventricular fibrillation at some stage of the operation. In spite of the high resistance measured in the coronary perfusion cannulae, an intraluminar coronary blood flow of 380 ml/min was recorded. The myocardial oxygen uptake decreased to 6.0 ml/min at 29 degrees C compared with 20.0 ml/min at 36 degrees C. The elevated coronary sinus lactate throughout the period of coronary perfusion and the increasing level of ASAT-enzyme indicated that this technique could not fully protect the myocardium from ischaemic changes. One patient died of myocardial infarction and two others needed vasopressor support postoperatively, in spite of documented effective coronary perfusion throughout the procedure. Cannulation of the coronary sinus is a valuable adjunct for the study of cardiac metabolism during ECC and it was accomplished without complications.

Adult

Establishment of a viable homograft cardiac valve bank: a rapid method of determining homograft viability.

A method for determining the viability of homograft valves has been developed based on sequential measurements of glucose and pH levels of the culture medium in which cardiac valves have been maintained for short periods at 37 degrees C. Viable valves, as determined by tissue culture, showed a characteristic pattern of glucose utilization and pH reduction that was absent in nonviable valves. Upon explantation of valve leaflet fragments into tissue culture, only fragments from valves that metabolized glucose produced viable fibroblast cultures. The method reported here is rapid, requires no specialized equipment, is nondestructive, and can directly determine the viability of the valve homograft within 24 to 48 hours.

Aortic Valve

Mapping temperature-sensitive mutations at a genome scale to engineer growth switches in Escherichia coli.

Temperature-sensitive (TS) mutants are a unique tool to perturb and engineer cellular systems. Here, we constructed a CRISPR library with 15,120 Escherichia coli mutants, each with a single amino acid change in one of 346 essential proteins. 1,269 of these mutants showed temperature-sensitive growth in a time-resolved competition assay. We reconstructed 94 TS mutants and measured their metabolism under growth arrest at 42°C using metabolomics. Metabolome changes were strong and mutant-specific, showing that metabolism of nongrowing E. coli is perturbation-dependent. For example, 24 TS mutants of metabolic enzymes overproduced the direct substrate metabolite due to a bottleneck in their associated pathway. A strain with TS homoserine kinase (ThrBF267D ) produced homoserine for 24 h, and production was tunable by temperature. Finally, we used a TS subunit of DNA polymerase III (DnaXL289Q ) to decouple growth from arginine overproduction in engineered E. coli. These results provide a strategy to identify TS mutants en masse and demonstrate their large potential to produce bacterial metabolites with nongrowing cells.

Escherichia coli

Myocardial oxygen supply in left ventricular hypertrophy and coronary heart disease.

Coronary arteriolar dilation adjusts blood flow according to local fluctuating metabolic needs of the myocardium. Because of high extravascular compression during systole, the subendocardial layer of the left ventricle is especially dependent on the duration and the perfusion pressure of the diastolic period. In patients with obstructive coronary artery disease, regional arteriolar dilation is utilized to compensate for focal arterial stenoses. Coronary blood flow may be compensated with the patient at rest, but loss of reserve arteriolar dilation limits further adjustment to superimposed transient increases in metabolic needs. Subendocardial perfusion in the region supplied by the stenosed artery is especially vulnerable to shortened diastolic time during tachycardia. In patients with chronic aortic valve disease, the metabolic rate of the left ventricle is increased in proportion to the increases in myocardial mass and work. Coronary blood flow and metabolic rate per gram of the hypertrophied myocardium are normal when the patient is at rest, at the expense of diminished coronary arteriolar reserve. High tissue pressure relative to the diastolic perfusion pressure probably contributes to the diffuse subendocardial ischemia that occurs in these patients during tachycardia.

Arterial Occlusive Diseases

[Myocardial function in patients with congenital pulmonary valve stenosis].

The studies of metabolism and morphology of the myocardium, and of ECG parameters in 72 patients with valvular pulmonary stenosis conducted with biopsy and autopsy material has demonstrated that while the workload on the right ventricle grows and the severity of the pathological process increases, the oxidative capacity of the myocardium also increase, the indices of its energy supply decrease, the degree of myocytes hypertrophy grows, and the number of mitochondria and the coefficient of their energy efficacy decrease. A correlation was established between the degree of these changes and the severity of electrocardiographic signs of hypertrophy and disorders in the repolarization process in the right ventricle.

Adenine Nucleotides

Liver drug metabolism in patients undergoing open-heart surgery.

The effect of open-heart surgery on the drug metabolism of the liver was investigated in 17 patients by using the rate of antipyrine elimination as an index. A correlation was found between the pre-operative heart size and the antipyrine elimination rate. In patients with a markedly dilated heart, the plasma antipyrine half-life was prolonged and apparent clearance significantly impaired. Immediately postoperatively, antipyrine elimination was impaired in all patients. Later, the drug metabolism improved in patients with atrial septal defect, changed temporarily in patients with aortic valve replacement, and remained unchanged in patients with mitral valve replacement. The results indicate that adaptive changes in drug metabolizing capacity occur in patients undergoing cardiac surgery. The changes are related to the type of lesion corrected, the pre-operative functional capacity of the liver, and the time lapse after surgery.

Adolescent

Influence of morphine anaesthesia on the endocrine-metabolic response to open-heart surgery.

Twelve patients scheduled for aortic valve replacement during extracorporal circulation were randomly allocated to either morphine anaesthesia or fluroxene anaesthesia. Morphine in a total dose of 4 mg/kg was administered before skin incision. At the start of extracorporal circulation all patients received 25 g glucose intravascularly. The endocrine-metabolic response to surgery, as expressed by changes in plasma ACTH, cortisol, insulin, growth hormone, cyclic adenosine-3',-5'-monophosphate (cyclic AMP), glucose, free fatty acids, blood b-hydroxybutyrate and cumulative nitrogen balance was measured before and during anaesthesia and surgery, and on the first five post-operative days. It was found that morphine anaesthesia blocked the increase in ACTH, cortisol, growth hormone, cyclic AMP, and glucose during surgery. However, after initiation of extracorporal circulation only ACTH, cortisol, and, to a lesser degree, the glucose and insulin response to glucose were lowered by morphine anaesthesia. From the first to the fifth days after operation no differences between the two groups could be demonstrated in any parameter. Cumulative nitrogen balance was similar in the two groups. It is concluded that morphine in large doses administered before skin incision inhibits the initial endocrine-metabolic response to open-heart surgery, but that the effect is short-lasting and without effect on overall postoperative protein catabolism.

Adolescent

The George M. Kober lecture: a genetical view of modern medicine.

A genetic approach to medicine provides a powerful concept for understanding of the etiology of many diseases. Significant investigative and therapeutic advances have already been made in the chromosomal and Mendelian diseases using genetic concepts which initially were discovered completely unrelated to medicine. The combination of unfettered basic biomedical research together with family and population studies is likely to bring new insights to understanding, prevention and treatment of the yet poorly understood multifactorial diseases which represent the greatest public health problems in the Western world. Identification of specific genes involved in susceptibility and resistance to these diseases and their interaction with various environmental factors will allow a more rational preventive medicine in the future.

Chromosome Aberrations

[On relapsing paraneoplastic cerebral embolism. Case report and survey of literature (author's transl)].

The disease of a 34-year-old patient with relapsing cerebral embolisms, endocarditis, thrombophlebitis and hypercoagulopathy had the characteristics of paraneoplastic syndromes described and discussed in literature. Autopsy yielded a clinically unrecognised, dedifferentiated adenocarcinoma of the bronchial system. At an early stage of the disease cerebral embolisms had produced severe cerebral neurological signs with varying manifestations. This influenced not only the clinical picture and course of the disease to a considerable extent, but also focussed diagnostic attention on these signs to such a degree that the possibility of a masked carcinoma did not seem to suggest itself. The assumption of paraneoplastic linkups is supported by experimental and postmortem examinations on metabolic and immunological remote action of tumours on cardiac valves and on the vascular and coagulation system. However, the exact pathogenetic details are still largely unknown.

Adenocarcinoma

[Peridural anesthesia during mitral commissurotomy on patients in the late stages of the disease].

Peridural anesthesia in T1--T6 regions was used together with general anesthesia in closed mitral commisurotomy in 40 patients with the disease in stages 4 and 5. The study was aimed at the evaluation of the effect of peridural anesthesia upon hemodynamics, gas exchange, adrenal cortex function, energy exchange in the myocardium and the evaluation of its expediency for these patients. The authors studied hemodynamic alterations (HR, AP, CVP, MV, CBV etc.), changes of acid-base equilibrium and in the blood gases, concentration of summary 11-oxycorticosteroids in the blood plasma and of creatinophosphate in the myocardium left auricle. On the grounds of these studies the authors have come to some practically important conlusions.

Adrenal Cortex

Comparative experimental study of myocardial energy metabolism during ventricular workload induced by chronic stenoses of ascendent aorta and pulmonary artery.

In this paper, an attempt was made to describe the alterations of the myocardial energy metabolism following moderate stenoses of aorta or pulmonary artery. Biochemical investigations regarding the main high energy phosphates and a large series of dehydrogenases in the myocardium of the overloaded ventricles have revealed the following facts: (1) the myocardial CP-CPK system appears to be more labile than the myocardial AMP-ATP system in response to a ventricular overload; (2) the changes in the amounts of myocardial high energy phosphates seem to be more important in the right chronic cardiac overload than in the left one; (3) before the overloaded ventricle becomes insufficient, the myocardial dehydrogenase system elicits no alteration, suggesting that the oxidative phosphorylation is not affected; (4) there is a closer relationship between the coronary flow and pressure and the myocardial energy metabolism than that existing between this metabolism and the tension of the myocardial fibres following a persistent increase in the systemic arterial resistance.

Adenosine Triphosphatases

Cellular pathology of homozygous familial hypercholesterolemia.

Tissues were studied from four subjects with homozygous familial hypercholesterolemia (FH). The specimens consisted of tissues obtained from a 20-week-old fetus at autopsy, samples from a 9-year-old girl during open-heart surgery, and biopsies of cutaneous xanthomas from a 13-year-old girl and a 21-year-old man. The FH fetus, but not the 3 control fetuses, exhibited multifocal lipid deposition particularly involving the stromal cells of the thymus, spleen, and skin and both the stromal and parenchymal cells of the kidney. Only one minute focus of intimal lipid accumulation was found in the aorta and coronary arteries of the FH fetus. A segment of the ascending aorta from the 9-year-old girl showed: 1) foam-cell transformation of many medial smooth-muscle cells, 2) abnormal vascularization of the inner media and intima, and 3) intimal involvement by a typical artherosclerotic plaque with lipid deposits in thin, elongated cells that showed some myocytic features and in foam cells that lacked such features. The mitral and aortic valves of this patient also contained numerous foam cells and showed mild to moderate fibrous thickening. A segment of the saphenous vein, however, contained no lipid deposits. The three xanthomas from two FH homozygotes exhibited marked lipid accumulation in histiocytic foam cells but no lipid deposits in the endothelium of blood vessels in the lesions. The findings in this study, in conjunction with those reported in studies of other FH homozygotes, indicate that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon, and, varibly, in other extravascular sites. Since most of the intracellular lipid was in the form of non-membrane-bound neutral lipid droplets, it appears that the cytoplasm is the major site of lipid storage in this disease.

Adolescent

PGA1 and PGF2 alpha metabolism by pig pulmonary endothelium, smooth muscle, and fibroblasts.

To determine the cellular site for uptake and degradation of circulating prostaglandins (PGs) by the lung, the metabolism of PGA1 and PGF2 alpha was studied in pig lung slices, smooth muscle preparations, and pulmonary valves, as well as in isolated and cultured endothelial cells and cultured fibroblasts. Formation of 15-keto metabolites of both PGA1 and PGF2 alpha by lung slices was confirmed. No evidence of PGF2 alpha degradation could be found in any of the remaining preparations. For PGA1, however, 15-hydroxyprostaglandin dehydrogenase activity was detected in the three smooth muscle preparations studied (trachea, aorta, pulmonary artery) and found to be similar to that measured in lung slices. But the inhibitory effect of diphloretin phosphate and bromcresol green was much more marked in smooth muscle tissues than in lung slices, which suggested that PGA1 metabolism by the lung was not due to smooth muscle cells. Endothelial cells, freshly isolated and cultured, originating from the pulmonary artery and from the aorta, formed a PGA1-glutathione adduct, poorly extractable in ethyl acetate. This reaction, also present in cultured fibroblasts, was inhibited by ethacrynic acid. The cellular site responsible for the pulmonary degradation of circulating PGs remains undetermined.

Animals