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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

[Intravital study of energy metabolism in the liver in mitral valve stenosis].

In 42 patients with mitral stenosis an intravital study was conducted comparing the liver energy exchange with the biochemical blood serum parameters and morpho-histochemical characteristics of the biopsy material. A correlation was established between the energy exchange and the clinical stage of the disease, the pigment function of the liver and the severity of its structural changes.

Adenosine Diphosphate

Combined application of metabolic myocardial arrest and general profound hypothermia in aortic valve replacement.

To determine the value of general hypothermia in combination with magnesium-aspartate-procaine induced metabolic myocardial arrest, the surgical results of 2 similar groups of patients subjected to aortic valve replacement were compared. Metabolic arrest of the myocardium was achieved under mild hypothermic conditions in group I (71 patients) and in profound hypothermia in group II (48 patients). The operative mortality was 5.6% in group I and 4.1% in group II. There was no cardiac related with in group II. In group I two deaths were due to a low cardiac output state. In addition, 3 patients required inotropic support during the early postoperative period. Our results indicate, that magnesium-aspartate-procaine induced cardioplegia in combination with general profound hypothermia can provide effective myocardial protection during aortic valve replacement.

Adult

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

Aortic valve replacement for ochronosis of the aortic valve.

A patient with generalized ochronosis developed severe cardiovascular symptoms related to ochronotic deposits on the aortic valve and in the coronary arteries. A transvalvular gradient of 100 mm Hg and obstruction of the left anterior descending coronary artery were found by catheterization. Aortic valvular replacement and aortocoronary bypass were performed successfully, and the patient has been well two years since operation. This represented the first reported case of aortic valve replacement for this rare metabolic condition. With increased mobility of these patients due to aggressive orthopedic joint treatment, more patients with this syndrome may require surgery for cardiovascular symptoms.

Aortic Valve

Chest pain and bilateral atrioventricular valve prolapse with normal coronary arteries in isolated corrected transposition of the great vessels. Clinical, angiographic and metabolic features.

A man evaluated for disabling chest pain was found to have isolated anatomically corrected transposition of the great vessels. Angiography demonstrated right and left atrioventricular (A-V) valve prolapse and normal coronary arteries. Atrial pacing produced chest pain, ischemic electrocardiographic changes, abnormal myocardial lactate metabolism and marked elevation of the left ventricular end-diastolic pressure; all of these changes returned to normal on termination of pacing. The association of corrected transposition and bilateral A-V valve prolapse and the possible causes of myocardial ischemia in this patient are discussed.

Fatty Acids, Nonesterified

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

Technetium-99m stannous pyrophosphate scintigrams in normal subjects, patients with exercise-induced ischemia and patients with a calcified valve.

Although technetium-99m stannous (99mTc[Sn]) pyrophosphate has been shown to be a specific and sensitive index of myocardial infarction, abnormal images have been reported in patients with unstable angina or ventricular aneurysm. Sixty-one subjects--33 patients subjected to maximal treadmill stress testing, 23 normal subjects and 5 patients with a calcified aortic or mitral valve--underwent imaging with 99mTc(Sn) pyrophosphate to determine whether abnormal images are associated with (1) exercise-induced ischemia, (2) delayed clearance of tracer from the blood pool, or (3) calcified intracardiac structures. Myocardial injury was excluded on the basis of normal MB creatine kinase (CK) values in all patients with stress testing. All eight patients with an abnormal exercise stress test had normal images. Four of 25 patients with a normal exercise stress test had diffusely abnormal images. In some normal subjects diffusely abnormal images were present 60 minutes after injection of the tracer, but became normal 90 to 120 minutes after injection. Variations in clearance of tracer from the blood pool were noted in this group. Patients with a calcified aortic or mitral valve had normal images. We conclude that (1) exercise-induced ischemia is not associated with abnormal 99mTC(SN) pyrophosphate images; (2) images are not necessarily abnormal in patients with a calcified valve; and (3) delayed removal of tracer from the cardiac blood pool may result in diffusely abnormal images even in normal subjects; in these cases, repeat images should be obtained at least 2 hours after injection of the tracer to avoid false abnormal images.

Adult

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