Fate of left ventricular thrombi in patients with remote myocardial infarction or idiopathic cardiomyopathy.

Although left ventricular thrombi that form acutely after myocardial infarction frequently resolve spontaneously or with anticoagulant therapy, the fate of left ventricular thrombi in patients with remote myocardial infarction or with idiopathic cardiomyopathy remains unknown. To determine the natural history of such chronic left ventricular thrombi, we performed serial echocardiograms on 51 patients with remote myocardial infarction (greater than or equal to 3 months; mean, 31 +/- 41 months) and on nine patients with idiopathic dilated cardiomyopathy. Mean follow-up was 24 +/- 22 months during which 3.5 +/- 1.4 echocardiograms were obtained. Studies were interpreted by blinded observers, and an increase or decrease of more than 5 mm in maximal thrombus thickness was defined as significant. Among all 60 patients left ventricular thrombi were unchanged in 24 (40%), completely resolved in 24 (40%), decreased in size in four (7%), increased in size in five (8%), and decreased and then increased in size in three (5%). Results in patients with remote infarction and idiopathic cardiomyopathy were similar. Warfarin therapy, which was at the discretion of the primary physician, was associated with a higher prevalence of thrombus resolution compared with no therapy (59% vs. 29%, p = 0.02). Definite systemic emboli occurred in seven patients (12%), all at times while they were not anticoagulated. Among the 48 thrombi that were present on two or more echocardiograms, changes in thrombus shape (classified as protruding or flat) occurred in only 16%, and changes in thrombus movement (classified as mobile or immobile) occurred in only 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased embolic risk in patients with left ventricular thrombi.

Although left ventricular thrombi are associated with an increased embolic risk in the first few weeks after acute myocardial infarction, the long-term risk remains undefined. To ascertain the incidence of strictly defined systemic emboli, we followed 85 patients with echocardiographically documented left ventricular thrombi. At the time of the entry echocardiogram, most patients (n = 57) had remote myocardial infarction, while 19 had recent (less than 1 month) infarction, and nine had idiopathic cardiomyopathy. Because of the difficulty in classifying events as embolic in patients with advanced atherosclerosis, a matched control group of 91 patients without thrombi was also studied. The thrombus and control groups were similar with regard to recent myocardial infarction, remote infarction, anterior infarction, ejection fraction, atrial fibrillation, echocardiographic referral for source of emboli, and warfarin therapy. During a mean follow-up of 22 months after echocardiography, embolic events occurred in 13% (11 of 85) of patients with thrombi compared with 2% (two of 91) control patients (p less than .01). The actuarial probability of being embolus free at 2 years after echocardiography was 86% in patients with thrombi compared with 97% in control patients (p less than .01). All embolic events occurred greater than 1 month after myocardial infarction (range 1 to 96 months). The only clinical or echocardiographic features predictive of embolization were protrusion and mobility of thrombus (both p less than .02). We conclude that the incidence of embolic events is definitely increased in patients with left ventricular thrombi compared with control subjects during long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

A critical assessment of the mechanism by which hyperoxia attenuates exercise-induced asthma.

Recent data demonstrate that the magnitude of the heat loss that occurs from the respiratory tract during exercise correlates with the degree of post-exertional obstruction that develops in asthmatics. Respiratory heat loss relates directly to the minute ventilation and heat capacity of the inspired gas and inversely to its water content and temperature. Because it has been shown that inhaling 100% oxygen during exercise blunts the obstructive response, we wondered if this effect could be accounted for by differing values of heat exchange with air and oxygen breathing. To examine this question, we studied 10 asthmatics by measuring multiple aspects of pulmonary mechanics before and after four bouts of exhausting leg work during which the subjects inhaled either air or oxygen conditioned to provide widely differing thermal burdens on their airways. Under all inspired gas conditions, oxygen breathing produced significantly less obstruction than air. Minute ventilation was also significantly less with oxygen as was the total heat lost. As the latter fell, so did the magnitude of the postexercise obstruction. When the differences in ventilation and respiratory heat loss between air and oxygen were eliminated by eucapnic hyperventilation, the differences in the obstructive responses also disappeared. Thus, the effects of hyperoxia on exercise-induced asthma can be accounteed for solely by alterations in heat exchange.

Biochemical parameters of glutamine synthetase from Klebsiella aerogenes.

The glutamine synthetase (GS) from Klebsiella aerogenes is similar to that from Escherichia coli in several respects: (i) it is repressed by high levels of ammonia in the growth medium; (ii) its biosynthetic activity is greatly reduced by adenylylation; and (iii) adenylylation lowers the pH optimum and alters the response of the enzymes to various inhibitors in the gamma-glutamyl transferase (gammaGT) assay. There are, however, several important differences: (i) the isoactivity point for the adenylylated and non-adenylylated forms in the gammaGT assay occurs at pH 7.55 in K. aerogenes and at pH 7.15 in E. coli; (ii) the non-adenylylated form of the GS from K. aerogenes is stimulated by 60 mM MgCl2 in the gammaGT assay at pH 7.15. A biosynthetic reaction assay that correlates well with number of non-adenylylated enzyme subunits, as determined by the method of Mg2+ inhibition of the gammaGT assay, is described. Finally, we have found that it is necessary to use special methods to harvest growing cells to prevent changes in the adenylylation state of GS from occurring during harvesting.

L-Asparaginase of Klebsiella aerogenes. Activation of its synthesis by glutamine synthetase.

An L-asparaginase has been purified some 250-fold from extracts of Klebsiella aerogenes to near homogeneity. The enzyme has a molecular weight of 141,000 as measured by gel filtration and appears to consist of four subunits of molecular weight 37,000. The enzyme has high affinity for L-asparagine, with a Km below 10(-5) M, and hydrolyzes glutamine at a 20-fold lower rate, with a Km of 10(-3) M. Interestingly, the enzyme exhibits marked gamma-glutamyltransferase activity but comparatively little beta-aspartyl-transferase activity. A mutant strain lacking this asparaginase has been isolated and grows at 1/2 to 1/3 the rate of the parent strain when asparagine is provided in the medium as the sole source of nitrogen. This strain grows as well as the wild type when the medium is supplemented with histidine or ammonia. Glutamine synthetase activates the formation of L-asparaginase. Mutants lacking glutamine synthetase fail to produce the asparaginase, and mutants with a high constitutive level of glutamine synthetase also contain the asparaginase at a high level. Thus, the formation of asparaginase is regulated in parallel with that of other enzymes capable of supplying the cell with ammonia or glutamate, such as histidase and proline oxidase. Formation of the asparaginase does not require induction by asparaginase and is not subject to catabolite repression.