Assay of serum cardiac myosin heavy chain fragments in patients with acute myocardial infarction: determination of infarct size and long-term follow-up.

To evaluate the correlation between myosin heavy chain release and the necrosis mass, serum levels of myosin heavy chain fragments were determined serially in 55 patients with acute myocardial infarction. Eight of these patients were successfully treated with thrombolytic agents: the others were not treated. The same myosin titration was applied to the sera of 25 dogs with an experimental myocardial infarction. Six of the dogs were successfully treated with thrombolytic agents. The time courses of the myosin concentrations are typical and monophasic for all patients with a noncomplex myocardial infarction. The values for the kinetic parameters of myosin release are comparable to those previously reported. We have now determined that cumulative myosin release significantly correlates with cumulative creatine kinase (CK), CK-MB, and lactate dehydrogenase release, as well as with thallium-201 distribution, as determined for different patient groups. Thrombolytic treatment does not seem to qualitatively upset myosin kinetics. The results obtained in dogs with or without thrombolysis conclusively indicate that myosin release is a quantitative index of the necrosis mass. From a practical point of view, a few serial determinations of serum levels of myosin heavy chains are enough to estimate the necrosed mass in patients with acute myocardial infarction. More generally, serum myosin titration could be useful in detecting any cardiac disturbance involving myocardial injury resulting in membrane leakage of cardiac cells.

Phosphorylation of high molecular weight proteins in platelets treated with 12-O-tetradecanoylphorbol-13-acetate.

Changes in the phosphorylation of three high molecular weight cytoskeletal proteins in platelets (actin binding protein, platelet talin and myosin heavy chain) were investigated after treatment with a phorbol ester. All three showed rapid increases in phosphate incorporation, reaching near-maximal values within three minutes. Phosphopeptide maps of the proteins before and after phorbol treatment revealed a single new site in myosin heavy chain, two new peptides in actin binding protein, and multiple sites in talin. These results point to multiple cytoskeletal targets of protein kinase C and suggest complex mechanisms for reorganizing microfilaments.

How does fluoroaluminate activate human platelets?

Platelet activation induced by NaF or fluoroaluminate (AlF4-) was studied. The latter has been described to substitute for the gamma-phosphate group of the GTP molecule. With 10 mM-NaF, a concentration unable to induce any measurable Ca2+ mobilization (as measured with Indo 1), addition of AlCl3 potentiated platelet aggregation, thromboxane synthesis, diacylglycerol formation and p43 phosphorylation, without any increase in intracellular Ca2+. Neither phosphoinositide hydrolysis nor phosphatidic acid formation could be detected. AlF4- induced the release through a granule centralization within a microtubule bundle, although no myosin light-chain phosphorylation could be detected. Addition of flurbiprofen (10 microM) resulted in only partial inhibition of diacylglycerol formation, with no effect on the release reaction or on p43 phosphorylation. The present results suggest that AlF4- does not stimulate a G-protein governing the phosphoinositide-specific phospholipase C. The AlF4(-)-induced diacylglycerol formation is discussed. Moreover, these results bring evidence that there is no correlation between granule centralization and myosin light-chain phosphorylation.

[Clinical application of immunoassays for cardiac myosin light chains].

We developed four types of immunoassays for cardiac myosin light chains (LC), which are two radioimmunoassays (RIA) for canine and human LC, and an immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA) for human LC. The first two assays make use of polyclonal antibodies and the last two use monoclonal antibodies. By using these immunoassays, we studied the release of cardiac LC into the serum following acute myocardial infarction (AMI). In experimental AMI in dogs, cardiac LC appeared in the serum within 4-12 hours, reached the maximum at 2-5 days and returned to normal at 7-10 days. This long time-course was suggested due to the continuous liberation of LC from the infarcted myocardium on the basis of a quick disappearance rate of LC from the circulation. The peak LC values were found to correlate well with the histological infarct size. Similar results were also obtained regarding the time-course of circulating LC in clinical patients with AMI. Thus LC measurement seems useful for diagnosis of AMI as well as for estimating the extent of myocardial damage. We also developed an IRMA and an ELISA for human LC by using anti-human LC monoclonal antibodies for a more rapid LC assay and for a consistent supply of antibodies. These assays showed sufficiently high sensitivities to measure 1-100 ng/ml of serum LC. Especially, serum LC can be assayed within 2.5 hours by our ELISA. Such progress in immunoassays for cardiac LC has made the measurement of LC an important laboratory test for the diagnosis of AMI.

[Perioperative risk of valve replacement surgery in the elderly]. / Perioperatives Risiko bei Klappenersatz-Operation im höheren Lebensalter.

The indication of surgical valva replacement also at older age (greater than 60 years) with chronically rheumatic valvular diseases requires both the assessment of the pre-operative constellation of findings and perioperative complications. From this combined point of view statements concerning the strategy of valve replacement at older age seem to be concludable. In the frame of a prospective study perioperative parameters were monitored in n = 90 patients with preoperative high-risk constellation out of a total of n = 300 patients for the quick recording of additional complications (such as perioperative myocardial damage, cardiac low output syndrome, and cases of death at the ICU). The average age of the whole group of patients was 52 years (25-68 years), that of the patients greater than 60 years was 63.6 years (61-68 years). In 72% of the older patients the preoperative high-risk constellation was confirmed by 50% deceased; 16% cLOS; 6% perioperative myocardial damage (PMD). On a total of 41% of the patients a combined operation was performed (valve replacement and bypass operation), there of 2/3 with aortic valve replacement and 1/3 with mitral valve replacement. The ejection fraction restricted heavily already before the operation (less than or equal to 30%) was the essential cause of perioperative complications (cases of death, cLOS) together with the combined operation. The immedicable pulmonary hypertension complicated the already preoperatively impaired left-ventricular function in a high percentage of patients with mitral valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

[Aortocoronary venous bypass operation in the elderly]. / Aortokoronare Venen-Bypass-Operation im höheren Lebensalter.

On the extended diagnosis for an aorto-coronary venous bypass operation, with a greater involvement of patients with instable angina pectoris symptomatik (inApS), left main artery disease (LAD), aneurysmal resection, and "bad" ventricle (ejection fraction global less than or equal to 30%), the preoperative risk was evaluated in n = 600 patients. In a total of n = 150 patients with preoperative high-risk constellation perioperative parameters were monitored to find complications (perioperative myocardial damage [PMD], cardiac low output syndrome [LOS]). Among them were n = 40 patients aged greater than 60 years (60-72), their average age being 62.9 years. In 30% of these older patients the preoperative high-risk constellation was confirmed: 15% PMD, 10% LOS, and 5% deceased. The further postoperative course (up to the 6th month) is objectified by the ejection fraction global (EFg) by multiple checks. As a whole, patients greater than 60 years with extended diagnosis for ACVB operation do not show any significant increase in hospital mortality, but an increase in PMD and LOS (p less than 0.001) compared to the age group less than 60 years. With corresponding individual intensive-therapeutic measures, however, both complications can be controlled in the majority of patients. Despite the demonstrated higher perioperative risk, the urgent ACVB operation proved to be strategically right (considering the results of EFg) for increasing the quality of life and improving the expectation of life also for patientes greater than 60 years, in particular with the operation indications of inApS and LAD.(ABSTRACT TRUNCATED AT 250 WORDS)