The long-predicted endocrine function of the heart has been proven by the discovery of atrial natriuretic peptide (atrial natriuretic factor, A-type natriuretic peptide; ANP) 20 years ago. This subsequently led to the description of a whole family of structurally similar but genetically distinct peptides, the natriuretic peptide family, which contributes to cardiovascular homeostasis. These looped peptides promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues. Two members, ANP and brain natriuretic peptide (B-type natriuretic peptide; BNP) are secreted by the heart mainly in response to myocardial stretch induced by volume load. The natriuretic peptides are synthesized as preprohormones. The C-terminal endocrinological active peptides (ANP, BNP) and their N-terminal prohormone fragments are found in plasma. The natriuretic peptide system is activated to its highest degree in ventricular dysfunction. However, natriuretic peptides are increased in all patients with edematous disorders which lead to an increase in atrial tension or central blood volume, such as renal failure or ascitic liver cirrhosis. It could be demonstrated that in chronic heart failure patients and during the subacute phase of myocardial infarction, of all tested neurohormones, the cardiac natriuretic peptides were best markers to identify heart failure and the most powerful predictors of morbidity and mortality. Natriuretic peptides are independent markers for risk assessment. In comparative studies BNP was superior to ANP and its N-terminal prohormone fragments in myocardial infarction as well as in chronic heart failure patients. Less data on N-terminal proBNP (NT-proBNP) is available, but BNP and NT-proBNP appear to be equivalent markers. For primary care physicians natriuretic peptide measurement is useful to decide which patient with suspected heart failure warrants further investigation, particularly when assessment of left ventricular function is not readily available. Natriuretic peptides have an excellent negative predictive value, particularly in high risk patients. An increase in BNP is serious enough to warrant follow-up examinations. For the cardiologists the natriuretic peptides are helpful for guidance of therapy and monitoring disease course in heart failure patients and for risk stratification in heart failure and myocardial infarction.

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The utility of skeletal troponin I (sTnI) as a plasma marker of skeletal muscle damage after exercise was compared against creatine kinase (CK), myoglobin (Mb), and myosin heavy chain (MHC) fragments. These markers were serially measured in normal physical education teacher trainees after four different exercise regimens: 20 min of level or downhill (16% decline) running (intensity: 70% maximal O2 uptake), high-force eccentric contractions (70 repetitions), or high-force isokinetic concentric contractions of the quadriceps group (40 repetitions). Eccentrically biased exercise (downhill running and eccentric contractions) promoted greater increases in all parameters. The highest plasma concentration were found after downhill running (median peaks: 309 U/l CK concentration (-CK-)), 466 microgram/l Mb concentration (-Mb-), 1,021 microU/l MHC concentration (-MHC-), and 27.3 microgram/l sTnI concentration ([sTnI]). Level running produced a moderate response (median peaks: 178 U/l -CK-, 98 microgram/l -Mb-, 501 microU/l -MHC-, and 6.6 microgram/l [sTnI]), whereas the concentric contraction protocol did not elicit significant changes in any of the markers assayed. sTnI increased and peaked in parallel to CK and stayed elevated (>2.2 microgram/l) for at least 1-2 days after exercise. In contrast to MHC, sTnI is an initial, specific marker of exercise-induced muscle injury, which may be partly explained by their different intracellular compartmentation with essentially no (MHC <0.1%) or a small soluble pool (sTnI: median 3.4%).

BACKGROUND:The specific forms of pro-B-type natriuretic peptide (proBNP) that occur in human blood are not yet clear. We demonstrated the presence of several proBNP forms in human plasma with a new affinity chromatography method that can be used in combination with nano-liquid chromatography electrospray ionization tandem mass spectrometry (nano-LC-ESI-MS/MS).

The effects of a single series of high-force eccentric contractions involving the quadriceps muscle group (single leg) on plasma concentrations of muscle proteins were examined as a function of time, in the context of measurements of torque production and magnetic resonance imaging (MRI) of the involved muscle groups. Plasma concentrations of slow-twitch skeletal (cardiac beta-type) myosin heavy chain (MHC) fragments, myoglobin, creatine kinase (CK), and cardiac troponin T were measured in blood samples of six healthy male volunteers before and 2 h after 70 eccentric contractions of the quadriceps femoris muscle. Screenings were conducted 1, 2, 3, 6, 9, and 13 days later. To visualize muscle injury, MRI of the loaded and unloaded thighs was performed 3, 6, and 9 days after the eccentric exercise bout. Force generation of the knee extensors was monitored on a dynamometer (Cybex II+) parallel to blood sampling. Exercise resulted in a biphasic myoglobin release profile, delayed CK and MHC peaks. Increased MHC fragment concentrations of slow skeletal muscle myosin occurred in late samples of all participants, which indicated a degradation of slow skeletal muscle myosin. Because cardiac troponin T was within the normal range in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for an injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Muscle action revealed delayed reversible increases in MRI signal intensities on T2-weighted images of the loaded vastus intermedius and deep parts of the vastus lateralis. We attributed MRI signal changes due to edema in part to slow skeletal muscle fiber injury.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo phosphorylation of the five histone H1 variants H1a-H1e including H1(0) in NIH 3T3 mouse fibroblasts was examined during the cell cycle by using a combination of HPLC techniques and conventional AU gel electrophoresis. Phosphorylation starts during the late G1 phase and increases throughout the S phase. In the late S phase, the H1 variants exist as a combination of molecules containing 0 or 1 (H1a, H1c), 0-2 (H1d), or 0-3 (H1b, H1e) phosphate groups with a share of unphosphorylated protein ranging between 35% and 75%, according to the particular subtype. Pulse-chase experiments show that phosphorylation during the S phase is a dynamic phosphorylation process with a limited phosphorylation maximum. In most H1 subtypes, phosphorylation occurs very rapidly at the G2/M transition with only small amounts of intermediate phosphorylated molecules. Phosphorylation of mouse H1c, however, occurs stepwise during this transition. Phosphorylated mouse histone subtypes from cells in mitosis contain four phosphate groups in the case of H1a, H1c, and H1e and five in the case of H1b and H1d. Comparison of the mouse phosphorylation pattern to that in rat C-6 glioma cells showed differences for H1e and H1d. By comparing the different phosphorylation patterns of the individual H1 variants during the cell cycle, we were able to classify the H1 histones into subtypes with low (H1a, H1c, H1(0)) and high (H1b, H1d, H1e) phosphorylation levels.

In the last several decades serum levels of cardiac enzymes and isoenzymes have become the final arbiters by which myocardial damage is diagnosed or excluded. Because conventionally used enzymes are neither perfectly sensitive nor specific, there is need for a new sensitive and cardiospecific marker of myocardial damage. Cardiac troponin T (TnT) is a contractile protein unique to cardiac muscle and can be differentiated by immunologic methods from its skeletal-muscle isoform. An enzyme immunoassay specific for cardiac TnT is now available in a commercial kit for routine use. The biggest advantage of this assay is its cardiospecificity. TnT measurements, however, are also highly sensitive in diagnosis of myocardial injury and accurately discern even small amounts of myocardial necrosis. TnT measurements are, therefore, particularly useful in patients with borderline CK-MB and in clinical settings in which traditional enzymes fail to diagnose myocardial damage efficiently because of lack of specificity--for example, perioperative myocardial infarction or blunt heart trauma. TnT release kinetics reveal characteristics of both soluble, cytoplasmic, and structurally bound molecules. It starts to increase a few hours after the onset of myocardial damage and remains increased for several days. TnT allows late diagnosis of myocardial infarction. The diagnostic efficiency remains at 98% until 6 d after the onset of infarct-related symptoms. TnT is also useful in monitoring the effectiveness of thrombolytic therapy in myocardial infarction patients. The ratio of peak TnT concentration on day 1 to TnT concentration at day 4 discriminates between patients with successful (greater than 1) and failed (less than or equal to 1) reperfusion. TnT measurements are very sensitive and specific for the early and late diagnosis of myocardial damage and could, therefore, provide a new criterion in laboratory diagnosis of the occurrence of myocardial damage.

This study examined eccentric exercise-induced muscle damage and rapid adaptation. Twenty-two male subjects performed 70 eccentric actions with the knee extensors. Group A (n = 11) and group B (n = 11) repeated the same exercise 4 and 13 days after the initial bout, respectively. Criterion measures included muscle soreness, muscle force generation (vertical jump height on a Kistler platform), and plasma levels of creatine kinase (CK), slow-twitch skeletal (cardiac beta-type) myosin heavy chains (MHC), and cardiac troponin I. Subjects were tested pre-exercise and up to day 4 following each bout. The initial exercise resulted in an increase in CK and MHC, a decrement in muscle force, and delayed onset muscle soreness in all participants. CK and MHC release correlated closely (rho = 0.73, p = 0.0001), both did not correlate with the decrement in muscle force generation after exercise. Because cardiac troponin I could not be detected in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for a injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Repetition of the initial eccentric exercise bout after 13 days (group B) did not cause muscle soreness, a decrement in muscle reaction force with vertical jump or significant changes in plasma MHC and CK concentrations, whereas in case of repetition after 4 days (group A) only the significant increases in CK and MHC were abolished. The decrement in reaction force with vertical jump did not differ significantly from that after the initial exercise session, but perceived muscle soreness was less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)