The laboratory diagnosis of myocardial infarction
Individuals erroneously classified as having sustained acute MIs (false positives) run up huge hospital bills, are denied life insurance, are "rated' on their health insurance coverage, and may be restricted in their occupational and recreational activities. Patients with acute MI who fail to be diagnosed on the basis of clinical presentation, ECGs, and lab tests (false negatives) are also ill-served. They are at high risk for sudden death in the immediate post-infarction period; if they survive, they are at high risk for reinfarction in the future.You might want to bring a pocket magnifier for close-up inspections and a field guide to seashore or desert wildflowers, mammals, reptiles, and insects. Wheels on the sand: controversy and compromiseIn this subset, the first step toward establishing the diagnosis is a high index of suspicion. Signs and symptoms among patients with "possible' or "probable' acute MI are not enough; further investigations are necessary to rule in or rule out the diagnosis. The diagnosis for many of these can be established with an electrocardiogram or a series of ECGs obtained as the infarct evolves. And for decades this was the only modality available other than the history and physical.The latest entrant into the field is an immunochemical assay based upon some clever monoclonal antibody technology. The procedure employs two monoclonal antibodies, one specific for CK-M and the second specific for CK-B.Photographers drool over the picture possibilities. Like chameleons, sand dunes change color as the day progresses: pale gold at dawn, glaring white at midday, rosy at sunset. Shooting at daybreak or sundown best captures the richest tones and the longest shadows. Carry camera gear in a tightly sealable bag to keep sand out.Early travelers saw dunes as desolate obstacles. In the late 1800s, surveyor George Wheeler described a traverse of Death Valley: "The route lay for miles over light, white, shifting sand. The stifling heat, radiation, and constant glare from the sand were almost overpowering."The harsh dune environment winnows out the weak. Plants must be tenacious enough to survive high winds (40 mph or more), abrasion, burial, drastic temperature ranges, incessant sun, and meager rain. Long taproots (40 feet deep on some species) and extensive root systems help plants cling and absorb scant moisture. Dunes actually retain subsurface water, and while the top layer may register an infernal 140 degrees on a summer day, just inches below it may be a cool, moist 60 degrees.Vehicular access remains a controversial issue at the Panamint Dunes near Lone Pine, California: they were closed to vehicles in 1980, but 500 acres are being considered for reopening by permit after requests from recreation groups and Inyo County officials.Methodology is critical to CK isoenzyme testing.3 Electrophoresis is the most popular and also is the reference method. But several "quick and dirty' assays have been advocated to assist in rapid diagnosis of acute MI, for electrophoresis is tedious and not available in most labs on a Stat basis.The first antibody is bound to a solid phase--sich as a plastic bead--which in turn is incubated with the serum to be tested. The solid phase binds both CK-MM and MB, isoenzymes sharing CK-M activity. The solid phase is then incubated with the second antibody, which is specific for CK-B. A "sandwich' is formed only with solid-phase bound molecules of CK-MB. The second antibody is conveniently coupled to an alkaline phosphatase marker (although other markers could be substituted), making detection of MB activity simple through use of traditional laboratory procedures.On the other hand, the coronary atrtery occlusion may have occurred several days previously, and CK-MB activity since peaked and disappeared. In this case, only the flipped LDH1 and and LDH2 fractions will establish a laboratory diagnosis.Children know instinctively what to do: they run, jump, slide. In open, unvegetated areas, you can try sliding on a lightly inflated truck inner-tube, snow dish, or thin plastic mat. If you have a castoff pair of downhill skis, apply silicone spray to the bases and try dune skiing. Don't do this with good gear: It's about as abrasive as skiing on sandpaper. Tenacious flora, adaptive faunaFailure to establish the diagnosis also precludes medical therapy and life-style modification programs designed to ameliorate positive risk factors for future vascular catastrophes: diabetes, high blood pressure, obesity, smoking, and insufficient exercise.Off-road vehicles are barred from seven of the dune systems we list. In the other areas, such vehicles have limited access or are allowed to range the dunes. Self-propelled explorers may find this vehicular presence intrusive. While most dune drivers follow the rules and regulations, those who stray into vegetated areas can cause more than visual disturbance. Some ephemeral plants--short-lived annuals that grow, blossom, and set seed in a brief time span--die out if disturbed. Desert plants take decades to regenerate; when they're crushed or the soil mantle is broken by tires, the delicate balance of the dunes is upset. Even the natural contours of dunes can give way: as vehicles cut trails through vegetation, blowouts occur, and the sand fans out through the cut.Over sometimes hundreds of years, grains of sand are blown overland, bouncing along not far off the ground, before piling up against a barrier, perhaps a mounting. At coastal systems, such as the Oregon and Pismo dunes, ocean current and tides deposit sand on wide, flat beaches where it is banked and held by prevailing winds and vegetation against natural backstops. The four distinct dune shapes shown above testify to the varied work of the wind. Leeward sides (slipfaces) of dunes are never steeper than 32 [deg.] to 34 [deg.], called the angle of repose--the maximum angle at which loose sand remains stable.In lieu of electrophoresis, these alternatives employ chromatography, immunoinhibition, radioimmunoassay, and immunochemistry to quantitate MB activity. Although these assays have fairly rapid turnaround times, none provides the correlation to the reference method demanded by clinicians. So the search goes on for the ultimate CK-MB procedure.It should be noted that not all CK-MB is biologically active. This immunochemical method will detect both active and inactive forms of the molecule. Thus the assay detects the mass of CK-MB present rather than its biologic activity. (The fact that an alkaline phosphatase marker is employed should not confuse one into believing that he is measuring biologic activity of an enzyme.)As the map at top right indicates, these big dunes--from nearly 4 to 40 square miles--are scattered over the West. We list 13 of the biggest and most accessible dune systms on the opposite page. Even if you visit just one of them (or stop by a smaller coastaul (dune) on a day or weekened outing, you might get hooked. Some aficionados can never get enough time hiking, sliding, and photographing these compelling formations.Now through April is perhaps the most clement season to visit most these dunes. The inland ones are in arid, almost rain-free regions offering clear, crisp winter days. You can hike for miles without gasping for water or bracing yourself against gritty blasts. (Late spring often brings high winds; summer brings savage heat.) And several are on or near routes to popular getaways: Palm springs and Las Vegas. The two coastal dunes we list take winter rain straight in the face, but between storms they offr sparkling vistas. How nature stockpiles sandSo now the laboratory diagnosis of acute MI is a reality. Or is it? Among patients with possible or probable acute MI whose ECGs are equivocal, how well can the lab rule in or rule out the diagnosis? This questions among patients increasing frequency by clinicians and pathologists alike, for it is important to diagnose the smallest acute MI at its earliest stage, while avoiding the significant implications of a false-positive diagnosis. The analogy to the diagnosis of early pregnancy or early malignancy should be apparent.
Since an elevated CK-MB is not, per se, an indication of cardiac muscle damage, an elevation is meaningful only activity is concomitantly of MB activity is concomitantly increased. It remains to be seen whether a biologic assay or a mass assay that measures both active and inactive forms to total CK will provide thebest denominator in detecting when the concentration of CK-MB is elevated.
Author: Henry B. Soloway
