Cardiac muscle lactate dehydrogenase

The myocardium contains bundles of striated muscle fibers, each of which is typically 10 to 15 pm in diameter and 30 to 60 pm in length. Work of the heart is generated by the alternating of the contraction and relaxation of these fibers. The fibers are composed of cardiac-specific contractile proteins actin and myosin, and regulatory proteins caEed troponins. They also contain a variety of enzymes that are vital for energy use, such as myoglobin, creatine kinase (CK), and lactate dehydrogenase (LD), some of which can be used as markers of cardiac injury. 

There are five enzymes that are commonly used in diagnosis of liver disease Aspartate aminotransferase (AST EC 2.6.1.1), alanine aminotransferase (ALT EC 2.6.1.2), alkaline phosphatase (ALP 3.1.3.1), and y-glutamyl transferase (GGT EC 2.3.2.2), are commonly used to detect liver injury, and lactate dehydrogenase (LD EC 1.1.1.27) is occasionaEy used. ALT and GGT are present in several tissues, but plasma activities primarily reflect liver injury. AST is found in liver, muscle (cardiac and skeletal), and to a liipited extent iti fed cells. LD has wide tissue distribution, and is thus relatively nonspecific. ALP is found in a number of tissues, but in normal individuals primarEy reflects bone and liver sources. Thus based on tissue distribution, ALT and GGT would seem to be the most specific markers for liver injury. 

Interruption of the heart s blood supply leads to the death of cardiac muscle cells. The symptoms of myocardial infarction include pain in the left side of the chest that may radiate to the neck, left shoulder, and arm, and irregular breathing. The initial diagnosis is based on these and other symptoms. Therapy is instituted immediately. Physicians then use several enzyme assays to confirm the diagnosis and to monitor the course of treatment. The enzymes most commonly assayed are creatine kinase (CK) and lactate dehydrogenase (LDH). Each enzyme s activity shows a characteristic time profile in terms of its release from damaged cardiac muscle cells and rate of clearance from blood (Figure 6A). 

Myocardial infarction occurs when the blood supply to the heart muscle is blocked for an extended time. If this lack of blood supply, called ischemia, is prolonged, the myocardium suffers irreversible cell damage and muscle death, or infarction. When this happens, the concentration of cardiac enzymes in the blood rises dramatically as the dead cells release their contents into the bloodstream. Although many enzymes are liberated, three are of prime importance. These three enzymes, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase/serum glutamate-oxaloacetate transaminase (AST/SGOT), show a characteristic sequential rise in blood serum level following myocardial infarction and then return to normal. This enzyme profile, shown in the ac-... 

Several of the common enzyme measurements aimed at detecting hepatotoxicity are not specific to the liver, show a widespread tissue distribution, and are therefore affected by damage to extrahepatic tissue (e.g., alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase following injury to cardiac or skeletal muscles). The development of troponin assays has provided an alternative to enzyme measurements as indicators of cardiotoxicity, but not for myotoxicity here, the timing and the methods of sample collection are particularly critical for the detection of cardiac or muscle damage (see Chapter 7). 

Historically, measurements of the isozymes of creatine kinase (CK) and lactate dehydrogenase (LD) have been used for the detection of myocardial injury. These are enzymes of intermediary metabolism found in both cardiac and skeletal muscle, although in different forms reflecting the different metabolic and functional properties of these tissues. There are also significant amounts of CK in nervous tissue and smooth muscle, whereas LD is expressed in most tissues (Aktas et al. 1993). 

The possible isozymes of lactate dehydrogenase. The symbol M refers to the dehydrogenase form that predominates in skeletal muscle, and the symbol H refers to the form that predominates in heart (cardiac) muscle. 

Lactate dehydrogenase Liver, cardiac muscle, tumours... 

Serum levels of this enzyme are elevated in diseases of skeletal muscle, cardiac muscle, and brain. It may be assayed by a u.v. meOiod uring ADP formation, pyruvate kinase in an auxiliary reaction and lactate dehydrogenase in an indicator reaction [336]. An alternate ultraviolet assay uses ATP formation, hexokinase in an auxiliary reaction, and glucose-6-phosphate dehydrogenase in the indicator reaction [337]. A colorimetric assay utilises creatine formation, complexing with diacetyl and colour complex formation with a-naphthol [338—339]. 

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