The objectives of MI therapy are to prevent potentially fatal
ventricular arrhythmias and to minimise the infarct size. The morphine initially
prescribed for pain relief and sedation also has valuable haemodynamic effects,
reducing preload (end diastolic pressure) through venodilation and
afterload (peak systolic pressure) through arteriolar dilation. Aspirin
(anti-platelet action) and heparin (anti-coagulant) are given as early as
possible to minimise further clot enlargement. The top priority is to unblock
the damaged coronary artery, either by emergency surgery, or by intravenous or
(better) intracoronary administration of a clot-dissolving enzyme such as tissue
plasminogen activator, streptokinase or urokinase. There are enormous benefits
in starting this treatment as early as possible, ideally within 60 minutes.
In the longer term, ACE inhibitors will reduce the cardiac
work load, possibly in conjunction with long-acting nitrates. Other therapy is
aimed at removing risk factors: stopping smoking, cholesterol reduction using
HMG-CoA reductase inhibitors (lovastatin), long-term aspirin therapy, exercise
and hormone replacement therapy in post-menopausal women. b-blockers
may also be useful, especially in non-diabetic patients.
Recent experiments in rodents suggest that it may be possible
to repair the damaged heart muscle either using
embryonic
cardiomyocytes, or with stem cells from
bone marrow after
cytokine treatment. It has already been shown that the new cardiac muscle cells
are functional and electrically coupled to the remainder of the myocardium. At
present the cytokine treatment must start before the myocardial lesion, which is
a clinically unrealistic scenario. If this work can be successfully extended to
humans and started after the event rather than before, then it is likely become
the preferred therapy.
Arrhythmias: These are disturbances in the normal
sequential pattern of cardiac activiation, (sinus rhythm) triggered by the
sino-atrial node. They range from the occasional ventricular ectopic beat (often
provoked by tiredness or caffeine in otherwise healthy people) to the completely
disorganised activity seen in ventricular fibrillation, which is fatal within
minutes. Between these two extremes there exists a bewildering variety of
abnormal behaviour, and an equally bewildering number of drugs to treat it. All
of them modify the pattern of ion channel opening and closing during the cardiac
action potential, usually with the hope of narrowing the window during which a
further unwanted action potential can be triggered. Controlled clinical trials
have shown that several antiarrhythmic drugs may actually make matters worse. A
better result can often be obtained by cardioversion (electric shock
treatment) and / or permanent pacing. Current practice is not to treat cardiac
arrhythmias with drugs unless the condition is life-threatening, and nothing
else seems likely to work.
Myocarditis: Inflammation of the heart which may arise
through a wide variety of causes, including staphylococci, streptococci and
other bacteria, Coxsackie B virus, rickettsiae (scrub typhus) and Trypanosoma
cruzi (Chagas disease). The symptoms include fatigue, weakness, tachycardia,
leucocytosis, arrhythmias, cardiomegaly (cardiac enlargement) and mitral valve
incompetence leading eventually to heart failure. It is suspected that viral
infections may be more common than was previously recognised, and may
pre-dispose to dilated cardiomyopathy (see below). Myocarditis is usually an
acute condition: the patients either die or get better.
Cardiomyopathies: This diverse group of serious
diseases are the most common reason for cardiac transplantation. They are all
characterised by long-term heart failure and cardiomegaly, usually with little
inflammation. Recognised classes include
i) Nutritional: e.g. cobalt-induced and alcohol-induced
cardiomyopathies.
ii) Hypertrophic cardiomyopathy: the ventricles are enlarged
with unusually thick walls. This may be caused by outflow obstruction,
but genetic factors may also be important.
iii) Dilated cardiomyopathy: the ventricles are grossly
enlarged with unusually thin walls. The disease affects all races, but is
particularly common in black males. About 75% of patients are believed to suffer
from an auto-immune condition, which may be precipitated by a previous Coxsackie
virus infection. Circulating antibodies may be internalised using
receptor-mediated endocytosis. Myosin, b-receptors
and the mitochondrial adenine nucleotide transporter have all been suggested as
possible auto-antigens. A variety of inherited factors can be identified in the
remaining patients, including both dominant and recessive mutations affecting
the dystrophin, tropomodulin and connexin-40 genes. There are huge individual
variations in the age of onset, time course and severity of the disease even
when a genetic mechanism has been identified.
Felix et al (2002)Removal
of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption
J. Am. Coll. Cardiol. 39(4), 646-652.
The treatment of dilated cardiomyopathy resembles that for
heart failure in general, except that there may be more emphasis on maintaining
adequate cardiac contractility using catecholamine analogue infusions (dopamine
or dobutamine), providing that the coronary arteries are intact. There is a
serious risk of pulmonary embolism as a result of venostasis, and
anti-coagulants may be indicated.
See
cardiomyopathy website.
| medical condition |
myocardial infarction |
dilated cardiomyopathy |
| physiological problem |
partially blocked coronary artery dead muscle in
ventricle wall |
heart failure, low contractility, extreme dilation |
| treatment strategy |
clear obstruction, relieve pain and reduce cardiac work
load |
reduce venous congestion maintain adequate output |
| drug 1 |
aspirin, heparin, morphine and proteases to dissolve
the clot |
diuretics (e.g. furosemide plus amiloride) remove
excess fluid |
| drug 2 |
ACE inhibitors or AT1 block to produce
arterial vasodilation |
ACE inhibitors to produce arterial vasodilation |
| drug 3 |
b-blocker (e.g. atenolol)
but care needed in diabetics |
catecholamines (e.g. dopamine) to increase
contractility |
| drug 4 |
lovastatin to control blood cholesterol long term |
|
Blood clotting and anti-coagulants: The cardiovascular
system requires a delicate balance between excessive clotting causing
obstructions, and leaks following a failure to clot. In most patients this
balance is more or less correct, and controlled clinical trials have only
supported the prophylactic use of anti-coagulants in two particular
circumstances: (1) aspirin appears to give real protection against myocardial
infarction, and (2) warfarin and heparin are of benefit in the management of
deep vein thrombosis among those at risk. There is, however, a very clear
benefit from speedy attempts to dissolve the clot blocking the coronary artery
through the use of injected proteases during or immediately after a heart
attack.
The coagulation system uses proteolytic cascades to amplify a
tiny initial stimulus and allow the formation of substantial clots. Most of the
required proteins are secreted by the liver into the bloodstream as inactive
precursors, which are subsequently cleaved to yield the active clotting factors.
Several of these proteins (factors II, VII, IX and X, and the inhibitory
proteins C and S) undergo a specialised post-translational modification in the
liver microsomal fraction, which converts glutamate residues near the amino
termini into g-carboxyglutamate. These modified
residues provide high-affinity Ca ++ binding sites which are
essential for the assembly of a functional clotting complex. The reaction
requires oxygen and carbon dioxide and is catalysed by a vitamin K dependent
carboxylase which produces vitamin K epoxide. Warfarin blocks this process by
inhibiting the first stage of the NADPH-dependent reductase system that recycles
the epoxide back to the fully reduced, hydroquinone form of vitamin K.
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