Depolymerization techniques
Either chemical or enzymatic depolymerization techniques or a combination of the two underlie the vast majority of analyses carried out on the structure and function of heparin and heparan sulfate (HS). Enzymatic
The enzymes traditionally used to digest heparin or HS are naturally produced by the soil bacterium Pedobacter heparinus (formerly named Flavobacterium heparinum). This bacterium is capable of using either heparin or HS as its sole carbon and nitrogen source. To do so, it produces a range of enzymes such as lyases, glucuronidases, sulfoesterases, and sulfamidases. The lyases have mainly been used in heparin/HS studies. The bacterium produces three lyases, heparinases I (EC 4.2.2.7), II (no EC number assigned) and III (EC 4.2.2.8) and each has distinct substrate specificities as detailed below. The lyases cleave heparin/HS by a beta elimination mechanism. This action generates an unsaturated double bond between C4 and C5 of the uronate residue. The C4-C5 unsaturated uronate is termed ΔUA or UA. It is a sensitive UV chromophore (max absorption at 232 nm) and allows the rate of an enzyme digest to be followed, as well as providing a convenient method for detecting the fragments produced by enzyme digestion. Chemical
Nitrous acid can be used to chemically depolymerize heparin/HS. Nitrous acid can be used at pH 1.5 or at a higher pH of 4. Under both conditions, nitrous acid effects deaminative cleavage of the chain. At both high (4) and low (1.5) pH, deaminative cleavage occurs between GlcNS-GlcA and GlcNS-IdoA, albeit at a slower rate at the higher pH.
Unstable angina (preinfarction, crescendo) – diltiazem may be particularly effective if the underlying mechanism is vasospasm. Myocardial bridge
DysmenorrheaFor supraventricular tachycardias (PSVT), diltiazem appears to be as effective as verapamil in treating re-entrant supraventricular tachycardia.Atrial fibrillation or atrial flutter  is another indication. The initial bolus should be 0.25 mg/kg, intravenous (IV). Because of its vasodilatory effects, diltiazem is useful for treating hypertension. Calcium channel blockers are well tolerated, and especially effective in treating low-renin hypertension.It is used as topical application for Anal Fissures as it promotes healing of fissures due to its vasodilatory property. Contraindications and precautions
In congestive heart failure, patients with reduced ventricular function may not be able to counteract the inotropic and chronotropic effects of diltiazem, the result being an even higher compromise of function. With SA node or AV conduction disturbances, the use of diltiazem should be avoided in patients with SA or AV nodal abnormalities, because of its negative chronotropic and dromotropic effects. Low blood pressure patients, with systolic blood pressures below 90 mm Hg, should not be treated with diltiazem. Diltiazem may paradoxically increase ventricular rate in patients with Wolff-Parkinson-White syndrome because of accessory conduction pathways.Diltiazem is relatively contraindicated in the presence of sick sinus syndrome, atrioventricular node conduction disturbances, bradycardia, impaired left ventricle function, peripheral artery occlusive disease, and chronic obstructive pulmonary disease. Side effects
A reflex sympathetic response, caused by the peripheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem.