Toxicants to the cardiovascular system may influence the contractile or electrophysiologic functions of the heart or they may interfere with normal vascular function.  Recall that specialised terms used to describe cardiac function include chronotropy (rate of contraction), inotropy (force of contraction), dromotropy (rate of electrical conduction), and bathmotropy (degree of excitation).

Response of the heart to a toxicant's effect is most often presented as changes in electrical conduction (arrhythmias) or contractility.

Arrhythmias may result from damage or alteration of function of the SA node, AV node, Bundles of His, or Purkinje fibres.  The effects that result in the damage are usually presented as disturbances in impulse formation, initiation, or propagation in any of these areas.  They may be due to disturbances in ATPase function (digoxin), channel blockade, changes in ionic concentration gradients (barium), direct action on nervous system input (digoxin's vagomimetic effect at the SA & AV node and chloroform's (and other halogenated hydrocarbons) ability to increase sensitivity of the sympathetic nervous system).

Toxicity involving contractility generally results in a negative inotropic effect (reduced contractility).

Aliphatic Alcohols (including ethanol), aldehydes, and glycols -- The classic example is ethanol, which through its active metabolite acetaldehyde produces direct negative inotropic activity.  Ethanolic cardiomyopathy, presenting as chronic congestive failure with cardiac hypertrophy, is one of the classic necrospy findings in alcoholics.

Heavy Metals -- in general produce negative inotropic and chronotropic effects (specific heavy metals are discussed below).

Anti-neoplastics -- Daunorubicin and Doxorubicin produce a dose dependent congestive cardiomyopathy (this limits the total dose of these agents that any one patient may receive).  It is thought to be due to a reactive oxygen species of the drug that causes lipid peroxidation of the myocardial membranes, thus reducing myocardial function.  5-Fluorouracil (5-FU) can cause myocardial ischaemia.  Cyclophosphamide causes myocardial microthrombosis, pericarditis, and ultimate cardiac failure, exhibiting both vascular and direct cardiac toxicities.

Specific agents that produce cardiovascular toxicity are provided below as examples:

Arsenic (Ar) -- arteriosclerosis and pulmonary vascular lesions
Copper (Cu) -- acute intoxication -- hypotension; chronic -- arteriosclerosis
Lead (Pb) -- endothelial damage to decrease blood brain barrier, decrease arterial elasticity, hypertension
Mercury (Hg) -- endothelial damage as with lead and aortic lesions
Boron (B) -- haemorrhage, disruption of the clotting mechanisms
Cobalt (Co) -- cardiomyopathy, vasodilatation (hypotension) (MOA -- calcium antagonism)
Manganese (Mn) -- vasodilatation/hypotension
Nickel (Ni) -- vasodilatation/hypotension
Lanthanum (La) -- vasodilatation/hypotension
Carbamylhydralazine -- pulmonary blood vessel tumours
Microcrotaline (an alkaloid) -- pulmonary hypertension
Paraquat -- vascular damage in the lungs and CNS
Organophosphate Insecticides -- cerebral arteriosclerosis
Gases --
Automobile Exhaust -- haemorrhage, atheroma, atherosclerosis, infarction (all due to CO)
Ozone -- arterial lesions, pulmonary œdema
Glycyrrhizin (in licorice) -- aldosterone-like effect, sodium retention and hypertension
Congo Red (an azo dye) -- increased platelet activity, thrombosis
Toxins and Venoms -- produce arrhythmias similar to digoxin
-- Aconitine (monkshood)
-- Veratrine and veratrum alkaloids (hellebore) -- also blocks the baroreceptor response
-- Taxine (yew)
-- Anemone toxin
-- Palytoxin (sea coral) -- intravenous LD₅₀ in rabbits is 25 ng/Kg!
-- Bufatoxin (toads)
-- Batrachotoxin (Columbian frogs)