The Cardiopulmonary System The Heart

Human angina (angina pectoris), a painful (or uncomfortable) visceral sensation, is transmitted through cardiac primary afferent neurons to the central nervous system. Angina is the result of ischemic episodes, i.e., any situation in which there is an insufficient supply of oxygen to the myocardium for its metabolic demands. This has been exploited in a wide range of species to produce animal models of cardiac ischemia, using chemical and surgical methods. Chemical approaches are based on reports of increased concentrations of bradykinin (BK) or adenosine in sinus blood after experimental coronary artery occlusion. For example, one study reported pseudaffective responses in dogs, following intracoronary injection of acetylcholine, BK, 5-hydroxytryptamine (5-HT), histamine, or K+ (potassium chloride) (8), although it is unclear how relevant any one chemical individually might relate to clinical angina. In the case of BK, human studies have shown that intracoronary injection will result in pain that is reported as both different to (9), and indistinguishable from (10), the ischemic pain normally experienced by study participants. Consequently, a study was instigated in our laboratory to investigate the effects of coadministration of a number of algogenic substances (BK, acetylcho-line, adenosine, histamine, 5-HT, and prostaglandin E2) into the pericardial sac of awake rats (11). Those animals that received the algogenic mixture showed a quicker establishment of passive avoidance behavior than those animals that received BK alone, saline, or the mixture without BK. This suggests that the mixture was aversive, but there is a paucity of behavioral data in the current literature to support such models as useful visceral pain models.

A logical and widely used model of cardiac pain is that of coronary artery occlusion, because myocardial ischemia is the major factor that leads to angina. Coronary artery occlusion is a procedure that, in the rat, can be achieved by either complete or partial ligation of the left descending coronary artery. Despite what is a relatively simple technique, such models result in a high initial mortality rate (typically 40-60%), a large variation in the size of any resultant myocardial infarction, and only a proportion of rats with an infarction will actually develop apparent heart failure. This said, angina is not experienced by all (or even most) patients in the clinic, even in the presence of severe coronary artery damage/disease; angina can also be seen in patients who exhibit no sign of coronary artery disease. Furthermore, as with chemical models, there is a lack of published studies showing that these models actually result in behaviors that can be interpreted as pain. This is not to say that pseudaffec-tive responses, attributed to pain, have not been reported in animal models of coronary artery occlusion; however, it is possible that these responses were artifactual, and due to the mechanical manipulation of the vessel, inflammation of the area, and too short a period between surgery and experimentation, or all three (12).

Your Heart and Nutrition

Your Heart and Nutrition

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