Coronary Artery Disease Manifestations in HIV: What,How, and Why

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.     

Dietary salt and blood pressure

Research evidence on the role of dietary sodium in the etiology and pathogenesis of hypertension is briefly reviewed. This matter is assuming new importance at present, given new data on the efficacy of normalization of blood pressure for adults with so-called "mild" hypertension (average diastolic 90-104 mm Hg), hence the need for safe nutritional-hygienic alternatives to years-long drug treatment for millions of people with such hypertension. Two trials by the authors deal with some unresolved questions in this area. The first, a preliminary study, involved 21 lacto-ovo-vegetarian high school students living in a boarding school. With decrease in daily Na intake from 216 to 72 meq for the experimental compared with the control group, red blood cell Na concentration was significantly lower in the former; systolic pressure was slightly but not significantly lower. The second trial, the Primary Prevention of Hypertension, involves over 200 hypertension-prone persons aged 30-44, and explores the ability in the experimental group to reduce blood pressure and prevent development of hypertension by safe nutritional-hygienic means (weight reduction, dietary Na decrease, avoidance of excess alcohol, rhythmic exercise). Initial results at 6 months are presented. Trials on the prevention and control of hypertension by nonpharmacologic means, including reduced Na intake, and involving analyses of the inter-relationships among dietary Na, other dietary factors, Na metabolism, and blood pressure in samples from different population strata, are an important present-day research need.     

Acute neurotoxicity of the Lathyrus sativus neurotoxin, L-3-oxalylamino-2-aminopropionic acid, in the squirrel monkey.

This paper provides the first evidence that the Lathyrus sativus neurotoxin, l-3-oxalylamino-2-aminopropionic Acid (OAP), is toxic when administered intraperitoneally to a primate with a mature bloodbrain barrier. Drowsiness, vomiting, muscle tremors, twitching, convulsions, and death occurred in young male squirrel monkeys (Saimiri sciureus) following injection of 4.26 and 11.4 μmol (0.750 and 2.00 mg) OAP/g body wt. Electroencephalographic changes characteristic of each stage of intoxication were observed. Unchanged OAP was recovered from brain of intoxicated animals. These observations support a possible role for OAP in the etiology of human neurolathyrism, a paralytic disease prevalent among adults in Central India who have consumed large quantities of L. sativus seeds for several months.     

When Is a Maze Procedure a Maze Procedure?

The initial surgical attempts to treat atrial fibrillation (AF) were isolation procedures designed to confine the arrhythmia to a specific area of the heart for relief of symptoms. The first surgical attempt to ablate AF was unsuccessful but was quickly followed by the Maze-I procedure on September 25, 1987. Because of several adverse sequelae of the Maze-I procedure, it was sequentially modified to the Maze-II and then Maze-III procedures. The Maze-IV procedure was introduced some 10 years later; these are the only 4 procedures that adhere to the concept of a maze pattern of lesions to ablate AF and leave both atria capable of being activated during normal sinus rhythm. The term maze procedure has become generic for virtually any operation designed to treat AF, but procedures that do not adhere to the concept of creating lesions of conduction block in the pattern of a maze are not maze procedures. These include, among others, the Wolf Mini-Maze, the Left-Sided Maze, and the 5-Box Maze, none of which are truly based on the maze-pattern concept. The cardinal feature of maze procedures that is necessary for both effectiveness and comparability to classical maze procedures includes lines of conduction block that preclude macro-reentry anywhere in either atrium while leaving both atria capable of activation by a sinus-generated impulse. Components essential to achieving this include appropriate lesions in both atria, the absence of gaps that allow electrical activity to bypass an intended line of block, and the absence of alternate pathways by which impulses can reach the intended maze exit.     

Suppressive effect of acetylcholine on automaticity of cannine atrioventricular node

The effects of acetylcholine on the spontaneous activity of the AV node of dog hearts were studied by recording transmembrane potentials of its fibers. Action potentials of most nodal fibers were characterized by prominent phase 4 depolarization and a smooth transition from phases 4 to 0. On the isolated AV nodes, acetylcholine at 1.0 μg/m1 suppressed the rate of phase 4 depolarization and increased the amplitude of the maximum diastolic potential, resulting in a slowing of spontaneous activity. At 2.0 μg/m1, spontaneous activity was completely suppressed. In comparison, spontaneous activity of the isolated His bundle was relatively insensitive to the suppressive effect of acetylcholine at the same concentrations. In the AV node-His bundle preparations in which the AV node was the pacemaker, acetylcholine decreased spontaneous activity by suppressing the phase 4 depolarization of the nodal fibers and shifted the pacemaker of the preparation to the His bundle. The findings provide a basis for predicting that under strong vagal influence, the automaticity of the AV node will be suppressed and the pacemaker of the junctional rhythm will be located at the His bundle.     

Endocardial cushion defect associated with cor triatriatum sinistrum or supravalve mitral ring

Clinical and angiographic or autopsy data, or both, on three children with a subdivided left atrium (cor triatriatum) and an associated endocardial cushion defect are reviewed. (One child had ostium primum defect, and two had complete atrioventricular [A-V] canal.) A fourth patient demonstrates the difficulties in differentiating subdivided left atrium from supravalve mitral stenosis in the presence of an endocardial cushion defect. The clinical findings are greatly influenced by the endocardial cushion defect. A pressure gradient between the pulmonary wedge and (left or right) ventricular end-diastolic pressures in patients with an endocardial cushion defect indicates pulmonary venous obstruction and should alert one to the possibility of these combined lesions. The exact diagnosis is made with injections of angiographic contrast medium into the proximal and distal left atrial chambers, to document the respective relations of the pulmonary veins, left atrial appendage and A-V valves to these atrial chambers. All three patients with an endocardial cushion defect and a subdivided left atrium had an associated patent ductus arteriosus. The common association of subdivided left atrium with intracardiac, pulmonary venous and aortic anomalies is again demonstrated.     

Electrophysiologic effects of atropine on human sinus node and atrium.

Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man.