Arthur C. Fox

Methionine intolerance: A possible risk factor for coronary artery disease

Homocystinuria, an inherited disorder associated with premature atherosclerosis, represents a severe form of methionine intolerance. To analyze the importance of milder forms of methionine intolerance in the genesis of vascular disease, the relation between provokable methionine intolerance and coronary artery disease was investigated. In a group of 138 men, aged 31 to 65 years (mean 53), referred for cardiac catheterization, plasma homocystine was measured before and 6 hours after an oral l-methionine load (0.1 g/kg). Thirty-nine subjects found to have normal coronary arteries had a mean post-load plasma homocystine level of 0.59 +/- 0.37 mumol/liter. A criterion at the 95th percentile (1.64 SD above the mean) was selected and applied to the remaining 99 subjects with coronary artery disease (0.70 +/- 0.68 mumol/liter). Sixteen (16%) of 99 subjects with coronary artery disease exceeded this level as compared with 1 (2%) of 39 subjects without coronary artery disease (p less than 0.04). The risk of coronary artery disease in men with provokable methionine intolerance was increased sevenfold as estimated by the odds ratio. By correlation matrix and multivariate regression analyses, provokable homocystinemia was predictive of coronary artery disease and was independent of tobacco smoking, hypertension, diabetes mellitus, serum cholesterol and age. It is proposed that men with mild methionine intolerance exposed to the high methionine content of the Western diet may develop intermittent homocystinemia and thus may be at greater risk for the development of coronary artery disease.

Release of adenosine from human hearts during angina induced by rapid atrial pacing.

This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = +/-9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K(+), but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na(+). THERE WAS NO DETECTABLE RELEASE OF ADENOSINE BY HEARTS DURING PACING OR EXERCISE IN THREE CONTROL GROUPS OF PATIENTS: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure. The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.

Hemodynamic Studies of Patients with Myocardial Infarction

Cardiac output, venous and arterial pressure, total peripheral resistance and blood volume were measured in patients with acute myocardial infarction, with and without shock, and on recovery, and in patients without heart disease. Cardiac output falls to below normal after myocardial infarction, and rises significantly, though not always to normal, on recovery. Cardiac output was very low when myocardial infarction was complicated by shock. Fall of cardiac output to very low levels following myocardial infarction does not necessarily lead to development of shock. Venous pressure tended to be elevated in patients in shock as a result of myocardial infarction. Cardiac output was subnormal in patients with arteriosclerosis but without clinical heart disease: this was not attributable to reduced body oxygen consumption.

Release of nucleosides from canine and human hearts as an index of prior ischemia.

During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly. In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased. The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia.

Surgically remediable complications of myocardial infarction

S HOCK and ventricular failure after acute myocardial infarction generally are related to the degree of loss of contractile muscle and therefore complicate large infarctions or repeated infarction of previously damaged hearts.’ Less frequent but often more dramatic complications of acute infarction follow disruption of strategic structures, such as the interventricular septum or papillary muscles, producing shock and acute or chronic ventricular failure. Infarction of the free wall may be followed by acute rupture or by the development of chronic and sometimes disabling aneurysms. Surgical correction of septal and papillary muscle rupture and of chronic aneurysms antedated coronary artery bypass grafting, and the indications for surgery have become more clearly defined. The management of patients with these complications in the critical period preceding operation has also evolved considerably in recent years. Catheterization of the right heart at the bedside now permits rapid diagnosis of acute septal or papillary muscle rupture and allows continuous monitoring of the effects of treatment with vasodilators, intraaortic balloon counterpulsation, and inotropic or systemic pressor agents.‘.3 Such monitoring helps to predict the need for emergent surgery. Radionuclide imaging methods are of increasing help in estimating ventricular function and assessing wall motion4.’ Definitive cardiac catheterization, with ventriculography and coronary angiography, has proved safe even after recent infarction.h Induction of anesthesia for surgery has been improved by monitoring of right heart pressures and by the use of vasodilators and intraaortic balloon counterpulsation when needed. Early physiologic and pathologic changes in the infarcted heart determine the proper timing of surgical therapy and are therefore reviewed briefly here.

Vermont Has A High Suicide Rate

Excerpt at least thats what Paul say sand he should know, hes a doctor there, near Burlington who supplements his income with farming and maple sugaring, and makes the kind of money in twelve mon...

Obesity: Impact on Cardiovascular Disease

Fletcher GF, Grundy SM, Hayman L, eds. 377 pages. Armonk, NY: Futura; 1999.

Sinus node dysfunction in spinal cord injury with quadriplegia

69.00. ISBN 0879934182. Order phone 800-877-8761. Field of medicine: General internal medicine, cardiology, endocrinology, and public health. Format: Hardcover book. Audience: Physicians who manage patients with obesity and its consequences. Purpose: To evaluate data on the etiology and biology of obesity; its measurement, prevalence, and metabolic sequelae; and its relationship to cardiovascular disease. Content: The book is a monograph comprising papers presented at a conference sponsored by several American Heart Association Councils in 1998. The first section examines the epidemiology of obesity and the influence of genetic and environmental factors on its increasing prevalence in children and adults. It considers the validity of the clinical standards for accurate measurement of obesity and the question of whether obesity affects the cardiovascular system directly or through its sequelae: hypertension, dyslipidemia, and insulin resistance. The second section on pathophysiology examines obesity-related genes, the mechanisms of weight regulation and its clinical control, and how the sequelae of obesity arise. The final section is a practical discussion of clinical assessment and treatment. Highlights: The book offers a critical and comprehensive approach to obesity. It dramatically documents a virtual epidemic of obesity and its varying consequences among different populations. A refreshingly skeptical perspective is taken in the evaluation of each concept in this often arcane discipline; the book features such suggestions as future studies of children who do not become obese even though they are sedentary and have poor eating habits and of adults who are obese but do not become hypertensive or develop insulin resistance. Single-gene models of obesity in mice and candidate gene linkages to obesity in humans are well described. Leptin is of particular interest; this peptide product of ob (the obesity gene), which is produced by adipocytes in proportion to their number, can reduce appetite and increase energy expenditure. Along with other gene products, it provides exciting clues to the etiology and treatment of obesity. Limitations: There is considerable repetition, as often occurs in such a compilation. Some of the discussions and literature reviews are too long. The impact of obesity and its sequelae on the molecular biology of atherogenesis, vulnerable venous bypass grafts, angioplasty sites, or the diseased or failing heart are discussed briefly or not at all. Related reading: The important concept that easy gainers are more likely than hard gainers to store food as fat is covered and deserves emphasis (Ravussin E, Danfort E Jr. Beyond sloth. Physical activity and weight gain. Science. 1999;283:184-5). A recent article discussed the possible importance of insulin receptors in the brain (Schwartz MW. Staying slim with insulin in mind. Science. 2000; 289:2066-7). Reviewer: Arthur C. Fox, MD, New York University School of Medicine, New York, New York.

High Energy Phosphate Compounds in the Myocardium during Experimental Congestive Heart Failure. Purine and Pyrimidine Nucleotides, Creatine, and Creatine Phosphate in Normal and in Failing Hearts*

Patients with recent spinal cord injury and quadriplegia often demonstrate sinus bradycardia (SB), sinus arrest (SA), AV block, and hypersensitivity to vagotonic maneuvers. The presumed mechanism is interruption of the sympathetic nerves to the heart, with a relative increase in parasympathetic tone. To determine the need for permanent pacing, we examined seven patients with recent spinal cord injury and quadriplegia prospectively, 1 to 2 weeks after injury. All patients had transient SB (35-60) and SA (2-8 set). These episodes often occurred with nasotracheal suctioning, despite prior treatment with atropine and hyperventilation. In 5 of 7 patients, His-Bundle Ek!CtFogramS and sinus node recovery times (SNRT)were determined and found to be normal (A-~=10&20 msec, H-V=443 msec, SNRT=llO??lO% of resting cycle length). In 4 of 5 patients there was no disturbance in sinus node function with carotid sinus pressure, during nasotracheal suctioning or with hypoxemia. One patient had SA (4-6 set) with carotid sinus pressure and during suctioning. 6 of 7 patients had later episodes of SA and SB requiring permanent pacemakers. We conclude that there is marked temporal variability in sinus node dysfunction in patients with recent spinal cord injury and quadriplegia. A normal response to sinus node testing does not assure continued normal function. We, therefore, recommend permanent pacemaker insertion in patients with recent spinal cord injury with quadriplegia who have had significant SA or SB.