Biomedical subjects
Publications and source records attributed to R H Helfant.
This report presents an overview of the problem of treating congestive heart failure. Emphasis is on the arrhythmia component and the complex interrelationships of critical electrolytes and pathophysiologic factors that can lead to sudden cardiac death.
Tumor necrosis factor (TNF) is a secretory product of normal macrophages that can cause cell necrosis, new blood vessel formation and thrombosis. These are also 3 characteristic features of the progression of stable atheroma to endothelial disruption. Accordingly, an immunohistochemical method was developed to detect TNF in human tissue. Using this method TNF positivity was demonstrated in 57 of 65 (88%) of tissue sections classified as atherosclerotic and in 5 of 11 (45%) sections classified as minimally atherosclerotic. TNF was absent in 6 sections classified as normal. TNF positivity was found not only in the cytoplasm of macrophages, but also in the cytoplasm and attached to the cell membrane of smooth muscle cells and endothelial cells of the human atheroma. Because TNF is known to cause new vessel formation, hemorrhagic necrosis and increased thrombogenicity, it may play a role in the evolution of uncomplicated to complex atheroma.
Nonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible.
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Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury.
We used immunohistochemistry to detect tumor necrosis factor (TNF) and in situ hybridization to detect TNF messenger RNA (mRNA) in the intimal mesenchymal-appearing cells and in the medial smooth muscle cells of human atherosclerotic arteries. Medial smooth muscle cells showed localization of immunoreactive TNF on the cell surface and did not express TNF mRNA. Conversely, in intimal mesenchymal-appearing cells, TNF was localized in the cytoplasm and TNF mRNA was expressed by in situ hybridization. Thus 89% of intimal cells were immunohistochemically positive for TNF, 96% of them were positive by in situ hybridization, and 76% were positive for the smooth muscle cell marker, HHF35. Our results suggest that intimal mesenchymal-appearing cells are mostly, but not exclusively, derived from smooth muscle cells. These cells express TNF, whereas the medial smooth muscle cells in the atherosclerotic human arteries do not. The expression of TNF by these mesenchymal-appearing cells may have implications regarding the evolution of the atherosclerotic plaque.
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Because the extent of myocardial bulging after acute coronary occlusion is primarily dependent on wall tension, this study examined whether the decrease in systolic bulging with postextrasystolic potentiation was due to contractile reserve or to changes in loading conditions. Seven dogs were atrially paced at 100 beats/min after the sinus node was crushed and atrial extrasystoles were generated. The left ventricular minor axis diameter and segment lengths in the ischemic and nonischemic zones were measured with sonomicrometers. Wall tension was estimated using Laplace's law, and regional tension-length loops were determined. By 5 min after the left anterior descending coronary artery was occluded, there was regional bulging. Postextrasystolic potentiation diminished the extent of bulging by increasing both isovolumic and ejection percent systolic shortening (isovolumic -9.1 +/- 2.0% to -5.9 +/- 1.7%, p less than 0.008; ejection 2.2 +/- 0.7% to 4.3 +/- 2.0%, p less than 0.008). The tension-length loops after coronary occlusion showed an exponential upstroke and almost superimposed downstroke consistent with passive movement. The loops were unchanged by postextrasystolic potentiation. Wall tension data showed that bulging was reduced because of a shift down the tension-length curve as end-systolic wall tension was reduced by augmented nonischemic contraction. Similar results were seen at 60 min of coronary occlusion. This study demonstrates that the decrease in bulging seen with postextrasystolic potentiation is due to changes in loading conditions and not to contractile reserve.
It has been shown that collaterals can develop rapidly during acute coronary occlusion, either due to thrombosis or during angioplasty (PTCA). However, the fate of well-developed collaterals immediately after a successful PTCA is unknown. Accordingly, 15 patients with Rentrop class 2 or 3 collaterals as visualized angiographically were studied immediately after successful single-vessel PTCA. The left anterior descending artery contained the stenosis in nine patients and the right coronary contained the stenosis in six patients. There was total occlusion of six vessels and subtotal occlusions of nine vessels pre PTCA. Immediately after PTCA, flow through the collaterals to the stenosed artery could no longer be visualized angiographically in eight patients (group 1), but remained faintly visible in seven patients (group 2). There was no difference between these two groups with regard to pre PTCA transstenotic pressure gradient (46 +/- 12 vs 42 +/- 14 mm Hg), post PTCA pressure gradient (13 +/- 7 vs 11 +/- 10 mm Hg), or post PTCA percent luminal diameter narrowing (26 +/- 18% vs 24 +/- 13%). These findings suggest that despite similar hemodynamic and angiographic improvement, the resolution of collaterals immediately after PTCA is variable.
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The clinical course and coronary angiographic features of symptomatic coronary artery disease (CAD) in patients younger than 40 years old are described with particular emphasis on the prevalence of myocardial infarction and the degree of diminished functional capacity. Eighty-five patients with CAD proven by coronary angiography were studied. There were 73 men and 12 women aged 27 to 40 years. Fifty-nine patients presented with acute myocardial infarction, most of whom denied previous chest pain, and 14% (12 patients) presented with less acute chest pain syndromes. Coronary angiography was performed in all patients, and greater than or equal to 70% luminal diameter narrowing was considered significant. Coronary angiographic findings reveal 51% with 1-vessel CAD, 31% with 2-vessel and 19% with 3-vessel. Subsequently, 23 patients had coronary artery bypass graft surgery, 7 underwent angioplasty and 55 were treated medically. Follow-up for a mean of 3 years revealed only 1 death and 4 subsequent hospital admissions for cardiac events. Fifty-three percent of the patients are entirely pain free, and only 4 (5%) have significant symptoms of angina pectoris. Although 15 (18%) are not employed regularly, the remainder work full- or part-time, or plan to work in the near future. These data suggest that the short-term prognosis and functional status of young patients with CAD is excellent.
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Rest and exercise ECGs are the most widely used "noninvasive" tests for detecting coronary heart disease, but their sensitivity and specificity are suboptimal. Therefore, the diagnostic value of myocardial perfusion scanning using thallous chloride Tl 201 during rest and stress electrocardiography was examined in 95 patients with a chest discomfort syndrome. Overall, thallous chloride Tl 201 perfusion scanning had a sensitivity of 75% and a specificity of 91% for coronary heart disease compared with 56% sensitivity and 86% specificity with exercise-induced ST segment depression on the ECG. Combining rest and stress ECGs resulted in a sensitivity of 71%. In patients with coronary heart disease, perfusion scanning had a sensitivity of 93% for asynergy compared with 58% for exercise-induced ECG ST depression. Rest and stress myocardial perfusion scanning with thallous chloride Tl 201 provides improved sensitivity with good specificity in the diagnosis of coronary heart disease compared with exercise electrocardiography alone.
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The detection of regional abnormalities of left-ventricular wall motion provides strong evidence for the presence of coronary heart disease. In 129 patients undergoing coronary arteriography, the relative value of radionuclide angiographic assessment of wall motion was compared with computer-generated regional ejection fraction, at rest and during handgrip exercise. Wall motion was determined by superposition of computer-derived end-diastolic and end-systolic perimeters. Relative regional ejection fraction was determined using a computer-generated 16-color isocount image that permitted a quantitative assessment of zonal contribution to ejection fraction. Of the 129 patients, coronary arteries were normal in 31 and diseased in 98. Of 24 patients with single-vessel disease, wall-motion abnormalities were present, at rest or during exercise in 15, whereas regional ejection fraction detected 20 patients. Seventy-four patients had multivessel disease. Of these, wall-motion abnormalities occurred in 52 but regional ejection fraction was abnormal in 69 (p less than .01). Overall, sensitivity was 67% by wall motion and 91% by relative regional ejection fraction (p less than .001). Specificity was 94% by wall motion and 87% by regional ejection fraction (not significant). Thus, radionuclide angiographic assessment of regional ejection fraction during handgrip exercise is both highly sensitive and specific for coronary heart disease and significantly enhances detection of coronary heart disease compared with wall-motion assessment, with little loss in specificity.