BACKGROUND The synthetic catecholamine dobutamine increases stroke volume in normal subjects and in patients with congestive heart failure. In addition to its direct influence on myocardial contractility, dobutamine may significantly modulate vascular tone because of its alpha- and beta-adrenergic agonist activity. METHODS AND RESULTS To test the hypothesis that such vasoactive properties significantly contribute to the improved ventricular performance noted with this agent, hemodynamic parameters were measured during stepped ascension infusion of dobutamine in a model that is insensitive to positive inotropic stimulation. Administration of dobutamine in nine calves that underwent replacement of the native right and left ventricles with pneumatically driven total artificial hearts resulted in a significant (p = 0.0001) increase in cardiac output from 7.0 +/- 1.8 to 8.2 +/- 1.8 l/min and a significant (p = 0.0001) decrease in total peripheral vascular resistance from 1,224 +/- 559 to 745 +/- 317 dyne.sec/cm5. A less marked influence was noted on the pulmonary vasculature, with pulmonary vascular resistance exhibiting a significant (p less than 0.05) decrease from its baseline value only at the peak infusion. Consistent with an increase in venous return, both left and right atrial pressures increased significantly (p less than 0.005) with dobutamine administration. CONCLUSIONS These data demonstrate that the vasoactive properties of dobutamine significantly contribute to improved ventricular performance independent of direct myocardial stimulation. This effect appears to result in part from a direct modulation of myocardial stimulation. This effect appears to result in part from a direct modulation of arterial and venous tones rather than from a reflex response to primary changes in contractility.
Accumulation of medical knowledge related to diagnosis and management over the last 5-6 decades has altered the course of diseases, improved clinical outcomes and increased survival. Thus, it has become difficult for the practicing physician to evaluate the long-term effects of a particular therapy on survival of an individual patient. Further, the approach by each physician to an individual patient with the same disease is not always uniform. In an attempt to assist physicians in applying newly acquired knowledge to patients, clinical practice guidelines were introduced by various scientific societies. Guidelines assist in facilitating the translation of new research discoveries into clinical practice; however, despite the improvements over the years, there are still several issues related to guidelines that often appear ‘lost in translation'. Guidelines are based on the results of randomized clinical trials, other nonrandomized studies, and expert opinion (i.e. the opinion of most members of the guideline committees). The merits and limitations of randomized clinical trials, guideline committees, and presentation of guidelines will be discussed. In addition, proposals to improve guidelines will be presented.
This study assesses the effect of aging on human myocardial morphology. Fifteen patients, ranging in age from 28 to 75 with normal cardiac history, physical examination and noninvasive tests of left ventricular function, underwent right ventricular endomyocardial biopsy prior to cancer chemotherapy. Cell diamater, nuclear area and fibrosis were quantified by light microscopy. Semiquantitative methods of electron microscopy were used to grade lipofuscin deposition, tubular dilation, myofibrillar loss, folding of discs and lipid deposition. The results demonstrated that myocardial cell diameter correlated directly with age (r = 0.73, p < 0.01) and systolic blood pressure (r = 0.51, p < 0.05). Nuclear area (r = 0.76, p < 0.01) and folded discs (r = 0.53, p < 0.05), two signs of increased protein production also correlated with age. Lipid deposition (r = 0.40), tubular dilation (r = 0.31) and lipofuscin deposition (r = 0.20) increased with, but did not correlate significantly with age. Lipid deposition (r = 0.56, p < 0.05) and tubular dilation (r = 0.43, p < 0.05) did correlate with cell diameter. Thus, the aging myocardium is characterized by increased cell size and some degenerative changes.
The adenine nucleotide content of the human myocardium in the distribution of the left anterior descending coronary artery (LAD) was measured before and after saphenous vein bypass grafting. The purpose of the study were twofold: (1) to relate the level of adenosine triphosphate (ATP) before bypass grafting to the percent stenoses of the LAD and (2) to determine the benefit or lack of benefit of bypass grafting on ATP content. Eighteen patients with angiographically determined LAD lesions of 40% to 100% underwent bypass grafting with standard cardiopulmonary bypass and cardioplegia. Transmural needle biopsy specimens were obtained from the center of the area perfused by the LAD immediately before cross-clamping of the aorta and 30 minutes after reperfusion of the myocardium via the native LAD and the graft. The tissue was divided into thirds: The endocardial and epicardial thirds were analyzed for ATP by high-pressure liquid chromatography and the middle third was viewed by light microscopy. The percent narrowing of the LAD correlated well (r = -0.71) with the ratio of ATP to total adenine nucleotides (TAN) in the endocardium. Epicardial ATP did not correlate with the percent stenoses of the LAD. The endocardial ATP/TAN ratio increased in the group as a whole from 0.51 +/- 0.27 (mean +/- SD) to 0.64 +/- 0.26 (p less than 0.01) after bypass grafting, and this was most impressive in those eight patients with LAD lesions greater than 90% (0.32 +/- 0.20 before grafting to 0.60 +/- 0.29 after grafting, p less than 0.005). However, the epicardial ATP/TAN ratio decreased from 0.75 +/- 0.15 before grafting to 0.64 +/- 0.17 after grafting (p less than 0.05), and this decrease occurred regardless of the percent narrowing of the LAD. There was no difference in vacuolization between the pre-grafting and post-grafting biopsy specimens, and intramyocardial hemorrhage was not observed. This study has demonstrated a close relationship between the degree of LAD stenosis and endocardial ATP content. Also, the endocardium supplied by arteries with greater than 90% lesions had significantly increased ATP while the epicardium had decreased ATP content after bypass grafting.
