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Catecholamine release in myocardial ischemia and its clinical implications
j Mol Cell Cardiol 18 (Supplement 3) (1986) MORPHOMETRICANALYSISOF REGIONALCORONARYBLOODFLOWDISTRIBUTIONAS MEASUREDBY NON-RADIOACTIVE MICROSPHERES. M. Korpan, C. Dulberg, K. Rakusan. Departments of Physiology and Epidemiology, University of Ottawa, Ottawa, Canada. In a new morphometric method for measuring coronary blood flow (CBF) distribution in the rat, non-radioactive microspheres (NRM) (10 um) were injected, the hearts excised, frozen, and sectioned, allowing for direct visualization of NRM. The results were analyzed with respect to the following variables: the effect of injection site (intraatrial IA vs. intraventricular IV), the effect of cardiac hypertrophy (aortic constriction), and the effect of NRM aggregation (single NRM vs. aggregates). Regional distribution was measured in 4 sections and 3 regions of the l e f t ventricular wall. Distribution across the wall was expressed by the endo/epi ratio, by the number of NRM in three zones divided according to muscle fibre orientation and by the number of NRM in deciles of the wall thickness. Aggregation varied around 22%. The spatial distribution of aggregates dependedon the modeof injection. IV injection resulted in preferential accumulation of aggregates in the endocardial region, which was not found after IA injection. Endocardialoverperfusion was also noticeable following IA injection in hypertrophic hearts which disappeared when aggregates were diregarded. Thus, estimates of CBF distribution which are based on measurements of radioactivity may be distorted by the uneven distribution of microsphere aggregates (Supported by the Ontario Heart and Stroke Foundation).
UP A N D D O W N P ~ T I O N
OF T H E S O D I ~ I N G SITES IN MYOCARDIUM. David D. Ku, Department of Pharmacology, University of Alabama at Birmingham, AL 35294, USA. Recently, we and a number of other investigators have reported significant alterations in the steady-state activity of myocardial sodium pump in various pathological states (diabetic, hypertensive, hypothyroid and ischemic) as well as following various hormonal (thyroid and insulin) and chemical (reserpine) treatments. The pathophysiological significance of these alterations in relation to myocardial function and their responsiveness to cardiac glycosides, however, remains unclear. Significant down-regulation of myocardial sodium pumping sites observed in the diabetic, thyroidectomized and hypertensive animals was accompanied by a decrease in myocardial contractile function, while similar sodium pump decreases in chronic reserpine-treated animals were associated with an increase in myocardial function. Sensitivity of these hearts to the positive inotropic effect of cardiac glycosides and their inhibition of myocardial sodium pump activity, however, were not altered. In contrast, an up-regulation of myocardial sodium pump in the ischemically jeopardized tissues, following a temporary coronary artery occlusion, was accompanied by an increase in the in vivo binding of cardiac glycosides. This latter finding could be attributed to the observed increased incidences of cardiac glycosides toxicity in ischcmic heart disease. Thus, it appears that modulation of sodium pumping sites in myocardium could and would alter efficacy of cardiac glycosides.
CATECHOLAMINE RELEASE IN MYOCARDIAL ISCHEMIA AND ITS CLINICAL IMPLICATIONS. W. KObler, R. Dietz, B. Kr~mer, W. M~urer, A. Soh~mig. AbteilunE Inhere Medizin III, (Kardiologie), University of Heidelberg, Germany In the isolated perfused rat heart an increased net release of noradrenaline (NA) during the first 10 minutes of isehemia is limited by the activity of the neuronal reuptake and only found after sympathetic stimulation. At a later second stage the mechanism of NA net release during ischemia is carrier mediated efflux. During the last and third phase spontaneous NA release is greatly augmented probably due to leakage because of membrane damage. In patients with coronary heart disease the situation is even more eomplex. Elevated plasma catecholamine levels as a consequence of increased net release can be due to: I. Emotional factors due to anxiety and pain, 2. hemodynamic factors related to impaired cardiac function leading to reduced neuronal uptake, 3. therapeutic factors - such as stimulation of the sympathetic system after beta-blockade, 4. metabolic isehemic factors, and 5. possibly additional factors related to myocardial perfusion.
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UP A N D D O W N P ~ T I O N
OF T H E S O D I ~ I N G SITES IN MYOCARDIUM. David D. Ku, Department of Pharmacology, University of Alabama at Birmingham, AL 35294, USA. Recently, we and a number of other investigators have reported significant alterations in the steady-state activity of myocardial sodium pump in various pathological states (diabetic, hypertensive, hypothyroid and ischemic) as well as following various hormonal (thyroid and insulin) and chemical (reserpine) treatments. The pathophysiological significance of these alterations in relation to myocardial function and their responsiveness to cardiac glycosides, however, remains unclear. Significant down-regulation of myocardial sodium pumping sites observed in the diabetic, thyroidectomized and hypertensive animals was accompanied by a decrease in myocardial contractile function, while similar sodium pump decreases in chronic reserpine-treated animals were associated with an increase in myocardial function. Sensitivity of these hearts to the positive inotropic effect of cardiac glycosides and their inhibition of myocardial sodium pump activity, however, were not altered. In contrast, an up-regulation of myocardial sodium pump in the ischemically jeopardized tissues, following a temporary coronary artery occlusion, was accompanied by an increase in the in vivo binding of cardiac glycosides. This latter finding could be attributed to the observed increased incidences of cardiac glycosides toxicity in ischcmic heart disease. Thus, it appears that modulation of sodium pumping sites in myocardium could and would alter efficacy of cardiac glycosides.
CATECHOLAMINE RELEASE IN MYOCARDIAL ISCHEMIA AND ITS CLINICAL IMPLICATIONS. W. KObler, R. Dietz, B. Kr~mer, W. M~urer, A. Soh~mig. AbteilunE Inhere Medizin III, (Kardiologie), University of Heidelberg, Germany In the isolated perfused rat heart an increased net release of noradrenaline (NA) during the first 10 minutes of isehemia is limited by the activity of the neuronal reuptake and only found after sympathetic stimulation. At a later second stage the mechanism of NA net release during ischemia is carrier mediated efflux. During the last and third phase spontaneous NA release is greatly augmented probably due to leakage because of membrane damage. In patients with coronary heart disease the situation is even more eomplex. Elevated plasma catecholamine levels as a consequence of increased net release can be due to: I. Emotional factors due to anxiety and pain, 2. hemodynamic factors related to impaired cardiac function leading to reduced neuronal uptake, 3. therapeutic factors - such as stimulation of the sympathetic system after beta-blockade, 4. metabolic isehemic factors, and 5. possibly additional factors related to myocardial perfusion.
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