Plasmacytosis is an uncommon reaction that may occur during the first weeks after the administration of streptokinase in the treatment of acute myocardial infarction. This article presents a case with prolonged fever, general discomfort and an unusual lymphoid cell reaction after an acute myocardial infarction treated with streptokinase. The cell morphology mimicked an adult T-cell leukemia, an M component was produced and serologic tests indicated a reactivation of the herpes viridae group. The condition improved and there was a prompt reduction in fever in response to doxycycline therapy. The data are interpreted to show that streptokinase induced a reactivation of a virus infection and a supervening proliferation of an atypical plasma cell clone. It is suggested that this was mediated by an activation of macrophages which was modified by the doxycycline therapy.
Activation of myocardial alpha-1-adrenoceptors results in a positive inotropic effect associated with an increase in the amplitude of intracellular Ca2+ transients in various mammalian species. alpha-1-Adrenoceptors may elicit the positive inotropic effect through a small but definite increase in intracellular Ca2+ transients, and an increase in Ca2+ sensitivity of myofibrils. Several subcellular mechanisms underlying these changes in Ca2+ signaling have been proposed: the regulation of ion channel activities, ion transport systems, and phosphorylation of functional proteins induced by myocardial alpha-1-adrenoceptors. Recent findings on patch-clamp experiments in single cardiac myocytes have revealed that alpha-1-stimulation scarcely or only slightly facilitates L-type Ca2+ channels, but inhibits transient outward current (I(to)), and activates Na+ -H+ exchange, which may indirectly result in an increase in Ca2+ influx. The facilitation of phosphoinositide hydrolysis that leads to a production of IP3 and diacylglycerol, and subsequent activation of protein kinase C, has been proposed as the biochemical process underlying these divergent changes in the myocardial alpha-1-adrenoceptor-mediated signal transduction system. The process involved in the myocardial alpha-1-adrenoceptor activation will be briefly reviewed, focusing the physiologic relevance of the recent electrophysiologic findings in single cardiac myocytes in the alpha-1-mediated regulation of Ca2+ signaling.
We examined the effects of age on coronary autoregulation (autoregulatory gain) and reactive hyperemic response (peak flow/myocardial tissue weight ratio, flow reserve, peak/resting flow ratio, repayment/debt flow ratio, and the duration of hyperemia) after brief ischemia in developmental (3 mo of age), young-adult (8 mo), and old rats (19 mo). Langendorff preparation was used to estimate coronary hemodynamics. Hearts were isolated and perfused with Tyrode's solution containing oxygenated bovine red blood cells and serum albumin. Resting coronary perfusion pressure - flow relationships and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In the 3-mo- and 8-mo-old rats, coronary autoregulation, i.e., a slight decrease in flow with reduction of perfusion pressure, was observed in the range of perfusion pressure between 50 and 100 mmHg. In contrast, hearts of the 19-mo-old rats showed that autoregulatory gain was significantly lower, compared to that in younger rats. Peak coronary flow during reactive hyperemia and flow reserve per myocardial tissue weight significantly decreased in hearts of the 19-mo-old rats. The repayment/debt flow ratio also decreased because of a shorter duration of reactive hyperemia. Thus, autoregulation and reactive hyperemic response are maintained constant during growth and maturation, but diminish in older subjects.
Small arteries, with a diameter of 200 mm or less, play an important role in the regulation of peripheral vascular resistance. Dysregulation of vascular tone of these arteries may contribute importantly to high blood pressure. The contractile state of blood vessels is regulated by peripheral neurons, vascular smooth muscle, and the endothelium. In perfused mesenteric resistance arteries of the rat, removal of the endothelium markedly augments the sensitivity and maximal response to norepinephrine and endothelin-1. Similarly, in vivo low concentrations of endothelin cause vasodilation, while higher concentrations of the peptide evoke an increase of vascular resistance. Acetylcholine causes profound endothelium-dependent relaxations of resistance arteries contracted with norepinephrine or endothelin-1. The potency of the muscarinic agonist is particularly pronounced with intraluminal application. The inhibitory effects of the endothelium against contractions to norepinephrine and endothelin-1 are reduced with aging and hypertension. The endothelium-dependent relaxations to intraluminal, but not extraluminal, acetylcholine are blunted in mesenteric resistance arteries of hypertensive rats and in the human forearm circulation of hypertensive patients studied in vivo. The sensitivity of vascular smooth muscle to the effects of endothelin decreases with advancing age and in spontaneous hypertension of the rat. Thus, endothelium-derived vasoactive substances can profoundly affect vascular tone of resistance arteries studied both in vitro and in vivo. The inhibitory effects of the endothelium against vasoconstrictor stimuli, as well as the potency of endothelium-dependent vasodilation, decrease with aging and hypertension, indicating a dysfunction of these regulatory mechanisms under these conditions.
Systemic hypertension and left ventricular hypertrophy may be associated with left ventricular ischemia. Reduced oxygenation of the hypertrophied left ventricle may lead to acceleration of anaerobic glycolysis. The present study was undertaken to determine if lactate production, an indicator of anaerobic glycolytic metabolism, is increased in the hypertrophied left ventricle, and if reductions of arterial pressure and left ventricular hypertrophy using antihypertensive treatment are associated with a decrease in myocardial lactate production. Three-month-old spontaneously hypertensive rats were treated with nifedipine for 3 mo. At 6 mo, arterial pressure, left ventricular weight and left ventricular lactate level were studied in 3 groups of rats: treated hypertensive, untreated hypertensive, and untreated normotensive. Arterial pressure, left ventricular weight, and myocardial lactate levels were significantly elevated in untreated hypertensive rats. Antihypertensive treatment resulted in moderate decreases in both arterial pressure and left ventricular hypertrophy. Myocardial lactate level remained elevated in treated hypertensive rats and was not different from the untreated hypertensive rats. The data suggest that moderate reductions of arterial pressure and left ventricular hypertrophy may not return accelerated glycolysis to normal.
The effect of increasing amounts of enalapril maleate (EM) on substrate utilization and oxidative phosphorylation by rat liver and kidney mitochondria was evaluated. EM significantly inhibits the activity of purified glutamate-oxalacetic transaminase, and modifies the activity of NADH oxidase and NADH cytochrome c reductase, probably inhibiting electron transfer between complex I and complex III of rat kidney mitochondria. No effect was observed with rat liver mitochondria. Experiments on biotransformation showed that de-esterification of enalapril to enalaprilat occurs in liver mitochondria.
Simultaneous measurements of cardiac output by impedance plethysmography (IPG-104) and thermodilution (Edwards Critical Care Model COM-2) were obtained in 25 patients whose primary condition was coronary ischemia. A total of 89 determinations were performed on 10 females and 15 males. Previous reports of thermodilution and impedance measurements of cardiac output have described electronically differentiated thoracic impedance variations and mathematical formulations that eliminate or disregard physiological variables. This study utilizes the assumed values of blood resistivity, the segmental resistance of a constant length thoracic cage defined anatomically between C7 and T12, extrapolated records of arterial-venous thoracic blood pulse volumes, and heart rate. Discrepancies in results of measurements of cardiac output by impedance variations between male and female populations existed (p < .05) because of differences in hematocrit values. There was no significant difference between thermodilution (4.67 + 1.16 L/min) and impedance (4.53 + 1.12 L/min) measurement of cardiac output for the total population studied. The impedance system is more reflective of cardiac hemodynamics than thermodilution because of sensitivity to beat-by-beat arterial-venous variation in cardiac dynamics compared with average flow properties characteristic of thermodilution methodologies.
The isolated perfused rat heart was made ischemic by the one-way ball valve and by lowering the aortic afterload pressure. The heart was perfused by the working heart technique with a left atrial filling pressure of 8 mmHg, and a hydrostatic afterload pressure in the aorta of 60 mmHg. The one-way ball valve did not severely reduce coronary flow with an afterload pressure of 60 mmHg. Lowering the aortic pressure to 0 mmHg made the heart severely ischemic. Heart ATP contents in control perfusions (nonischemic), ischemia produced by the one-way ball valve for 20 minutes, and ischemia produced by lowering afterload pressure to 0 mmHg for 20 minutes were 19.7 +/- 0.9, 13.5 +/- 1.2, and 3.7 +/- 0.3-mu-mol/g dry weight, respectively. Lowering the afterload pressure can reduce coronary flow as much or more than the one-way ball valve in the perfused working rat heart. The limitation of the one-way ball valve in making the heart ischemic is the opening of the aortic valve when the left ventricular pressure exceeds aortic pressure.
The ultrastructure of atrial muscle was examined in Wistar rat hearts at 6 mo after irradiation with 20 Gy or at 3 mo after irradiation with 30 Gy. These conditions represented stages of reduced myocardial function (20 Gy) and myocardial failure (30 Gy), respectively. Atrial myocyte damage under either condition was more severe than that previously found in the ventricle. Although the response appeared more severe after 30 Gy, for example, larger increases in collagen and acute inflammation, at both doses a general pattern of structural injury emerged following irradiation. The production of fibrillar connective tissue was greatly stimulated and myocyte damage was frequently localized, at times even at a cellular level. In damaged myocytes myofibrolysis was common and often associated with mitochondrial changes. Extensive systems of sinuous mitochondria were also observed. Lysosomal activity was increased and associated with spherical microparticles and residual bodies. Possible degradation of atrialspecific granules and their subsequent inclusion into multivesicular bodies was also noted. These studies have shown important differences between atrial and ventricle response to irradiation and may indicate an increased sensitivity in the former to irradiation.
Despite a high incidence of cardiac toxicity, digoxin continues to be a frequently used drug for the care of cardiac patients. D-37 is a semisynthetic cardiac glycoside that may have a greater margin of safety than digoxin. To compare the inotropic and cardiac toxic properties of digoxin and D-37, open chest anesthetized dogs received a constant intravenous infusion of either digoxin (n = 7) or D-37 (n = 7). Cardiac toxicity was evaluated by scanning the right ventricle for a repetitive ventricular response, and monitoring an electrocardiogram for ventricular tachycardia. A micromanometer-tipped catheter was placed in the left ventricle, and contractility was measured as the rate of rise of left ventricular pressure (dP/dt). At equipotent doses, defined as the dose of drug that increased contractility by 50%, neither drug was associated with a repetitive ventricular response, and ventricular ectopy was infrequent in both drug infused groups. With continuing infusion, dP/dt increased in the digoxin group until the onset of ventricular tachycardia, which occurred in all digoxin-infused dogs. In the D-37 group, contractility plateaued despite continuing infusion, and no ventricular tachycardia occurred in any D-37 dogs. Maximum contractility was higher in digoxin (103 + 22% above baseline) (p < 0.05). Thus, at equipotent doses, both D-37 and digoxin exhibit similar degrees of toxicity and, at doses which increase contractility by 50%, neither drug has a high likelihood of toxicity. Increasing doses of D-37 do not cause a progressive rise in contractility. Increasing doses of digoxin result in a progressive rise in contractility which continues until the onset of ventricular tachycardia. Compared with digoxin, D-37 provides the benefits of increased contractility with a reduced risk of serious ventricular arrhythmias.
High-fidelity micromanometer recordings of ascending aortic pressure consistently show a small wave immediately preceding the onset of the aortic pressure upstroke. To investigate the etiology of this phenomenon, simultaneous left atrial, left ventricular, and ascending aortic pressures were measured in 10 anesthetized pigs. Atrial, ventricular, and A-V sequential pacing with R-R intervals ranging from 50-200 msec did not alter the position of the waves. The waves did occur with premature ventricular contractions, independent of atrial activity and their timing appeared to relate, in part, to aortic diastolic pressure. Echocardiography showed that the onset of the waves coincided with the initial systolic outward movement of the aortic valve prior to opening, just after mitral valve closure. The waves were absent with low aortic diastolic pressure, and were not present in the distal arterial system. Human aortic pressure recordings were also examined in 14 patients with acquired calcific aortic stenosis, and 4 subjects with no aortic valve pathology. None of the 14 patients with aortic stenosis had waves preceding the aortic pressure upstroke; in all 4 of the normal subjects, however, these waves were present. It appears that these waves are related to ventricular, and not atrial activity, and that they arise from the initial outward movement of the aortic valve during isovolumic contraction, prior to valve opening. Their absence at low diastolic pressures may be due to pressure dependence of aortic visco-elastic properties and the decreased load imposed the ejecting ventricle at these pressures.
Vascular endothelial cell damage from hemodynamic and/or chemical factors is thought to be the initiating stimulus for atherosclerosis. Once the endothelial cells are physically or functionally altered, a series of events which include loss of thrombo-inhibitory property, depressed synthesis and release of the antiplatelet aggregatory factor prostacyclin and increased vascular permeability to blood macromolecules LDL, fibrinogen and circulating immune complexes occur and promote atherogenesis. These changes are also preceded and/or accompanied by lipid peroxidation, and the latter appears to be involved in the initiation as well as progression of the disease. In this article, we present a concise review of mechanisms that may influence the pathogensis of atherosclerosis.
Coronary artery embolization may allow destruction of arrhythmogenic areas, but could produce new arrhythmia foci. To assess this possibility, myocardial infarction was produced by selective cannulation and embolization of glutaraldehyde cross-linked collagen into the mid-portion of the left anterior descending (8 experiments), median ramus (2 experiments), or circumflex (2 experiments) coronary arteries of 12 dogs. Four animals suffered immediate ventricular fibrillation, 2 of whom had apparent reflux of collagen solution into adjacent coronary arteries with resultant massive infarction. Programmed ventricular stimulation 7-14 days later failed to induce monomorphic ventricular tachycardia in any of the 6 late survivors. Infarcts occupied 10-62% of left ventricular circumference. Histology revealed dense areas of fibrosis with occasional islands of surviving myocytes in the infarct border areas. Thus, collagen coronary artery embolization produces dense, relatively large infarctions, by occluding small intramyocardial vessels. The incidence of inducible monomorphic ventricular tachycardia resulting from such infarctions is low. Thus, cross-linked collagen embolization of blood vessels supplying arrhythmogenic foci is likely to cause infarction without producing new arrhythmogenic areas, and may be a useful agent for embolization of arrhythmogenic myocardium. Careful avoidance of reflux during rapid injection to avoid producing larger than desired infarctions and vigilant monitoring for immediate and early ventricular arrhythmias will be required.
Acetylcholine (ACH) and adenylates, adenosine (ADO), and adenosine triphosphate (ATP), regulate vascular reactivity, including that of the coronary arteries. There is also evidence that these agents directly influence metabolism in organs such as the liver; however, data concerning the effect of these agents on myocardial metabolism are limited. Since changes in redox state (NAD/NADH) have been implicated in regulation of myocardial function, the present study was designed to explore the effects of each of the aforementioned vasoactive agents on cytoplasmic and mitochondrial redox state. The pyruvate/lactate ratio was used to estimate the cytoplasmic redox state, and the oxoglutarate/glutamate ratio was used to estimate the mitochondrial redox state. These biochemical data were obtained from perchloric acid extracts of Langendorff-perfused rat hearts which were previously exposed to each of these agents. ATP and ADO significantly increased coronary flow but had no effect on either the cytoplasmic or the mitochondrial redox state. ACH significantly decreased coronary flow, did not change the mitochondrial redox state, but significantly decreased the cytoplasmic redox state, as indicated by an increased pyruvate/lactate ratio. These data suggest that ACH (but not ADO or ATP) may effect changes in myocardial function by changing cytoplasmic redox state.
It has been demonstrated that hyperbaric oxygen therapy may reduce the severity of ischemic injury during acute coronary artery occlusion. However, whether this effect results in a permanent reduction of myocardial cell necrosis has never been investigated. In the present study, we tested whether administration of hyperbaric oxygen can reduce infarct size. Infarct size was evaluated at two different time points after occlusion. In the acute protocol, rats undergoing coronary artery occlusion were randomly divided in two groups. One group was exposed to 100% O2 (2 atm for 3 hr); treatment started 30 min after occlusion, and was repeated twice a day for 48 hr. A second group of control rats did not receive any treatment. An additional group of rats was sham-operated. Seventeen controls, 19 treated, and 17 sham-operated rats were killed 48 hr after coronary occlusion, and the extent of myocardial necrosis was determined from left ventricular creatine kinase content. In the chronic protocol, rats with coronary artery occlusion were subjected to 48 hr of treatment with the same modalities as in the acute study, but infarct size was assessed, from left ventricular collagen content, 21 days after coronary artery occlusion, when myocardial scarring process was completed. Infarct size, measured 48 hr after coronary artery occlusion, was significantly smaller in treated animals than in controls (26.9 +/- 9.1 vs. 45.4 +/- 6.7% of left ventricle, respectively; p < 0.05). In contrast, no beneficial effect of oxygen therapy was observed in rats killed 21 days after occlusion, with infarct size averaging 34.4 +/- 6.6% of left ventricle in treated rats (n = 24) and 28.8 +/- 5.6% of left ventricle in controls (n = 21). Thus, hyperbaric oxygen therapy can acutely reduce the severity of ischemic injury following coronary artery ligation. However, our data suggest that, in the setting of a permanent occlusion, this effect may only delay the progression of ischemic cell death, without affecting the ultimate extent of myocardial necrosis.
Patients with or without chest pain as the presenting complaint of acute myocardial infarction were studied by assessing changes in plasma atrial natriuretic factor levels for 7 days. Twenty patients were divided into two groups according to pain symptoms (group I: no pain, n = 9; group II: severe pain, n = 11). On admission, atrial natriuretic factor values were higher than those in control subjects, but in patients presenting with severe pain, they were significantly lower than levels in the pain-free patients. Pain resolution was not accompanied by immediate changes in atrial natriuretic factor values. Plasma levels of aldosterone, renin activity, antidiuretic hormone and blood pressure, heart rate, and central venous pressure values were normal, and did not differ significantly in the two groups throughout the study period. In all patients, ejection fraction values were lower than in control subjects; in patients with severe pain, values were significantly higher than those in pain-free patients. Regression analysis revealed an inverse relation between ejection fraction and atrial natriuretic factor levels in both groups of patients showing a similar regression line for patients with severe pain with respect to patients with no pain. These results confirm the major role played by impaired myocardial contractility in inducing high atrial natriuretic factor levels during acute myocardial infarction, and show that pain as a presenting complaint appears to exert a minor influence on the relation between ejection fraction and atrial natriuretic factor values. The higher plasma atrial natriuretic factor levels found in pain-free patients suggest that this peptide may affect pain intensity in acute myocardial infarction.
Oxygenated fluorocarbon cardioplegia has been shown to limit myocardial damage during ischemic arrest, but the clinical use of fluorocarbon compounds is still hampered by the cumbersome handling and poor biocompatibility of current emulsions. A perfluoromethyladamantane-based fluorocarbon solution emulsified with lecithin, which offers high stability and low retention, has recently been developed. We have used P-31 NMR spectroscopy at 4.7 T to test its efficacy to maintain aerobic metabolism in 30 isolated, isovolumic rat hearts subjected to 90 min of global ischemia at 30-degrees-C, followed by 30 min of reperfusion. During arrest, hearts received multidose infusions of either crystalloid hyper K+ cardioplegia, lecithin-enriched cardioplegia or lecithin-emulsified fluorocarbon cardioplegia. Compared to control and lecithin-based cardioplegic solutions, oxygenated fluorocarbon-based cardioplegic solutions resulted in a better preservation of pHi and high energy phosphate compounds during ischemia and in a greater and faster recovery of myocardial function during reperfusion. These results demonstrate the efficacy of this new lecithin-emulsified fluorocarbon preparation; it may become clinically relevant in view of improved biocompatibility and ease of use.
Uremia of any cause is associated with a high incidence of cardiovascular complications which cannot be prevented by dialysis. Although uremia, hypertension, ischemic heart disease, fluid overload, electrolyte imbalances, and abnormalities in Ca2+ metabolism may all contribute to cardiac dysfunction in uremia, the exact mechanism of heart failure in uremic patients still remains elusive. This review discusses the hypothesis of a specific uremic cardiomyopathy which is the result of alterations in intracellular Ca2+ hemostasis and which, in turn, can be traced to a metabolic defect in some of the key reactions involved in myocardial energy transformation (pyruvate dehydrogenase, enolase, and pyruvate kinase). If the hypothesis proves to be correct, it may then be possible to reverse functional abnormalities by specific metabolic or pharmacologic interventions.
Conventional hemodynamic measurements and left ventricular end-systolic wall stress were retrospectively assessed to determine readiness for arterial switch operation in infancy following left ventricular preparation in eight infants (4.5-18.5-months-old; mean = 9 mo). Six had preparatory operations while the other 2 patients did not require a preparatory operation because of a large VSD and PDA in 1 and native left ventricular outflow tract obstruction in the other. Data from echocardiography and cardiac catheterization were obtained before arterial switch operation. Two infants required prolonged cardiopulmonary bypass support postoperatively and were considered to have inadequate left ventricular preparation. There were no significant differences in left ventricular end-diastolic and end-systolic wall thickness, left ventricular end-systolic dimension, left ventricular mass, predictive wall stress (diastolic wall stress following the switch operation predicted from pre-switch data), left ventricular geometry, nor left ventricular:right ventricular pressure ratio between these 2 patients and the 6 who did well. However, left ventricular end-systolic wall stress was significantly lower in the poor outcome group compared to the favorable outcome group (87 +/- 24 mmHg versus 235 +/- 57 mmHg, p = 0.014). These data suggest that preoperative assessment in left ventricular end-systolic wall stress may predict the postoperative left ventricular response following arterial switch operation.
