Normal Canine Myocardium Research Articles

N-acylation of ethanolamine phospholipids in canine myocardium

N-Acylethanolamine phospholipids, which are found in infarcted but not in normal canine myocardium, were produced by preparations of normal myocardial tissue incubated in the presence of millimiolar concentrations of Ca 2+. Biosynthetic activity from endogenous substrates was associated with both microsomal and mitochondrial fractions and exhibited an alkaline pH optimum. The time course of N-acylethanolamine phospholipid synthesis and degradation was followed after pulse labeling of myocardial ethanolamine phospholipids with [1,2- 14C]ethanolamine. Enzymic N-acylation of both phosphatidylethanolamine and lysophosphatidylethanolamine was demonstrated by incubating these substrates with homogenates of myocardial tissue. Neither free fatty acids nor acyl-CoA derivatives served as acyi donor but some of the constituent fatty acids of exogenous phosphatidylethanolamine were recovered among the amide-linked fatty acids of the N-acylethanolainine phospholipids. N-Acylation may thus occur by the transfer of O-acyl groups catalyzed by a Ca 2+-dependent transacylase. Since N-acylethanolamine phospholipids are precursors of the biologically active N-acylethanolamines, their biosynthesis may constitute an important injury-induced metabolic event aimed at the protection of ischwmic myocardial tissue.

Spatial distribution of [ 14C]-lidocaine and blood flow in transmural and lateral border zones of ischemic canine myocardium

The purpose of this study was to determine the spatial distribution of lidocaine relative to blood flow in ischemic, normal and border zone canine myocardium. Ischemic zone tissue was distinguished from normal zone tissue by a special microsphere technique in adjacent sections 4 to 5 mm wide from the center to the lateral border of the ischemic region in 14 open chest dogs. Gamma-labeled microspheres were separated by a special technique from carbon-14 ([ 14C])-lidocaine in the same tissue sample. Blood flow (mean value ± 1 standard deviation) was reduced to 46 ± 25 percent of normal in the ischemic subepicardium and 17 ± 18 percent of normal in the subendocardium. [ 14C]-lidocaine was 0.56 ± 0.12 μg/g in normal myocardium 10 minutes after bolus injection of [ 14C]-lidocaine; it was reduced to 91 ± 15 percent of normal in ischemic subepicardium and 58 ± 12 percent of normal in the subendocardium. Blood flow and lidocaine concentration were uniformly lowest in gross samples from the central and intermediate ischemic zones, and highest in the gross samples from the border normal zone (p < 0.05). The values for flow and lidocaine in samples from the border ischemic zone were intermediate, that is, higher than values from central ischemic (p < 0.05) and lower than values from border normal zone samples (p < 0.05). However, the labeling technique for normal zone tissue revealed that the values of blood flow and lidocaine in the gross samples from the lateral border of the ischemic zone were intermediate between those of adjacent ischemic and normal samples because of the mixture of overlapping normal and ischemic tissues components—not because of a unique mildly ischemic region. Both blood flow and lidocaine concentration were lower in the subendocardial third than in the subepicardial third of the ischemic zone (p < 0.05) even after the contribution of normal zone tissue was subtracted, suggesting a gradient of ischemia across the transmural border zone. In conclusion, lidocaine is distributed uniformly in ischemic components from the center to the lateral border of the ischemic zone, but there is an endocardial to epicardial gradient. Both lateral and transmural border zone distributions must be considered to understand the mechanisms of drug effects in myocardial ischemia.

Myocardial kinetics of thallium-201 after dipyridamole infusion in normal canine myocardium and in myocardium distal to a stenosis.

The purpose of the present study was to define myocardial and blood thallium-201 (Tl-201) kinetics after infusion of dipyridamole in normal canine myocardium and in myocardium distal to a coronary artery stenosis. Miniature radiation detector probes were implanted in the left ventricle in 39 open-chest dogs. A balloon constrictor was placed around the proximal left circumflex coronary artery. Electromagnetic flow probes were positioned proximally around both the left circumflex and left anterior descending coronary arteries. In five control dogs (group 1) the balloon occluder was not inflated; in 12 dogs (group 2) a mild stenosis was created such that resting flow was not reduced, yet the hyperemic response after 10 s of total occlusion was partially attenuated; in nine dogs (group 3) a moderate stenosis was created such that resting flow was not reduced, yet the hyperemic response was completely eliminated; and in 13 dogs (group 4) a severe stenosis was created such that resting flow was reduced. After intravenous dipyridamole (0.08 mg/kg . min-1 x 4 min), 1.5 mCi Tl-201 was injected intravenously and probe counts were collected continuously for 4 h. The mean 4-h fractional myocardial Tl-201 clearance for nonstenotic zones was 0.35, 0.27 for group 2 stenotic zones, 0.19 for group 3 stenotic zones, and 0.05 for group 4 stenotic zones (P less than 0.0001). After reaching peak activity, myocardial Tl-201 activity cleared biexponentially with a final decay constant lambda 2 = 0.0017 +/- 0.0001 min-1 (SE) for nonstenotic zones, 0.0011 +/- 0.0001 min-1 for group 2 stenotic zones, and 0.0006 +/- 0.0001 min-1 for group 3 stenotic zones (P less than 0.01). Group 4 stenotic zone Tl-201 clearances were negligible (decay constant essentially zero). Blood Tl-201 activity decayed triexponentially with a final blood lambda 3 = 0.0018 +/- 0.0001 min-1, which was almost identical to the final myocardial lambda 2 decay constant. Thus, the rate of myocardial Tl-201 clearance can distinguish between coronary stenoses of graded hemodynamic severity. These results may be applicable to quantitative techniques for determining myocardial Tl-201 clearance rates on serial clinical images after dipyridamole administration.

Electrophysiological effects of alprenolol on depressed canine myocardium.

The electrophysiological effects of the beta-adrenergic antagonist, alprenolol, were compared in normal and depressed canine myocardium. Both (+) and (+/-)-alprenolol (5 x 10(-6) and 10(-5) mol.litre-1) decreased action potential amplitude and Vmax in Purkinje fibres superfused with Tyrode's solution in tissue bath. These concentrations shortened action potential duration and effective refractory period of Purkinje fibres but prolonged those of ventricular muscle. Alprenolol more markedly decreased Vmax and sometimes prevented action potential propagation in Purkinje fibres overlying infarcted regions. Similar depressant actions were noted in Purkinje fibres depolarised by exposure to 9 mmol.litre-1 K+. Depolarised and diseased myocardium is more sensitive to alprenolol and the drug's membrane depressant actions may be significant in terminating arrhythmias in such tissue.

Analysis of tissue extraction of radiopotassium analogues and 13N-ammonia

Conceptual and mathematical techniques for processing data on diffusible radiotracer uptake, obtained from perfusion studies, were outlined. From the Renkin equation, a theoretical relationship between tissue clearance of molecules and the rate of flow, derivative equations were obtained which expedited calculations. One easily plotted approximation gave tissue clearance as a function of the reciprocal of flow. Deviations from “ideality” were discussed as being due to 3 contributing factors: dependence of the permeability-surface area coefficient on flow, continued extraction at near zero flow, and the nonideal behavior of membranes (not fully permeable, and the presence of back diffusion). Tissue extraction of both 42K and 86Rb was characterized by the clearance value at extrapolated zero flow, by the extraction fraction at zero flow, and the slope of the line of extraction versus flow. Although the situation is likely more complex with ammonia (since it can exist in both ionized and nonionized forms), this treatment gave a reasonable description of 13N-ammonia uptake by normal canine myocardium.

Studies on the subcellular localization of electrolytes in normal and infarcted canine myocardium with special reference to calcium ion.

1. Alterations in subcellular distribution of electrolytes were studied with particular emphasis on Ca++ in normal and ischemic myocardium produced by ligating the coronary artery in the dog, by means of the histochemical method using potassium pyroantimonate. 2. In the normal myocardium, the antimonate precipitates were observed most abundantly in TC of SR and on N-line within sarcomeric I-band, but found scarcely in mitochondria, M-line, Z-line, intercalated disc or T-system. 3. In the infarcted myocardium, the precipitates were strikingly increased in both number and size in disrupted mitochondria, while they were markedly decreased in swollen TC with the progress of ischemia. 4. Most of the precipitates in TC and on N-line were removed by chelation with EGTA but a few larger precipitates were consistently found mainly on N-line. And the presence of Ca++ in the antimonate precipitates was confirmed by energy dispersive X-ray microanalysis.

Topobiochemistry of ATP: Creatine phosphoretransferases (CK) and L-lactate NAD-oxidoreductases (LDH) in normal and infracted canine myocardium

Topobiochemistry of ATP: Creatine phosphoretransferases (CK) and L-lactate NAD-oxidoreductases (LDH) in normal and infracted canine myocardium

Protective Effect of Prenylamine Against Vulnerability to Ventricular Fibrillation in the Normal and Ischemic Canine Myocardium

SummaryObstruction and reestablishment of coronary artery flow both markedly lower the threshold for ventricular fibrillation (VF). This reduction in threshold is partially reversed by infusion of Prenylamine, a drug with slow channel blocking and coronary artery vasodilating properties. Mean blood pressure and heart rate were unaltered. Prenylamine administration also elevated the VF threshold in the nonischemic myocardium. Its effect on reperfusion VF threshold is unique, since commonly used antiarrhythmic drugs exert no such effect.

The role of β-adrenoceptors in coronary blood flow distribution in normal and ischemic canine myocardium

β-Adrenoceptor agonists increase myocardial ischemic injury, mainly by elevating myocardial oxygen consumption. Moreover, it has been shown that isoprenaline may “steal” regional myocardial blood flow (RMBF) from ischemic to non ischemic areas and from epicardium to endocardium. The mechanisms of these two isoprenaline-induced redistributions of RMBF have been investigated by the use of radioactive microspheres in an experimental model of canine myocardial ischemia with simultaneous measurement of ST-segment elevation. Isoprenaline increased RMBF in both epi- and endocardial non ischemic areas and in epicardial ischemic areas, leading to a significant decrease in the endo/epi ratio. After atenolol, isoprenaline still increased RMBF but to a lesser extent and the endo/epi ratio was still decreased. Salbutamol, in doses inducing no significant changes in cardiac parameters or myocardial oxygen consumption, produced effects similar to those of isoprenaline. These results indicate a non-homogeneous β 2-stimulation-induced vasodilation in endo- and epicardium, which might be due either to the higher epicardial coronary vasodilatory reserve or to a heterogeneous distribution of transmural β 2-adrenoceptors. Isoprenaline also decreased the ischemic/non ischemic total blood flow ratio (I/NI) and caused further increases in ST-segment elevation. These effects were abolished by atenolol pretreatment, indicating the deleterious effects of isoprenaline-induced tachycardia in this I/NI decrease and in the ischemic injury.

Comparative Hemodynamic Effects of Coronary Vasodilators and Contrast Material on the Normal and Ischemic Canine Myocardium: Determination of the Optimal Agent for Clinical Augmentation of Coronary Blood Flow

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.

Differences in the Velocity-Displacement Relationship of Systolic Contraction of Normal and Ischemic Canine Myocardium

In the canine model there exist major differences in the velocity-displacement relationships of systolic contraction between normal and ischemic myocardium. These differences are noninvasively measurable in vivo from video recordings of the fluoroscopic image of the heart, and can be detected within the time period of one cardiac cycle. Velocity data is plotted against the corresponding wall displacement on orthogonal axes (phase-space), producing characteristic loops which give an immediate visual indication of myocardial dysfunction.

Left ventricular end-diastolic pressure volume relationships with experimental acute global ischemia.

The mechanism of elevation of left ventricular end-diastolic pressure during acute global ischemia was evaluated by examiniation of the relative contributions of a decrease in contractility and an alteration of the pressure-volume relationship. The external circumference (mercury-in-silastic gauge) pressure relationship, as an index of the pressure-volume relationship, was studied in beta adrenergic and ganglionic blocked, open chest dogs on right heart bypass at constant heart rate ane aortic pressure. Ischemia of one and two hours' duration was produced by reducing total coronary blood flow in cannulated left and right coronary arteries until left ventricular end-diastolic pressure rose significantly. At a constant stroke work, left ventricular end-diastolic pressure rose from 5.0 +/- 0.5 to 15.0 +/- 0.5 cm H2O in the experiments of one hour of ischemia, and from 7.0 +/- 1.0 to 17.0 +/- 1.0 cm H2O in experiments of two hours of ischemia. Ischemia was followed by one hour of restoration of coronary blood flow. Ischemia produced a marked depression of ventricular function: stroke work, considered at a left ventricular end-diastolic pressure of 15 cm H2O, decreased from 21.0 +/- 3.0 to 3.5 +/- 0.5 gm-m, and from 15.0 +/- 2.0 to 2.5 +/- 0.5 gm-m, in the experiments of one and two hours, respectively. Neither ischemia nor reflow changed the pressure-volume relationship. Thus, the elevation of left ventricular end-diastolic pressure during ischemia in an otherwise normal canine myocardium is due to a decrease in systolic performance of the heart rather than to an alteration of the pressure-volume relationship.

Effect of dipyridamole on the glycogen metabolism in the normal and ischemic canine myocardium.

Pretreatemtn of the dog with dipyridamole tended to increase the rate of acceleration of anaerobic metabolism in the myocardium induced by ligation of a small branch of the coronary artery.

The effects of dipyridamole on blood flow and oxygen handling in the acutely ischaemic and normal canine myocardium.

1. The effects of the intravenous administration of dipyridamole (0.25 mg/kg) were examined in a canine preparation that enabled simultaneous measurements to be made of blood flow in ischaemic and in essentially normal areas of the myocardium and also of oxygen handling (availability, consumption and extraction) in both these regions.2. When administered to dogs anaesthetized with trichlorethylene 2-3 h after acute ligation of the descending branch of the left coronary artery, dipyridamole markedly increased blood flow in essentially normal regions (left circumflex flow) but failed to increase flow in the area supplied by the ligated vessel (measured by (133)xenon clearance and by retrograde flow). In five of the six animals definite decreases in flow (; stealing ') were observed in the ischaemic region. These flow changes were related to the decreased trans-ventricular perfusion pressure (diastolic peripheral coronary pressure minus left ventricular end-diastolic pressure) and were accompanied by electrocardiographic evidence of increasingly severe myocardial ischaemia. The results support the suggestion that only increasing the perfusion gradient will usefully improve blood flow (and hence oxygen availability) to the acutely ischaemic myocardium.3. Despite these effects on ischaemic muscle blood flow, the oxygen tension of the blood draining the infarcting muscle was markedly elevated. The conclusion is drawn that dipyridamole decreases the efficiency of the myocardial circulation by opening up vessels that do not take part in tissue exchange.

Intermyofibrillar and nuclear-myofibrillar connections in human and canine myocardium an ultrastructural study

Cytoplasmic filaments, which measure 100 Å in diameter, and which differ morphologically from actin and myosin filaments, are described in normal canine myocardium and in normal and hypertrophied human myocardium. These filaments were found between Z bands, near the sarcolemma, in regions of intercalated discs, and in the vicinity of nuclear membranes. The 100 Å filaments appeared to form transverse connections between adjacent Z bands and between Z bands and outer nuclear membranes. These filaments probably function as a cytoskeleton.

A Microangiographic Investigation of the Normal and Fibrotic Canine Myocardium

A Microangiographic Investigation of the Normal and Fibrotic Canine Myocardium

A Microangiography Investigation of the Normal and Fibrotic Canine Myocardium

A Microangiography Investigation of the Normal and Fibrotic Canine Myocardium

A Microangiographic Investigation of the Normal and Fibrotic Canine Myocardium

A Microangiographic Investigation of the Normal and Fibrotic Canine Myocardium

Differentiation of Ribosomes and Beta Glycogen in Canine Myocardium

During the ultrastructural examination of the canine myocardium, it became apparent that the positive identification of specific granules as either ribosomes or β glycogen was very difficult in sections stained with lead citrate and uranyl acetate. In the normal adult canine myocardium ribosomes are not a prominent organelle, but in certain conditions, free ribosomes may become greatly increased in number. Unlike some other species, glycogen and ribosomes are very nearly the same size (200-250 Å) in the canine myocardium. Following glutaraldehyde fixation and epoxy resin embedding there is considerable variation in electron density of glycoen (Fig. 1).In an attempt to differentiate glycogen from free ribosome particles, myocardial samples from four normal dogs and six dogs with experimental right ventricular hypertrophy were processed 1) according to routine procedure, 2) following autolysis, 3) following diastase digestion and 4) by the periodic acid silver proteinate method of Theiry (J. Microscopie 6:986, 1967).

Effects of carbochromen and dipyridamole on blood flow and heat production in the normal and ischaemic canine myocardium.

The coronary vasodilator drugs carbochromen and dipyridamole were capable of increasing local myocardial blood flow and decreasing myocardial metabolic heat production both in the normal canine myocardium and in the myocardium rendered ischaemic by acute ligation of a coronary artery. This is taken as further evidence for the existence of an active myocardial vasoconstrictor reflex, triggered off by coronary ligation.