Showing papers in "European Heart Journal in 1980"

Calcium transients in mammalian ventricular muscle.

Abstract: The calcium-sensitive photoprotein aequorin was microinjected into cells of rat and cat ventricular muscle. During subsequent stimulation of the muscle light emission could be detected and this signal is a function of the intracellular [Ca++]. The time course and amplitude of the intracellular [Ca++] transient occurring during contraction is described. The effects on tension and light emission of changing external [Ca++] and stimulus frequency and of adding adrenaline and caffeine to the bathing solution are described. These results show that changes in external calcium and stimulus frequency alter tension by means of changes in the intracellular [Ca++] whereas adrenaline in addition alters the sensitivity of the contractile system to intracellular [Ca++]. The results also suggest that although a fall in intracellular [Ca++] always precedes relaxation, the time course of the fall of [Ca++] is not generally a rate limiting step in the lime course of relaxation.

Myocardial bridges and ischemic heart disease

Abstract: The clinical, electrocardiographs and angiocardiographic data are reported of 37 patients with myocardial bridges, in the absence of coronary atherosclerosis. An intramyocardial course of the left anterior descending coronary artery was present in all cases: myocardial bridges on the posterior descending and first diagonal branch were associated in one patient. The clinical presentation was that of ischemic heart disease in all cases, with stable angina in nine, unstable angina in 19, the intermediate syndrome in five, and a history or evidence of previous myocardial infarction in four. In 20 cases, left ventricular wall motion appeared to be abnormal on the antero-lateral or apical profile. One patient died suddenly the day following hospital discharge; of 27 patients followed over a 3–36 month interval, only four (15%) were free of symptoms on medical treatment. The frequent association of myocardial bridges with a clinical picture of ischemic heart disease which is sometimes severe, is emphasized together with the disappointing results of medical treatment.

Sotalol-induced delayed ventricular repolarization in man

Abstract: Sotalol is the only beta-adrenergic blocking agent, that has been shown to produce delayed repolarization following acute administration. In this study an intravenous injection of 40–100 mg sotalol was given to eight patients with chronic atrial fibrillation. One patient was reverted to sinus rhythm, while the other patients were electro-converted 2 h after the injection. Three patients still in sinus rhythm 24 h later received chronic treatment for at least 12 weeks. They maintained sinus rhythm throughout the study. Identical electrophysiological investigations were performed after the acute injection and after chronic treatment. Following acute administration, sotalol produced a consistent increase in the ventricular repolarization time as measured from refractory periods and monophasic action potential duration, the change being of the magnitude of 13 to 17%. After chronic treatment the three remaining patients still showed an increase in the ventricular repolarization time, but no conclusions can be made from these few observations. However, the study confirms the existence of a class III mode of action at the cellular level following intravenous sotalol injections of40–100 mg in man.

Propafenone — a new antiarrhythmic drug

Abstract: Propafenone is a new antiarrhythmic drug with class-I action and some additional sympathicolytic activities. Due to its pharmacokinetic properties the drug is appropriate for long-term oral treatment. Propafenone is especially successful in suppressing ventricular arrhythmias and in preventing tachycardias in patients with WPW syndrome. So far, final conclusions concerning the side effects cannot be drawn.

Quantification of incomplete left ventricular relaxation: relationship to the time constant for isovolumic pressure fall

Abstract: We initially found that the fall in left ventricular pressure during isovolumic relaxation is exponential and therefore characterized by a time constant (T). To the extent that isovolumic pressure fall reflects myocardial events during relaxation, T indexes the time course of relaxation of the left ventricle. In isolated canine hearts sudden beat to beat loading changes from isovolumic to ejection shorten T. In contrast, under stable hemodynamic conditions T is independent of load across a broad, physiologically significant range. For example:(1) in nine isovolumic hearts with end-diastolic pressure from 7±0.5 to 22±0.5 mm Hg and peak left ventricular pressure (LVP) from 95 ± 11 to 155 ± 12 mm Hg, T did not change significantly; (2) in seven ejecting hearts from a stroke volume of 10 to 20 ml and from a peak LVP of 85 to 192 mm Hg, T was not altered. T changed significantly with factors thought to affect the active cardiac relaxing system such as heart rate, catecholamines and recovery from ischaemia. To quantify the extent of incomplete left ventricular relaxation between beats and to identify the time at which relaxation no longer influences the diastolic ventricular pressure-dimension relationships, we measured pressure and endocardial dimension by sonomicrometry in ten working dog hearts. We obtained the fully relaxed pressure-dimension relationship for individual hearts from pressure-dimension values following prolonged diastoles. From the linear relationship between pressure and dimension we predicted the left ventricular dimension which would be present at any observed diastolic pressure if relaxation were complete. At intervals of 0.25 T or less we compared this predicted fully relaxed dimension with the actual dimension. The predicted and actual dimension were not significantly different at end-diastole in any beat where the next beat began > 3.5 T after maximal negative dP/dt. This indicates completion of relaxation prior to end-diastole in all such beats. An end-diastolic difference in predicted v. actual dimension (when the beat began < 3.5 T after maximal negative dP/dt) identified incomplete relaxation. This difference between the predicted fully relaxed dimension and the actual dimension quantified the extent of incomplete relaxation. Earlier in diastole this difference quantified the effect of relaxation on ventricular dimension and thus diastolic filling. Under widely varying hemodynamic conditions, except with severe failure, the time of the end of the effect of relaxation on diastolic pressure-dimension was 2.85 ± 0.33 (s.d.) T after maximal negative dP/dt. Under severe hemodynamic stress this time occurred earlier in diastole. This early end of the influence of relaxation on diastolic pressure-dimension relationships could be predicted from P at maximal negative dP/dl, T, and the fully relaxed diastolic pressure-dimension relationship. Thus, T is a load-independent index of left ventricular pressure fall under stable hemodynamic conditions. Use of T aids in the identification of changes in the relaxation time course, quantification of incomplete relaxation and the time course and extent of the effect of relaxation on pressure-dimension relationships during the diastolic filling period. The extent of incomplete relaxation and/or the effect of relaxation on diastolic dimensions throughout diastole can be quantified by comparing the actual dimension to the fully relaxed dimension at any pressure during diastole.

Cardiovascular protection by Ca antagonists

Abstract: The application of Ca antagonists as antianginal, antiarrhythmic, antihypertensive, or cardioprotective drugs makes use of the different manifestations of the same fundamental inhibitory action on transmembrane Ca conductivity. The beneficial influence of Ca antagonists in coronary disease is probably complex because at least three therapeutically important factors seem to work together: (1) direct reduction of myocardial energy expenditure and, therefore, oxygen demand: (2) indirect decrease in cardiac oxygen requirement by facilitation of heart work at a reduced level of arterial blood pressure: and (3) improvement of myocardial oxygen supply due to vasodilator or spasmolytic effects particularly on extramural coronary vessels (stem arteries, collaterals, anastomoses).

Recommendations for standardization of measurements from M-mode echocardiograms

Abstract: Measurement sites and their landmarks on the M-mode echocardiogram have not been clearly standardized. AS a result, significant interobserver and even intralaboratory variation in measurement techniques and results exists The extent of these variation has recently been studied by the American Society of Echocardiography, who have made recommendations regarding quantification in M-mode echocardiography[1]. These recommendations were based on measurement techniques that gave most reproducible results when used by a group echocardiographers. It was also assumed that complete standardization was possible, and that for a single measurement, recommendations could be made that were valid in all circumstances. The Working Group in Echocardiography of the European Society of Cardiology has adopted a slightly more flexible approach to this problem, and the following criteria are recommended for standardization and quality control of M-mode echocardiograms.

‘Angina’ and normal coronary arteriograms: a follow-up study

Abstract: Follow-up of patients with possible angina but normal coronary arteriograms suggests that coronary artery spasm or other causes of myocardial ischaemia are rare in these patients. Oesophageal spasm proved a common cause of diagnostic difficulty.

Contrast echocardiography: transmission of echoes to the left heart across the pulmonary vascular bed

Abstract: All available reports indicate that the echoproducing quality of agents used for contrast echocardiography is lost during their passage through the pulmonary or systemic capillary bed. A technique has been developed to transmit echoes to the left heart across the pulmonary vascular bed with the use of venous catheterization. In 43 patients with acquired or congenital heart disease, a balloon-tipped catheter was wedged in a pulmonary arterial branch, the balloon was inflated, then rapidly deflated after injection of an echoproducing substance, while M-Mode or two-dimensional echocardiograms were recorded. Echoes consistently appeared in the left heart following injection of indocyanine green (5–10 mg), saline (5 ml) or CO2 (0.5–1 ml). In 25 patients with a documented left-to-right shunt, echoes also appeared in the right heart chamber receiving the shunt. There were no false negatives nor false positives. No complications or side effects were observed. The presumed mechanism of transmission is the achievement of a high concentration of echoes and/or bypassing of pulmonary capillaries through physiological intrapidmonary shunts. The method is proposed as a screening procedure to be used during right heart catheterization so as to avoid, if possible, the injection ofradioopaque contrast and the invasion of the left heart

Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris

Abstract: Although the major myocardial energy supply comes from oxidation of lipid, carbohydrate requires less oxygen for the same energy yield. Oxfenicine has been shown experimentally to favour carbohydrate utilisation and its effect in a dose of 3–12 mg/kg was studied in 18 patients with obstructive coronary artery disease, both at rest and during angina induced by rapid atrial pacing. No major haemodynamic changes or side effects were observed after the drug. The mean pacing time to angina was significantly increased from 289 ± 33 s to 360 ± 35 s ( P < 0.05) and during pacing, myocardial oxygen consumption fell. After the drug there was a significant increase in myocardial extraction of carbohydrate in the form of lactate, pyruvate and glucose during pacing and in contrast, the myocardial extraction of free fatty acids fell significantly. This increase in myocardial carbohydrate extraction associated with a reduced myocardial oxygen consumption, is of potential value not only in the treatment of angina pectoris, but also in the early phases of acute myocardial infarction.

Transluminal recanalization of coronary artery thrombosis: a preliminary report of its application in cardiogenic shock

Abstract: In a 75 year old male patient with cardiogenic shock due to an acute inferior myocardial infarction the occluded right coronary artery was recanalized via a catheter. The occlusion consisted in an old stenotic lesion with an acute thrombus superimposed. Contrast injection appeared to result in the mobilization of the thrombus with partial reopening of the vessel. After 45 min of intracoronary streptokinase infusion the thrombus appeared to be completely resolved. Reperfusion was associated with the reversal of shock.

Torsades de Pointes: Occurrence in myocardial ischaemia as a separate entity. Multiform ventricular tachycardia or not?

Abstract: Torsades de pointes (Tdp) were evaluated with respect to aetiology, morphology and response to treatment in 16 patients admitted to the CCU. Analysis was based on monitor strip charts and conventional 12 lead ECGs. Underlying disease was total AV block in four patients, acute myocardial ischaemia in nine patients, with acute ventricular aneurysms in four patients; one patient had chronic ventricular aneurysm, one idiopathic hypokalaemia, and one was on quinidine therapy. Heart rate was less than 30 beats min−1 in patients with total AV block and above 90 beats min−1 in six out of 12 patients with basic sinus rhythm. QT prolongation was not present in six patients with acute myocardial ischaemia. Tdp were always initiated by PVCs either falling on the downslope of the T wave of the preceding normal beat or shortly after it in the range of a U wave. Coupling intervals in a run of Tdp were variable in most patients, with an increase in eight patients and a decrease in five patients. In patients with total AV block Tdp could be controlled by increasing the heart rate through pacemaker stimulation. Patients in sinus rhythm (heart rate above 60 beats min−1) received antiarrhythmic drugs: propafenon was effective in 80% (eight out often patients). Ten patients were long-term survivors. Outcome of the acute stage of the disease seemed to be determined by underlying myocardial function. Differentiation between Tdp and multiform ventriadar tachycardia (i.e. VT with torsion of QRS complexes occurring in acute myocardial ischaemia) seems unnecessary to us, since morphological features were similar in both groups with the exception of QT prolongation, which was absent in six out of nine patients with acute myocardial ischaemia. Propafenon was active in patients without as well as with QT prolongation.

Oesophageal spasm and angina : diagnostic value of ergometrine (ergonovine) provocation

Abstract: Oesophageal spasm can be difficult to distinguish from cardiac pain. Ergometrine (ergonovine) provocation with oesophageal manomelry offers a useful diagnostic test.

Serial electrophysiological testing of antiarrhythmic drug efficacy in patients with recurrent ventricular tachycardia.

Abstract: The purpose of the present study was to determine the predictive value of serial electrophysiological testing during antiarrhythmic therapy in patients with recurrent ventricular tachycardia and/or ventricular fibrillation in regard to symptomatic status and outcome. Eleven patients (ten male, one female, mean age 54 ± 10 years, mean ± S.D.J with recurrent ventricular tachycardia were studied. Mean ejection fraction was 34 ± 12%. Most patients suffered from coronary artery disease. The median duration of recurrent ventricular tachycardia before the study was 12 weeks (minimum one week, maximum 16 years). In seven patients between one and 61 cardioversions had been performed before the study to terminate ventricular tachycardia. Ventricular tachycardia could be initiated by programmed right ventricular stimulation in all patients. After control recordings had been obtained, the stimulation tests were repeated during antiarrhythmic therapy until an effective regimen was found. The following drugs were used in this sequence: disopyramide, mexiletine, propafenone, aprindine plus beta-adrenergic blocking drugs and digitalis. In three patients, there was no change in the inducibility of ventricular tachycardia during therapy whereas in eight patients, ventricular tachycardia was more difficult to induce or no longer inducible. Patients were followed at regular intervals (mean follow-up time 41 ± 22 weeks). In those three patients in whom ventricular tachycardia was still inducible, two sudden deaths occurred; one patient was referred to surgery because of persistent spontaneous and inducible attacks of ventricular tachycardia despite antiarrhythmic therapy. No cardiac death occurred in the eight patients in whom ventricular tachycardia was more difficult to induce or no longer inducible. All patients were asymptomatic, and had no recurrence of their ventricular tachycardia in their Hotter ECGs. Thus far, serial electrophysiological testing has been useful in predicting antiarrhythmic drug efficacy in patients with recurrent ventricular tachycardia. It may help to prevent sudden death in these highly endangered patients.

Comparison of dipyridamole and treadmill exercise for enhancing thallium-201 perfusion defects in patients with coronary artery disease

Abstract: Dipyridamole was compared with exercise as a method of enhancing myocardial perfusion defects on thallium-201 scintiscans. Twenty patients with angina had scans after treadmill exercise to near the limit of effort tolerance, and again 4 h later in the redistribution phase. On a separate occasion the same patients had scans after intravenous dipyridamole 0.6 mg/kg. Fifteen of them were also investigated by coronary angiography. Exercise and drug-induced coronary dilatation caused segmental abnormalities of similar degree but the anatomical areas showing these perfusion defects correlated less well. Neither technique offered any clear advantage over the other in predicting the site of coronary stenosis, or in the quality of images obtained. Unwanted drug effects after intravenous dipyridamole were minor but included chest pain in four patients. Intravenous dipyridamole can reasonably be used instead of exercise for thallium-201 scintiscans. The technique will be of particular value when exercise testing is impracticable.

Restoring forces and relaxation of rat cardiac muscle.

Abstract: Sarcomeres in cardiac muscle can actively shorten to a length which is shorter than their length at slack length of the resting muscle. The aim of this study on rat cardiac trabeculae was to analyse the origin and magnitude of forces, which restore sarcomere length to slack length during relaxation. Three possible sources of restoring forces were considered: (1) passive elastic elements: (2) repulsive forces between thin filaments in double overlap, (3) opposing forces, which may result from deformation of thick filaments. Sarcomere length was measured and controlled with the use of light diffraction techniques. The results show that: (a) Hypotonic solutions, which led to increase in cross-sectional area of the trabeculae of 15%, i.e. equivalent to sarcomere shortening of about 0.25 μm, did not produce changes of sarcomere length at slack length of resting muscle. (b) Active force, which was developed in conventional Krebs-Hcnseleil solution at 25°C, depended on sarcomere length (SL) and has been found to be zero at SL = 1.58 μm (minimal active SL) and maximal at SL = 2.35 μm. Passive force was developed if sarcomeres were stretched beyond 2.15 μm. (c) Minimal active sarcomere length at the plateau of tension during tetani which were evoked in the presence of caffeine (10 mmol I−1) equalled 1.35 μm (d) The effect of rapid length perturbations during contractions at controlled sarcomere length consisted of diminution of force development. This deactivating effect of sarcomere motion was manifest if motion occurred after peak tension and increased sigmoidally during the twitch. (e) Minimal sarcomere velocity of lengthening (3–5μm s−1) was found to exist during unloaded contractions following a rapid length perturbation, which led to deactivation. Rcapplication of a load of less than 1% of maximal tension during the unloaded relaxation phase led to a 10-fold increase of lengthening velocity. The results suggest that total restoring force in isolated cardiac muscle which is mainly due to repulsion of thin filaments is smaller than a few percent of maximal actively developed tension. The contribution of passive elastic elements to restoring force is probably negligible. Opposing forces are not sufficiently large to prevent sarcomeres from shortening to well below the length of thick filaments. The deactivating effect of sarcomere motion and the effect of external load seem to be more important to relaxation than the presence of restoring forces at short sarcomere lengths.

Cardiac relaxation and myofibrillar interactions with phosphate and vanadate

Abstract: Covalent alterations of cardiac myofibrils by protein phosphorylation may alter the free Ca**-force relation in a way that would affect the relaxation properties of the heart independent of the sarcoplasmicfree Ca concentration. The clearest picture for such an alteration is emerging from studies of phosphorylation of troponin I. Troponin I is phosphorylated in situ as a specific response to p-adrenergic stimulation and in vitro phosphorylation of cardiac myofibrils results in a rightward shift of the free CA**-myofibrillar activation relation. The mechanism for this effect appears to be an alteration of calcium binding properties of myofibrillar TnC induced by phosphorylation of Tnl. This effect may be responsible, in part, for the relaxant effect of catecholamines. P-light chains of myosin are partially phosphorylated in beating hearts but there is as yet no clear indication that the covalent phosphate content of myosin changes with the physiological state of the heart. Vanadate, a transition state analogue of phosphate, present in most tissues including heart, may modulate relaxation of the heart by a non-covalent interaction with myosin. We found that vanadate ion inhibits isometric tension and immediate stiffness of chemically skinned heart muscle fibers with a Ki of 50 HM. Vanadate did not affect myofibrillar calcium binding or the Ca dependence of normalized isometric force development by the heart fibers. Vanadate also depressed shortening velocity of the chemically skinned fibers contracting with zero external load. Our data therefore indicate that vanadate may not only alter the affinity of cardiac myosin for actin but also the rate ofcross-bridge turnover.

Myocardial relaxation IV: mechanical determinants of the time course of left ventricular pressure decline during isovolumic relaxation

Abstract: Relaxation of isolated mammalian cardiac muscle is known to be influenced by loading conditions, but the mechanical determinants of relaxation velocity in the intact heart are not well defined. Accordingly, we measured the time constant (T) of left ventricular (LV) isovolumic pressure decline during descending and ascending thoracic aorta cross-clamp (single beat interventions) and during constriction of the descending and ascending thoracic aorta (5-min steady-state experiments). The single-beat interventions which acutely increase systolic pressure and length and decrease shortening resulted in a prolonged (increased) T. In steady-state interventions, descending aorta constriction produced an increase in T, while ascending aorta constriction produced a decrease in T. In these studies, the mean arterial pressure in the arch of the aorta increased in the descending constriction experiments and decreased in the ascending constriction experiments, and thus baroreceptor reflex activity may have been responsible for the observed differences. These studies confirm the dependency of LV relaxation on systolic pressure and suggest that other factors are superimposed on the load-dependency of relaxation in the intact heart.

The role of non-uniform sarcomere behaviour during relaxation of striated muscle

Abstract: It has previously been shown that there are marked non-uniformities in the pattern of sarcomere length changes during relaxation of a muscle fibre. This problem has now been studied in more detail during both twitch and tetanus in frog single muscle fibres and some of these results are presented to elucidate the mechanical consequences of the non-uniform sarcomere movements. The sarcomere behaviour during an isometric twitch is essentially the same as that observed during a tetanus in a given fibre: the sarcomere pattern is stable during the rising phase, the peak and the initial portion of the relaxation period. The pattern becomes non-uniform at a point (approx. 73% of peak force) which coincides with the beginning of a rapid fall in tension. At this point some segments (altogether c. 70% of the fibre length) start to shorten at the expense of others which are overextended. Maximum shortening, and elongation, is attained as the isometric tension approaches zero (2–5% of peak force). The majority of the sarcomeres in the fibre thus produce mechanical work (against a decaying load) during the isometric relaxation phase. The onset on non-uniformity varies with the time at which peak twitch force is attained. Thus, if a fibre is released to redevelop tension at different times during a twitch, the onset of non-uniformity is found to shift correspondingly to coincide with the beginning of the rapid tension fall in each case. The results suggest that the mechanical activity decays at different rates along the length of the fibre. The cross-bridges (reduced in number) in the weaker segment(s) will be stretched and when the stretch exceeds approximately 18 nm/half sarcomere the bridges start to slide. It appears that the yielding somehow further reduces the activity in this segment leading to a steeper decline in tension. It is possible to induce the non-uniform behaviour (and the rapid relaxation phase) at an earlier time by applying a stretch to the fibre so that the weak segments start to yield. In this way the rapid relaxation phase may be initiated already at the peak of the isometric twitch. The results suggest that the non-uniform behaviour provides a mechanism by which the isometric relaxation is speeded up. Evidence is presented to show that a similar mechanism may be effective also during relaxation of cardiac muscle.

Can unstable angina pectoris be due to increased coronary vasomotor tone

Abstract: In this study it is argued that the clinical manifestations of unstable angina pectoris, with at its extreme end impending myocardial infarction, may be due to increased coronary arterial vasomotion superimposed on a pre-existing obstruction in a coronary artery. As nifedipine, a powerful calcium antagonist, has initially proven its efficacy in relieving the symptoms of Prinzmetal's angina, a condition in which severe spasm of the coronary artery is now proven to be the main cause, the drug was given to two groups of patients in whom abnormal vasomotion was suspected and its effects scrutinized. Twelve patients with symptoms of coronary artery disease (CAD) were studied with repeated arteriograms after injection of 0.15 mg nifedipine in the left coronary artery. Two control cine-angiograms were made prior to drug administration and two cinefilms were repeated 30 s and 5 min after administration of nifedipine. The mean diameter of the normal, stenotic and poststenotic segments showed a statistically significant increase after drug administration. Vasodilalion persisted after coronary O2 saturation, and presumably coronary flow, had returned to normal. In 52 other patients, who were seen in the coronary care unit for impending myocardial infarction and who had been treated with maximal beta-adrenergic blockade, nitrates and bedrest, but who remained symptomatic, nifedipine 60 mg orally for 24 h was added to the treatment. Within 2 h after administration 42 of the 52 became asymptomatic. In the 10 non-responders, all with extensive multi-vessel disease, two sustained a myocardial infarction and eight received urgent coronary artery bypass grafting in an effort to alleviate their symptoms. All had severe 3 vessel disease in contrast to the responders in whom 1 or 2 vessel disease was predominant. These data show that increased coronary artery vasomotion can be influenced by nifedipine. The excellent clinical response to the drug in this group of patients with unstable angina pectoris indicates that nifedipine may become the preferred agent to be used particularly when the cause of the angina pectoris is suspected to be the result of abnormal coronary vasomotor tone.

Partial atrial electrical standstill: report of three cases and review of clinical and electrophysiological features

Abstract: Three patients with partial atrial electrical standstill are described. Serial electrocardiograms and electrophysiological studies were performed after a clinical follow-up ranging from four to ten years. Two patients had valvular heart disease and one patient had a sick sinus syndrome. Case I presented, on the admission electrocardiogram, an atrioventricular (AV) junctional rhythm whereas paroxysmal atrial fibrillation had been previously documented. Case 2, who had had long-standing atrial fibrillation presented on admission absence of fibrillation waves and simulated AV junctional rhythm. In case 3 with known sino-atrial block, electrocardiographic monitoring showed sinus rhythm with episodes of slow AV junctional rhythm. Atrial endocardial mapping showed an electrically silent area ranging from a small region near the sinus node (case 1) to the entire right atrium except for a discrete area near the tricuspid valve (case 2). AV dissociation between the electrical activity recorded in the remaining atrium and the junctional escape rhythm was present in every patient. The clinical and electrophysiological features of this entity are reviewed. This study emphasizes the limitations of the electrocardiogram in making the diagnosis of atrial standstill. However, partial atrial electrical standstill should be suspected in patients with AV junctional rhythm or atrial fibrillation with fine waves. This diagnosis may have important therapeutic implications.

Clinical significance of early diastolic changes in left ventricular wall thickness

Abstract: Continuous measurement of posterior left ventricular wall thickness on one or two-dimensional echocardiograms or left ventriculograms has demonstrated an early diastolic period of rapid thinning at a peak rate of 10 ± 1.7 cm/s, significantly greater than the peak thickening rate during systole. In normal subjects, this period ends abruptly, and is coterminous with rapid filling. Thinning rates are greatest at the level of the tips of the papillary muscles, and are significantly lower towards the mitral ring. In patients with ischaemic heart disease, mitral valve opening may be delayed until rapid thinning is complete, showing that it is not a function of left ventricular filling, and therefore likely to be a manifestation of relaxation itself. Thinning rate is reduced in patients with left ventricular hypertrophy due to hypertension, aortic stenosis or hypertrophic cardiomyopathy, when it is associated with a corresponding reduction in the peak rate of dimension increase. It persists when the cause of the hypertrophy is removed as after resection of coarctation of the aorta, even if wall thickness returns to normal. Variation in peak rapid thinning rate with position in the cavity appears to underly abnormal filling patterns in pure mitral regurgitation, and determines the distribution of abnormal wall movement during isovolumic relaxation in patients with coronary artery disease. This distribution also correlates with fibre orientation in normal human hearts as demonstrated by dissection. The period of rapid thinning is associated with intraventricular pressure gradients. It is also exactly synchronous with the early diastolic period when calculated wall stress remains constant in spite of increasing cavity size, an effect that has previously been attributed to viscosity. We conclude that rapid early diastolic wall thinning depends on the integrity of regional fibre arrangement, and is a major determinant of the rate and pattern of the rapid phase of left ventricular filling in normals. Its loss causes disturbances of wall movement during relaxation and filling in disease.

Retrograde P wave polarity in reciprocating tachycardia utilizing lateral bypass tracts

Abstract: Electrophysiological study of 26 patients with paroxysmal supraventricular tachycardia showed that the tachycardias were due to a circus movement using a lateral atrioventricular bypass tract as a retrograde limb of the circuit. The Wolff-Parkinson-White syndrome was overt in 19 cases and concealed in the remaining seven. Retrograde P wave polarity and morphology during tachycardia were studied and related to the location of the bypass tract on the left or right side of the heart. In all cases the P wave during tachycardia was located after the QRS complex. Of 19 cases with left bypass tract, the retrograde P wave in lead I was negative in 14, diphasic (−.+) in four, and indeterminate in one case. In lead V, the P wave was positive in 16 cases and indeterminate in three. Of seven cases with right bypass tract, the retrograde P wave in lead I was positive and bimodal in six cases and indeterminate in the remaining case, while it was negative and bimodal in lead V1 in all but one case. Hence, it may be concluded that analysis of retrograde P wave morphology during tachycardia, together with other electrocardiographs factors, can be useful in determining the type of circuit used in reciprocating tachycardia.

Effects of nifedipine on coronary blood flow and coronary resistance during cold pressor test and isometric exercise in patients with coronary artery disease

Abstract: Eight patients with coronary artery disease performed a cold pressor test (CPT) and hand-grip isometric exercise (HG) before and 20 min following sublingual administration of nifedipine. CPT performed before nifedipine did not change coronary blood flow determined by the thennodilution technique, but increased coronary resistance (control 0.95 ± 18 mm Hg/ml/min; CPT 1.17 ± 0.30, P < 001). Nifedipine prevented the increase of coronary resistance induced by CPT (control after nifedipine 0.74 ± 018 mm Hg/ml/min; CPT after nifedipine 0.76 ± 0.19, NS) and the absolute value of coronary resistance was significantly lower when CPT was repeated after nifedipine. In contrast, during HG, coronary blood flow increased while coronary resistance did not change (control 0.94 ± 0.10 mm Hg/ml/min; HG 0.99 ± 0.23, NS). When HG was repeated after nifedipine, coronary blood flow was greater and coronary resistance lower than during the test performed before nifedipine. The drug's ability to block inappropriate coronary vasoconstriction induced by cutaneous cold stimuli and to increase coronary blood flow during isometric exercise further substantiates its usefulness in the treatment of patients with coronary artery disease.

Treatment of spasm of the coronary artery with nifedipine

Abstract: In nine out of 13 cases in which, under direct visual control, 0.2 mg of nifedipine was injected into a coronary artery in spasm, prompt vasodilation was noted. In 37 other patients, in whom spasm of the coronary artery had been documented at another time, the oral administration of 30 to 60 mg nifedipine led to the suppression of all pain attacks in 26 individuals (71%) and to a significant reduction of these attacks in another four (14%). Nifedipine is a powerful agent capable of relieving coronary artery spasm in the majority of patients.

The diastolic filling of the left ventricle

Abstract: In the intact heart, the determinants of myocardial function are closely interrelated. Alterations in enddiastolic volume indirectly influence afterload and inotropism, whereas alterations in systolic function indirectly affect diastolic filling. The direct determinants of diastolic left ventricular filling include capacitance blood volume, diastolic filling time, atrial contraction, ventricular geometry and the passive visco-elastic properties of the myocardium. Diastolic mural inertia is insignificant. Simultaneous relaxation and filling occur during the early rapid-filling phase, but this period is brief compared to the remainder of diastole. Therefore, at physiological heart rates, systolic relaxation has a relatively minor influence on filling. Diastolic filling appears to be a completely passive phenomenon. The relationship between diastolic mural force and fiber length is determined principally by the elastic properties of the muscle and by viscous properties during dynamic filling. The compliance of the myocardium significantly influences the degree of diastolic mural deformation, end-diastolic fiber length, and therefore systolic function. The geometry of diastolic filling is determined by the anisotropic characteristics of the left ventricular wall. The stiffer major axis circumference increases less than the minor axis circumference during filling, and chamber eccentricity decreases linearly as end-diastolic volume increases. Under normal conditions, right ventricular pressure and volume have minimal effects on left ventricular filling. However, increased diastolic right ventricular pressure can alter the geometry of the left ventricle and influence filling significantly. Thus diastolic filling of the intact left ventricle represents the complex interaction of multiple physiological variables.