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The afterload-corrected end-systolic volume index (ratio of end-systolic stress to end-systolic volume index [ESS/ESVI]) was previously useful in predicting outcome in patients with mitral regurgitation undergoing valve replacement. Therefore we tested ESS/ESVI together with standard hemodynamic variables as possible predictors of outcome in 39 patients with various valvular lesions who underwent valve replacement. Thirteen patients had preoperative mitral regurgitation, 16 had aortic stenosis, nine had aortic regurgitation, and one had mitral stenosis. Twenty-seven patients (group S) had a satisfactory outcome as defined by a return to NYHA class I or II together with a normal postoperative ejection fraction. Twelve patients who died, remained in class III or IV, or had a subnormal postoperative ejection fraction were deemed to have an unsatisfactory result (group U). Mean right atrial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, end-diastolic volume index, end-systolic volume index (ESVI), and end-systolic wall stress were all greater in group U, whereas ESS/ESVI and ejection fraction were lower in group U. When these and other factors were submitted to stepwise discriminant multivariate analysis, ESS/ESVI and ESVI were the only independent predictors of outcome. However, when patients with mitral regurgitation (who might have biased the study) were excluded, discriminant analysis showed ESVI as the only independent predictive variable. We conclude that end-systolic indicators of ventricular function are superior to other standard hemodynamic variables in predicting outcome of valve replacement.

MITRAL-valve prolapse is a common disorder whose prevalence has been reported to be from 6 to 21 per cent in otherwise normal subjects.1 , 2 It is approximately three times more common in females than in males, and it appears in some instances to be familial.3 Its pathogenesis is unknown, although in some cases there may be myxomatous transformation of the valve leaflets or abnormalities of the chordae tendineae, papillary muscles, or adjacent myocardium. An apparent association with heritable disorders of connective tissue, such as Marfan's syndrome,4 Ehlers-Danlos syndrome,5 osteogenesis imperfecta,6 and pseudoxanthoma elasticum,7 suggests that in some cases a common developmental . . .

Unlike most adults with compensated pressure overload of the left ventricle, children with moderate to severe aortic stenosis exhibit pronounced left ventricular muscle hypertrophy, enhanced ejection performance and diminished wall stress. To determine whether these findings are present in other forms of left ventricular pressure overload in children, left ventricular mechanics were studied by catheterization in 14 children with coarctation of the aorta (average peak gradient 39 +/- 17 mm Hg) and in 10 normal children. Ejection fraction and mean velocity of circumferential fiber shortening in the coarctation group (0.74 +/- 0.09 and 1.71 +/- 0.43 circumferences/s, respectively) were significantly higher than in normal subjects (0.65 +/- 0.05 and 1.27 +/- 0.26 circumferences/s, respectively) (p = 0.008), but the ranges for both groups overlapped. End-systolic stress in children with coarctation (77 +/- 20 dynes X 10(3)/cm2) was less than in normal children (121 +/- 24 dynes X 10(3)/cm2) (p less than 0.001), again with overlap of the ranges for both groups. The ratio of end-systolic stress to end-systolic volume index, an estimate of contractile function, was similar in both groups. Relations between severity of obstruction (left ventricular peak systolic pressure, coarctation gradient) and end-systolic stress and between stress and ejection performance were present within the coarctation group. Comparison of these data with those found in children with moderate to severe aortic stenosis shows a similar but less pronounced response to pressure overload due to coarctation of the aorta.

Unique capabilities have been developed to monitor the dynamics behavior of fuel droplets during rapid heating. These capabilities have been applied to study the evaporation, explosive boiling, and secondary atomization behavior of CWF droplets. The objective was to determine the energy flux (heating rate) requirements for explosive boiling and to evaluate the potential for secondary atomization in practical combustion systems. Single CWF droplets were suspended electrodynamically and irradiated from two sides with well-characterized heating pulses. The dynamic response of the droplets was recorded using high-speed cinematography. Explosive boiling thresholds were measured as a function of CWF droplet size and composition. Heat flux intensities were varied from 0.3 to 10 kW/cm2 (equivalent heating rates of 104 to 106 K/s), and heating times were varied from 0.2 to 8.0 ms. Results of this study suggest that fuel additives play a vital role in establishing conditions necessary for internal superheating and explosive boiling. A mechanism is proposed which involves elimination of the water-air interface, inhibition of surface evaporation, and the formation of a fused surface layer during the rapid heating process. In order to achieve fine atomization, droplets must be heated volumetrically. The energy requirements for explosive boiling were proportional to the mass for droplets with equivalent coal loadings and scaled with the weighted average heat capacity for droplets with differing composition. The time domain over which explosive boiling was observed spanned from about 2 to 8 ms. For longer times (lower heating intensities) heat losses due to droplet evaporation prevented the internal superheating required for explosive boiling. At shorter times, the required heat fluxes were well beyond practical technological limitations. The energy fluxes required to cause explosive boiling and secondary atomization are on the order of 1 kW/cm2 for droplets ranging from 75 to 160 μm in diameter (50 percent by mass coal). This may be considered as a target level for advanced combustor designs.

Platelets have been implicated in the pathogenesis of coronary artery disease, and a number of studies have examined platelet function and coagulation parameters in such patients. We have examined platelet coagulant activities, volumes, and aggregate ratios in 23 patients with chest pain, seven of whom had normal coronary angiograms (group I) and 16 of whom had angiographically proven coronary artery disease (group II). There were no significant differences in the mean values for platelet volume or platelet aggregate ratios between the two groups. The platelet coagulant activities concerned with initiation and the early stages of intrinsic coagulation were significantly increased in patients in group II as compared with those in group I. No significant differences were noted between the two groups with respect to prothrombin time, partial thromboplastin time, and plasma levels of fibrinogen and coagulation factors V and VIII. However, the mean activity in plasma of antithrombin III (but not the level of antithrombin III antigen) was significantly lower in patients of group II compared with group I. Overall, our observations provide evidence for an enhanced contribution of platelets to the intrinsic coagulation system in patients with coronary artery disease. The platelet coagulant hyperactivity noted in these patients may reflect a role of platelets in the pathogenesis of coronary artery disease or may be secondary to the underlying arterial disease.

Left ventricular muscle and pump performance were evaluated in 12 normal subjects and 21 patients with aortic regurgitation (10 with minimal symptoms and 11 with congestive heart failure). A computer-based quantitative analysis of biplane left ventriculograms was used. Both patient groups had significant aortic regurgitation documented by ventriculography. Contractile function measured by peak systolic stress/end-diastolic volume and end-systolic pressure/volume curves was poorer than that in normal subjects in patients with heart failure but not in asymptomatic patients. When normalized for muscle mass, stroke work was not depressed in either asymptomatic patients (mean +/- standard error of the mean 0.008 +/- 0.001 joules/g) or patients with heart failure (0.009 +/- 0.004) by comparison with the value in normal subjects (0.010 +/- 0.001). Angiographically determined cardiac index (CI) increased with increasing volume overload even though forward cardiac index measured by the Fick method remained essentially unchanged: normal subjects (total CI 3.7 +/- 0.4 liters/min per m2, Fick CI 2.4 +/- 0.1); asymptomatic patients (total CI 7.6 +/- 0.7, Fick CI 2.3 +/- 0.2); patients with heart failure (total CI 9.1 +/- 0.82, Fick CI 2.1 +/- 0.18). Left ventricular peak stress increased significantly in patients with heart failure (511 +/- 55 dynes/cm2 x 10(-3)) compared with values in normal subjects (360 +/- 33) and asymptomatic patients (428 +/- 50). The combination of decreased muscle function and increased demands on pump function causes a significant increase in end-diastolic pressure only in patients with heart failure (23 +/- 2 mm Hg), which results in pulmonary congestive symptoms.

Primary myocardial sarcomas are rare. We report the scintigraphic findings observed with TI-201, Ga-67, Tc-99m pyrophosphate, and Tc-99m pertechnetate labeled red cell gated cardiac imaging in a patient with this tumor. We found that thallium and gated blood pool imaging can be used both in the diagnosis of these tumors and the assessment of the effects of chemotherapy on the tumor and normal myocardium. The thallium study was particularly helpful in identifying the malignant nature of the tumor by showing extensive infiltration into surrounding areas.

MENAPACE, FRANCIS J., WILLIAM J. HAMMER, THEODORE F. RITZER, KENNETH M. KESSLER, HOWARD F. WARNER, JAMES F. SPANN, and ALFRED A. BOVE. Left ventricular size in competitive weight lifters: an echocardiographic study. Med. Sci. Sports Exercise, Vol. 14, No. 1, pp. 72–75, 1982. To determine if increased left ventricular mass is present in athletes who predominantly perform isometric exercise, this study utilized echocardiograms (echo) from 13 nationally ranked weight lifters (WL) who engaged in isometric exercise while lifting. The thickness of the ventricular septum (VS), the thickness of the posterobasal free wall (LVFW), the diameter of the left ventricular cavity at end-systole (Ds) and end-diastole (Dd) were measured in the weight lifters, all of whom were free of cardiac disease. The findings were compared with 10 normal subjects (N), as well as nine patients with idiopathic hypertrophic subaortic stenosis (IHSS) and eight patients with asymmetric septal hypertrophy (ASH). The septal thickness of the weight lifters was higher than that of the normal subjects. Weight lifters resemble ASH and IHSS patients with an increased VS and a VS/LFVW ratio greater than 1.3. Although meeting the criteria for the diagnosis of hypertrophic cardiomyopathy (HCM), it is unlikely that the weight lifters had this disorder. Two measurements provide a means to separate weight lifters from patients with HCM. Septal thickness, normalized to body surface area (mm/M2), was normal in weight lifters (N=5.81 ±0.56; WL=6.81 ± 0.29; ASH=9.37±0.44; and IHSS= 10.37 ±0.48) and mass/volume ratio VS/Dd (N=0.21 ± 0.02; WL=0.28±0.01) was different from patients with ASH (VS/Dd = 0.40±0.01) or IHSS (0.48 ±0.02). Weight lifters had larger left ventricular cavities than patients with IHSS or ASH as expressed in ratios of VS/DS and VS/Dd. These data indicate that weight lifters have normal left ventricular mass/volume ratios, in spite of an increased septal/free wall ratio.

Examination of the time course of left ventricular ejection has been found useful in several clinical applications. Equilibrium gated radionuclide angiography provides non-invasive means to obtain the ventricular ejection curve. To evaluate the accuracy of the equilibrium gated radionuclide left ventricular volume curve we compared equilibrium gated radionuclide date with biplane cine-angiography in 16 patients examining each set of data on a point by point basis. The cine-angiographic data consisted of 60 frame per second biplane cineangiograms and the radionuclide data consisted of 28 points spanning the cardiac cycle. All data was normalized for the patient's heart rate and stroke volume. The equilibrium gated radionuclide angiographic data accurately reproduced the contrast angiographic data at each point on the curve. This result justifies using the equilibrium gated radionuclide time activity curve to evaluate parameters such as early systolic ejection rates or rates of maximum ventricular ejection.

An acute thrombus at the site of an atherosclerotic obstruction is the usual cause of myocardial infarction. Thrombolytic therapy is an exciting new therapy for reducing the extent of myocardial infarction by lysing intracoronary clots. Such therapy has now been widely applied by: prolonged intravenous infusion of streptokinase during the first 24 hours of infarction; intracoronary infusion of streptokinase, urokinase, or tissue plasminogen activator; early, high dose, brief duration intravenous infusion of streptokinase; or intravenous infusion of tissue plasminogen activator. Intracoronary streptokinase or urokinase achieves reperfusion of the coronary artery in 75% of patients and is associated with serious bleeding in 4.8% of patients. Intravenous infusion of streptokinase achieves reperfusion of the coronary artery in 50 to 80% of patients. The incidence of serious bleeding with intravenous streptokinase averaged 0.8% in 5 studies of 237 patients and was 12.8% in 1 additional study of 80 patients. Salvage of the jeopardised myocardium and improvement in left ventricular function occurred when coronary reperfusion was achieved. Mortality in streptokinase-treated patients was significantly reduced at 30 days and at 6 months after infarction in the single randomised mortality study done to date; however, more data are needed on this important question. Reocclusion after thrombolysis averages 17% in patients treated with streptokinase by either intracoronary or intravenous infusion. The newly reperfused coronary artery has been stabilised in some patients by coronary bypass surgery or percutaneous transluminal angioplasty, but further studies are needed to define criteria for appropriate patient selection for these procedures.

This investigation was designed to determine if chronic volume overload is associated with altered collagen content of five regions of the myocardium. Five adult cats were subjected to a 6-week period of chronic volume overload induced by atrial septotomy and five untreated animals served as controls. Significant (P < 0.05) right ventricular hypertrophy was present as indicated by the right ventricular body weight ratio. For control animals this ratio was 0.68 ± 0.04 g/kg; for volume overloaded animals it was 0.83 ± 0.05 g/kg.) The collagen content was assessed by measuring the hydroxyproline content of the dried cardiac muscle. Right ventricular endocardium hydroxyproline in volume overloaded animals was significantly elevated above that in control animals (in the latter it was 5.30 ± 0.36 μg/mg; in the former it was 6.33 ± 0.18 μg/mg) while the epicardial collagen content was unchanged. Similarly, the amount of collagen found in the left ventricle was significantly increased in the endocardium and normal in the epicardium. Septal collagen concentration was unaltered in volume overloaded animals. This study demonstrated that alterations in cardiac muscle collagen concentration are associated with volume overload and that these cellular changes are nonuniform.

In recent years it has become clear that the fundamental action of digitalis in the relief of congestive heart failure is its ability to enhance the contractile state of the ventricle. This positive inotropic effect is a direct action of the drug and is observed in both the failing and normal heart. In patients without a lowered cardiac output, the contractile effect is not translated into an elevation of total blood flow, principally due to the direct arteriolar constrictor action of the drug which increases the resistance to ventricular ejection, and perhaps the constrictor effect on the hepatic veins which results in little change or a decline in venous return to the heart. In contrast, in patients with congestive heart failure, the glycoside produces a marked rise in the reduced cardiac output and thereby allows relaxation of the intense sympathetic-mediated vasocontriction characteristic of the heart failure state; thus, arteriolar and venous dilation due to reflex withdrawal overrides the mild direct vasoconstrictor effect of the drug. From these observations, it is concluded that the digitalis glycosides have important direct and indirect actions on the heart and peripheral circulation, and the overal effects of these agents on the cardiac output and other hemodynamic variables are dependent on the presence or absence of heart failure at the time the drugs are administered. Thus, the glycosides' enhancement of the contractile state of the heart, viewed as a muscle and considered in terms of the mechanics of contraction, is observed as an improvement of the heart examined as a pump only when there is abnormal cardiac performance. Present evidence implies that the basic contractile action of digitalis rests upon its cellular effect of potentiating excitation-contraction coupling. This effect appears to be mediated by glycoside-induced enhancement of the intracytoplasmic concentration of calcium ions around the myofibrils during electrical activation, thereby potentiating contraction. More specifically, it is speculated that digitalis has the ability to alter the configuration of the cell membrane of cardiac muscle, thus increasing calcium and sodium influx during depolarization; these cations then are taken up by sarcoplasmic reticulum which results in the release of microsomal-bound calcium into the myoplasm surrounding the contractile machinery. It is likely that the arrhythmia-provoking properties of digitalis are related to the loss of intracellular potassium and the inhibition of the membrane pump ATPase system required for maintaining intracellular potassium concentrations. This postulation that the inotropic and certain toxic actions of digitalis are mediated by different mechanisms is important clinically, since the two properties of the glycoside can be dissociated by the administration of potassium. The increase in myocardial contractility produced by digitalis requires an increase in myocardial oxygen consumption, as it does for other inotropic agents. In the presence of heart failure, this direct effect on myocardial oxygen consumption may be masked by the drug's favorable indirect effects on certain hemodynamic variables which result in the reduction of total myocardial oxygen requirements. From the above observations, it is apparent that a thorough understanding of the hemodynamic and cellular actions of the glycosides is essential for the proper application of these extraordinarily beneficial drugs in patients.

Oxidative phosphorylation was measured polarographically in mitochondria isolated from normal ventricles and from the ventricles of guinea pigs and cats with experimental heart failure produced by constriction of the aorta or pulmonary artery. The presence of heart failure was proved by the study of myocardial mechanics in vitro, by cardiac catheterization, and by postmortem examination. Mitochondria from failing ventricles had normal oxidative phosphorylation, and P-O ratios, respiratory control, oxygen consumption and ATPase activity did not differ from those of mitochondria from normal hearts. Results were the same whether incubations were performed at 25° or 37°C and whether glutamate or pyruvate and malate were used as the substrate. Mitochondria showed functional deterioration, probably due to fatty acid accumulation, when incubated for more than 10 min at 37°C or when isolated from hearts made hypoxic in vivo for as little as 3 min. The results of this study suggest that decreased myocardial contractility in experimental heart failure is not due to an intrinsic defect in mitochondrial function.

Although previous studies have suggested a depression of myofibrillar ATPase in the presence of heart failure, their interpretation has been limited by failure to exclude mitochondrial contamination and lack of information regarding the contractility of the tissue studied. To explore this fundamental question, myofibrils were prepared from the right and left ventricles of 15 normal cats, 10 cats with right ventricular hypertrophy and 19 with right ventricular hypertrophy and right ventricular failure, the latter groups following graded pulmonary artery stenosis. The contractility of these hearts was assessed using their right ventricular papillary muscles isolated in a myograph. Myofibrillar ATPase in all groups was maximally activated by 5 mM ATP, 5 mM MgCl 2 at pH 7.0 and 37°C, while mitochondrial contamination was eliminated by sodium azide. In right ventricular failure, right ventricular myofibrillar ATPase was depressed by 39% from an average of 0.18±0.01 in normal cats to 0.11±0.01 µmole inorganic phosphate/mg protein per min (P

Paired electrical ventricular pacing has been shown to be an effective means of overcoming digitalis-induced arrhythmias, but it has not been used clinically because of the danger of inducing ventricular fibrillation and because the second contraction interferes with ventricular filling. For these reasons, the possibility that ventricular pacing with a single electrical stimulus might accomplish the same effect was examined. A pacing catheter was passed by way of the jugular vein into the right ventricle of 16 dogs, and ouabain was infused at the rate of 1 μg/kg per min. In 9 control animals serious ventricular arrhythmias occurred at 51.0 ± 3.6 (SEM) min and death at 94.9 ± 5.9 min. In 7 dogs arrhythmias occurred at 51.6 ± 3.7 min but were completely abolished by pacing at a frequency 20 percent above the intrinsic rate. However, the total cumulative dose of ouabain that caused death remained unchanged, and the animals with pacing died of ventricular fibrillation at 94.6 ± 8.2 min. In other studies in 23 dogs infusion of potassium was started at the time of initial toxicity, but it had no effect on the cumulative dose of ouabain considered lethal. Neither pacing nor infusion of potassium altered the maximal tolerated dose of ouabain. We found that arrhythmias can be completely suppressed by ventricular pacing, but that they recur during administration of potassium. We conclude that ventricular pacing with a single electrical stimulus will effectively overcome serious digitalis-induced arrhythmias and that it should be considered for trial in patients with refractory digitalis toxicity.

CARDIAC arrhythmias are frequent, serious complications of acute myocardial infarction1 2 3 and are associated with a 7 to 17 per cent increase in mortality.2 , 4 The extent to which arrhythmias are a direct cause of death in acute myocardial infarction has been estimated from clinical and pathological studies,5 6 7 but there has been little electrocardiographic documentation of the immediate preterminal rhythms. Documentation of possible transient disturbances of rhythm before the terminal arrhythmias has also been limited. Availability of a continuous electrocardiographic monitoring device has made it possible to detect and document the arrhythmias that follow myocardial infarction. The cardiac rhythm of 30 patients . . .

It would appear that when the ventricle is chronically stressed by an abnormal pressure load, its initial response is to increase the total muscle mass. This increase in muscle mass, operating in conjunction with the Frank-Starling mechanism and increased sympathetic stimulation,15 maintains over-all circulatory compensation despite depression of the intrinsic contractile state of each unit of myocardium. This depression is expressed as a reduction in the intrinsic velocity of shortening and tension development of each myocardial fiber. The marked reduction of cardiac norepinephrine stores, which occurs in the failing heart,5, 15, 16 impairs the potential support available to the myocardium from sympathetic stimulation,17 although it is not responsible for the intrinsic depression of myocardial contractile state.2 Although an improvement in function in response to positive inotropic stimuli can occur in failing muscles, the augmentation is decreased and the resultant level of contractility remains less than normal. As the intrinsic contractile state of each unit of myocardium becomes more severely depressed, there is a more extensive fall in the maximal velocity of shortening (Vmax), a decrease in maximal isometric force and a decrease in the rate of force development. At this point, circulatory compensation can no longer be maintained despite maximal utilization of the compensatory mechanisms provided by the Frank-Starling mechanism and the increases in muscle mass; overt congestive heart failure then occurs.

The sympathetic nervous system exerts an important direct effect on cardiac function which is mediated by the release at the terminal sympathetic nerve endings of the neurotransmitter norepinephrine. These nerve terminals are complex structures involved in synthesis, uptake, binding and storage as well as release of norepinephrine. The evidence for alteration of many of these functions in congestive heart failure, which is characterized by a depletion of myocardial norepinephrine stores, is reviewed. Although cardiac norepinephrine depletion alone is not responsible for the intrinsic depression of cardiac contractility in failing heart muscle, this depletion probably removes a potentially important compensatory mechanism for augmenting myocardial force development and velocity of contraction in the failing heart. Evidence for parasympathetic-sympathetic system interactions as they affect the heart, as well as alterations in the parasympathetic nervous system in heart failure, is also presented briefly.

HE FUNDAMENTAL PHYSIOLOGIC DERANGEMENTS, the disturbed events comprising cardiac contraction, the altered modulation of cardiovascular function, and the role of compensatory mechanisms in patients with congestive heart failure have been the subject of intense interest and investigation for many years. In the past, considerable attention has been focused on the clinical manifestations of heart failure and the hemodynamic alterations characteristic of this common pathologic condition. More recently, following the development of a multiplicity of improved technics and their application to experimental biologic systems and patients, a great body of new information has been provided which has permitted important advances in our understanding of the pathophysiology of congestive heart failure. Therefore, it is desirable at this time to examine certain of these findings, methods of evaluation, and current concepts concerning the mechanisms and regulation of contraction of the failing heart in man. This work begins with consideration of the principal determinants governing the performance of the intact ventricle and progresses to interpretation of the experimental data which form the basis for the conclusion that, of these major determinants, the fundamental abnormality in congestive heart failure

WHEN the pharmacologic basis of therapy in angina pectoris is under consideration, it has been traditional to focus attention principally on alterations of coronary blood flow.1 2 3 A more accurate view is that the pain of myocardial ischemia is related to an unfavorable relation between myocardial oxygen demands and the availability of oxygen to the heart.4 Thus, in the analysis of the therapeutic measures available for the relief of angina pectoris, it is important to take into account the possibility of their actions of diminishing myocardial oxygen consumption as well as of improving coronary blood flow. The three important hemodynamic variables . . .

The three-component model for muscle proposed by A. V. Hill (1) has been useful in describing the contractile activity of cardiac muscle in vitro (2) and in vivo (3). The contractile element (CE) of this model is assumed to be freely extensible at rest, but with activation it shortens according to a characteristic inverse relation between the velocity of shortening and the load (4). The CE is in series with an elastic element (SE) so that during isometric contraction, the activated CE shortens and stretches the SE, the rate of tension development (dP/dt) being determined by the CE velocity and the stress strain relation of the SE (1). Thus the external manifestations of CE activity depend to a large extent on the properties of the SE.Although the stiffness of the SE is unaffected by inotropic interventions, or the course of active state (5,6), it does become somewhat stiffer following damage from segmental compression (7). With the recent application of cardiac muscle mechanics to the study of pathologic ...

The aim of this study was to determine whether the impairment of contractility in the myocardium obtained from hypertrophied and failing hearts is due to a decreased store of energy and whether an imbalance exists between energy production and energy utilization in these hearts in vivo. Right ventricular hypertrophy and right ventricular failure were produced in cats by constriction of the main pulmonary artery. Concentrations of creatine phosphate (CP) and adenosine triphosphate (ATP) were determined in samples removed from the right ventricles of these animals during life and in papillary muscles isolated from these same hearts. The papillary muscles from the cats with hypertrophy and failure exhibited depressed intrinsic contractility. The stores of ATP were normal in both the ventricular muscles and the papillary muscles in animals with hypertrophy and failure. Although the stores of CP were significantly depressed in the right ventricles of these animals, the stores had increased toward normal in papillary muscles isolated from these same hearts in vitro. The finding of normal energy stores in the papillary muscles from animals with hypertrophy and failure indicates that their intrinsically depressed contractility cannot be due to reductions of their energy stores in vivo such as were found in the samples from the ventricular wall. The differences between high energy phosphate stores in failing heart in vivo and these stores as they are replenished in vitro also indicate that the in vivo depressions are secondary to an imbalance between energy production and energy utilization in the overloaded, hypertrophied and failing heart.

Digitalis toxicity is among the most common adverse drug reactions, and may cause arrhythmias and conduction disturbances in as many as 1 of 5 patients. Particularly responsible are the electrophysiologic properties of digitalis in increasing the automaticity of subsidiary pacemakers, reducing the refractory period and prolonging conduction velocity in the atria and ventricles, and delaying conduction in the atrioventricular (A-V) node. Underlying these electrophysiologic effects are digitalis-influenced alterations of cardiac cell transmembrane movements of sodium and potassium; the induction of ectopic impulses due to increased automaticity appears to be caused by inhibition of the activity of the sodium-potassium membrane adenosine triphosphatase (ATPase) pump. Digitalis can provoke every type of cardiac arrhythmia, and no specific disorder of rhythm can be considered absolutely pathognomonic of digitalis toxicity. The factors that predispose to digitalis toxicity, as well as the onset and duration of action of the agent, must be taken into account. Potassium has relatively little influence on the toxic and the contractile actions of digitalis when the cation is administered after the glycoside has been taken up by the myocardium. In contrast, alterations in serum potassium effected before treatment with digitalis may have drastic effects on the electrophysiologic and contractile actions of the glycoside; hyperkalemia reduces the binding of digitalis to the myocardium. Diphenylhydantoin, lidocaine and propranolol are effective in terminating digitalisprovoked tachyarrhythmias, usually without inducing or worsening A-V block. Atrial or ventricular pacing to achieve electrical overdrive of the ectopic focus may be used if standard measures fail. In complete heart block, potassium should not be administered; atropine and electrical pacing should be used.

A new and easily applicable means based on force-velocity principles within the framework of muscle mechanics is presented for quantification of ventricular contractility, independent of loading, in conscious patients. In the intact heart during isovolumic contraction, alterations in ventricular geometry are small, and thus contractile element velocity (VCE) can be assumed to equal series elastic elongation. It was therefore considered in this study that VCE during isovolumic portion of ejecting beats could be determined entirely from isovolumic pressure (IP) and its rate of rise ( dP dt ) without requiring knowledge of tension; this provided the rational basis for accurate calculation of instantaneous isovolumic VCE in the spherical or ellipsoidal ventricle as ( dP dt )/( K × IP ) , where K is series elastic constant of 32 per muscle length (ML) at body temperature. Further, it was recognized that VCE at the ordinate is identical when derived from pressure-velocity or tension-velocity curves, and since the left ventricular pressure-velocity relation can be defined precisely, construction of the isovolumic IP to VCE curve and extrapolation to zero load allowed determination of maximal VCE (vmax), the independent numerical measure of contractility. High fidelity left ventricular pressures and corresponding dP dt were continuously recorded in 23 studies in 8 conscious patients without valvular regurgitation or ventricular segmental disease. Increasing contractility by leg exercise raised VMAX from 1.19 to 1.58 ML/sec and by isoproterenol to 2.03 ML/sec (P dP dt during isovolumic systole affords a new, practical, sensitive and valid means of quantifying left ventricular contractility Without influence of preload and afterload from beat to beat in individual patients. In addition, since VMAX is expressed in terms of muscle units and is free of variables of left ventricular loading and wall thickness, this method permits specific comparison of inotropic state among different patients.

Contractile properties of soleus muscles isolated from 31 euthyroid (EU), 20 hyperthyroid (HT), and 18 myxedematous (MY) rats were studied in a myograph. At 100 stimuli/sec maximum isometric tension was essentially identical in EU (17.2 +/-0.5 g/mm(2)) and HT (17.7 +/-0.5 g/mm(2)) muscles, but was significantly depressed in MY muscles (11.5 +/-0.7 g/mm(2)). The rate of tension development was increased in HT (103 +/-4.5 g/sec per mm(2)) as compared to both EU (86.2 +/-4.6 g/sec per mm(2)) and MY (38.4 +/-2.2 g/sec per mm(2)) muscles, while the duration of the active state was shortened in HT (77.1 +/-2.3 msec) as compared to EU (105.1 +/-1.1 msec) muscles and was prolonged in MY muscles (153.3 +/-6.0 msec). The mean rate of isometric relaxation was 26.5 +/-4.9 g/mm(2) per sec in EU muscles, more rapid in HT muscles (33.1 +/-1.3 g/sec per mm(2)), and slower in MY muscles (16.0 +/- g/mm(2) per sec). The fusion frequency was greater in HT muscles, averaging 68.5 +/-3.6 stimuli/sec compared to EU muscles (38.1 +/-1.2 stimuli/sec) and to MY muscles (33.3 +/-4.0 stimuli/sec). At 40 stimuli/sec tension averaged 16.4 +/-0.8 g/mm(2) in EU muscles while at the same frequency tension was reduced in HT muscle, averaging 14.2 +/-0.5 g/mm(2). All differences were significant (P < 0.01). In conclusion, HT and MY result in profound alterations in the intrinsic contractile properties of skeletal muscle. While tension in HT muscles is maintained in vitro at a stimulus frequency of 100 stimuli/sec, the reduction in duration of active state may lower tension in vivo by preventing complete fusion of contractile events. In MY tension is reduced as a consequence of the lowered intensity of the active state. These changes explain, at least in part, the weakness of muscle activity in both HT and MY.

The responses of isolated cat papillary muscles and left atrial strips to a variety of procedures were classified systematically according to the induced changes in peak tension (T), mean rate of tension development (δT/δt), and time to peak tension (TTP). Increasing temperature from 25° to 37°C augmented δT/δt but reduced TTP reciprocally so that T remained constant. Increased frequency of contraction, thyroid hormone, and increased temperature markedly augmented δT/δt but shortened TTP, with relatively little alteration in T. Norepinephrine, tyramine, paired electrical stimulation, strophanthidin, and calcium increased T by augmenting ΔT/δt proportionately more than they reduced TTP. Acetylcholine and serotonin augmented T by raising δT/δt with relatively little effect on TTP. Strontium increased T by causing both a prolongation of TTP and an augmentation of δT/Δt. Depression of T in muscles from failing hearts occurred primarily by a reduction of δT/δt, and the negative inotropic effects of hypoxia or pentobarbital resulted from reductions in both δT/δt and TTP. In muscles from hypothyroid cats, depression of δT/δt was partially compensated for by prolongation of TTP. Since δT/δt is related to the intensity of the active state and TTP to its duration, such analysis of these variables should provide a framework for the characterization and quantitative comparison of various types of inotropic stimuli.

In an attempt to bring patient-oriented bedside cardiovascular physical diagnosis to large numbers of students, a highly mobile electronic and television teaching facility has been assembled and utilized which can provide up to 300 students with sound, pulse and visual data from patients. While one patient is being examined, a teacher can instruct an entire class of students, all hearing, seeing and palpating the same events. Heart sounds and pulsations can be provided as actual or recorded data. Information can be projected by television camera from the physical findings of the patient being presented or from data recorded on video tape. Any combination of sounds, pulsations and visual information in real time can be provided, thus permitting the actual physical examination to be reproduced. In addition, while the student is listening to heart sounds through a stethophone and feeling pulsations on a palpator unit, he can see on television monitors near his seat a visual display of those events programmed in a variety of ways. Immediate visual correlation of what is being heard and felt can be achieved, and direct correlations between physical signs and underlying anatomic and physiologic features can be provided to the student by utilizing this system during cardiac catheterization. The system can be used for full class teaching or self-instruction from freshman through postgraduate levels of medical education. Experience with application of this system to teaching and testing during one academic year demonstrated its effectiveness in (1) enhancing efficiency of learning clinical skills, (2) increasing student-patient contact time, and (3) evaluating clinical skills of an entire medical student class.

It is not known if the favorable changes in preload and afterload that augment ejection performance in acute experimental aortic and mitral regurgitation are also present in patients with chronic regurgitation. Additionally, observations that patients with mitral versus aortic regurgitation respond differently to valve replacement suggest that differences exist preoperatively between these two types of volume overload. Therefore, ventricular mechanics were compared in nine patients with severe aortic regurgitation, eight patients with severe mitral regurgitation and seven normal subjects. The amount of volume overload was similar in both groups with regurgitation. In both aortic and mitral regurgitation, ejection performance was reduced compared with findings in normal subjects. Preload estimated as enddiastolic stress was comparably elevated above normal in both groups with regurgitation: 69 +/- 24 dynes X 10(3)/cm2 in mitral regurgitation compared with 81 +/- 34 dynes X 10(3)/cm2 in aortic regurgitation and 36 +/- 11 dynes X 10(3)/cm2 in normal subjects. However, afterload estimated as mean systolic stress was normal in mitral regurgitation (186 +/- 34 dynes X 10(3)/cm2) but markedly elevated in aortic regurgitation (260 +/- 41 dynes X 10(3)/cm2) (p less than 0.01). Contractile depression tended to be more severe in mitral regurgitation despite similar ejection performance in mitral and aortic regurgitation. Thus, in mitral regurgitation favorable loading conditions may mask contractile dysfunction, and in aortic regurgitation excessive afterload contributes to poor pump performance, possibly accounting for previously observed differences in the response to valve replacement.

Prediction of peak left ventricular pressure by echocardiography in children with aortic stenosis assumes that wall stress is normal. The recent finding that stress is subnormal in many children with aortic stenosis and elevated ejection performance requires reevaluation of this noninvasive technique. By using M-mode echocardiography, left ventricular end-diastolic dimension and wall thickness and left ventricular shortening fraction were measured in 27 children with aortic stenosis undergoing left ventricular pressure measurement by cardiac catheterization. Similar echocardiographic measurements and systolic blood pressure determinations by the cuff method were obtained from 29 normal children.Peak circumferential wall stress and shortening fraction were calculated from the echocardiographic and pressure data. It was found that stress was inversely proportional to shortening fraction for all patients with aortic stenosis (p < 0.001, r = −0.86). In a subgroup of patients with a shortening fraction of less than 0.40, stress was 262 ± 20 mm Hg, similar to 280 ± 30 mm Hg in the normal group but greater than 205 ± 27 mm Hg in patients with a shortening fraction of 0.40 or greater (p < 0.001). In patients with aortic stenosis, the ratio of left ventricular end-diastolic wall thickness to cavity dimension predicted peak left ventricular pressure moderately well (r = 0.83, standard error of the estimate [SEE] = 23). The stress-shortening fraction relation was used to estimate stress and correct this ratio in patients with diminshed stress and a shortening fraction greater than or equal to 0.40. This yielded a significantly improved correlation (r = 0.93, SEE = 15, p < 0.05). It is concluded that echocardiographic prediction of peak left ventricular pressure should include correction for diminished wall stress in children with an elevated ejection performance.

A patient is described who developed hypoglycemia and generalized neurologic depression after cardiac surgery, while receiving an infusion of glucose, insulin, and potassium (GIK). Hypoglycemia as a complication of the use of GIK solution in patients with hepatic dysfunction, malnutrition and low cardiac output is discussed.

CARDIAC muscle has less strength in comparison with skeletal muscle. It has therefore been suggested that there may be fundamental differences in their processes of force generating1–3. While skeletal muscle can develop isometric forces ranging from 17 to 40 g/mm2 (refs. 4–9), maximum forces of only 2 to 7 g/mm2 are reported2,10–15 for heart muscle. Certain functional differences should be considered, however, before intrinsic differences in the mechanism of contraction of cardiac and skeletal muscle are suggested. Thus the lower isometric tension of cardiac muscle could result from any or all of the following: (1) cardiac muscle cannot be tetanized, and maximum force might be limited by the finite duration of active state during the twitch contraction2; (2) the contractile state of heart muscle is variable and generally less than maxima12,11, whereas the contractile state of skeletal muscle is essentially constant3; and (3) a large proportion of myocardium consists of non-contractile structures such as mitochondria and nuclei, unlike skeletal muscle16. It is not known whether correction for these factors would explain discrepancies in force development. Accordingly, the maximum contractile force of cardiac muscle has been examined during maximum potentiation of contractile state, and corrected for non-contractile muscle mass. These corrections permit more meaningful comparisons of the maximum capacity for contraction of cardiac and skeletal muscle.

The clinically important hemodynamic consequences of epicardial coronary artery vasoconstriction were examined in the presence of stenosis of major vessels. For this purpose, a special isolated canine circumflex coronary artery preparation was used to provide elimination of reflex, humoral, and distal coronary vasculature resistance influences. Without stenosis, active vasoconstriction induced by either phenylephrine (10-3 M), angiotensin (10-5 M), or acetylcholine (10-5 M) had no effect on flow through the circumflex artery. Coronary arterial stenosis was created by intraluminal obstruction, which itself produced only insignificant effect on vessel flow. When the vasoconstrictor agent stimulation was superimposed on the fixed underlying vascular stenosis, there occurred dose-dependent marked flow decreases through the partially obstructed vessel accompanied by major trans-stenotic pressure gradient increases. Phenylephrine, angiotensin, and acetylcholine separately caused significant (54%, 59%, and 46%) flow decreases with 48, 54 and 50 mm Hg pressure gradient increases respectively. This study demonstrates that vasoconstriction and stenosis act synergistically to reduce flow through obstructed major vessels in coronary artery disease.

A 66-year-old female with known mitral stenosis presented with symptoms of progressive pulmonary congestion. Concomitantly, subvalvular left ventricular outflow obstruction was suspected clinically and both lesions were confirmed at cardiac catheterization. At operation, marked septal hypertrophy and rheumatic mitral stenosis were observed, the mitral valve was replaced, and a septal myomectomy was performed.

The passive stress-strain relationship of right ventricular papillary muscles from 10 normal and 9 experimental cats with short-term pressure-overload right ventricular hypertrophy-failure was examined by plotting the logarithm of instantaneous stress (ln sigma) against the natural strain calculated as ln(l/l0) where l = instantaneous length and l0 = length at zero force. Such a stress-strain relationship was well approximated by a linear relationship. The slope K obtained from this linear relationship was higher in the hypertrophy-failure muscles (normal, 15.01 +/- 0.87 (SEM); hypertrophy-failure, 31.79 +/- 4.09; P less than 0.005). The value of the intercept, ln C was similar in the two groups (normal, -4.33 +/- 0.20; hypertrophy-failure, -4.71 +/- 0.10). This analysis indicates the the ln sigma-natural strain relationship is linear in the papillary muscle and the slope of this relationship, an index of stiffness, is increased in hypertrophy-failure muscles. Using a three-element muscle model, it is shown that increased diastolic stiffness may contribute to the decreased systolic performance.

The contractile capacity of the human ventricle when chronically pressure-overloaded by aortic stenosis remains a subject of major debate. The compensatory mechanisms used to maintain normal resting cardiac output and ejection fraction, and the relation of compensatory mechanisms to symptoms, have not been fully documented. In this report we examined ventricular performance and the relationship of compensatory mechanisms to symptoms in 11 patients with severe aortic stenosis and congestive heart failure symptoms (ASCHF group), in 10 patients with significant aortic stenosis but no heart failure symptoms (AS-C group), and in 12 normal subjects. Alterations in afterload, preload and wall thickness in aortic stenosis may adversely affect the validity of indexes of contractile function, so we attempted to account for or avoid the effect of such alterations. The natural variations in ventricular volume were used to estimate group ventricular function relationships relating peak systolic wall stress to end-diastolic volume index (Frank-Starling), and to estimate group relationships of end-systolic pressure or stress to end-systolic volume (Sagawa). The slope of the linear regression lines that estimated the Frank-Starling index and the Sagawa index showed statistically significant depression (p < 0.01) of left ventricular contractile function in the AS-CHF patients, while ventricular contractile function was relatively normal in the AS-C patients. End-diastolic volume index and pressure were significantly increased (p < 0.01) only in the AS-CHF group. Peak systolic left ventricular wall stress, ejection fraction, resting cardiac index, and the ratio of ventricular mass to volume were not statistically different from normal in either group.

Recent research findings regarding the pathophyslology of acute myocardial infarction, newer concepts of treatment, and better means of identifying high- and low-risk patients after acute myocardial infarction are presented, along with practical clinical considerations.

Cardiac muscle myosin ATPase activity is depressed and contractile function impaired when the heart is subjected to a chronic pressure overload. Administering digitalis in the presence of chronic pressure overload significantly attenuates the decline in mechanical function. The current study sought to determine if the cardiac muscle myosin ATPase activity of cats treated with digitalis in the presence of pressure overload remains normal in parallel with the mechanical function. Four groups of cats were studied: normal controls (C), animals with pressure-overload hypertrophy with or without failure (HF), normal cats that received treatment with digitalis (D), and animals that received digitalis prior to and together with pressure overload (DHF). Compared to C, the maximum myosin ATPase activity of HF was significantly (P less than 0.05) depressed, but the maximum ATPase activity of D and DHF was not altered significantly (P greater than 0.05) from C. In parallel with the enzyme maximum activity, the papillary muscle isometric rate of force development was significantly (P less than 0.005) depressed in HF compared to C; D and DHF were not significantly (P greater than 0.05) different from C. It is concluded that the depression of myosin ATPase observed in HF is not present when digitalis is administered concomitant with the pressure overload.

Echocardiograms were performed in 11 patients with symptomatic mitral regurgitation. The cause of the regurgitation, determined at the time of mitral valve replacement in 9 of the 11 patients, was either torn chordae tendineae or an avulsed papillary muscle head. Flail mitral leaflet was secondary to infective endocarditis in seven patients and to coronary heart disease in two patients; in the other two patients the cause of the flail leaflet was not determined. Echocardiograms from the 11 patients exhibited at least one of four distinct patterns: systolic left atrial echo, coarse diastolic fluttering of the anterior leaflet, paradoxical movement of the posterior leaflet throughout the cardiac cycles or early diastolic fluttering of the posterior leaflet. The last pattern was noted in two patients who refused surgery and in six patients who had mitral valve replacement. Although early diastolic fluttering of the posterior leaflet has not previously been reported to be indicative of a flail leaflet, it was the most frequent pattern observed in those with an untethered posterior leaflet (eight of nine patients). Five of the 11 patients had one of the four patterns, and the remaining 6 had at least two. The specific echocardiographic abnormalities were not related to the cause or severity of the mitral regurgitation but were determined by the location of the tear and the portion of the flail leaflet traversed by the ultrasonic beam. These patterns appear to represent an echocardiographic spectrum characteristic of a flail mitral leaflet. Detection of any of the four patterns in the presence of mitral regurgitation suggests torn chordae tendineae.

Using attenuation-corrected radionuclide volumes and arm-cuff peak systolic pressures, we established the mean value for the ratio of left ventricular (LV) peak systolic pressure/end systolic volume at rest for 15 healthy persons. In 43 patients with coronary disease, this ratio was more sensitive as an indicator of abnormal LV function and for predicting coronary artery disease than the resting ejection fraction. The slope of an end systolic pressure-volume line was also calculated from data obtained under three loading conditions: at rest, during isometric handgrip testing, and after the sublingual administration of nitroglycerin. The sensitivity of the slope for predicting the presence of coronary artery disease was not significantly different from the resting peak systolic pressure/end systolic volume ratio but was helpful in identifying patients with coronary artery disease. These results represent an improvement over previous radionuclide pressure-volume measurements that have not used attenuation correction and show the need for accurate, nongeometric measurements of the LV end systolic volume.

An acute thrombus at the proximal border of a high-grade atherosclerotic obstruction is the usual cause of myocardial infarction. Although intracoronary thrombolysis is potentially an exciting new therapy for reducing the extent of myocardial infarction by lysing coronary clot, a number of major difficulties limit its widespread application. It is a complex procedure requiring intracoronary visualization and infusion within a few hours of onset of symptoms. Since intravenous streptokinase could be widely applied if effective, we and others have wondered whether high-dose, brief-duration intravenous streptokinase infusion given early in myocardial infarction would lyse coronary clots without bleeding. To date we have treated 13 patients within 6 hours of onset of symptoms and with ECG and angiographic evidence of typical myocardial infarction caused by coronary clot. Clot lysis and angiographically proved coronary reperfusion were achieved in 6 patients within 1 hour of starting a systemic intravenous infusion of 850,000 IU of streptokinase. Schroeder et al., 21 in Berlin, West Germany, achieved angiographically proved coronary reperfusion in 11 of 21 patients with acute myocardial infarction following a 30-minute intravenous streptokinase infusion of 500,000 IU. Neuhaus et al., 22 in Gottingen, West Germany, achieved angiographically proved coronary reperfusion in 24 of 39 similar patients within 48 minutes by intravenous infusion of 1,700,000 IU of streptokinase. In these three studies, no serious bleeding occurred; left ventricular function was improved in patients who achieved coronary reperfusion. We conclude that rapid intracoronary clot lysis and coronary reperfusion can be achieved early in myocardial infarction by brief-duration systemic intravenous infusion of high-dose streptokinase without a high incidence of serious bleeding.

The volume and pressure overload that aortic regurgitation imposes upon the left ventricle may be tolerated for a prolonged period of time. Eventually, however, hemodynamic overload leads to muscle dysfunction. It is generally agreed that the amount of left ventricular dysfunction present in aortic regurgitation is a key determinant of the disease’s prognosis. Implicit in this concept is the need to measure left ventricular function accurately in order to make proper clinical decisions regarding surgical intervention in the disease. Ejection fraction and mean velocity of circumferential fiber shortening (Vcf) are two indicators of left ventricular function commonly used in clinical cardiology. Unfortunately, both have their limitations when used to evaluate the left ventricle of the patient with aortic regurgitation. In aortic regurgitation, both preload and afterload are altered[l]. Preload is elevated by the volume overload of the lesion itself. While aortic regurgitation was previously categorized as a volume overload lesion, recent studies have demonstrated that afterload is usually increased in this disease and, thus, elements of both volume and pressure overload exist [1,2]. Since ejection fraction is altered by preload, afterload, and contractile state [3,4] (as opposed to contractile state alone) and Vcf is affected by afterload and contractile state [5], both might not measure contractile state accurately in this disease, where preload and afterload are abnormal.

The electrophysiological effects of chronic 3,5,3'-triiodo-L-thyronine (T3) administration on cardiac Purkinje fibers were studied using intracellular recording techniques. Adult mongrel dogs receiving T3 injections (1 mg/kg sc) three times daily for 7-12 days demonstrated elevated resting heart rates and serum total T3 content, atrophied thyroid glands, and a small body weight loss when compared with controls. Isolated Purkinje fibers from control and T3-treated animals were superfused with an oxygenated Tyrode solution containing 4 mM K+ at 35 degrees C. Preparations were stimulated externally at 1.0, 2.0, and 3.1 Hz for 2-3 min while measurements of action potentials were made. At 1.0 Hz, action potential duration (APD) of T3-treated Purkinje fibers was significantly (P less than 0.01) greater than controls at both 20% (APD20) and 80% (APD80) of repolarization to the maximum diastolic potential (Emax). The overshoot, plateau height, and Emax were not different. Raising the stimulus frequency to 2.0 and 3.1 Hz produced a slight increase in the overshoot and a rate-dependent shortening of the action potential duration until it resembled controls. APD20 shortened proportionately more than APD80, giving the action potential a triangular appearance. The K+ selectivity of the resting membrane was not affected as evidenced by Nernst plots, which were identical in normal and T3-treated fibers. These results demonstrate that thyroid hormone influences the action potential of isolated cardiac Purkinje fibers.