Exercise-induced increases in atrial natriuretic factor are attenuated by endurance training.

Short-term exercise has been associated with increased plasma levels of atrial natriuretic factor, a potent dilating and natriuretic hormone. In this study, the effect of exercise training on atrial natriuretic factor release during short-term exercise was investigated in men without a history of cardiovascular or other major disease. A well trained group of 10 men who exercised an average of 6,618 kcal/week was compared with a minimally trained group of 9 men who exercised 1,479 kcal/week. Maximal oxygen uptake was 55.2 ml/kg per min in the well trained group and 42.5 ml/kg per min in the minimally trained group (p less than 0.05). Plasma for atrial natriuretic factor, norepinephrine and epinephrine was obtained at rest, at 4 min of exercise and at maximal exercise. Atrial natriuretic factor was lower at rest in the minimally trained than in the well trained men (23 vs. 35.9 pg/ml, p less than 0.05). At maximal exercise, atrial natriuretic factor increased 2.6 times the value at rest in minimally trained men (59.8 pg/ml, p less than 0.05 vs. rest), but did not change in well trained men (34 pg/ml). In minimally trained men at rest, at 4 min of exercise and at maximal exercise, plasma levels of atrial natriuretic factor correlated with heart rate, cardiac output, mean arterial pressure and plasma levels of norepinephrine and epinephrine; these correlations were not found in the well trained group. Thus, short-term exercise results in a significant increase in atrial natriuretic factor in minimally trained but not in well trained men.(ABSTRACT TRUNCATED AT 250 WORDS)

Indomethacin attenuates the constriction of canine epicardial coronary arteries to acetylcholine in the absence of endothelium: contribution of platelets to vasoconstriction in vivo.

This study was designed to evaluate the in vivo effect of acetylcholine on endothelial-damaged canine epicardial coronary arteries and the potential contribution of platelets to those acetylcholine-induced responses. Changes in left anterior descending artery cross-sectional area were determined by quantitative angiography in the closed chest anesthetized dog. Baseline cross-sectional area of the left anterior descending artery was not changed by removal of the endothelium by balloon-tipped catheter. Increased constrictor tone produced by prostaglandin F2 alpha was comparable in endothelium-intact and endothelium-removed vessels, supporting an endothelium-independent mechanism for prostaglandin F2 alpha in vivo. Acetylcholine produced anterior descending artery vasodilation with the endothelium intact; a comparable maximal dilator response was also obtained in the presence of increased constrictor tone (prostaglandin F2 alpha). In contrast, acetylcholine produced vasoconstriction of the anterior descending artery when the endothelium was removed. To evaluate the mechanism of acetylcholine-induced vasoconstriction in endothelium-removed vessels, the same protocol was completed in the presence of the platelet inhibitor indomethacin. Indomethacin did not alter baseline cross-sectional area or the dilator response to acetylcholine in endothelium-intact vessels. In contrast, the constrictor response in endothelium-removed vessels was antagonized, and a dilator response comparable with that in endothelium-intact vessels was produced by acetylcholine. The results of this study provide an experimental basis for the observations in human studies in which apparently atherosclerotic vessels constrict in response to acetylcholine. Removal of the endothelium in vivo abolishes the dilator response to acetylcholine and converts the acetylcholine response to vasoconstriction or vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Technological advances and the next 50 years of cardiology.

The fiftieth anniversary of the ACC and the end of the twentieth century are arbitrary points in time, yet they seem to coincide with a true watershed. The last 50 years have brought a rush of new techniques and understandings that have, for the first time, given cardiovascular specialists real tools to prevent and fight cardiovascular disease. Only now, for the first time, has science begun to understand exactly what happens when plaque forms in an artery, when heart muscle fibers cross-link and weaken, when an atrial chamber fibrillates, and when heart muscle cells die en masse after a heart attack. We are beginning to track down the actual chemical, mechanical, and electrical pathways by which the heart is damaged or dies. When we can interfere with those pathways and stop the chain of events, we will have defeated heart disease. Imagination is rapid, but progress is often both uncertain and slow because of the many constraints of cost, regulation, and time needed to test and evaluate new developments. Yet we can now foresee a future in which medical science might actually defeat cardiovascular disease the way it has defeated polio, smallpox, and other serious scourges of the past.

Angiographic demonstration of spontaneous diffuse three vessel coronary artery spasm.

The spontaneous occurrence of diffuse three vessel coronary artery spasm was documented during routine coronary angiography in three patients with a history of variant angina. Quantitative angiographic analysis of 18 arterial segments demonstrated that the mean luminal diameter of 1.47 mm during spasm increased to 2.47 mm after the administration of nitroglycerin (p less than 0.0001). The underlying coronary arteries were normal or near normal. Although multivessel spasm has previously been considered to be uncommon and its spontaneous occurrence during angiography only rarely documented, these cases suggest that it may be more common than previously recognized. In addition to important diagnostic considerations, this phenomenon may have important implications regarding the pathophysiologic role of endothelium in coronary artery spasm.

Assessment of myocardial perfusion by videodensitometry in the canine model.

Assessment of the functional severity of coronary stenoses has become increasingly important as the intrinsic limitations of coronary angiography have been documented. Videodensitometric coronary flow reserve has been proposed as a means to assess the physiologic significance of a coronary stenosis in humans. This study compared videodensitometric assessment of coronary flow with microsphere quantitation in the closed chest canine model. In five dogs, flow rates were assessed at baseline, after vasodilation with adenosine, after vasoconstriction with vasopressin and during rapid cardiac pacing. The videodensitometric peak density, time to one-half peak density and washout time (time from peak to one-half peak density) were compared at each flow state with flow assessed by microsphere injection. Reproducibility of videodensitometric measurements from two different coronary injections during the same flow state was best with peak density (r = 0.94). Videodensitometric flow ratios (flow state under study to flow at rest) using peak density demonstrated a fair correlation with flow ratios by microsphere (r = 0.81). There was poor correlation between flow ratios when time to one-half peak or washout time was used. Videodensitometric flow measurements used in vivo to assess a wide range of drug-induced coronary flows may not accurately reflect coronary flow measured by microsphere.

Action and localization of vasoactive intestinal peptide in the coronary circulation: evidence for nonadrenergic, noncholinergic coronary regulation.

Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Instantaneous pressure gradient: a simultaneous Doppler and dual catheter correlative study.

To more precisely measure the beat to beat and instantaneous pressure gradients across outflow stenotic lesions, simultaneous Doppler and dual catheter pressure gradient measurements were performed in 95 patients (mean age 42 years, range 1.5 to 85). There were 38 right ventricular and 62 left ventricular outflow obstructive lesions. Forty-nine patients also had a nonsimultaneous Doppler study performed within 7 days before catheterization. The simultaneous pressure waveforms and Doppler spectral velocity profiles were digitized at 10 ms intervals deriving maximal, mean and instantaneous gradients (mm Hg). For simultaneous maximal Doppler and catheter gradient measurements, the correlation coefficient (r) was 0.95 (SEE = 10 mm Hg), for Doppler and catheter mean gradients it was 0.94 (SEE = 8 mm Hg) and for maximal Doppler and peak to peak catheter gradients it was 0.92 (SEE = 13 mm Hg). The correlation of maximal and mean Doppler gradients with the respective catheter gradients was similarly high when the right and left ventricular outflow lesions were analyzed separately. However, the maximal Doppler gradient was significantly higher than the peak to peak catheter gradient. This was more evident with left ventricular outflow stenotic lesions. The correlation of the outpatient maximal Doppler and catheter gradients (r = 0.80, SEE = 17 mm Hg) was significantly lower than the simultaneous correlation (r = 0.96, SEE = 10 mm Hg) in the 49 patients with two Doppler studies. Continuous wave Doppler echocardiography accurately measures the instantaneous pressure gradient across both left and right ventricular outflow obstructive lesions. The maximal Doppler gradient should not be equated with the peak to peak catheter gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional and morphologic adaptation of undersized donor hearts after heart transplantation.

OBJECTIVES: This study analyzes our experience with transplantation of small donor hearts in a subgroup of moribund patients who could not be bridged to transplantation with mechanical assist devices. BACKGROUND: The major problem facing transplant programs in the United States is the lack of donor heart availability. One method of expanding the donor pool may be to liberalize the criteria for an acceptable donor heart. METHODS: We analyzed the growth and adaptation of 14 undersized and 14 conventionally sized donor hearts over a period of 10 weeks after heart transplantation. The left ventricular systolic and diastolic diameters, septal and posterior wall thicknesses, left ventricular mass calculated by the Penn convention and left ventricular ejection fraction were obtained by M-mode and two-dimensional echocardiography and documented by a single reader in blinded manner. Echocardiographic measurements were obtained before implantation and at 5 and 10 weeks after orthotopic heart transplantation. RESULTS: The mean (+/- SD) donor/recipient weight ratios were 0.53 +/- 0.06 for undersized hearts and 0.98 +/- 0.05 for normal-sized hearts. All 28 patients received similar immunosuppressive regimens, including intravenous steroids, cyclosporine and azathioprine. The length of hospital stay after transplantation did not vary significantly between the two groups. All the patients had at least one rejection episode during the 10-week study period. There was a tendency toward higher pulmonary pressures in undersized hearts, which was not statistically significant. Heart rate was significantly higher for undersized hearts, due in part to the use of theophylline or terbutaline to maintain tachycardia. There was a significant increase in left ventricular systolic and diastolic dimensions in undersized hearts compared with conventionally sized hearts. Undersized hearts increased in left ventricular mass over the 10-week period, whereas the conventionally sized donor hearts did not change between 5 and 10 weeks. CONCLUSIONS: In undersized hearts the increase in left ventricular mass and internal dimensions, with preservation of the posterior/septal wall thickness ratio, suggests that the left ventricle adapts to the larger recipient circulation early after transplantation. Despite denervation and a mismatched load, undersized transplanted hearts adapt appropriately to their new hemodynamic milieu.

Angioplasty in total coronary artery occlusion.

Percutaneous transluminal coronary angioplasty was attempted without streptokinase in 24 patients with total coronary artery occlusion but without acute transmural myocardial infarction. The maximal duration of occlusion was estimated to be 1 week or less in 10 patients, more than 1 to 4 weeks in 6, more than 4 to 12 weeks in 3 and more than 12 weeks in 5. Dilation of the occluded artery was attempted in the left anterior descending coronary artery in 17 patients, in the right coronary artery in 4 and in the circumflex coronary artery in 3. Angioplasty was successful in 13 patients (54%): left anterior descending coronary artery in 59%, right coronary artery in 50% and circumflex coronary artery in 33%. In patients with successful dilation, there was a mean decrease in coronary artery stenosis from 100 to 23%. In the 19 patients whose occlusion was estimated to be of 12 weeks' duration or less, angioplasty was successful in 68%. In the five patients whose occlusion was estimated to be of more than 12 weeks' duration, dilation was not successful in any (p = 0.006). It is concluded that in selected patients with symptomatic coronary artery disease and recent coronary artery occlusion without associated acute myocardial infarction, percutaneous transluminal coronary angioplasty alone may be effective in restoring patency.

Gender-related differences in cardiac response to supine exercise assessed by radionuclide angiography.

This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography. Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus -2 ml/m2, p = 0.002). The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end-diastolic volume that are not explained by differences in exercise capacity.

Intracoronary thrombus: role in coronary occlusion complicating percutaneous transluminal coronary angioplasty.

Angiograms from 238 consecutive patients who underwent percutaneous transluminal coronary angioplasty at the Mayo Clinic were reviewed to determine the presence of intracoronary thrombus before dilation. Patients with previously occluded vessels and those receiving streptokinase therapy were excluded. Intracoronary thrombus before dilation was present in 15 patients (6%); complete occlusion occurred in 11 (73%) of these during or immediately after dilation. None of these patients had angiographic evidence of major intimal dissection. In contrast, among the 223 patients in whom no intracoronary thrombus was present before dilation, complete occlusion occurred in 18 (8%) and in 12 was associated with major intimal dissection. The difference between the complete occlusion rates for patients with and without prior intracoronary thrombus was highly significant (73 versus 8%, respectively, p less than 0.001). Therefore, the presence of intracoronary thrombus identifies a group of patients who are at increased risk of developing complete occlusion during or after attempted coronary artery dilation.

Myocardial blood flow and mechanics in volume overload-induced left ventricular hypertrophy in dogs.

Chronic volume overload and subsequent left ventricular hypertrophy (LVH) were produced by a surgical shunt between the left subclavian artery and the left atrial appendage in eight dogs. A sham operation was performed on six control dogs. Analysis of biplane ventriculograms showed no significant differences in ejection fraction, mean wall stress, tension-time index, or stress-time index. A significant increase was found in stroke work per gram of left ventricle (P less than 0.005). Myocardial blood flow (MBF) was measured using 9 micrometers, radioactive microspheres at rest, at a constant treadmill workload (CWL) of 2 mph, 2% grade, and at a constant heart rate (CHR) of 175 beats.min-1. Total LVMBF (cm3.min-1) in the shunt dogs was increased at rest (P less than 0.05) with CWL (P less than 0.05) and a CHR (P less than 0.05). However, no differences were found between the groups in the LVMBF.g-1 of myocardium (cm3.g-1.min-1) at rest or during exercise, or in the endocardial to epicardial blood flow ration. Volume overload hypertrophy, without the presence of heart failure, is associated with normal haemodynamic and mechanical function at rest, normal LVMBF.g-1 of myocardium and normal flow distribution at rest and during exercise.

Importance of endothelial function in stenotic haemodynamic responses.

STUDY OBJECTIVE: The aim was to examine endothelium mediated flow dependence in a dynamic stenosis. DESIGN: The coronary circulation was modelled as a proximal compliant stenosis and a fixed distal resistance. Pressures and flow were calculated using standard haemodynamic equations. Within the stenosis, the vessel wall was composed of normal and rigid sections, and the normal section dilated proportionally with flow. From this theoretical analysis, three perfusion pressures (150, 100, and 75 mm Hg) and two distal resistances (high and low) were examined. MAIN RESULTS: In a stenotic artery (93% area reduction) with high flow dependence, decreasing distal resistance increased flow substantially. At 75 mm Hg perfusion pressure, flow increased from 40.8 to 81.6 ml.min-1. With moderate flow dependence, flow increases were attenuated. Without flow dependence, flow increases were smaller, and at low perfusion pressure, flow paradoxically decreased (39.0 to 0.0 ml.min-1) when distal resistance decreased. Vasoconstriction responses with and without flow dependence were analysed. In a stenotic artery, vasoconstrictors caused a concentration dependent decrease in flow. Without flow dependence, the flow dose-response curve was shifted to the left: a lower level of arterial vasoconstriction resulted in a greater flow decrease. CONCLUSIONS: The theoretical analysis shows significantly different flow responses to decreasing distal resistance and to vasoconstriction depending on endothelial function. Endothelial dysfunction may be important in the pathophysiology of angina pectoris.

A simple technique for producing supravalvular aortic stenosis in animals.

A safe and reproducible technique to create supravalvular aortic stenosis was developed, which avoids many of the difficulties encountered in the production of aortic stenosis. Dogs were anaesthetised and artificially ventilated. The chest was opened and the venae cavae were encircled with umbilical tapes. The ascending aorta was then encircled by a 1.5-2 cm wide, 6-7 cm long dacron patch, venous return was stopped by tightening the tapes, and a J-shaped clamp applied to the ascending aorta at the dacron patch. Two layers of continuous mattress suture were placed adjacent to the clamp, plicating the aortic diameter by about 50%. After releasing the clamp and restoring normal venous return, left ventricular (LV) and aortic (AO) pressures were measured. Subsequently, one or two deep mattress sutures were placed below the running mattress sutures to increase the stenosis and to obtain the desired gradient. The LV-AO systolic pressure gradients obtained immediately after the operation ranged from 40 to 75 mm Hg. Two to 6 months after the operation the pressure gradients ranged from 50 to 200 mm Hg. Left ventricular to body weight ratios were 6.41 (SEM 0.26) v 4.24(0.20) for the controls. Heart weight to body weight ratios were 8.37(0.35) v 5.65(0.33). LV end diastolic pressures were normal. This technique can be used either in puppies or adult animals. The problem of aortic rupture is eliminated. The pressure gradient can be easily controlled during the operation and reproducible LV hypertrophy can be obtained in a shorter time than with aortic banding of puppies.

Myocardial blood flow and capillary density in chronic pressure overload of the feline left ventricle.

The effects of chronic pressure overload hypertrophy on myocardial blood flow and capillary density was measured in the feline left ventricle. Myocardial hypertrophy was produced by and 84% banding constriction of the ascending aorta 2.8 +/- 1.2 months before the experiments. In seven cats with aortic constriction, cardiac hypertrophy produced a 40% increase in left ventricular mass. Seven cats served as normals. Our findings show that, in chronic pressure overload hypertrophy, coronary blood flow at control (resting) levels is increased compared with normals. In both normal and hypertrophy cats endocardial/epicardial flow ratios were equal at the control level. In the hypertrophied hearts, coronary reserve, measured as the percentage increase in myocardial blood flow from control to near maximal flow during adenosine infusion, was reduced. In the hypertrophy group a shift in the transmural distribution of blood flow in the left ventricle was noticed, as indicated by a reduced endo/epi flow ratio, during adenosine infusion. A decreased capillary density in hypertrophy, most marked in endocardial tissue regions, was demonstrated by this study. These findings indicate that capillary growth does not parallel myofibre growth in the endocardium of pressure overload hypertrophied left ventricles. The resultant anatomical imbalance causes a compromise of flow reserve in the endocardium, making this region vulnerable to ischaemia.

Mechanisms underlying spinal cord damage in decompression sickness.

Decompression sickness, which damaged the spinal cord, was produced in anesthetized dogs using a compression chamber. Cerebrospinal fluid pressure and several intravascular and intracardiac pressures were monitored during the course of the simulated dives. Manometric responses to forcible lung inflation and abdominal compression were measured both predive and postdive after signs of spinal cord damage were evident. Cinevenography of the epidural vertebral venous system was performed both predive and postdive. Histopathologic studies of the brains and cords of both predive and postdive. Histopathologic studies of the brains and cords of paretic animals were carried out. The results indicate that the epidural vertebral venous system becomes obstructed during spinal cord damaging decompression sickness and strongly suggests that spinal cord infarction in decompression sickness is caused by obstruction of cord venous drainage at the level of the epidural vertebral venous system.

Complexes of .NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects.

Selected nucleophile/nitric oxide adducts [compounds which contain the anionic moiety, XN(O-)N = O] were studied for their ability to release nitric oxide spontaneously in aqueous solution and for possible vasoactivity. The diversity of structures chosen included those in which the nucleophile residue, X, was that of a secondary amine [Et2N, as in [Et2NN(N = O)O]Na, 1], a primary amine [iPrHN, as in [iPrHNN(N = O)O]Na, 2], a polyamine, spermine [as in the zwitterion H2N(CH2)3NH2+(CH2)4N[N(N = O)O-](CH2)3NH2, 3], oxide [as in Na[ON(N = O)O]Na, 4], and sulfite [as in NH4[O3SN(N = O)O]NH4, 5]. The rate constants (k) for decomposition in pH 7.4 phosphate buffer at 37 degrees C, as measured by following loss of chromophore at 230-260 nm, were as follows: 1, 5.4 x 10(-3) s-1; 2, 5.1 x 10(-3) s-1; 3, 0.30 x 10(-3) s-1; 4, 5.0 x 10(-3) s-1; and 5, 1.7 x 10(-3) s-1. The corresponding extents of nitric oxide release (ENO) were 1.5, 0.73, 1.9, 0.54, and 0.001 mol/mol of starting material consumed, respectively, as determined from the integrated chemiluminescence response. Vasodilatory activities expressed as the concentrations required to induce 50% relaxation in norepinephrine-constricted aortic rings bathed in pH 7.4 buffer at 37 degrees C (EC50) were as follows: 1, 0.19 microM; 2, 0.45 microM; 3, 6.2 microM; 4, 0.59 microM; and 5, 62 microM. Vasorelaxant potency (expressed as 1/EC50) was strongly correlated with the quantity of .NO calculated from the physicochemical data to be released in the interval required to achieve maximum relaxation at the EC50 doses (r = 0.995). This suggests that such nucleophile/.NO adducts might generally be useful as vehicles for the nonenzymatic generation of nitric oxide, in predictable amounts and at predictable rates, for biological purposes. The particular significance for possible drug design is underscored in the very favorable potency comparison between several of these agents and the established nitrovasodilators sodium nitroprusside and glyceryl trinitrate (EC50 values of 2.0 and greater than 10 microM, respectively) in parallel aortic ring tests.

Redistribution on the thallium scan in myocardial sarcoidosis: concise communication.

Resting and redistribution thallium studies were performed in four young patients with sarcoidosis to evaluate the possibility of myocardial involvement. In each case the resting scan showed marked defects that resolved on the redistribution studies. In a different patient population, these results would have implied significant coronary artery disease.

Effects of serotonin and histamine on proximal and distal coronary vasculature in dogs: comparison with alpha-adrenergic stimulation.

The effect of several vasoactive agents on epicardial conductance arteries and distal resistance arteries was studied in intact dogs using a special catheter system to infuse vasoactive mediators directly into the left anterior descending coronary artery of intact dogs. Serotonin produced significant epicardial vasoconstriction (42% cross-sectional area reduction, p less than 0.01), whereas histamine had no effect on proximal coronary arteries. Phenylephrine, an alpha-adrenergic agonist, produced an 11% reduction in cross-sectional area. Distal coronary vascular resistance (pressure/flow) changes were small for serotonin and phenylephrine, whereas histamine significantly dilated the peripheral vascular bed and caused flow measured by xenon-133 washout to increase from 30.4 +/- 4.0 to 72.4 +/- 12.6 ml/min . 100 g (p less than 0.05). These results show that vasoactive mediators can have different actions on coronary resistance and conductance vessels. Serotonin is a potent vasoconstrictor of epicardial coronary arteries but does not produce significant constriction of coronary resistance vessels.

Use of left ventricular filling and ejection patterns in assessing severity of chronic mitral and aortic regurgitation.

To determine whether left ventricular (LV) filling and ejection patterns can be used to characterize the severity of mitral and aortic regurgitation (MR and AR), normalized volume vs time curves derived from left ventriculograms were plotted using a computer-based image analysis system. These patterns were measured in 20 normal subjects, 14 patients with MR and 21 patients with AR. In addition, time-averaged volume changes (dV/dt) and diameter changes (dD/dt), stroke or filling volume, and ejection or filling fraction were measured during systole and diastole. The patients with volume overload were separated into 4 groups based on symptoms: asymptomatic (MR, 7 patients, AR, 10 patients); congestive heart failure (CHF) (MR, 7 patients, AR, 11 patients). Ejection fraction was significantly depressed in both CHF groups, even though stroke volume index was significantly increased in all groups. The temporal pattern of diastolic filling in patients with CHF secondary to MR and AR demonstrated slower, later diastolic filling compared with normal subjects, while in asymptomatic MR, diastolic filling was more rapid than in normal subjects. Diastolic filling patterns were similar to normal in asymptomatic AR patients. Temporal systolic emptying was slower in patients with CHF secondary to AR; emptying patterns in asymptomatic MR patients were similar to those of normal subjects; late systolic emptying was accelerated in patients with asymptomatic AR. Thus, there were filling and emptying abnormalities in all stages of volume overload secondary to regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)