Hyperphagia and polydipsia in socially isolated rhesus monkeys.

Three rhesus monkeys which had been isolated from social contact during their first year of life persistently overate and overdrank during adulthood. These monkeys ingested approximately twice as much fluid and food as the control animals reared normally.

Preload dependence of fiber shortening rate in conscious dogs with left ventricular hypertrophy.

Employing the new concept of systolic myocardial stiffness, this study addresses the questions of linearity of the end-systolic stress-strain relations in left ventricular hypertrophy and the preload dependence of fiber shortening rate. Pressure overload hypertrophy was induced in six puppies by banding the ascending aorta. Ultrasonic crystals were implanted for measurement of short axis and wall thickness in the six dogs with hypertrophy and in five control dogs. A pressure catheter was inserted through the apex for left ventricular pressure measurement. Load was altered by graded infusions of phenylephrine in the setting of beta-adrenergic blockade. Linearity of the end-systolic stress-strain relations was observed in all cases, and preload-corrected shortening rate-afterload relations were derived from these stress-strain relations. Without preload correction, mid wall and endocardial shortening rate were depressed (p less than 0.05 and p less than 0.005, respectively) in the hypertrophy group. However, with preload correction at 35 g/cm2, there was no significant difference in shortening rate between the control and hypertrophy groups at afterloads of 150, 200 and 250 g/cm2. Endocardial shortening rate at a preload of 25 versus 35 g/cm2 demonstrated a preload dependence in both the control (p less than 0.04) and the hypertrophy group (p less than 0.01). Mid wall shortening rate displayed a preload dependence only in the hypertrophy group (p less than 0.05). It is concluded that end-systolic stress-strain relations are linear in control conditions and in hypertrophy, fiber shortening rate is preload-dependent and, thus, shortening rate-afterload relations currently used to assess myocardial contractility need to be modified to account for these preload effects.

Left ventricular systolic and diastolic function during acute coronary artery balloon occlusion in humans.

Left ventricular function during percutaneous transluminal coronary angioplasty was studied in 16 patients undergoing the procedure. All measurements were performed before and during the first episode of balloon coronary occlusion. In 16 patients (Group A), data were recorded before and 30 or 50 s after balloon inflation, and in 8 of these patients (Group B) data were also recorded 15 min after the complete procedure. Left ventriculograms indicated a marked dyskinesia of the anterior and apical wall in all patients. After balloon inflation, there was a marked depression in stroke index and ejection fraction and an increase in left ventricular end-diastolic pressure and the time constants of relaxation in all patients. Simultaneous recording of left ventricular pressure (Millar micromanometer) during cineangiography permitted the assessment of myocardial and chamber stiffness. Although there was a strong tendency for both myocardial and chamber stiffness to increase after 30 to 50 s of occlusion, these increases were statistically insignificant. In Group B, a third set of angiographic and pressure measurements obtained 15 min after completion of the coronary angioplasty procedure indicated no residual left ventricular dysfunction, and in this respect, the results are of added clinical importance.

Left ventricular volume determined echocardiographically by assuming a constant left ventricular epicardial long-axis/short-axis dimension ratio throughout the cardiac cycle.

OBJECTIVES: The purpose of this study was to develop and test a simplified echocardiographic method to calculate left ventricular volume. BACKGROUND: This method was based on the assumption that the ratio of the left ventricular epicardial long-axis dimension to the epicardial short-axis dimension was constant throughout the cardiac cycle. With use of this constant ratio, the method developed to calculate left ventricular volume at a given point in the cardiac cycle required the left ventricular endocardial long-axis dimension to be measured at only one point in the cardiac cycle. METHODS: Studies were performed in 13 normal dogs, 8 normal puppies, 9 normal pigs, 12 dogs with aortic stenosis, 13 dogs with acute mitral regurgitation, 12 dogs with chronic mitral regurgitation, 7 dogs that had undergone mitral valve replacement and 6 pigs that had had chronic supraventricular tachycardia. Animals with aortic stenosis developed left ventricular pressure overload hypertrophy with a 60% increase in left ventricular mass; chronic mitral regurgitation caused left ventricular volume overload hypertrophy with a 46% increase in left ventricular volume; supraventricular tachycardia caused a dilated cardiomyopathy with a 55% decrease in left ventricular ejection fraction. RESULTS: The left ventricular epicardial long-axis/short-axis dimension ratio remained constant throughout the cardiac cycle in each animal group. End-diastolic and end-systolic volumes calculated with the simplified echocardiographic method correlated closely with angiographically measured volumes; for end-diastolic volume, echocardiographic end-diastolic volume = 1.0 (angiographic end-diastolic volume) -1.8 ml, r = 0.96; for end-systolic volume, echocardiographic end-systolic volume = 0.98 (angiographic end-systolic volume) -0.7 ml, r = 0.95. CONCLUSIONS: Thus the left ventricular epicardial long-axis/short-axis dimension ratio was constant throughout the cardiac cycle in a variety of animal species and age groups and in the presence of cardiac diseases that significantly altered left ventricular geometry and function. The simplified echocardiographic method examined provided an accurate determination of left ventricular volumes.

Effects of chronic sodium depletion on function of isolated normal and hypertensive hypertrophied rat heart.

Since in vivo ejection fraction is said to be reduced in chronically sodium depleted dogs, this study was conducted to investigate the direct effects of sodium deprivation on intrinsic ventricular contractility, independent of haemodynamic or adrenergic influences. Since low sodium diet and/or diuretics are commonly used in the treatment of hypertension, we included a hypertensive group in the study. Normotensive male Sprague-Dawley rats and age matched renovascular hypertensive rats were subdivided into three groups. The first group was fed regular sodium diet (RS) for 6 weeks. The second (LS) and third (LSD) groups received low sodium diet for 6 weeks, and the LSD group also received diuretic (frusemide) treatment to achieve marked sodium depletion (last dose given 2 weeks before the cardiac study). Left ventricular (LV) contractility was investigated in the isolated isovolumetric rat heart (Langendorff preparation) paced at 180 beats-min-1. Results showed that LV +dP/dt max at zero LV end diastolic pressure was higher (p less than 0.01) in the LSD group than in the other groups in normotensive rats [2672 (SEM127) mm Hg.s-1 in LSD, 2267(96) in LS, 2174(111) in RS] and higher in LSD (p less than 0.01) and LS (p less than 0.05) groups than in the RS group in hypertensive rats [2332(110) mm Hg.s-1, 2287(93), 1781(104), respectively]. Calculated LV balloon volume at zero LV end diastolic pressure was not significantly different in any dietary group. These results suggested that after 6 weeks of in vivo sodium depletion, in vitro LV contractility was enhanced rather than depressed under these experimental conditions. This enhancement is contrary to the in vivo findings in the dog model and could not be explained by differences in myocardial flow rate, LV chamber stiffness or myocardial stiffness constant. The mechanism of this accentuated ventricular contractility under these experimental conditions remains to be determined.

Cardiac hypertrophy and performance of Dahl hypertensive rats on graded salt diets.

The relationship between arterial pressure and left ventricular (LV) functional capacity and LV mass during the natural development of cardiac hypertrophy was assessed in Dahl-resistant (R) and -sensitive (S) hypertensive rats maintained on three dietary NaCl regimens (0.4%, 4.0%, and 8.0% for 9 weeks, then 4.0%) from 5 until 20 weeks of age. In R rats, arterial pressure and LV mass were unaffected by diet. In contrast, S rats demonstrated levels of arterial pressure and LV hypertrophy that were graded according to dietary NaCl. Hemodynamic studies on rats under ether anesthesia demonstrated that the graded pressure elevation in S rats was produced by corresponding increases in total peripheral resistance, as cardiac output did not vary. During acute volume loading, the S rats on all diets achieved the same maximum stroke volume as did R rats, despite the marked increase in the arterial pressure of S rats. An analysis of the ejection fraction/afterload relationship demonstrated preserved contractile state. The ability of the left ventricle to generate pressure was increased in S rats in direct proportion to the degree of LV hypertrophy. Thus, in young adult S rats, cardiac performance was well compensated since pump and contractile functions were maintained and pressure-generating capacity was increased in relation to the degree of LV hypertrophy.

Prediction of postoperative performance in aortic valve disease.

A new direct method has been developed for predicting postoperative performance in patients undergoing aortic valve replacement. Employing micromanometry and cineangiography, a number of conventional hemodynamic and angiographic variables, including the peak value of the first derivative of ventricular pressure divided by ventricular pressure (dP/dt/P)max, were evaluated in 171 patients studied preoperatively and in 44 patients studied pre- and postoperatively with an additional 14 patients serving as control subjects. Normal contractile state relations (dP/dt/P)max versus end-diastolic pressure (over a range of 125 mm Hg or less to more than 15 mm Hg) were derived from patients whose preoperative ejection fraction and peak wall stress were equal to or more than control mean--2 standard deviations. Postoperative function was predicted to be abnormal (ejection fraction less than control mean--2 standard deviations) if preoperative values of (dP/dt/P)max and end-diastolic pressure fell below the 95 percent confidence bands of these contractile state relations. The method accurately predicted postoperative function in 40 of 44 patients with a sensitivity of 100 percent. This result was confirmed by a discriminant function analysis (based on preoperative ejection fraction, end-diastolic pressure and [dP/dt/P]max) that yielded correct classifications in 42 of 44 patients. These studies indicate that the preoperative contractile state of the myocardium is the major determinant of postoperative performance in aortic valve disease.

Myocardial contractile function in aortic stenosis as determined from the rate of stress development during isovolumic systole.

To assess myocardial contractile function in the chronically hypertrophied human left ventricle, the rate of stress development (dsigma/dt) as a function of developed stress (sigmaD) during isovolumic systole was examined. Results for eight patients with aortic stenosis were compared with those for seven subjects with normal left ventricular function and with those for five patients with idiopathic congestive cardiomyopathy. The rate of stress development (dsigma/dt) was nearly identical in patients with aortic stenosis and in normal subjects over a wide range of values of sigmaD but was significantly lower in patients with cardiomyopathy (P less than 0.01 versus control subjects and patients with aortic stenosis). Normal values for dsigma/dt held not only for patients with compensated pressure overload, but also for those patients with aortic stenosis with depressed left ventricular ejection fraction and overt congestive failure. Similar findings were obtained when the first derivative of left ventricular pressure (dP/dt) was examined as a function of developed left ventricular pressure in normal subjects and patients with aortic stenosis or cardiomyopathy. These results indicate that contractile function as characterized by the isovolumic rate of stress development is not necessarily impaired in chronic pressure overload hypertrophy.

Wall motion asynchrony is a major determinant of impaired left ventricular filling in patients with healed myocardial infarction.

Left ventricular (LV) diastolic filling is impaired in hearts with healed myocardial infarction. Possible hemodynamic parameters related to impaired LV filling include left atrial pressure, time constant of isovolumic relaxation, chamber stiffness and wall motion asynchrony. Previous studies demonstrated univariate correlations between each of these parameters and LV filling. The current study was designed to compare relative importance of these parameters in patients with a myocardial infarction. Left ventriculograms with simultaneous LV pressure measurement were analyzed in 15 patients with a myocardial infarction and in 10 control subjects. Every frame of the left ventriculogram was divided into 8 segments and the volume of each segment was obtained frame-by-frame by planimetry and area-length method. Asynchrony was quantitated as the sum of areas of discrepancy between each segmental and global volume-time curve. Patients with myocardial infarction had greater asynchrony (20 +/- 2 vs 10 +/- 1%, p < 0.01), greater atrial filling fraction (46 +/- 4 vs 35 +/- 5%, p < 0.05) and slower peak early filling rate (2.5 +/- 0.1 vs 4.1 +/- 0.4 end-diastolic volume/s, p < 0.01) than the control subjects. Multiple regression analyses with hemodynamic variables (asynchrony, LV pressure at mitral valve opening, time constant of LV isovolumic pressure decrease and LV chamber stiffness constant) showed that asynchrony and LV pressure at mitral valve opening were significant determinants of LV filling in patients with myocardial infarction, whereas LV pressure at mitral valve opening was the only significant determinant in control subjects.

Comparison of echocardiography and radionuclide angiography as predictors of mortality in patients with left ventricular dysfunction (studies of left ventricular dysfunction).

Left ventricular (LV) systolic dysfunction, as indicated by a reduced LV ejection fraction (EF) is a potent predictor of cardiovascular mortality. Radionuclide angiography accurately and reproducibly assesses LVEF; however, echocardiography is used more frequently in clinical practice. Whether these methods predict similar mortality has not been fully investigated. We performed a retrospective analysis of patients with baseline radionuclide angiographic (RNA; n = 4,330) and echocardiographic (echo; n = 1,376) based EFs < or =0.35 who were enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to address this hypothesis. After adjusting for important prognostic variables, the risk of death (RR 1.15; 95% confidence interval 1.01 to 1.30; p = 0.03) and of cardiovascular death (RR 1.15; 95% confidence interval 1.01 to 1.32; p = 0.04) was higher for patients with ECG-based EFs. To compare the 2 techniques across a range of EF values, we divided the cohort into tertiles of EF. The adjusted risk estimates for all-cause and cardiovascular mortality were similar within each tertile. Of note, the mortality difference in patients with echo- versus RNA-based EFs was most prominent in women. Further, patients with echo-based EFs had significantly higher mortality at sites where this technique was less frequently used to assess the EF. Thus, for a given EF < or =0.35, an echo-based value was associated with a higher risk of death compared with the RNA-based method of measurement. These data suggest that EF values determined by echocardiography and radionuclide angiography predict different mortality and this may, in part, be related to technical proficiency as well as patient characteristics.