Intracellular sodium in cardiomyocytes using 23Na nuclear magnetic resonance.

Intracellular sodium content in superfused isolated rat cardiomyocytes was measured using 23Na nuclear magnetic resonance. The shift reagent dysprosium tripolyphosphate was added to the buffer to distinguish between NMR signals from the intracellular region and the extracellular buffer. The NMR visibility of the intracellular sodium signal was experimentally determined by measuring the changes induced in the sodium NMR signals by application of ischemia as an intervention. Intracellular volume was accounted for by determining the change in the sodium signal upon adding cells (in beads) to the buffer solution at the beginning of each experiment and by killing the cells (in beads) with Triton X-100 at the end of each experiment. The visibility of intracellular sodium (relative to extracellular) was 0.47 +/- 0.12 (mean +/- S.D., n = 12). The average intracellular sodium concentration using this visibility is 29 +/- 4.5 mM (n = 12). This value is much higher than results obtained by some investigators using NMR techniques and by others using different standard methods, with the exception of those methods which evaluate the total intracellular sodium (atomic absorption spectroscopy and X-ray microanalysis). We conclude that total Nai is higher than generally reported, using other accepted techniques such as ion-specific electrodes, and that 23Na-NMR analysis can be used to accurately determine Nai in intact cells.

Creatinine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy.

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 microgram/kg per min), used to increase heart rate x systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption. Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p less than 0.05) even though changes in hemodynamic and functional variables were similar in both groups. These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of exercise perfusion and ventricular function imaging: an analysis of factors affecting the diagnostic accuracy of each technique.

Exercise thallium-201 perfusion scans and gated equilibrium blood pool scans were performed in 120 catheterized patients with a chest pain syndrome. Eighty-six patients had coronary artery disease and 34 patients did not. The effects of gender, propranolol, exercise level, exercise ischemia, history of typical angina, history of previous myocardial infarction, electrocardiographic Q waves, number of diseases vessels and extent of coronary artery obstruction on diagnostic accuracy were evaluated. The overall sensitivity and specificity of thallium scans were 76 and 68%, respectively, and those of gated blood pool scans 80 and 62% (p = not significant). Propranolol decreased the specificity of thallium scans (propranolol = 42%; no propranolol = 87%, p less than 0.05). Thallium scans and anginal history were less sensitive for detecting coronary disease in women (men: thallium = 79%; angina = 77%; women: 54 and 46%, respectively; p less than 0.05). Exercise level did not significantly affect the diagnostic accuracy of either scan. Thallium and gated scans were both highly sensitive (95%) in detecting disease in 20 patients with a prior myocardial infarction, angina and a positive electrocardiogram. The sensitivity of the thallium scan significantly decreased as the number of diseased vessels decreased. Both thallium and gated scans were less frequently positive in patients with atypical angina or no Q waves, but were not significantly influenced by electrocardiographic ischemia. The sensitivity and specificity of both scans were low in 57 patients with the combination of atypical angina, no history of infarction and equivocal stress electrocardiogram thallium = 61 and 63%, respectively; gated = 61 and 67%). When stress thallium scan evaluation included the electrocardiogram and thallium scan interpretation, the diagnostic accuracy was 81%. When all the information from gated scans (wall motion, ejection fraction, pulmonary blood volume) was combined for final gated scan evaluation, the diagnostic accuracy was 83%. When electrocardiographic data were added to all three gated scan variables, diagnostic accuracy was 77%. In conclusion, thallium perfusion and gated blood pool scans have reasonable diagnostic accuracy for coronary artery disease in a group of patients with a moderately high prevalence of disease. However, combined variables from each test are needed to provide reliable diagnostic accuracy.

In vivo correlation of myocardial metabolism, perfusion, and mechanical function during increased cardiac work.

STUDY OBJECTIVE: The aim was to study the in vivo interaction and regulation of myocardial perfusion, metabolism, and pump function in an open chest canine model using a combination of potentially non-invasive and clinically useful techniques. DESIGN: To assess potential regulatory mechanisms and the interaction of myocardial perfusion, metabolism, and contractile function responses during changes in cardiac workload, noradrenaline (1 microgram.kg-1.min-1) was infused and hypoxia was produced by increasing the inspired ratio of nitrogen to oxygen to produce a PaO2 of 2.6-4.0 kPa in separate interventions. SUBJECTS: Nine mongrel dogs of either sex, age 2-5 years, weight 8.5(SD 2.2) kg, were studied in separate interventions. MEASUREMENTS AND MAIN RESULTS: Myocardial perfusion was determined using 2H nuclear magnetic resonance (NMR) measured washout of deuterium oxide from the left ventricle interpreted with a one component Kety-Schmidt exponential model. High energy phosphate bioenergetics were determined by 31P NMR measurements of the phosphocreatine/ATP ratio. Redox state was estimated by nicotinamide adenine dinucleotide fluorometry expressed as percent change from the baseline, normalised to maximum response measured at 100% inspired N2. Mechanical function was evaluated using heart rate X systolic blood pressure and oxygen consumption measurements. During both noradrenaline infusion and hypoxia, mechanical function increased significantly from control values: heart rate X systolic blood pressure = 1.9(SD 0.5), 3.6(0.1), and 2.6(0.4), respectively; oxygen consumption = 0.9(2), 1.6(0.1), and 1.2(0.6) ml.min-1.100 g-1. Myocardial perfusion increased to support the increased workloads, from 87(10) to 131(20), and from 60(12) to 182(14) ml.min-1.100 g-1, respectively. ADP, estimated by the phosphocreatine/ATP ratio, did not change during noradrenaline infusion [2.4(0.2) to 2.4(0.7)], but decreased during hypoxia [2.4(0.4) to 1.7(0.5)]. Redox state decreased during noradrenaline infusion, from 100% to 84(0.7)%, and increased during hypoxia, from 100% to 140(10)%. CONCLUSIONS: Similar changes in workload induced by different physiological stimuli are associated with different biochemical responses even though changes in perfusion are similar. The data suggest that myocardial function is regulated by different biochemical mechanisms under different physiological conditions, ie, there is probably no universal regulator of myocardial function. It is now possible to evaluate potential metabolic regulators of myocardial function in an in vivo animal model.

Irbesartan reduces QT dispersion in hypertensive individuals.

Angiotensin type 1 receptor antagonists have direct effects on the autonomic nervous system and myocardium. Because of this, we hypothesized that irbesartan would reduce QT dispersion to a greater degree than amlodipine, a highly selective vasodilator. To test this, we gathered electrocardiographic (ECG) data from a multinational, multicenter, randomized, double-blind parallel group study that compared the antihypertensive efficacy of irbesartan and amlodipine in elderly subjects with mild to moderate hypertension. Subjects were treated for 6 months with either drug. Hydrochlorothiazide and atenolol were added after 12 weeks if blood pressure (BP) remained uncontrolled. ECGs were obtained before randomization and at 6 months. A total of 188 subjects (118 with baseline ECGs) were randomized. We analyzed 104 subjects who had complete ECGs at baseline and after 6 months of treatment. Baseline characteristics between treatments were similar, apart from a slight imbalance in diastolic BP (irbesartan [n=53] versus amlodipine [n=51], 99.2 [SD 3. 6] versus 100.8 [3.8] mm Hg; P=0.03). There were no significant differences in BP normalization (diastolic BP <90 mm Hg) between treatments at 6 months (irbesartan versus amlodipine, 80% versus 88%; P=0.378). We found a significant reduction in QT indexes in the irbesartan group (QTc dispersion mean, -11.4 [34.5] milliseconds, P=0.02; QTc max, -12.8 [35.5] milliseconds, P=0.01), and QTc dispersion did not correlate with the change in BP. The reduction in QT indexes with amlodipine (QTc dispersion, -9.7 [35.4] milliseconds, P=0.06; QTc max, -8.6 [33.2] milliseconds, P=0.07) did not quite reach statistical significance, but there was a correlation between the change in QT indexes and changes in systolic BP. In conclusion, irbesartan improved QT dispersion, and this effect may be important in preventing sudden cardiac death in at-risk hypertensive subjects.

Regression of left ventricular hypertrophy in human hypertension with irbesartan.

BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.

Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication.

A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of radiocolloids. For injection of the left ventricle, the catheter is introduced through the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renografin (to confirm the endocardial injection site) and radiolabeled colloid was injected in 13 animals. Ten minutes after injection, scintigraphy was begun and continued for up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method.

Pulmonary capillary wedge pressure, as inferred from lung areas in gated blood-pool scintigrams: concise communication.

To determine whether the apex-to-base distribution of pulmonary blood volume, as obtained from gated cardiac blood-pool scans, could be used as a noninvasive method to estimate mean pulmonary capillary wedge pressure (PCWP), gated blood-pool scans were analyzed in 77 patients who also had PCWP measurements at cardiac catheterization. Ten of these patients had gated cardiac blood-pool scans and PCWP measurements both at rest and during exercise. The apex-to-base distribution of pulmonary blood volume was determined from the end-systolic frame of the left anterior oblique view by placing equal-sized regions of interest over the apex and base of the right lung. The ratio of apex counts over base counts (A/B ratio) was considered abnormal if greater than unity. The mean A/B ratio was 1.15 +/- 0.27 (1 s.d.) for the 32 studies associated with an abnormal mean PCWP (greater than 12 mm Hg). The mean A/B ratio was 0.85 +/- 0.23 for the 55 studies associated with a normal mean PCWP (p less than 0.01 comparing normal group with abnormal). The sensitivity of the A/B ratio for a mean PCWP greater than 12 mm Hg was 81%R (26/32). The specificity of the A/B ratio for a mean PCWP greater than or equal to 12 mm Hg was 89% (49/55). Thus, noninvasive determination of the pulmonary apex-to-base ratio from gated cardiac blood-pool scans appears to differentiate subjects with normal and abnormal mean pulmonary capillary wedge pressures.

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)

Left ventricular function in chronic aortic regurgitation with reference to end-systolic pressure, volume and stress relations.

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.

Left ventricular regional wall motion and velocity of shortening in chronic mitral and aortic regurgitation.

Left ventricular regional wall motion (percent systolic shortening) and velocity of shortening were studied in patients with heart failure due to chronic volume overloads of mitral and aortic regurgitation. Biplane left ventriculograms were analyzed by computer and divided into four regions: anterior, inferior, posterolateral and septal. The study patients included 12 normal subjects; 21 patients with aortic regurgitation (10 asymptomatic and 11 with congestive heart failure); and 11 patients with mitral regurgitation (4 asymptomatic and 7 with congestive heart failure). No patient had coronary artery disease. With heart failure, ejection fraction was decreased (p less than 0.05) in both aortic and mitral regurgitation (normal 62 +/- 3 percent [mean +/- standard error of the mean], aortic regurgitation 48 +/- 3 and mitral regurgitation 51 +/- 5). In mitral regurgitation with heart failure, the percent segment shortening in anterior (normal 42 +/- 2, mitral regurgitation 27 +/- 5) and posterolateral (normal 23 +/- 3, mitral regurgitation 16 +/- 4) regions was significantly decreased (p less than 0.05), whereas this value in the inferior (normal 32 +/- 2, mitral regurgitation 28 +/- 6) and septal (normal 46 +/- 4, mitral regurgitation 47 +/- 5) regions was normal. In aortic regurgitation with heart failure, anterior (27 +/- 2), inferior (17 +/- 3) and septal (5 +/- 1) segment shortening was significantly decreased, whereas posterolateral segment shortening was significantly decreased, whereas posterolateral segment shortening was normal (24 +/- 3). In both groups with heart failure, mean shortening velocity showed regional variations similar to those of percent shortening, whereas peak instantaneous shortening velocity was not reduced in mitral regurgitation compared with normal values. In the asymptomatic group, shortening and mean shortening velocity were normal, whereas peak instantaneous shortening velocity was increased in mitral regurgitation. In aortic and mitral regurgitation with decreased left ventricular function demonstrated by a reduced ejection fraction, there are regional wall motion abnormalities that are not caused by coronary disease.

Positive exercise thallium-201 test responses in patients with less than 50% maximal coronary stenosis: angiographic and clinical predictors.

The incidence and causes of abnormal thallium-201 (TI-201) myocardial perfusion studies in the absence of significant coronary artery disease were examined. The study group consisted of 100 consecutive patients undergoing exercise TI-201 testing and coronary angiography who were found to have maximal coronary artery diameter narrowing of less than 50%. Maximal coronary stenosis ranged from 0 to 40%. The independent and relative influences of patient clinical, exercise and angiographic data were assessed by logistic regression analysis. Significant predictors of a positive stress TI-201 test result were: (1) percent maximal coronary stenosis (p less than 0.0005), (2) propranolol use (p less than 0.01), (3) interaction of propranolol use and percent maximal stenosis (p less than 0.005), and (4) stress-induced chest pain (p = 0.05). No other patient variable had a significant influence. Positive TI-201 test results were more common in patients with 21 to 40% maximal stenosis (59%) than in patients with 0 to 20% maximal stenosis (27%) (p less than 0.01). Among patients with 21 to 40% stenosis, a positive test response was more common when 85% of maximal predicted heart rate was achieved (75%) than when it was not (40%) (p less than 0.05). Of 16 nonapical perfusion defects seen in patients with 21 to 40% maximal stenosis, 14 were in the territory that corresponded with such a coronary stenosis. Patients taking propranolol were more likely to have a positive TI-201 test result (45%) than patients not taking propranolol (22%) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Spectrum of global left ventricular responses to supine exercise. Limitation in the use of ejection fraction in identifying patients with coronary artery disease.

Left ventricular function was evaluated with rest and supine bicycle exercise-multigated blood pool scans in 53 patients who had previously undergone coronary angiography for evaluation of a chest pain syndrome. There were 21 normal patients (less than 25% stenosis in any coronary artery, left ventricular end-diastolic pressure less than or equal to 12 mm Hg, and normal left ventriculography) and 32 patients with coronary artery disease (CAD) (greater than 50% narrowing in 1 or more major coronary arteries). Thirty-two (60%) were receiving propranolol at the time of the study. The normal patient group had a significant increase in mean ejection fraction (EF) during exercise (+0.08 +/- 0.09), while the CAD group had no increase (0 +/- 0.11; p less than 0.05). Mean end-systolic volume decreased significantly in the normal group (-5 +/- 8 ml/m2) but demonstrated no significant change in the CAD group (1 +/- 12 ml/m2; p less than 0.05 compared with normal patients). There was no significant change in mean end-diastolic volume in either group. Mean ejection rate, mean peak systolic pressure/end-systolic volume ratio, and mean pulmonary blood volume ratio also differed in the normal versus CAD patients. Despite mean differences, there was considerable overlap in both groups of individual EF responses: 8 of 21 (38%) of the normal group did not have an increase in EF of 0.05 with exercise, while 15 of 32 (47%) of the CAD group did have an increase in EF of 0.05 with exercise. However, the addition of peak systolic pressure/end-systolic volume ratio and pulmonary blood volume (exercise/rest) ratio improved the sensitivity for detecting CAD from 53 to 84% without adversely affecting specificity. Thus, there is a wide spectrum of left ventricular EF responses to supine exercise. In our patient population, EF alone was an insensitive and nonspecific marker of CAD. The addition of other parameters of global left ventricular function, which may be generated using radionuclide angiography, helps distinguish patients with CAD from normal subjects.

Mitral valve replacement for isolated mitral regurgitation: analysis of clinical course and late postoperative left ventricular ejection fraction.

One hundred five patients underwent mitral valve replacement for relief of isolated mitral regurgitation between 1974 and 1979. There were 4 in-hospital deaths (4 percent) and 12 late deaths giving an 82 percent predicted 5 year survival rate. An age of 60 years or more at the time of surgery and a preoperative left ventricular ejection fraction of less than 0.40 were the only variables that correlated with decreased survival at 3 to 5 years after operation (p less than 0.05). Postoperatively, 87 (98 percent) of 89 long-term survivors were in New York Heart Association functional class I or II (68 in class I and 19 in class II). Survival did not differ between patients with porcine versus mechanical valve replacement, but patients with a mechanical valve had a greater incidence of postoperative cerebrovascular accident (8.6/100 patient years) than did patients with a porcine valve (2.8/100 patient years) (p less than 0.002). Ejection fraction at rest was determined with multigated cardiac imaging 12 to 75 months postoperatively in 34 of 89 long-term survivors. The mean preoperative ejection fraction was 0.62 +/- 0.09 (mean +/- 1 standard deviation) and the mean postoperative ejection fraction was 0.50 +/- 0.15 (p less than 0.001). When the preoperative value was compared with the postoperative value at rest the ejection fraction increased by 0.10 or more in 1 patient (3 percent), remained within +/- 0.09 of the preoperative value in 12 patients (35 percent) and decreased by 0.10 or greater in 21 patients (62 percent). Sixteen (94 percent) of 17 patients whose postoperative ejection fraction was greater than 0.50 were in functional class I postoperatively compared with 11 (65 percent) of 17 patients whose postoperative ejection fraction was 0.50 or less (p less than 0.05). No preoperative factor, including preoperative ejection fraction or cardiothoracic ratio, predicted the postoperative ejection fraction. A postoperative exercise ejection fraction was obtained in 29 patients, and an abnormal ejection fraction change with exercise (increase less than 0.05) was observed in 20 patients (69 percent). Patient age at the time of study correlated inversely with the change in ejection fraction from rest to exercise; no other variables were predictive. It is concluded that, in addition to age, only preoperative left ventricular function as measured by ejection fraction predicts survival in patients undergoing mitral valve replacement for isolated mitral regurgitation. Clinical recovery is good even though the majority of long-term survivors have a postoperative decrease in ejection fraction.

Improvement of myocardial mitochondrial function after hemodynamic support with left ventricular assist devices in patients with heart failure.

OBJECTIVES: Mitochondrial abnormalities have been described in cardiac tissue of patients with heart failure. These changes may result from chronic hypoxia. Our goal was to determine whether mitochondrial functional capacity can be improved in patients with heart failure by means of long-term left ventricular assist device therapy, which improves myocardial oxygen supply by decreasing myocardial work. METHODS: Mitochondria were isolated from myocardial tissue obtained from 13 patients with heart failure without a left ventricular assist device (HF group) and seven patients with heart failure treated with a left ventricular assist device (LVAD-HF group). Mitochondrial respiratory rates (State 2, State 3, and State 4) were measured by means of polarographic techniques with reduced nicotinamide adenine dinucleotide-dependent (pyruvate/malate, alpha-ketoglutarate, glutamate) and -independent (succinate) substrates. The respiratory control index of Chance (State 3/State 4) and Lardy (State 3/State 2) and phosphorus to oxygen ratios were determined. RESULTS: The respiratory control index of Chance was higher in LVAD-HF than in HF when using NADH-dependent substrates pyruvate/malate and alpha-ketoglutarate (pyruvate/malate HF: 4.9 +/- 1.0; LVAD-HF: 6.5 +/- 1.5; alpha-ketoglutarate HF: 8.5 +/- 2.4; LVAD-HF: 11.8 +/- 2.9; both p = 0.04). Similarly, the respiratory control index of Lardy was greater in the LVAD-HF than the HF group when alpha-ketoglutarate and glutamate were used as substrates (alpha-ketoglutarate HF: 7.8 +/- 1.7; LVAD-HF: 9.9 +/- 1.5; glutamate HF: 7.6 +/- 2.2; LVAD-HF: 10.7 +/- 2.1; both p = 0.04). The phosphorus to oxygen ratio was comparable for both groups using all substrates. No change in mitochondrial respiration was observed after left ventricular assist device therapy with the NADH-independent substrate, succinate. CONCLUSION: Cardiomyocyte mitochondrial function is improved by long-term therapy with a left ventricular assist device. This improvement suggests that cardiomyocyte metabolic dysfunction in heart failure may be reversed with left ventricular assist device support.

Serial changes in left ventricular ejection fraction in the early hours after aortocoronary bypass grafting.

To determine the course of left ventricular ejection fraction (LVEF) in the early hours after aortocoronary bypass grafting, 24 patients underwent serial gated bloodpool scanning. Twenty-two had received propranolol until the day of surgery. ECGs showed no evidence of perioperative infarction. Preoperatively, the mean (+/- SD) LVEF was 0.56 +/- 0.13; after bypass, it was 0.38 +/- 0.11 at 4 hours, 0.42 +/- 0.12 at 5 hours, 0.43 +/- 0.11 at 6 hours, 0.48 +/- 0.13 at 7 hours, 0.52 +/- 0.15 at 8 hours, and 0.54 +/- 0.15 at 10 to 14 days. The LVEFs at 4, 5, and 6 hours postoperatively were significantly lower than preoperatively (p less than 0.05). Postoperative mean heart rate was higher at all times; mean temperature was depressed at 4 and 5 hours and elevated at 7 and 8 hours; and mean arterial blood pressure was depressed at 7 hours, 8 hours, and 10 to 14 days (p less than 0.05). The degree of the early postoperative LVEF depression correlated with the daily preoperative propranolol dose (p less than 0.05) and was unrelated to bypass time, aortic cross-clamp time, or changes in temperature, heart rate, and blood pressure. The LVEF at 10 to 14 days postoperatively was not significantly different from the preoperative value. The LVEF is depressed in the early hours after aortocoronary bypass grafting and approaches the preoperative value with time. The magnitude of the early depression appears to be related to the preoperative propranolol dose, but does not significantly correlate with factors related to surgical technique.

Successful management of right ventricular failure with the ventricular assist pump following aortic valve replacement and coronary bypass grafting.

Right ventricular failure is an infrequent but potentially lethal complication of cardiac surgical procedures. We have successfully treated a patient with right ventricular failure with the use of a right ventricular assist pump (RVAP). This patient had aortic stenosis and coronary artery disease involving the circumflex and right coronary arteries. He also had chronic obstructive pulmonary disease with mild pulmonary hypertension (mean pulmonary artery pressure of 26 mm Hg) and evidence of mild right ventricular failure (right ventricular pressure of 40/14 mm Hg). Gated radionuclide angiography, performed preoperatively, showed that the right ventricle had normal wall motion. Right ventricular failure prevented discontinuation of cardiopulmonary bypass despite use of an intra-aortic balloon pump. The right atrial pressure was 20 mm Hg with a left atrial pressure of 8 to 10 mm Hg. Bypass was readily discontinued following implantation of the RVAP. Recovery of the patient's right ventricle was evaluated with serial determinations of right ventricular work. The RVAP was removed on the fifth postoperative day and the patient made a complete recovery. Postoperatively, gated radionuclide angiography demonstrated moderate recovery of right ventricular function. We suspect that the perioperative right ventricular failure was a result of unsatisfactory myocardial protection due to total occlusion of the proximal right coronary artery, which resulted in a maldistribution of the cardioplegic solution. This case demonstrates that right ventricular function can be restored following circulatory support with a mechanical assist device.

Anatomic features of the eye disclosed with nuclear magnetic resonance imaging.

Nuclear magnetic resonance (NMR) imaging of the eye and paraorbital areas was performed in 35 volunteers and in four patients with ocular pathology. Two- and three-dimensional images were performed with saturation recovery (SR), inversion recovery (IR), and spin echo (SE) pulse sequences. Fat was brighter than surrounding tissue on images obtained with all pulse sequences, while muscle and optic nerve were of decreased intensity. The optic chiasm and vitreous were of decreased intensity compared with orbital fat on SR. The lens had even less signal intensity than the vitreous on SR and IR images and blended into the surroundings on SE images. A melanoma of the ciliary body and a lymphoma of the lacrimal gland were identified. In conclusion, NMR images can be used to identify normal and pathologic orbital and eyeball anatomy. Image contrast is provided by high intensity fat, which is interspersed throughout other orbital structures.

Cardiovascular monitoring during elective aortic surgery.

We designed a prospective study to determine whether cardiac ejection fraction as measured noninvasively could isolate a subset undergoing aortic surgery for whom central venous pressure (CVP) predicted pulmonary artery wedge pressure (PAWP). Sixteen patients were studied. Simultaneous values of PAWP and CVP were analyzed, using linear regression analysis. A significant correlation between CVP and PAWP was found for the entire patient population and for each of four time periods: preoperative, before and after aortic cross-clamping, during aortic cross-clamping, and postoperative. A significant correlation between PAWP and CVP was found during the entire perioperative period for 14 of the 16 patients. However, the slope of the regression line, or the sensitivity of the CVP in reflecting changes in PAWP, was greater than 0.5 in only seven of the 16 patients. There was no correlation between the preoperative ejection fraction and the CVP/PAWP. We conclude that the CVP is an insensitive indicator of left ventricular filling pressure in most patients accepted for elective infrarenal aortic surgery, and monitoring of the PAWP is recommended.