Thyroid-induced alterations in myocardial sodium-potassium-activated adenosine triphosphatase, monovalent cation active transport, and cardiac glycoside binding.

The effects of thyroid hormone on guinea pig myocardial NaK-ATPase activity, transmembrane monovalent cation active transport, and cardiac glycoside binding were were examined. NaK-ATPase activities of left atrial and left ventricular homogenates of control and triiodothyronine (T3)-treated animals were determined, and compared to activities of skeletal muscle and liver. T3 administration was associated with a significant increase of 18% in left atrial and left ventricular NaK-ATPase specific activities. This increment was less than that noted in skeletal muscle (+42%) and liver (+30%). To determine if enhanced NaK-ATPase activity was accompanied by increased monovalent cation active transport, in vitro 86Rb+ uptake by left atrial strips and hemidiaphragms was measured. Transition from the euthyroid to the hyperthyroid state resulted in a 68% increase in active 86Rb+ uptake by left atrium, and a 62% increase in active uptake by diaphragm. Passive 86Rb+ uptake was not affected in either tissue. Ouabain binding by atrial and ventricular homogenates of T3-treated animals was increased by 19 and 17%, respectively, compared to controls, in close agreement with thyroid-induced increments in NaK-ATPase activiey. Taken together, these results are consistent with enhanced myocardial NaK-ATPase activity and monovalent cation activt transport due to an increase in the number of functional enzyme complexes.

Characterization of the human right ventricular pressure-volume relation: effect of dobutamine and right coronary artery stenosis.

Right ventricular function was assessed in 15 patients using right ventricular pressure-volume loops. Right ventricular pressure using a micromanometer-tipped catheter, thermodilution cardiac output and gated blood pool scintigrams were simultaneously obtained. To help isolate the right ventricle, a slant hole collimator was used. The measurements were repeated during dobutamine infusion, which was titrated so there was minimal change in systemic pressure and heart rate. The right ventricular pressure-volume loop resembles the usual left ventricular loop except that the isovolumic contraction phase is often not as distinct, and right-sided ejection may continue well beyond right ventricular peak systolic pressure. Systolic but not diastolic function improved with dobutamine administration. There was no significant difference in right ventricular systolic function (ejection fraction, stroke work index, stroke volume index and cardiac index) or in end-diastolic volume index between patients without (Group I) and with (Group II) significant right coronary artery stenosis. However, there was a small but significant difference in right ventricular end-diastolic pressure (5.3 +/- 2.5 and 8.1 +/- 1.8 mm Hg [p less than 0.05]) for Group I and II, respectively. Thus, the right ventricular pressure-volume loop can be used to graphically display right ventricular function and improvement in contractility with dobutamine. The right ventricular isovolumic contraction phase and ejection phase differ from those in the usual left ventricular loop. Although there was a small difference in right ventricular end-diastolic pressure in patients with and without right coronary artery stenosis, the right ventricular pressure-volume loop did not provide additional discriminatory information between these two groups of patients.

Correlation of echocardiographic and clinical findings in patients with pericardial effusion.

Clinical data and echocardiographic findings were correlated in 20 patients with pericardial effusion. Moderate to large effusions were associated with increased motion of the entire heart within the pericardial sac. A correlation was found between the estimated volume of fluid and the diastolic excursion and velocity of the right ventricular and left ventricular walls (P less than 0.01). For any given volume of fluid as estimated from the echocardiogram neoplastic effusions resulted in greater increments in wall motion (P less than 0.02). Patterns of "pseudo" mitral valve prolapse occurred and were correlated with the extent and timing of cardiac swinging and heart rate. A diminished E-F slope of the mitral valve echo and notch on the right ventricular epicardial echo during early systole were found in all four patients with pericardial tamponade. These preliminary observations suggest that echocardiographic examination of patients with pericardial effusion may provide clues to the presence or absence of tamponade in addition to providing an estimate of the quantity of fluid in the pericardial sac.

Oral amrinone in refractory congestive heart failure.

The acute effects of an oral preparation of amrinone, a recently synthesized cardiotonic agent, were assessed noninvasively in nine patients who had advanced heart failure that persisted despite treatment with digitalis, diuretic drugs and afterload-reducing agents. All patients demonstrated an improvement in left ventricular ejection fraction determined by radionuclide ventriculography (20.3 +/- 2.8 to 30.8 +/- 4.8 percent [mean +/- standard error of the mean], p less than 0.005) after a single dose of amrinone. Initial effects were seen within 1 hour, with the peak effect occurring at 1 to 3 hours; persistent effects were demonstrable at 4 to 6 hours. No change in blood pressure, heart rate or rhythm was observed, and there was no clinical evidence of myocardial ischemia. Continued benefit was demonstrated by radionuclide ventriculography in two patients treated for 1 and 6 weeks, respectively, although two other patients experienced major side effects with the chronic administration of amrinone. Although orally administered amrinone shows promise as a potentially useful agent in the treatment of advanced heart failure, the safety of this drug remains to be established.

Aging and exercise performance.

Diverse physiologic changes occur in the oxygen transport system during the aging process. Physical performance and VO2max decline with age, but the changes may be attenuated by exercise training. Increased ventilation is required during exercise in order to compensate for reduced efficiency of gas exchange. Cardiovascular alterations include prolonged duration of myocardial contraction, a slightly reduced left ventricular ejection fraction during exercise, decreased heart rate during both submaximal and maximal exercise, and attenuation of myocardial response to beta-adrenergic stimulation. Cardiac output during exercise can be maintained in the elderly owing to a greater dependence on ventricular filling. Appropriate exercise training leads to enhanced efficiency of the lungs, heart, and skeletal muscles. These physiologic benefits contribute to an increase in functional capacity and an enhanced sense of well-being. Exercise testing is recommended for individuals who have cardiorespiratory symptoms and for those at risk for the development of coronary artery disease. Reasonable goals for an aerobic training program are continuous activity for 30 minutes at a moderate intensity of exertion at least 3 days per week. The intensity of exercise should be based on a prescribed training heart rate. The exercise prescription should be individualized and should incorporate one or more activities for optimal enjoyment and compliance. Opportunities and facilities for indoor exercise are important during inclement weather. Regular physical exercise is important at any age!

Intravenous nitroglycerin in the treatment of spontaneous angina pectoris: a prospective, randomized trial.

A prospective, randomized study of i.v. nitroglycerin (TNG) in the management of repetitive spontaneous angina pectoris was undertaken in 40 consecutive patients. The clinical effectiveness of i.v. TNG (group A) was compared with that of oral isosorbide dinitrate (ISDN) and topical 2% nitroglycerin ointment (NO) in combination (group B) during a 72-hour treatment period. The doses of both nitrate regimens were adjusted so that the mean arterial pressure in the two groups was reduced by 15 +/- 3% of control values to the same level (77 mm Hg). The i.v. TNG dose of 10-200 micrograms/min yielded arterial plasma TNG levels of 1.2-65.3 ng/ml and estimated plasma (arterial) clearance of 106 +/- 55 ml/min/kg of body weight (mean +/- SD). In group B, the doses were 20-60 mg (oral ISDN) and 1/2-2 inches (NO) every 6 hours. Intravenous TNG reduced the number of spontaneous ischemic episodes from 3.3 +/- 0.8 per 24 hours during the control period to 1.0 +/- 0.3 per 24 hours during the treatment period (p less than 0.01), while the ISDN/NO combination reduced the number of episodes from 3.1 +/- 0.4 to 1.4 +/- 0.3 (p less than 0.01). Overall, the magnitude of the therapeutic effect of i.v. TNG was statistically indistinguishable from that of ISDN/NO, although i.v. TNG did have somewhat greater clinical benefit on day 2 of the 3-day treatment period. Furthermore, the data suggested more consistent control of ischemic episodes with i.v. TNG during the first 24 hours of the trial. Although both regimens markedly reduced the frequency of spontaneous ischemic episodes, only 36% of patients in group A and 17% in group B experienced no ischemic episodes during the study period (NS). Forty-three percent of patients in group A and 61% in group B (NS) required early coronary artery bypass surgery to control recurrent ischemic episodes refractory to medical therapy. We conclude that i.v. TNG and ISDN/NO, when administered in doses adjusted to produce similar effects on systemic arterial pressure, have nearly equivalent clinical effects in the management of patients with frequent episodes of spontaneous angina pectoris. Intravenous TNG offers the advantage of more consistent control of ischemic episodes during the first 24 hours of treatment. Nevertheless, the recurrence rate of spontaneous ischemic episodes during medical therapy is high with both regimens, and early coronary artery bypass surgery may be required for long-term management.

Suppression of myocardial protein degradation in the rat during fasting. Effects of insulin, glucose, and leucine.

To study the effects of leucine, glucose, and insulin on myocardial protein degradation in fed and fasted nutritional states, we developed and validated a sensitive method for measuring rates of total protein degradation in rat isolated left atrial preparations. Fasting resulted in a progressive decrease in myocardial protein breakdown to 71% of control over a 24-hour period, with no further reduction in degradation rate between 24 and 72 hours of fasting. Insulin (100 mU/ml) suppressed atrial protein degradation by 38% in fed animals (P less than 0.001) and by 51% in fasted animals (P less than 0.001). Glucose alone had no effect on protein degradation in either nutritional state. At 5 times normal plasma levels, leucine suppressed protein breakdown by 21% in fed and by 15% in fasted animals. The decrease in degradation induced by fasting and the absence of an effect of glucose are in contrast to the behavior reported for skeletal muscle.

Valve replacement for aortic regurgitation: long-term follow-up with factors influencing the results.

One hundred consecutive cases of valve replacement for aortic regurgitation performed between 1967--1971 were analyzed to identify and quantitate factors related to a favorable result. Of 83 perioperative survivors, 78% (n = 65) became asymptomatic and 58% (n = 48) were alive 5--9 years postoperatively. The cause of aortic regurgitation affected both the speed of progression of symptoms and the postoperative result. Death due to myocardial failure may be prevented by optimal timing of operation. Accordingly, we identified variables that discriminated between patients who had an excellent postoperative result and those who died of myocardial failure. The most important discriminators were the severity (p = 0.03) and duration (p = 0.04) of dyspnea, the extent of therapy for heart failure (p = 0.001), physical findings of left ventricular failure (p = 0.002), the cardiothoracic ratio (p = 0.007), the resting pulmonary capillary wedge pressure (p = 0.01), and a cardiac index less than 2.2 1/min/m2 (p = 0.03). The data suggest that evidence of left ventricular failure, even of mild degree, is an indication for operation in patients with severe aortic regurgitation.

Exercise electrophysiology testing: the effect of exercise on the induction of ventricular arrhythmias by programmed ventricular stimulation.

In order to assess the effect of acute, reversible myocardial ischemia on the outcome of programmed ventricular stimulation (PVS), ventricular stimulation was performed at rest, during exercise, and during recovery in 10 patients with coronary artery disease. Of these ten patients, four were tested while off antiarrhythmic drugs and six were tested on antiarrhythmic drug therapy. Nine of the ten patients developed acute myocardial ischemia during exercise PVS. However, in only two of these ten patients ventricular arrhythmia could be induced by PVS, one during exercise and one during recovery.