The electrical activity of embryonic chick heart cells isolated in tissue culture singly or in interconnected cell sheets.

Embryonic chick heart cells were cultured on a plastic surface in sparse sheets of 2-50 cells mutually in contact, or isolated as single cells. Conditions are described which permitted conjoint cells to be impaled with recording microelectrodes with 75% success, and isolated single cells with 8% success. It is proposed that cells in electrical contact with neighbors are protected from irreversible damage by the penetrating electrode, by a flow of ions or other substances from connected cells across low-impedance intercellular junctions. Action potentials recorded from conjoint and isolated single cells were similar in form and amplitude. The height or shape of the action potential thus appears not to depend upon spatial relationships of one cell to another. As the external potassium concentration was increased from 1.3 mM to 6 mM, cells became hyperpolarized while the afterhyperpolarization was reduced. At higher potassium levels, the afterhyperpolarization disappeared, the slope of the slow diastolic depolarization decreased, and resting potential fell along a linear curve with a slope of 61 mv per 10-fold increase in potassium. In pacemaker cells the diastolic depolarization consists of two phases: (a) recovery from the afterpotential of the previous action potential and (b) the pacemaker potential. These phases are separated by a point of inflection, and represent manifestations of different mechanisms. Evidence is presented that it is the point of inflection (PBA) rather than the point of maximal diastolic potential, that should be taken as the resting potential.

The electrical activity of embryonic chick heart cells isolated in tissue culture singly or in interconnected cell sheets.

Embryonic chick heart cells were cultured on a plastic surface in sparse sheets of 2-50 cells mutually in contact, or isolated as single cells. Conditions are described which permitted conjoint cells to be impaled with recording microelectrodes with 75 % success, and isolated single cells with 8 % success. It is proposed that cells in electrical contact with neighbors are protected from irreversible damage by the penetrating electrode, by a flow of ions or other substances from connected cells across low-impedance intercellular junctions. Action potentials recorded from conjoint and isolated single cells were similar in form and amplitude. The height or shape of the action potential thus appears not to depend upon spatial relationships of one cell to another. As the external potassium concentration was increased from 1.3 mM to 6 mM, cells became hyperpolarized while the afterhyperpolarization was reduced. At higher potassium levels, the afterhyperpolarization disappeared, the slope of the slow diastolic depolarization decreased, and resting potential fell along a linear curve with a slope of 61 mv per 10-fold increase in potassium. In pacemaker cells the diastolic depolarization consists of two phases: (a) recovery from the afterpotential of the previous action potential and (b) the pacemaker potential. These phases are separated by a point of inflection, and represent manifestations of different mechanisms. Evidence is presented that it is the point of inflection (PBA) rather than the point of maximal diastolic potential, that should be taken as the resting potential.

Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: a randomized, placebo-controlled, crossover trial.

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Reciprocal ST change in acute myocardial infarction: assessment by electrocardiography and echocardiography.

To evaluate the incidence, time course and significance of reciprocal change, 25 consecutive patients admitted with their first acute transmural myocardial infarction were studied with serial electrocardiography and two-dimensional echocardiography. Reciprocal change was noted in all patients with inferior infarction (mean maximal ST segment depression 3.53 +/- 1.97 mm) and 70% of patients with anterior infarction (mean maximal ST depression 1.45 +/- 0.8 mm, p = 0.001). When initially present, reciprocal change had resolved within 24 hours in 59% of patients. The sum of reciprocal ST depression correlated with the sum of ST elevation in anterior (r = 0.92, p less than 0.001) and inferior (r = 0.55, p = 0.035) infarction, and this relation persisted when maximal ST depression and elevation were considered. Echocardiographic evidence of contraction abnormalities in areas of the left ventricle remote from the infarction was seen in 45% of patients. However, its presence did not correlate with the presence of reciprocal change. Although reciprocal change progressively diminished on serial electrocardiograms (maximal ST depression 2.73 +/- 1.77 mm at 19 hours after onset of symptoms; 1.0 +/- 0.92 mm at 2 to 3 days; and 0.22 +/- 0.26 mm at 7 to 10 days; p less than 0.05), the corresponding serial echocardiograms showed no change in the function of the remote wall (remote wall motion index 1.87 +/- 0.65, 1.81 +/- 0.62, 1.86 +/- 0.47, respectively, p = NS). These data, therefore, do not support the hypothesis that reciprocal ST depressions during early acute transmural myocardial infarction reflect remote ischemia. Rather, these changes are influenced by factors determining the degree of acute ST elevation, previously shown to include infarct size, shape, location, transmurality and duration.

Is digoxin really important in treatment of compensated heart failure? A placebo-controlled crossover study in patients with sinus rhythm.

To assess the efficacy of digitalis in patients with chronic clinically compensated congestive heart failure and normal sinus rhythm, we performed a double-blind crossover study with digoxin and placebo in 30 consecutive outpatients fulfilling these criteria; serum digoxin levels, clinical symptoms and signs, and objective indexes of cardiac function were monitored. No patient's clinical condition deteriorated during three months of placebo administration. Discontinuation of digoxin resulted in a small increase in echocardiographically determined resting left ventricular end-diastolic dimension (1.8 +/- 0.6 mm, p less than 0.001) and a similar decrease in velocity of circumferential fiber shortening (-0.08 +/- 0.04 circ/sec, p less than 0.05) from the corresponding values of 55.8 +/- 2.3 mm and 0.90 +/- 0.08 circ/sec during digitalis therapy. Resting left ventricular ejection time and pre-ejection period were prolonged by digoxin withdrawal. Maximal exercise capacity was unchanged. No clinical exacerbation of heart failure attributable to digitalis withdrawal occurred over a follow-up period averaging 19 months. The results indicate that long-term digoxin therapy has only a minor effect on cardiac performance that is without apparent clinical importance in a representative population of ambulatory patients treated with cardiac glycosides.

Mitral valve prolapse: from syndrome to disease.

Mitral valve prolapse (MVP) is due to a heterogeneous group of conditions that may affect the mitral valve or the mitral valve apparatus. Although MVP may progress later in life to frank mitral insufficiency requiring mitral valve repair or may predispose to bacterial endocarditis, in most cases it is a benign, idiopathic condition without serious consequences. However, many investigators have documented that MVP is often associated with a constellation of signs and symptoms, which appear to constitute a distinct syndrome. These associated findings include autonomic dysfunction, frequent complaints of chest pain, palpitations, orthostasis, fatigue, dyspnea on exertion and anxiety. Although the risk of significant myocardial dysfunction or bacterial endocarditis appears to be related to patient sex, age and the severity of valvular prolapse and insufficiency, there appears to be little or no relations between the extent of prolapse and the degree of autonomic dysfunction or the severity of symptoms of chest pain, palpitations, dyspnea on exertion and anxiety. The development of uniform diagnostic standards for mental disorders has helped to make it possible to identify several related entities, including generalized anxiety disorder, panic disorder and agoraphobia; patients with these disorders frequently somatize their anxiety and complain of many symptoms which may be seen in patients with MVP. Although several studies have reported an increased frequency of MVP in patients with anxiety disorders, recent studies suggest that the conditions are not linked. Iatrogenic cardiac neurosis is common in both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Death after acute myocardial infarction: interrelation between left ventricular dysfunction, arrhythmias and ischemia.

Patients who survive an acute myocardial infarction face an increased risk of sudden death for approximately 6 months after hospital discharge; their prognosis is determined by the severity of their coronary arteriosclerosis and the degree of left ventricular dysfunction. Frequent ventricular premature complexes and evidence of ischemia either spontaneously or on treadmill are also markers for early morbidity and mortality in patients who are discharged from the hospital after acute myocardial infarction. The degree of left ventricular dysfunction is the strongest predictor of mortality; patients who have both left ventricular dysfunction, frequent premature ventricular beats and evidence of ischemia are at the highest risk of mortality after hospital discharge. It appears likely that all 3 of these risk factors interact and that therapy to reduce morbidity and mortality after myocardial infarction should aim at the amelioration of each of these risk factors. A model for the interaction of these risk factors is proposed and an approach to treatment for patients at high risk of mortality after hospital discharge after myocardial infarction is suggested.

Insensitivity of the electrocardiogram in apical myocardial infarction.

The ability of the standard ECG to identify myocardial infarction (MI) involving primarily the left ventricular (LV) apex is controversial. Therefore, the ECGs of 62 consecutive patients with acute infarction and isolated akinesia or dyskinesia of the LV apex on gated blood pool scintigraphy performed at rest 9 +/- 4 days after MI, were reviewed. The following distribution of Q waves was found: none, 26%; inferior leads only, 23%; anterior leads only, 32%; inferior + 1 or more V leads, 13%; lead I and/or aVL + 1 or more V leads, 6%. Only 12 patients (19%) demonstrated one of the "combination" Q-wave patterns thought to indicate apical infarction. Although the 20 patients with a history of MI did not differ in age or ejection fraction from those with a first MI, the combination of inferior and anterior Q waves was present in 6 of them (30%), vs only 2 of the remaining 42 patients (5%) (p less than 0.02). The 24 patients with apical dyskinesia had a lower ejection fraction (36 +/- 14 vs 48 +/- 12, p less than 0.001), a lower prevalence of isolated inferior Q waves (8 vs 32%, p less than 0.05) and a greater prevalence of isolated anterior Q waves (46 vs 24%, p = 0.09) than those with akinesia. Thus, in patients with recent MI localized to the LV apex on radionuclide ventriculography, pathologic Q waves are commonly confined to the anterior or inferior leads or absent altogether. The insensitivity of the various proposed criteria for the electrocardiographic diagnosis of apical MI emphasizes the value of imaging techniques in detecting this common clinical entity.

An angiographic and functional comparison of patients with silent and symptomatic treadmill ischemia early after myocardial infarction.

Sixty consecutive patients were studied who had positive responses to Naughton exercise treadmill testing (at least 1.5 mm of ST-segment shift in at least 2 leads or thallium reperfusion abnormalities) with or without symptoms of angina 11 +/- 1 days after acute myocardial infarction (AMI). All patients had undergone coronary angiography 24 +/- 4 days after infarction. Thirty-eight patients (63%) had no treadmill angina (silent ischemia, group I) and 22 patients had typical treadmill angina (symptomatic ischemia, group II). Use of beta-blocking drugs, calcium antagonists and nitrates at the time of exercise testing did not differ in the 2 groups. All 9 patients with diabetes mellitus were in the asymptomatic group (p less than 0.40) and group I had a greater proportion of inferior wall AMI (30 of 38) than group II (11 of 22, p = 0.02). Total exercise treadmill test duration (group I 422 +/- 31 seconds, group II 400 +/- 46 seconds) and rate-pressure product were not different in the 2 groups. The number of patients unable to exercise 5 minutes (12 in group I and 7 in group II), the number with diffuse electrocardiographic changes (9 in group I and 7 in group II), and the number with inadequate blood pressure response (8 in group I and 4 in group II) were also similar. At coronary arteriography the mean number of arteries with at least 70% diameter stenosis was 2.0 +/- 0.2 in group I and 2.2 +/- 0.2 in group II (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of OPC-8212, a quinolinone derivative, for chronic congestive heart failure in patients with ischemic heart disease or idiopathic dilated cardiomyopathy.

To evaluate the safety and efficacy of the inotropic agent OPC-8212 in patients with chronic congestive heart failure, 76 patients with impaired cardiac function and diminished exercise tolerance were studied. They were randomized to 12 weeks of double-blind therapy with either 60 mg/day of OPC-8212 or placebo. The study drug was added to their baseline medical regimen. The primary study outcome was the combined outcome of the time to either mortality (of all cause) or substantial worsening of heart failure (major morbidity), whichever occurred first. Treatment with OPC-8212 significantly (p less than 0.01) decreased the combination of major morbidity/mortality over 12 weeks of therapy. Quality of life, assessed by the Sickness Impact Profile questionnaire, was significantly improved in patients receiving OPC-8212 (p less than 0.01). Furthermore, ventricular premature contractions as assessed by 24-hour Holter monitoring were not increased with OPC-8212 treatment. Although patients treated with OPC-8212 were able to reach a significantly higher peak oxygen uptake and exercise longer during symptom-limited exercise, when data were analyzed as percent change from baseline, the absolute increases were small. These results suggest that OPC-8212 is beneficial in treating patients with congestive heart failure and that further evaluation of this new inotropic agent is warranted.

Smoking following myocardial infarction: a critical review of the literature.

This paper critically reviews the available research on the effects of smoking cessation following acute myocardial infarction (MI). Studies that have examined the rate of smoking cessation following an MI indicate that approximately 1/3 to 1/2 of the smokers who suffer from MI subsequently reduce or quit smoking. Furthermore, studies that have examined subsequent mortality and morbidity suggest that individuals who quit smoking following MI exhibit lower mortality and morbidity than those who continue to smoke. It is argued that past studies may have overestimated post-MI smoking cessation rates, and by failing to control for a priori differences between quitters and continuing smokers (e.g., MI severity) may have underestimated the negative effects of smoking following MI. Suggestions for future research are proposed.

Rapid resumption of cigarette smoking following myocardial infarction: inverse relation to MI severity.

In order to identify factors associated with relapse to cigarette smoking, medical and interview data were collected from 66 chronic smokers hospitalized for acute myocardial infarction (MI). Relapse to smoking during the in-hospital recovery period was prevalent (38% of patients). The major correlate of smoking relapse was MI severity, with relapse probability declining as MI severity increased; patients who relapsed to smoking during the recovery period had experienced less severe MIs, as indicated by their serum creatine phosphokinase (CPK) enzyme levels and their requiring significantly shorter intensive-care treatment. Smoking relapse was not related to patients' smoking histories, their reported craving experiences, their reported health beliefs or demographic characteristics. The fact that relapse is most likely among patients with the best medical prognostic status suggests that the benefits of post-MI smoking cessation may have been underestimated in previous studies.

Dermatoglyphic (fingerprint) evidence for a congenital syndrome of early onset constipation and abdominal pain.

Chronic idiopathic constipation and abdominal pain are the most common gastrointestinal symptoms but their cause is rarely determined; therefore, they usually are called functional. To determine if congenital factors play a role in these disorders, we examined dermatoglyphic (fingerprint) patterns, a congenital marker, in 155 consecutive patients with gastrointestinal complaints. Sixty-four percent of patients with constipation and abdominal pain before age 10 yr had one or more digital arches, compared with 10% of patients without constipation and abdominal pain (p less than 0.001). Seventy percent of constipated patients with arches had the onset of symptoms before age 10 yr compared with 23% of constipated patients without arches (p less than 0.001) and 14% of patients with symptoms other than constipation (p less than 0.001). Compared with an age- and sex-matched sample of patients without arches, patients with arches had a higher prevalence of constipation and abdominal pain before age 10 (p = 0.003), were more likely (p less than 0.001) to have chronic intestinal pseudoobstruction (an organic disorder), and were less likely (p = 0.013) to have irritable bowel syndrome (a functional disorder). Identification of a congenital marker, digital arches, associated with early onset constipation and abdominal pain may help to differentiate a congenital organic syndrome from functional disorders such as the irritable bowel syndrome.

A cross-national study of differences in length of stay of patients with cardiac diagnoses.

To determine the reason for large regional differences in average hospital length of stay shown in federal discharge abstract data, the medical records of 482 cardiac patients from hospitals belonging to two metropolitan area PSROs of Baltimore, Maryland, and 438 cardiac patients from hospitals in the Metropolitan area PSRO from Portland, Oregon, were reviewed, stratified by diagnosis and complications, and compared for length of stay. Cardiac patients were hospitalized between 2.5 and 7 days longer in Baltimore than in Portland. Federal data on length of hospital stay were basically correct for the diagnostic categories studied. Length-of-stay differences could not be explained by patient differences and appeared to be due to differences in physician practice patterns.

Elimination of central sleep apnoea by mitral valvuloplasty: the role of feedback delay in periodic breathing.

Central sleep apnoea is a form of periodic breathing which resembles Cheyne-Stokes respiration but occurs only during sleep. One mechanism in the pathogenesis is a delay in chemical feedback from the lungs to the medullary respiratory centre. We explored the relationship between circulatory feedback delay in a patient with central sleep apnoea and Cheyne-Stokes respiration before and after mitral valve repair. Preoperatively the patient had severe central sleep apnoea and an increased circulation time. Following mitral valvuloplasty the circulation time was decreased with resolution of central sleep apnoea. This case demonstrates the role of feedback delay in central sleep apnoea and suggests that similar haemodynamic mechanisms may lead to central sleep apnoea and Cheyne-Stokes respiration.

Physical fitness, physical activity, and fatness in relation to blood pressure and lipids in preadolescent children. Results from the FRESH Study.

PURPOSE: The cross-sectional gender patterns of fitness, activity, and fatness were examined in relation to blood pressure and lipids in 9- to 10-year-old children. METHODS: Subjects were fourth graders (26 boys and 27 girls) participating in FRESH, a school-based heart health program. The main variables of interest were fitness determined on a treadmill, habitual physical activity by self-report, fatness by skinfolds and body mass index, blood pressure, and lipoprotein lipids. RESULTS: Physical fitness and activity were higher in boys, whereas fatness and triglycerides were higher in girls. Systolic blood pressure correlated positively with fatness in girls, and there was a trend for this relationship in boys. In boys, total LDL cholesterol correlated positively with fatness and negatively with fitness. By multivariate analysis, fitness was the primary correlate of total and LDL cholesterol. In girls, fitness correlated positively with total and LDL cholesterol. This finding was opposite in boys. Fatness correlated negatively with HDL cholesterol in boys. CONCLUSION: Boys are more fit and active and less fat than girls. Fatness in young children already shows a relationship with heart disease risk factors. In boys, fitness shows a favorable relation to lipids. These data along with other studies suggest that more consistent relationships among fitness, activity, fatness, blood pressure, and lipids are likely to emerge as children approach adolescence. The findings also underscore the complexity of defining these relationships in young children.

Silent ischemia on Holter monitoring predicts mortality in high-risk postinfarction patients.

The relative prognostic significance of ischemic ST changes on two-lead continuous electrocardiographic (Holter) monitoring in 103 high-risk postinfarction patients was examined. Ischemic ST changes were detected in 30 patients, with a median number of five episodes per day and median total daily duration of 157 minutes. Only one third of these patients reported any angina in the hospital, and 28 of the 30 patients had silent ST changes on Holter monitoring. The remaining 73 patients had no ischemic ST changes on Holter monitoring. At one year, nine (30%) of 30 patients with ischemic ST changes were dead vs only eight (11%) of 73 patients without such changes. Multivariate Cox's hazard function analysis on 18 variables, including age, type of infarction, Lown and Killip class, ejection fraction, and medications, showed that the presence of ST changes on Holter monitoring was a significant predictive variable for one-year mortality in the overall study population and particularly in the subgroup of 59 patients who could not undergo early exercise treadmill testing. Thus, ischemic ST changes on Holter monitoring, the majority of which are silent, occur in nearly one third of high-risk postinfarction patients and are significantly associated with one-year mortality.

Portable intraaortic balloon counterpulsation: clinical experience and guidelines for use.

Intraaortic balloon (IAB) counterpulsation is a proven treatment for patients with refractory ischemia or cardiogenic shock; however its use has been largely limited to tertiary centers due to the difficulties and risks encountered in transporting patients with this device in place. We report our initial experience with 11 patients who underwent IAB counterpulsation at a community hospital utilizing a portable transport IAB system. All 11 patients had successful IAB insertion, resulting in prompt stabilization. Immediate transportation during uninterrupted IAB counterpulsation was successfully accomplished in each case using routine ambulance vehicles, allowing for the prompt initiation of further tertiary care. The role of portable IAB counterpulsation in the community hospital and guidelines for the implementation of this portable IAB system are outlined.

Nifedipine in acute myocardial infarction: an assessment of left ventricular function, infarct size, and infarct expansion. A double blind, randomised, placebo controlled trial.

The influence of nifedipine on left ventricular ejection fraction, infarct size, and infarct expansion was studied in a prospective, double blind, randomised, placebo controlled trial in 132 patients with low risk acute myocardial infarction of less than 12 hours duration, defined by an initial left ventricular ejection fraction greater than 35% and clinical Killip class of less than or equal to II. Sixty four patients were assigned to nifedipine 120 mg/day and 68 to placebo. Treatment was started on average (SEM) 8.0 (0.2) hours after onset of pain and continued for six weeks. Gated blood pool scans, thallium scans, and cross sectional echocardiograms were performed before treatment and at 10 days. There were no significant differences between the two groups in age, sex, cardiac risk factors, or use of other medications. Mean (SEM) global left ventricular ejection fraction was not different before treatment (nifedipine group 53 (2%), placebo group 55 (2%) and did not differ at 10 days (nifedipine group 54 (2%), placebo group 52 (2%). There were also no differences in regional wall motion or regional ejection fractions. Thallium defects quantified by computer analysis were similar in both groups before treatment (nifedipine 7.8 (0.7), placebo 7.9 (0.7)) and at 10 days (nifedipine 5.3 (0.7) placebo 5.3 (0.7)). In the subgroup of patients with transmural infarction who had good quality echocardiograms and serial studies (n = 30), there was no difference in mean (SEM) baseline infarct segment lengths between the two groups (nifedipine 70 (4) mm, placebo 65 (4) mm); however, the nifedipine group demonstrated no significant change in infarct segment length between the initial and 10 day studies ( + 0.6 (3) mm) while there was a significant increase in the infarct segment length in the placebo group (+ 7.8 (4) mm). The infarct segment length increased by >/= 1 cm in seven (47%) placebo patients but in only one (7%) nifedipine patient. The nifedipine group had a significant initial 10% decrease in mean arterial pressure whereas there was no change in the in the placebo group; this blood pressure difference persisted for 10 days. Thus although the early administration of nifedipine has no detectable effect on clinical outcome and infarction size, it may reduce early infarct expansion via an afterload reduction mechanism in patients with transmural infarction. These initial results must be interpreted with caution and need to be confirmed in a larger trial.