Duration and extent of antianginal effects of a sustained-release formulation of nifedipine in angina.

Twenty-four patients with chronic stable exertional angina pectoris were randomized in a double-blind, placebo-controlled, crossover trial to assess the efficacy and durability of a newly developed, sustained-release formulation of nifedipine (nifedipine CC) in a single 40-mg oral dose. Symptom-limited graded treadmill exercise tests were performed just before, and at 4, 7, and 24 h after a single administration of the drug or the placebo was given. Exercise tolerance at 4, 7, and 24 h after the drug were compared with the corresponding placebo values. Data could be analysed for 19 patients. Maximal exercise time, time to the onset of angina, and time to 1 mm ST segment placebo. The average maximal exercise time was significantly increased by 72, 76, and 37 s at 4, 7, and 24 h. Rate-pressure product at rest and at peak exercise showed significant changes only at 24 h compared with placebo (both P < 0.05). The maximal increase in exercise tolerance was most marked at 7 h nifedipine CC, at which time plasma drug concentration was 99.4 +/- 14.0 ng.ml-1. Thus, in patients with chronic stable exertional angina pectoris, nifedipine CC showed a prolonged improvement in exercise tolerance up to 24 h after a single oral administration.

Long-term efficacy of acute thrombolytic therapy for myocardial infarction.

We conducted a retrospective study (1981-1990) to determine whether the efficacy of intracoronary thrombolysis (ICT) could be evaluated from data obtained solely after recanalization. We investigated 55 successful ICT patients (38 with anterior and 17 with inferior myocardial infarction (MI)), and 31 control infarct patients without recanalization. The total serum creatine phosphokinase release (sigma CPK), the extent of infarction measured by T1-201 single photon emission computed tomography (total DS) and the disturbance of regional wall motion (asyn.%) were investigated as parameters for distinguishing the successful ICT and control groups. Discriminatory ability for the two groups was highest with the total DS in all patients. Only the total DS differed significantly between the two groups in patients with inferior infarction. Misidentification of control patients as successful patients was least frequent (25.5%) when using the total DS. These findings suggest that the effectiveness of ICT for acute MI may be assessed on the basis of data obtained solely after recanalization, with the total DS being particularly useful.

Blood coagulability and fibrinolytic activity before and after physical training during the recovery phase of acute myocardial infarction.

The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1-antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2-plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.

[Analysis of circulatory responses to orthostatic stress in the elderly].

An active orthostatic stress test was conducted on 32 elderly patients over 65 years (elderly group) and 17 normal adults, for a comparative evaluation of their blood pressure, heart rates, and plasma catecholamine responses. In addition, 8 patients in the elderly group underwent a study of orthostatic responses with or without sublingual administration of isosorbide dinitrate (ISDN). The results of the orthostatic responses were evaluated by Schellong's method. The elderly group produced a positive reaction in one (3.1%), and a weakly positive reaction in two (6.3%), while the remaining 29 (90.6%) and all of the normal adults showed negative responses. The systolic blood pressure pattern that developed in response to rising among the elderly group was significantly different (p less than 0.001) from that of the normal adult group, but the response pattern seen in the heart rates of the former approximated that of the latter. The plasma norepinephrine concentration 10 minutes after rising increased significantly (p less than 0.001) in both the elderly and normal adult groups. This increase amounted to 1.5-fold in the elderly group and 2-fold in normal subjects, with a less prominent increase shown by the elderly. The norepinephrine levels of the elderly group were significantly higher than those of the normal adults both before and 10 minutes after rising (p less than 0.001 and p less than 0.01, respectively). In the elderly, ISDN caused a significant drop in the systolic blood pressure immediately after rising and a significant increase in the heart rate. Sublingual ISDN administration resulted in a significant increase in the norepinephrine level (p less than 0.05) in association with rising. These findings indicated that the circulatory responses to orthostatic stimuli are inappropriate as clinical data among the elderly and the administration of ISDN exaggerates this shortcoming further.

Left ventricular performance at rest and during exercise in patients with dual-chamber pacemakers.

In 13 patients with an implanted dual-chamber atrioventricular (AV) demand pacemaker, left ventricular performance was elicited by pacing mode manipulation for study using gated cardiac pool scintigraphy at rest and during exercise. There was no significant difference between DDD and VVI at 70 and 90 beats/min with respect to cardiac output, peak ejection rate or peak filling rate. At 110 beats/min, the cardiac output was greater with DDD as compared to VVI. The peak filling rate was also significantly greater with DDD as compared to VVI (DDD: 3.6 vs VVI: 2.8 EDV/s, p less than 0.05). During exercise the cardiac output was greater with DDD as compared to VVI at the same rate. The peak filling rate during exercise was significantly greater with DDD as compared to VVI (DDD: 3.0 vs VVI: 2.5 EDV/s, p less than 0.01). We conclude that DDD is more beneficial than VVI in maintaining cardiac performance during exercise.

Sex and age differences in ventricular gradient.

Sex and age differences of ventricular gradient (G) were analyzed and normal ranges were determined in normal Japanese subjects (120 men and 74 women), whose resting heart rate was within the range of 65 to 75 beats/min. Women showed a larger Z component in AT and a smaller Y and larger Z component in G than men. The common trend in age differences was a decrease in Y component of G in both men and women. The ranges obtained in the present study can be applied in automatic VCG analysis, in particular for the differentiation of primary and secondary ST-T changes.

Suppressive effect of SUN1165 on supraventricular tachycardia.

The electrophysiologic properties of SUN1165 and its suppressive effect on supraventricular tachycardia were assessed in 14 patients, nine with atrioventricular reentrant tachycardia (AVRT) and five with atrioventricular nodal reentrant tachycardia (AVNRT). This new agent prolonged the PR interval and QRS duration but did not alter the QT interval or the corrected QT interval. It did not alter the sinus cycle length or sinus node recovery time. The drug prolonged the AH interval, HV interval, and intraatrial conduction time but did not change the effective refractory periods of the right atrium or right ventricle. SUN1165 prevented the induction of tachycardia in six of nine patients with AVRT by a complete retrograde block of the accessory pathway and prevented AVNRT in four of five patients by a complete retrograde block of the fast atrioventricular nodal pathway as well. We conclude that SUN1165 is very effective in preventing AVRT or AVNRT. Larger studies with more patients are warranted.

Effects of vasodilators on venous tone in vivo in dogs.

The authors investigated, in vivo, the effects of four vasodilators on venous tone in dogs. Baseline venous tone was determined from the pressure: diameter relationships in the inferior vena cava (VSIVC) and femoral vein (VSFV) as measured during several seconds of occlusion of the proximal inferior vena cava. All of the slopes were nearly linear. All vasodilators were administered in dosages sufficient to lower blood pressure by approximately 20%; these dosages also decreased systemic vascular resistance by 15% to 30%. Isosorbide dinitrate reduced VSIVC from 7.17 +/- 0.81 to 5.81 +/- 0.73 mmHg/mm and VSIVC from 59.4 +/- 13.5 to 37.2 +/- 6.6 mmHg/mm. Neither nifedipine nor nisoldipine altered VSIVC or VSFV. However, prazosin decreased VSIVC from 13.2 +/- 3.3 to 10.7 +/- 2.7 mmHg/mm and VSFV from 43.5 +/- 11.3 to 29.9 +/- 8.8 mmHg/mm. These results suggest that isosorbide dinitrate and prazosin decrease venous tone in vivo, whereas nifedipine and nisoldipine do not.

Prognostic value of abnormal postexercise systolic blood pressure response: prehospital discharge test after myocardial infarction in Japan.

To assess the prognostic value of an abnormal postexercise response in systolic blood pressure (SBP), treadmill exercise testing was performed in 217 survivors of acute myocardial infarction at an average of 9.3 weeks after infarction. During the mean follow-up period of 4 years, cardiac events were noted in 34 patients (16%), including cardiac death in 13 (6%), nonfatal reinfarction in 12 (6%), and coronary artery bypass graft surgery in nine (4%). An abnormal postexercise SBP response was defined as the ratio of SBP at 3 minutes of recovery to peak exercise SBP of 0.9 or more, on the basis of the cutoff point with the highest sensitivity and specificity to predict cardiac events. An abnormal postexercise SBP response occurred in 90 patients (42%). Patients with an abnormal postexercise SBP response had more exercise-induced myocardial ischemia. more left ventricular impairment, and more extensive coronary artery lesions than those without. Cox proportional hazards model demonstrated that the abnormal postexercise SBP response was ranked first in ability to predict cardiac death (p = 0.025, relative risk 15.41). Bypass surgery was associated with an abnormal postexercise SBP ratio (p less than 0.05). Nonfatal reinfarction could not be predicted by any clinical or exercise variables. In conclusion, an abnormal postexercise SBP response could be useful for predicting cardiac death and the need for bypass surgery after myocardial infarction. This response is probably the result of myocardial ischemia and left ventricular impairment.

Application of the Karhunen-Loeve expansion to evaluate regional cardiac excitation in body surface potential maps.

The authors investigated the usefulness of the Karhunen-Loeve technique applied to body surface maps to study regional cardiac excitation. Eigenvectors were derived from the body surface potential maps of 120 healthy adults using the Karhunen-Loeve expansion theory. Then, in the maps of various types of ventricular hypertrophy, each eigenvector coefficient was calculated for a statistical comparison. The first eigenvector coefficient in early QRS and the second in mid QRS were larger in patients with asymmetrical septal hypertrophy and in patients with left ventricular hypertrophy, respectively. The third was larger in patients with right ventricular hypertrophy. In the maps of patients with previous anteroseptal myocardial infarction, the second eigenvector coefficient decreased with asynergy of the anterior to apical wall, and the first decreased with the asynergy of the interventricular septum. They conclude that some eigenvector components and coefficients at particular times in the QRS are sensitive to changes in regional cardiac excitation and that they may facilitate the detection of local excitation changes such as occur in hypertrophy or infarction.

Effects of oral elastase on lipid metabolism, platelet function, and blood coagulability in patients with diabetes mellitus.

Lipid metabolism, platelet function, and blood coagulability were evaluated in 20 patients with diabetes mellitus and stable fasting blood sugar levels before, during, and after treatment with the pancreatic enzyme elastase for 16 weeks. Serum high-density lipoprotein cholesterol levels increased from 46.9 mg/dl before treatment to 53.2 mg/dl after treatment (P less than 0.001) and serum triglyceride levels decreased from 151.4 to 125.4 mg/dl (P less than 0.05); no significant changes in total cholesterol levels were noted. Platelet counts in whole blood and in platelet-rich plasma increased from 17.1 and 27.5 X 10(4)/mm3, respectively, to 19.8 and 31.3 X 10(4)/mm3 after treatment (P less than 0.01 and less than 0.05). Plasma beta-thromboglobulin levels decreased from 117.0 to 72.7 ng/ml after treatment (P less than 0.001). No significant changes in platelet sensitivity to adenosine diphosphate aggregation were noted. Plasma fibrinogen and antithrombin III levels increased from 421.0 and 25.8 mg/dl, respectively, to 470.6 and 32.0 mg/dl after treatment (P less than 0.05 and less than 0.001). It is concluded that, since it has been shown that elastase improved lipid metabolism, inhibited platelet release, and increased antithrombin III levels, it may play a useful role in the prevention of vascular complications in diabetic patients.

The important role of left ventricular relaxation and left atrial pressure in the left ventricular filling velocity profile.

To evaluate the determinants of left ventricular filling, left ventricular filling velocity was measured by pulsed Doppler flowmetry during catheterization of the right and left sides of the heart in 37 patients with cardiac disease before and during leg elevation. During leg elevation, despite no significant change in the time constant of isovolumic relaxation (T), the peak rapid filling velocity (PVRF) increased in association with an increase in pulmonary wedge pressure (PWP), but the peak atrial filling velocity was unchanged. The PVRF correlated with the pulmonary wedge V wave - left ventricular minimum pressure difference (r = 0.68) and in multivariate regression with both T and mean PWP (R = 0.73). These results indicate that left ventricular filling is determined by both left ventricular relaxation and left atrial pressure and that an increase in left atrial pressure changes the left ventricular filling velocity profile in a manner that mimics the pattern with normal diastolic function.

Influence of risk factors on long-term survival following acute myocardial infarction: a follow-up study in central Japan.

The long-term survival rate following acute myocardial infarction (AMI) was studied in 358 patients in central Japan who were monitored for 8 to 20 years after discharge from hospital for AMI. Fifteen-year cardiac survival rates were 65% in males and 72% in females. In both sexes, the survival rate decreased with increasing age at the time of AMI. The survival rate was significantly lower in recurrent MI than in first MI patients. Those who had smoked cigarettes before AMI or had hyperlipidemia during hospitalization did not show any significant decrease in cardiac survival rate, which may be due to cessation of smoking or control of hyperlipidemia after AMI. The 15-year survival rate was significantly lower in patients with a past history of angina pectoris or hypertension. Patients with a large infarct had a lower survival rate, as did those with a large cardiothoracic ratio on chest x-ray, and those who received digitalis during hospitalization. On the other hand, patients who were administered anticoagulants during hospitalization had a higher survival rate. Multiple regression analysis gave similar results. In conclusion, factors that reduced long-term survival rate after AMI were older age at time of the first attack, reduced cardiac function, and a history of angina pectoris or hypertension. Anticoagulant therapy appeared to improve the long-term survival rate.

Localization of coronary artery narrowings by applying R-wave amplitude correction to exercise-induced ST depression in angina pectoris and single-vessel coronary artery narrowing.

This study investigated whether coronary artery narrowings can be localized by applying R-wave amplitude correction to exercise-induced ST depression in multiple unipolar precordial lead electrocardiography using 20 electrodes covering the left chest wall. Ten normal subjects and 29 patients with stable angina pectoris and single-vessel coronary artery narrowing (greater than or equal to 75% luminal diameter stenosis in only 1-vessel) participated. Of the 29 patients, 5 had left main coronary artery disease (CAD), 14 had left anterior descending CAD, 4 had right CAD and 6 had left circumflex CAD. The exercise-induced ST depression with R-wave amplitude correction was defined as the exercise-induced ST depression divided by the R-wave amplitude. The 20 points of the lead system were divided into 4 areas: the left main, left anterior descending, right and left circumflex coronary arteries. Coronary artery narrowing was supposed to be in an artery corresponding to the area where the maximal value of the exercise-induced ST depression with and without R-wave amplitude correction was situated. By applying R-wave amplitude correction, the diagnostic ability of localization of coronary artery narrowings was improved significantly from 52% to 86% (p less than 0.005). In particular, localization of the left main coronary artery narrowing was correctly diagnosed in 100% (5 of 5) of angina pectoris patients with left main CAD.

Usefulness of rate responsive atrial pacing in patients with sick sinus syndrome.

We studied heart rate response and blood lactate changes during treadmill exercise testing in 10 patients with sick sinus syndrome (SSS) and normal atrioventricular (AV) conduction in whom an activity detecting multi-programmable rate responsive pacemaker was implanted for atrial pacing (AAI pacing). Treadmill exercise testing was performed twice in each patient under the two different AAI pacing modes: rate responsive function off (fixed rate 60 pulses per minute [ppm]; RR-off) and rate responsive function on (rate response 10, activity threshold medium, basic rate 60 ppm, and maximum rate 150 ppm; RR-on). Chronotropic response and blood lactate change during exercise were compared among patients under each pacing mode and eight healthy volunteers of ages matching those of the patients. In patients under the RR-off pacing mode (RR-off patients), chronotropic response was lower (P less than 0.01) and blood lactate level was higher (P less than 0.05) than those in patients under the RR-on pacing mode (RR-on patients) and volunteers during exercise. In RR-on patients, however, both chronotropic response and lactate level changes during exercise were comparatively improved, with no significant differences between RR-on patients and volunteers. These data suggested that improvement of chronotropic response by rate responsive pacing, in comparison with nonrate responsive pacing, increased the blood supply to the working muscles and resulted in less lactate production during exercise. It was concluded that rate responsive AAI pacing which could maintain AV synchrony and normal intraventricular conduction was an optimal physiological pacing mode for SSS patients with normal AV conduction.

Accuracy of cardiac output measured by continuous wave Doppler echocardiography during dynamic exercise testing in the supine position in patients with coronary artery disease.

To estimate the accuracy of cardiac output measured by continuous wave Doppler echocardiography from the suprasternal notch and the utility of this method for evaluating left ventricular function during dynamic exercise, simultaneous thermodilution and Doppler cardiac output were measured in 34 patients with coronary artery disease during multistage ergometer exercise in the supine position. Cardiac output was measured at rest and during each stage of exercise. Twenty-five of the 34 patients whose thermodilution curves were adequate for analysis were studied during exercise. The correlation coefficient for the two methods was 0.85 at rest and 0.84 during exercise. Differences between the two methods were not significant at rest but were significant during exercise, with the thermodilution method giving the higher values. Underestimation by the Doppler method is probably due to technical problems and changes in aortic diameter during exercise. The 25 patients were classified into two groups according to pulmonary artery wedge pressure at peak exercise. There were 11 patients in Group 1 pressure (greater than or equal to 20 mm Hg at peak exercise) and 14 in Group 2 pressure (less than 20 mm Hg at peak exercise). There were significant differences in the change in cardiac index and in peak aortic velocity from rest to peak exercise between the two groups. A significant linear correlation between the percent change in peak aortic velocity and in pulmonary artery wedge pressure from rest to peak exercise was observed (r = -0.66, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of Q waves outside standard precordial lead points in left anterior myocardial infarction undetectable by standard 12-lead electrocardiogram.

Body surface potential maps were recorded for 52 patients with solitary anterior myocardial infarction and 57 normal subjects. All patients had pure anterior wall asynergy on a left ventriculogram but no diagnostic Q wave on the standard 12-lead electrocardiogram. Q wave (greater than 30 msec) distributions on the body surface of the patients and normals were compared. The frequency of Q waves in the area above V1-V2 and in the right middle chest was significantly higher in patients than in normals. The sensitivity of Q waves for asynergy in leads from both these areas was 19-60%. The positive predictive value was 67-94%. The frequency of Q waves was significantly higher in severe asynergy than in mild asynergy. A combination of two selected unipolar leads from these areas yielded a sensitivity and specificity of 33% and 95%, respectively. With a combination of three leads, these values were 42% and 93% and with four leads 48% and 88%, respectively. The results indicate that several unipolar leads from the area above V1-V2 and from the right middle chest in addition to the standard 12-lead electrocardiogram may improve the electrocardiographic diagnostic accuracy of myocardial infarction.

[Echocardiographic findings in a case of Fabry's disease with aortic regurgitation and complete AV block, and in his family members].

A 46-year-old man with Fabry's disease having aortic regurgitation and complete atrioventricular (AV) block was presented. In spite of severe aortic regurgitation (Seller's grade 3/4), his two-dimensional (2-D) echocardiogram revealed increased thickness of the left ventricular wall with mild dilatation. The myocardial echo showed a fine granular sparkling texture suggesting phospholipid deposition in the myocardial tissue. The membranous portion of the interventricular septum was thickened, and the aortic valve was thickened and had imperfect coaptation. Endomyocardial biopsy of the right side of the interventricular septum revealed intramyocardial vacuolization by light microscopy. Electron microscopy confirmed the presence of myelinoid lamellar inclusion. Electrophysiologic examination revealed an intra-Hissian AV block. A DDD pacemaker was implanted and the patient's symptoms were improved. Valvular replacement was not attempted due to the danger of suture failure. The patient's brother (41-year-old) also had increased thickness of his left ventricular wall on echocardiography, and a complete AV block by ECG, but no valvular abnormalities. His sister (45-year-old) had increased thickness of the left ventricular wall on echocardiography, and negative T waves by ECG, but she had no cardiac symptoms. The possibility of cardiac involvement in this heterozygous woman with Fabry's disease should also be considered. The patient's 38-year-old sister and all the children of all family members had normal left ventricular wall thicknesses and normal ECG. These findings may correspond to the age-related disease severity. The possibility of cardiac abnormalities should be considered in heterozygous women with Fabry's disease.